, Trepar~~d ;;. M.L. Thompson, Ph. D., Dspt. Of Pharmacology. Tufts Medical School

Pharmacology Board v ~ ~ ~ a i l y a t l e a ~ t ~ n e q ~ e ~ t i ~ n ~ ~ m e ~ ~ a s k i n g y ~ ~ t ~ calculate how many mg of local anestRetic a atient has Review 1997 received, lidocaine e.g. solution? how many 2% lidocaine mg of lidocaine is a r r n / 1 0 0 in i.tPml ml of or a 2% 20

- --V ' mg/l ml, so 36 in 1.8 ml.

This list of questions and topics is the result of going through about 10 years worth of old Board Exams in Pharmacology, cutting out all the questions, cate orizing them into topic areas (e.g. antibiotics, local anesketics. etc.), and then further grouping them into the r p of information about a cat ory of drugs that was being asked for. When you d o x s , you see that many exams repeat questions (sometimes they reword them a little bit to make them look different!), but in actuality it is possible to e ta feel for the various facts that you are expected to

&now, and that there arent that man of them. As you go through this handout, you will see t L t I point out to you the major facts that tend to get asked aver and over again for the various ma' r drug categories, and I also give you actual examples o P questions (and the reworded versions), as well as the correct answer. In some cases, I have written out a detailed explanation of the answer, just to enlighten you further. So good luck and enjoy.

The 2nd part of this handout rovides some clinical scenarios that may help you regarling Part B.

Local Anesthetics I. The largest category of LA questions focuses on your ability

to distinguish amide LAs from esters:

esters = procaine, tetracaine, cocaine. All the rest are amides: lidocaine, mepivacaine, bupivacaine, prilocaine, dibucainc. They also require you to know that amides are metabolized in the liver, esters mainly b esterases in plasma. An infrequent question asks iviich class of drugs has the most consistency in structure. LAs are the drug group most consistent in drug structure, because LAs are either amides or esters, differing only in their structure in the intermediate chain (its either an amide or an ester) that connects the aromatic group to the secondary or tertiary amino terminus.

11. The next cate ory of uestions has to do with toxic reactions to local anestietics, e k e r due to high systemic levels of local anesthetics in general (cardiovascular collapse due to myocardial depression, h tensive shock) or to a specific agent such as prilocaine, w%h causes methemoglobinemia.

III. A 3rd class of questions are aimed at your knowledge of the mechanism of action of local anesthehc,:: they revent the generation of nerve impulses by interfering wit! sodium transport into the neuron.

IV. The last most frequent ty of question regarding local anesthetics has to do witKssues re arding absor tion of R local anesthetics. Remember, only t e non-ionizei'(or free base form) form can penetrate tissue membranes. Inflamed tissue has a lower than normal pH, which decreases the amount of non-ionized form available to penetrate.

1. Which of the following is a local anesthetic subject to inactivation by plasma esterases?

a. Procaine b. Lidocaine c. Prilocaine d. Mepivacaine e. Bupivacaine

(n) ~ r o c c i i ~ r e is tlre ollly ester listed -- nll the rest nre nntides

2. Procaine differs from lidocaine in that a. Procaine is a p-aminobenzoic acid ester and lidocaine

is not b. Lidocaine is a meta-aminobenzoic acid ester and

rocaine is not c. r h e duration of action of procaine is longer than that of

an equal total dose of lidocaine d. Procaine hydrochloride is metabolized into

diethylaminoethanol and benzoic acid.

(n) this is bnsicnlly n true-filse type qlrestio~r. (n) is tile oltly s tnten~att tlmt is true

3. Which of the following local anesthetics would be expected to produce a sensitization reaction in a patient allergic to lidocaine?

a. Mepivacaine b. Tetracaine c. Procaine d. Prilocaine e. Dibucaine

i. (a), (b) and (c) ii. (a), (d) and (e) iii. (b) and (c) only iv. (b), (c) and (dl v. (b), (dl and (el

( i i ) nllotiler ester us. antde t pe ide~tfificatiott q~testio)t.lidoccni~te is nn nnti X e , thtrs other nmdes will be cross-allergetric - mepivnmirre, prilocnine atrd diblrcailte nre the other anrides listed. Procnitre a d tetracaine are esters and will trot be cross-allergenic.

9. The h drolysis of procaine occurs mainly in the a. liver b. Lungs c. Plasma d. Muscles e. Kidneys

rocaine is nlr ester; esters nre nzetabolized F d n l i n n i c l t j by pscudoodtolirtesleraser in the plnsma.

10. Which of the following is local anesthetic subject to

inactivation by plasma esterases? a. Lidocaine b. Prilocaine c. Tetracaine d. Mepivacaine e. Bupivacaine

(c) esters nre nretnbolized plnsnln esternses - tet rncniiie "r is tlle ollly ester listed, nli t re rest nre nnrides

11. The activity of procaine is terminated by a. ELimination by the kidney b. Stora e in adipose tissue c. ~e ta%ol i sm in the liver on1 d. Metabolism in the liver angby pseudocholinesterase in

the plasma

(dl renlenrber #9 nbove? see tlle zc~ord "nrnhrly"? snnle qltestio~r, brrt worded n little differently to tlrroru yorr off . Agni~r, procabre is n11 ester; esters nre nletnbolized

redonlirtntely by psercdoclrolirresternses in the ylnsnrn, &ct nlso to sonw exte~rt by esters br tlre liver.

2. All of the follo\\.in factors are significant determinants of the duration of coniuction block with amide-type local anesthetics EXCEPT the

a. H of tissues in the area of injection b. begree of vasodilatation caused by the local anesthetic c. Blood lasma cholinesterase levels d. Blood i o w through the area of conduction block e. Concentration of the injected anesthetic solution

( c ) tlre word "EXCEPT" slrortld nlert voll tllnt this is bnsicall n trice-fnlse ty\~e qrrestiorr with 4 true stntenle~rts arm I g lse sfnten~e,rt; yorr rcrt llrlz~e to fi lire orlt tohicli one! 111 tlris cnse, yorl pot bnzle to renrenrfer tllnt lnsnrn R clroli~lesternse Iez~els nre ollly inrportnlrt for the itrntiorr of nctio~r of ester-ty e LAs, rot anrides, wllicll nre nretabolized br tlre i z r r . All tlie otlrr stntmte,rts ore z~nrinbfes tohiclr nffect drirntioll of the block, blct apply to botlr esters nrrd nnrides.

13. Which of the following is contraindicated for a patient who had an allcr ic reaction to procaine six months ago?

a. Nerve Aock with lidocaine b. Topical application of lidocaine c. To ical application of tetracaine d. 1ntf;tration with an antihistamine

(c) agnitl, just anotller qriestiot~ tllnt requires yo14 to be nble to pick out an ester or all nnride from n list. Si~rce procairre is all ester, oirly nnotller ester L A worrM be cross-nllerge~ric. 111 tlris list tlre o ~ l l y estcr listed is tet racaine.

14. Bupivacaine (Marcaine 1 has all of the following properties relative to lidocaine (Xylocaine 1 EXCEPT bupivacaine

a. Is more toxic b. Is an ester-type local anesthetic c. Has a slower onset of action d. Has a longer duration of action

(d ) Accordi~rg to textbooks, local n~restlletics fall ill to tlle

13. Amide-type local anesthetics are metabolized a. Serum b. Liver

e. Axoplasm

(b ) do1l.t forget: esters ill plnsnrn; nnrides in liver

16. Severe liver disease least affects the biotransformation of which of the following?

a. Lidocaine b. Procaine c. Prilocaine d. Mepivacaine

(b) Alrswer is (b)- Yorc slrorcM be nble to recog~ii:e tlmt nll of tllese drrcgs nre local nnesthetics. Local nnesthetics nre of olre of two t pes, eitller esters or nnrides. Ester types nre sub~ect to ~ydrolysis irr tlle pbsnln n ~ l d thus llnw short llnl liz~es. Anrrdes nre nretnbolized prinlnrily in tlre liver nn d llnve loll er llnlf liz~es. Tlrrcs t l ~ b io tm~~sfornrnt io~~ feg., ndnbolisnt; ngnin, t l ~ rats are ltsilrg n difiere~rt word to corrfrcse oil, even thouglt t l q ore asking the snnle basic questiorlr o an n n d e type local nlrcstlletrc would be tlle most nlter a/ in tlre presetrce of sezper liver disease. Tlle key word here is "least ". O f tlre drrcgs listed, oirly procni~le is a11 ester. Tlle rest are n nr rdes.

Questions regardi~zg toxicity:

17. A patient has been given a large volume of a certain local anesthetic solution and subsequently develops cyanosis with methemoglobinemia. Which of the following drugs most like1 was administered?

a. Locaine b. Prilocaine c. Dibucaine d. Lidocaine e. Mepivacaine

(b) strictly rnemorizat ion

18. Use of prilocaine carries the risk of which of the following adverse effects?

a. Porphyria b. Renal toxicity c. Gastric bleeding d. Methemoglobinernia

(d ) snnre as above but a s k d backwards. Metllenloglobi~lenria nlny resrilt from a tolliiditte

1-repared L?. M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

nretnbolite oj prilocnittc, ortlrotolrt idine.

19. The most robable cause for a serious toxic reaction to a local anestEetic is

a. Psychogenic b. Deterioration of the anesthetic agent c. Hypersensitivity to the vasoconstrictor d. Hypersensitivity to the local anesthetic e. Excessive blood level of the local anesthetic

(e) Most toxic renctio~ts o j n seriorrs tmtrrre nre rehted to excessive blood levels arising fronr ittndvertnrtt i~rtravascrtlnr inject io11. Hypersertsitiz)ity react iotts (options b b c ) are rare, brtt excessiz~e blood Zez~els will induce toxic renctions like CNS stintrtlntio~t in ntost eveyotte. This is n cnse wllere optiort (e) is the "best "n~tszuer, becnrtse it is nrore likely tlmtr tlle other altotrntiz)es, which ntight be true, but are ttot as likely (e.g, "nrost probnble") to lmppmt.

20. High lasma levels of local anesthetics may cause a. 1nRibition of eristalsis b. stimulation oPbaroeceptors resulting in severe

hv~otension c. 16fiibition of the vagus nenle to the heart d. Depression of inhibitory neurons in the CNS

c. Lidocaine d. Tetracaine e. Mepivacaine

(n) A~rswer is (0)- A11 tlre listed locnl ntrestl~etics e x q t cocaitte are z~nsodilntors, especinlly ester-dy e drrtgs suclt as proccnbte ntrd tlre nnride lidoca6te. &caitte is the only local anestlretic tlrat predictably prodlrces vasocorrstridiott . Cocnitte I S nlso tlle o1tly Jocnl nrtestlletic to block tlle rertptnke o NE i ~ t t o ndrelrer 'c trertro~ts, n~rd thus potetrtinte f l u NE! tlrat lras bee11 r e g d fronl rterve endirrgs

24. Which of the followin anesthetic dmgs produces powerful stimulation of the ceretral cortex?

a. Cocaine b. Procaine c. Lidocaine d. Tetracaine e. Mepivacaine

(n ) see explntrntiotr nborle

Questions regarditig mechanisnz of actiotz:

(dl itr itinlly LAs irrlribit cetrtrnl itrlribitory rtertrotrs, 25. Local anesthetics block nerve conduction by wlriclt resrtlts in CNS stinrrtlntioir, wlliclr cntt :,roceed to a. Depolarizing the nerve membrane to neutrality corrr~rrlsio~rs. At lriglter doses, t l q itrlribit bar!; i~rlribitory b. Increasing membrane permeability to K+ nitd excitntoy ~rertrotrs, lendirrg to n geirernlized stnte of c. Increasing membrane permeability to Na+ CNS depressiott zulriclr cn~r res~t It itt respirnto y d. Preventing an increase in membrane permeability to K+ depresstort ntrd denth. e. Preventing an increase in membrane permeability to Na+

21. Cardiovascular collapse elicited by a high circulating dose of a local anesthetic may be caused by

a. S ncope b. &gal stimulation c. Histamine release d. Myocardial depression e. Medullary stimulation

( d ) Cnrdior)nsncrthr colhpse is drre to n direct nctio~r oj tlre locnl ntrestlretic otr tlte lrenrf ntrtscle itself (LA'S itr toxic doses dcpress nrentbm~re ercitnbility n ) d cotrdrtctio~t zrlocity), tlrrrs ( d ) is tlle correct nirszoer. All oj tlre otlrer nlter~tatives nre i~rdirect wnys to nfiect tlre lzeart.

22. The most serious consequence of systemic local anesthetic toxicity is

a. Vertigo b. Hypertension c. Hyperventilation d. Post depressive central nervous system convulsions e. Postconvulsive central nervous system depression

(e) Of the aptior~s listed, tlris is tlle one t h t will kill the patient, whrclr I guess m k e s it tlle most serious.

23. Hypotensive shock may result from excessive blood levels of each of the following local anesthetics EXCEPT

a. Cocaine b. Procaine

(c-! didtt't 1 nuke yorc ntenrorize this?You should at kenst rcntenrber Na+ iorts are i~tz)olz)ed, whiclt Jintits your clroices to ( c ) a ~ t d (e). (c ) wottld irrcrease or jacrlitnte rrervous intprt lse cotrdrtct iorr, zolriclt is the opposite oj wlrnt yorc want tlle locnl nttestlletic to do, so pick (e).

26. Which of the following is true regarding the mechanism of action of local anesthetics?

a. Usually maintain the nerve membrane in a state of hyperpolarization

b. Prevent the generation of a nerve action potential c. Maintain the nerve membrane in a state of

depolarization d. Prevent increased permeability of the nerve membrane to

tassium ions e. Kerfere with intracellular nerve metabolism

(b) this should be really obz)ious!

27. Local anesthetic agents prevent the generation of nerve impulses by

a. Decreasing threshold for stimulation b. Decreasing restin membrane potential % c. Decreasing inwar movement of sodium ion d. Increasing inward movement of potassium ion

(c) Answer is (c)- strni ht memorizntiotr- nerve impulses are gerrerated b y the infBux oj sodiunr resulting in depolarization. repolarrzatio~r nttd itractivity occurs wlletr

otassirrm moves out. (sodiunr-potassittnt pltmp). LAs act Ey b l o c ~ n g NO+ nrovenrettt.

28. Local anesthetics interfere with the transport of which of the following ions during drug-receptor interaction

a. Sodium b. Calcium c. Chloride d. Potassium e. Magnesium

(n) see lrow nmtry differeirt wnys tlrcy cnir nsk tlrr snnie qrtestioir?

Questions regarding pH effects on absorytiorr of local anestlzetics

30. If the pH of an area is lower than normal body H, the

local anesthetic activity would be J membrane theory of local anesthetic action pr icts that the

a. Greater, owing to an increase in the free-base form of the drug

b. Greater, owing to an increase in the cationic form of the drug

c. Less, owing to an increase in the free-base form of the d% d. Less, owing to a decrease in the free-base form of the d%

e. None of the above

31. A local anesthetic injected into an inflamed area \\*ill NOT give maximum effects bccausc

a. The pH of inflamed tissue inhibits the release of the free base

b. The drug will not be absorbed as rapidly because of the decreased blood supply

c. The chemical mediators of inflammation will present a chemical antagonism to the anesthetic

d. Prostaglandins stabilize the nente membrane and diminish the effectiveness of the local anesthetic

(n) zulrile sonre o tlle otlrer n1terirntiz)es solrild plnrrsible, tlibik nborrt tlre /Rctoids you were tnlrglrt "bout lourl niiestlletics nild twrinbles thnt n cct tlreir nctioir. Air inrportniit oire runs tlle role of p 1 nird ioirizntioir fnctors. Remeniber, tlle free bnse or rrotrioirized fornr is the fornr tlrnt passes throiiglr nrenibmircs, yet oirce iiiside tlle neuron oirly tlte roirized form is e ective. lnflnnrnred tissue Ims a lower pH tlrnil irornrn "f tissrre niid will slrift the equilibriunr of the L A solirtion srrclr t h t niost of it remains i o n i d and thus rlirnz~nilnble to perretrnte

32. The penetration of a local anesthetic into nervous tissue is a function of the

a. Length of the central alkyl chain b. Lipid solubility of the ionized form c. Lipid solubility of the unioniztd form d. Ester linkage between the aromatic nucleus and the

alkyi chain e. Amide linkage between the aromatic nucleus and the

alkyl chain

Menibrnire pernrenbility is nffected by zulretlter or i1ot tlte nlolecrrle is "clrarged" or ioiritd or irot (e. ., ~ilrioirizcd). Oiily tlre latter jornr pnsses rendily tlrrorcgTr nrenrbmiies. See, tlrey're nskrrrg the snnze tlriirg tlrey nsked iti tlle prezjiorrs qlrestioir, just conriirg nt it front airother nirgk. Renrenrber tlre fact nrrd yorr cnir correr tlle niigles.

35. At a pH of 7.8, lidocaine (pKa = 7.8) will exist in a. the ionized form b. the nonionized form c. an equal mixture of ionized and nonionized forms d. a mixture 10 times more ionized than nonionized forms

(c) the ratio ofioirizeri to uirionized forms is giveif by tlle formula lo A I M = H-pKa. In this instniice tlre diJfereirce %etwrcn pfl aiid pKa is 0. Thrrs lidocnhre will exist as air eqrral mixtrrre ( so (c) is correct). Most lourl nnestlletics nre wenk bnses with pKn rniigiiig from 7.5 to 9.5. LA'S i~iteirded for iirjectioii are rrstrally prepared iii snlt fornr additioii of HCI. Tlrey peiretrnte as tlre rririotrizec.i%rnr iirto tlre ireuroir ~ulrere t l q reeqrrilibrnte to botli clmr ed nird rrirclrnr ed ornrs iirside tlle ireuroir - tlre positive& clinrged ioir f loc ,! s irerzr coirdrrction.

33. The more rapid onset of action of local anesthetics in small nenres is due to

a. The slightly lower pH of small nerves b. The jyeater surface-volume ratio of small nerves c. The increased rate of penetration resulting from

depolariza tion d. Smaller nerves usually having a higher threshold

Wlro kirorus? Who cores? probnbly tlle nirswer is (b) - tlle tlreo goes tlrnt tllere is n srre depeildeirt criticnl leirg;): of ai~estlrtetic exposure irecessary to block a give11 trerve. Snmll fibers zuill be blocked irst becnrise tlre nirestlrefic cor~ceiitratiotr to It criticnl 1 engtlr iii n snlnll fiber ulill be renclred fnster tllnir tlre criticnl leirgtlr iii n Inr er fiber. Yorr lmve to block tlrrec irodcs of rniir~ier, aird t l e y nre fnrtller npnrt br lnrger fibers tlmir they nre iir snrnll dinnreter fibers. Mnke s n r d

34. Which of the followin statements are true regarding onset, degree and duration ok action of local anesthetics?

a. The reater the dru concentration, the faster the onset and k e greater the %e of effect

b. Local anesthetics b loc !n ly myelinated nerve fibers at the nodes of Ranvier

c. The lar er the diameter of the nerve fiber, the faster the onset of effect

d. The faster the penetrance of the drug, the faster the onset of effect

i. (a), (b), and (c) ii. (a), @) and (dl iii. (a) and (c) only iv. @I, (c) and (d)

(ii) if you knew the act above about small nerves, then I this uestion basica ly becomes a true false t pe thin , nild rc) is thefalse statement. (a) and (d ) m a h lo .caf sense so you are stuck picking between fb) and (c f You h u e your ick of ntemorizirrg tlre smnll irerve thing or tlre myelrirata!nerue nodes of rairoier thiiig.

(c) oirly optioirs (b) nird (c) nre relez~nirt lrere - the otlrers lmzv ilotlriirg to do ruitlr LA peiretrntioir iirto nrenrbrni~es.

prepared b}' M.L. Thompson, Ph. D., Dept. Of Pharnlacology, Tufts Medical School A >I" b .f

35. A dentist administers 1.8 ml of a 2% solution of lidocaine. HOW* many mg of lidocaine did the patient receive?

a. 3.6 b. 9 c. 18 d. 36 e. 180

36. Three ml of a local anesthetic solution consisting of 2% lidocaine with 1 :100,000 epinephrine contains how many milli ams of each?

a. Fmg. lidmine, 0.3 mg. epinephrine b. 6 mg. lidocaine, 0.03 mg. epinephrine c. 60 mg. lidocaine 0.3 mg. epinephrine d. 60 mg. lidocaine 0.03 mg epinephrine e. 600 mg lidocaine, 0.3 mg. epinephrine f. 600 mg. lidocaine, 0.03 mg. epinephrine

( d ) 2% lidocniltc = 20 nrglnrl x 3 = 60 nrg lidocni~le 1:100,000 epi = 0.01 nrg/n~l x 3 = 0.03 nrg cpi

37. The maximum allo~\.able adult dose of mepivacainc is 300 mg. How many milliliters of 2% mepivacaine should be injected to atta~n the maximal dosage in an adult patient?

a. 5 b. 10 c. 15 d. 20 e. 25

38. A recently introduced local anesthetic agent is claimed by the manufacturer to be several times as potent as procaine. The roduct is available in 0.05% buffered aqueous solution in I.&. cartridge. The madmum amount recommended for dental anesthesia over a Chour period is 30 mg. The amount is contained in approximately how many cartridges?

a. 1-9 b. 10-18 C. 19-27 d. 28-36 e. Greater than 36

( d ) 0.05% = 0.5 niglnrl . To gizle 30 nrg, yorc irate to give 30nrg/0.5 nrg/ml or 6 0 nrl. 1 cnrtridge = 1.8 ml, thus 60nrl /1.8ml = 33.3 cnrtridges. - irst express the percentnge of solutiorr as a fraction o 1 O d the11 add tiw units gm/ml. 0.05% unls 0.5 or 1 h gms per 100 nrl. The cnrtrd e is 1.8 rnl %ich you can routtd off to almost 2 mls total. fn firis 2 nrl you wouM ltazpe 1 gnr of the local altestlzetic. You need to p v e 30 I S , wlticir would reqiiire 3 0 cartridges. The alternative 1% meets tlris answer is ( d ) . Dotr't get tricked by tlre plncentetrt of tlze decinlnl poitrt-many peo le remi tlw 0.05% ns bebtg tlte sunw ns 5 gnrs rntlwr tlul1l gS gnrs.

Antibiotics 1. The most frequently asked type of question rquires you to be

able to compare various penicillin antibiotics m terms of potency against certain bugs, allergenicity, drug of choice against certain conditions, etc. For example:

a. Penicillin V vs. enicillin G: the latter is more sensitive to acicfdegradation and thus is usually injected rather than taken orally

b. Which nicillin has the best gram-negative spectrum: ampiciKn

c. Which dru s from a list are or are not cross-allergenic with penic!hin: most usually asked about ones are: cephalosporins and ampicillin are, erythromycin isn't

d. Which penicillin is useful against penicillinase- producing bugs such as staphylococcus: dicloxacillin

e. Which is specific for Pseudomonas infections: an extended spectrum such as carbenicillin

f. Which combination of agents should be used prophylactically for atient with heart valve to prevent bacterial enxmarditis: ampicillin and gentamycin (1988- according to latest recommendation of AHA and ADA, although use the latest guidelines that you have heard about))

2. The 2nd lar est category expects you to know the mechanism of action o h h e various antibiotics:

a. Bactericidal a ents such as penicillin kill rapidity growing cells%y inhibiting cell wall synthesis

b. Bacteriostatic agents such as tetracycline limit population growth, but do not kill bu s by interfering with protein synthesis on bacterial ri % osomes

c. Antifungals such as nystatin bind to ergosterol in fungal cell walls to weaken the wall

d. Bacteriostatic a ents such as the sulfonamides compete with PABA in klic acid synthesis, thus resulting in folic acid deficiency

3. Many uestions are asked regarding drug interactions or side ezects or toxicities of penicillins, tetracyclines, clindamycin, etc:

a. What are symptoms seen during allergic reactions to penicillins: dermatitis, stomatitis, bronchoconstriction and cardiovascular collapse

b. What agent produces GI upset and pseudomonas colitis: clindamycin

c. Which agents are most likely or least likely to cause superinfection: most-broad spectrum agents such as tetracyclines; least-narrow spectrum agents such as penicillin G

d. Aplastic anemia is associated with chloramphenicol

e. Liver damage or hepatotoxicity is associated with tetracycline

f. Erythromycin estola te associated rvi th allergic cholestatic hepatitis

4. Questions involving interactions between antibiotics and other drugs:

a. Tetracycline and penicillin cancel each other out due to opposing mechanisms of action

b. Probenecid alters the rate of renal clearance of penicillin

c. Effectiveness of tetracyclines is reduced by concurrent ingestion of antacids or dairy products

d. Broad spectrum antibiotics enhance the action of coumann anticoagulants because of the reduction of Vitamin K sources

e. Antibiotics such as am icillin decrease the effectiveness of oral contraceptives Bue to suppression of normal GI flora involved in the recycling of active steroids from bile conjugates, leading to more rapid excretion of the steroids from the body

Frequelztly asked questio~ls on n~itibiotics:

5 . For treatin most oral infections, enicillin V is preferred to penicillin because penicillin

a. Is less allergenic b. Is less sensitive to acid degradation

eater am-negative spectrum i. E: X n 6 e r %ration of action e. Is bactericidal, whereas penicillin G is not

(b) nrenrorizntiorr: bnsicnlly !\re oilly diffcrerlce

6 . The sole therapeutic advantage of penicillin V over penicillin G is

a. Greater resistance to penicillinase b. Broader antibacterial spectrum c. More reliable oral absorption d. Slower renal excretion e. None of the above

(c) reworded zlersiorl of tlle abozle

7. Which of the following penicillins is administered ONLY by deep intramuscular injection?

a. Am itillin b. ~ i c ~ x a c i l l i n sodium c. Penicillin G procaine d. Penicillin V potassium

(c) Answer is (c)- (a), (b) ntrd (d ) are all used orally. Penicillirr G is destroyed b ncid itr tlte stonrnclt resultittg in rwriablc arrd irregular n!sorptiorr. Perricillin V is acid stable and ar~ailnble for oral use. Petricillirr G procaine is typically g'vetr iir tmnrrrscrtlnrl in repository form, yieldins n tiss~ie i f ot hont ioficb the drlt b nbsorbd over horrrs. In this T r m , if cnrtrrot be girrrl fV or srtbcrttnrreoalsly.

8 The principal difference a m o n g ~ t a r s i u m , procaine and benzathine salts of penicillin is their

a. Potency b. Toxicity c. Duration of action d. Antibacterial spectrum e. Diffusion into the cerebrospinal fluid

(c) agairr, just nskirtg yori to hiow sonrething about tlte zlnriorrs fornrs of poricilliir. Since irr niost cnses yori nre goirrg to use Perf VK ornlly, this qriestiorr is nrr old orre slrowirrg i f s age and probably not likely to a p p r atrynrore orr bonrd excams

'10. All of the following antibiotics are considered to have a high rate of allergenicity EXCEPT

a. Penicillins b. Erythromycin c. Sulfonamides d. Amphotericin B

11. Which of the followin antibiotics is cross-allergenic with penicillin and should $0~ he administered to the penicillin- sensitive patient?

a. Am icillin b. ~r-yt\rom~cin c. Cllndamycin d. Lincomycin e. Tetracycline

(n) an~picillii~ sort of sortrlds like perricillirr so it mrtst be fhe nrrswer

12. Which of the following antibiotics may be cross-allergenic with enicillin?

a. 8mmycin b. Cephalexin c. Clindamycin d. E thromycin e. ~ y o f the above

(b) nt is is n nrenroriznfiorr rlestiorr, witlr (b ) tlle correct n~rsruer. Yorr h u e to rentenier tlmt the ceplulosporira (like cephalexitr) are clunricnlly relnted to tlle penicillitrs. Tlle otl~ers nre not clrenlicnlly relnteci nrrd thrrs cross- nllergeiricity is urllikely

13. Which of the following antibiotics shows an incidence of approximately 8% cross-allergenicity with penicillins?

a. neomycin b. cephalekn c. bacitracin d. vancom cin e. tetracycLne

(b) 'ust slight1 reworded version of the above questiorr, brrt with some drf&ent alternatives throwrr in. Obviously, ij yort a n recognrze w h t k r or not a drug is a penicillin or a ceplralospori~t , and you remember that these are the classes t h t show cross-allergetricity, therr you cart handle any rezoordirrg of this question.

14. Which of the following groups of antibiotics is related both structurally and by mode of action to the penicillins?

a. Polymyxins

Prepared by M.L. Thompson, Ph. D., Dqt. Of Pharnlacolog-, Tufts Medical School

b. Cycloserines c. Ce halosporins d. ~ h r o r a m ~ h e n i c o l s

c. Methicillin d. Penicillin V e. Phenethicillin

(c ) see nboae (bj

13. For the dentist, the most reliable method of detecting a patient's allergy to nicillin is by

a. Injecting penic~ FP lin intradermally b. Taking a thorou h medical history c. Placing a drop of penicillin on the e e d. Having the patient inhale a penicilin aerosol e. Injecting a small amount of penicillin intravenously

(b) all of the other metlrods itrz~olr)e trrtncceptnbk risk. Orlce setrsitized, evert a snrnll anrotort cnrr cnrtse arr nllergic resporlse. Renrenrber, it is riot n dose-relnted respotrse t h t worl't be problenrntic if yorr only irlject ti little bit.

14. Which of the following antibiotics is the substitute of choice for penicillin in the penicillin-sensitive patient?

a. Bacitracin b. Erythromycin c. Tetracycline d. Chloramphenicol

15. Most anaphylactic reactions to penicillin occur a. When the drug is administered orally b. In patients who have already exper~enced an allergic

reaction to the d rug c. In atients with a negative skin test to penicillin allergy d. ~ R e n the drug is administered parenterally e. Within minutes after drug administration

i. (a), (b) and (d) ii. (b), (c) and (d) iii. (b), (d) and (e) iv. (b) and (e) only v. (c), (dl and (el

Which of the following penicillins has a broader gram- trum than penicillin G? n?a%,'iK

b. Am icillin c. cepRalexin d. Methicillin e. Penicillin V

17. Which of the following penicillins has the best gram- negative sst;ectrum?

a. Nafci lin b. Ampicillin

18. Which of the following antibiotics should b e considered the drug of choice in the treatment of infection caused by a penicillinase-producing staphylococcus?

a. Neomycin b. Ampicillin c. Tetrac cline d. ~ e n i c i i i n V e. Dicloxacillin

19. Oral infections caused by organisms that produce penicillinase should be treated with

a. Am icillin b. ~ i c K x a c i l l i n c. Erythromycin d . Any of theabove e. Only (a) o r (c) above

(b) of those listed orrly ( b ) is yetricillitrnse resistnrlt. Anrprcillirr is nri extertded spectrtrnr poricilliil, nrrd is trot pet~icillirlnse resistntrt .

20. Which of the following antibiotics is LEAST effectikle against penicillinase-producing microorganisms?

a . Am icillin b. cepRalexin c. Methicillin d. Clindamycin e. Erythromycin

(n) snnle qrrestiotr nsktd bncknsswnrd

21. Which of the following is a bactericidal antibiotic used ifically in the treatment of infections caused by

SEdonrorras species and indole-positive Proteus species? a. Ampicillin b. Penicillin V c. Tetracycline d. Dicloxacillin e. Carbenicillin

(el Wow, I bet you didrr't thirrk t l q woitld ask sonlrtllittg like this!. An extended spectrunt agetrt is required. Anrpicillin is ineffectizw, while Peii-V is too narrow irl spectrum.

22. Penicillin's effectiveness against rapidly growing cells is primarily d u e to its effect o n

a . Protein s nthesis b. Cell wal&nthesis c. Nucleic acld synthesis d. Chelation of metal ions e. CeU membrane permeability

23. Chlortetra cline acts b y interfering with ?' a. Cell wa 1 synthesis b. Nuclear a a d synthesis

c. Protein synthesis on bacterial but not mammalian ribosomes

d. Protein synthesis on mammalian but not bacterial ribosomes

24. The probable mechanism of the bacteriostatic action of sulfonamides involves

a. Disruption of the cell membrane b. Coagulation of intracellular proteins c. Reduction in oxy en utilization by the cells d. Inhibition of met&olism by binding acetyl grou s e. Competition with para-aminobenzoic acid in foyic acid

synthesis

23. The sulfonamides act by a. Sup ressin bacterial protein synthesis b. lnhi[iting tge formation of the cytoplasmic bacterial

membrane c. Inducing the formation of "lethal" bacterial proteins d. Inducing a deficiency of folic acid by competition \\*ith

para-aminobenzoic acid

26. Which of the follot\*ing statements is true regarding streptom cin?

a, It is gactericidal b. It has a gram-positive spectrum c. It is usual1 administered orally d. It disruptsiacterial cell membranes e. It is associated a low incidence of bacterial

resistance

(n) c is ,tot trrtc: streytonrycitr is ndntirristerd o t~ ly z~in itljectiotr; (e ) is fnlse: resistnrrce dez)elops rnpidly

27. Tetracycline reduces the effectiveness of cencemitantly administered penicillin by

a. Reducingabso tionof 'go penicillin b. Increasing meta lism o penicillin c. Increasing renal excretion of penicillin d. Increasin binding of penicillin to serum proteins e. Nenc ef t f e s k v e

(e) tetrn clirre is bnderiostntic ntlii would slow tlre rpii i owth o F h r nlicrobinl populntiott tlmt n bnctericidal

%trg rtrclr ns petticillitt t t d s to be effectirr

28. Which of the following antibiotics is most likely to cause liver damage?

a. Streptomycin b. Penicillin G c. Tetrac cline d. ~ e ~ h a r o s p o r i n s e. Amphotericin 0

(c) Answer is (c)- (n), streptonrycitr cntr dnmnge the eigltth nerve, affectitrg botlt bnlntlce nrtii lmri~tg , , brrt is trot associatd witlt ltver daninge. (b): otlrer tjmn nllergic renctiotrs, erricillills are extremely snfe, with rio efect ort the liver. &), tlte ceplmlosporite nre clrenricnlly re I n t d to tlre petricillitts nrtd slmre tlteir relntively rto~rtoxic trntrire. (e), nnrpltotericitt B, is nrt ntitifiotgnl ngetzt tlmt prodrices

suclt ndz)erse side effects ns rleplrrotoxicity nnd lrypoknlentia, btrt lizler toxicity.'Tlttts (c) ts tlte correct nrrswer. Tetrncyclirres llnzre beer1 sltozutt to be llepntotoxic follozoitrg high doses irt pregrrnttt pntiettts luitlt n lristoy of rertnl disense.

29. Which of the following erythromycins associated with an aller ic cholestatic hepatitis?

a. Erythromycin base b. Erythromycin stearate c. Erythromycin estola te d. Erythromycin succinate

30. Which of the following antibiotics is LEAST likely to cause superinfection?

a. Gentarnicin b. Tetrac cline c. ~ e n i c i i i n G d. Streptomycin e. Chloramphenicol

( c ) srrperiufectio,~ nre rrsrtnlly s ew follozuilrg the trse of brood spectrrrnt ngertts. Of tlrose l i s t d , nll nre wide spectrrrnr except Pen-G

31. Gastrointestinal upset and seudomembranous colitis has been rominently a s s o c i a t e k t h

a. 8ystatin b. Cephalexin c. Clindamycin d. Polymyxin B e. Erythromycin

32. Sym toms that may be characterized as allergic manirestations during penicillin therapy are

a. Deafness, dizziness and acute anemia b. Crystalluria, nausea, vomiting and anaphylactic shock c. 011 uria, hematuria, bronchoconstriction and

carsiovascular collapse d. Dermatitis, stomatitis, bronchoconstriction and

cardiovascular collapse

33. Aplastic anemia is a serious toxic effect that occurs articularIy after a course of treatment with which of the

Pollowing antibiotics? a. Penicillin b. Lincomycin c. Tetracycline d. Streptomycin e. Chloram phenicol

34. Each of the followin is a side effect of rolonged tetracycline hydrochforide therapy EX(!EW

a. Suprainfection b. Photosensitivity

Prepared by M.L. Thompson, Ph. D.. Dept. Of Phannacolop, Tufts Medical School

c. Vestibular disturbances d. Discoloration of newly formin teeth e. Gastrointestinal symptoms ( d e n administered orally)

35, Gastrointestinal upset and seudomembranous colitis have been prominently asvxiatefwith use of which of the follow$ng anti-infective agents?

a. Nystatin (M costatin ) b. Cephalexin keflex ) c. Clindamycin (Cleocin ) d. Polymyxin B (Aeros K""" e. Erythromycin (Eryt roan )

Antibiotics, Miscellaneous

36. In accordance with the latest recommendations of the American Heart Association and the American Dental Association, a dental patient tvith a prosthetic heart valve with no drug allergik should receid prophylactically which of the follo!zring antibiotic com inations?

a. Ampicillin and cephalexin b. Ampicillin and entamicin c. Gentamicin anterythromycin d. Erythromycin and tetracycline e. Penicillin G potassium and vancomycin

( b ) - Pntieirts toitlr prostlretic llenrt z~alz~es nre nt risk for bncterinl eirdocnrcfitis, aird t h i s req~!ire nrnxinrrlnr prop11 lnxis n nirrst possible iirfectiotr fronr deirtnl procdures. T f i s reqiqlles n conrbhmtiotr of arrtibiotics ojferirrg rotectioir ngaiirst both gmnr rtegntitre nitd positizr Rncterin. (b ) is the conrbrrrntiort yorr sltorrM E:' nrenrorized. It is tlre orrly derttnl use of the nnrirroglycoside gerttnnrycirt. T l ~ e conrbinntiort of ,~nnrprcillir~ nrtd ge~rtnnryciit / u s n syrrergrstic efect n nirrst streptococci arrd atterococcnl tmrrsiarts irr 1 I re orn f cnvity tlwt nlny be relntively iilseirsititpe to eiricilliir nlo~re. Anrpicillitr nrrd gerrtnnryciir conrhirre botRbnctericidnl a id imcteriostntk nctioir. Mniiy strlderrts nirstoer (e), becnrlse vnrrconrycirr cnrr nlw be tised iir this sittlntioir, brtt oirl ns arr nltcrrrntizr to perricilliir iir peiricilliir nllrgic pntieirts. nrrls the conrbiirntiorr of z~nirconryciir nrrd perricillirr nukes 110 ser15e.

37. The action of which of the following drugs will most likely be im aired by concurrent administration of tetracycline?

a. &loramphenicol b. E hromycin c. Su 'I; onamide d. Penicillin e. Lincomycin

38. A distinct advantage that tetracyclines have over penicillins is that tetracyclines

a. Have no side effects b. Do not cause superinfections c. Are safer to use during prepancy d. Have a wider range of antibacterial activity e. Produce higher blood levels faster after oral

administration

(A)

39. Which of the following has the broadest antimicrobial spectrum?

a. Vancomycin (Vancocin ) b. Clindarnycin (Cleocin ) c. Erythromycin (Erythrocin ) d. Chlortetracycline (Aureomycin ) e. A third generation cephalosporin

(if) Arrswer is (d)- renrenrber, tetracyclirtes are brond spectrrt nr antibiotics ellfectir~e agninst both gram-negntizv nr~d gram-positiz)e cocci nnd bacilli. Clirianrycirr has a spectrrtm of actiz)ity similnr to erthyrom cin arid zvnconrycin, wlriclr is less tlvtrr tlurt of t h tetrncyl6res, nrnirrly aflect irrg r r n - p o s i t ive nricroorgarrisnrs. 1st generatiori cephn osporrris are eflective agninst both gmnt-negative arrd gram-positit~e or airisnrs, bilt the third gerrerntion orres imoe irrcreasei nctizlity ngnirrst gmnr-rregntive brlt grently decrensed nctivity ngniirst grnnr-positive nricroorgnrr isnrs.

40. Sulfonamides and trimethoprim are synergistic bacteriostatic agents because in bacteria they

a. Both inhib~t folic acid synthesis b. Interfere sequentially with folinic acid production c. Are both antimetabolites of para-aminobenzoic d. Are both inhibitors of dihydrofolic acid reductase e. Are both transformed iir ziw into a single active

compound

41. Which of the followin substances is the most effective agent against fungus ~~$ections of the mucous membrane?

a. Nystatin ointment b. Undecylenic acid c. Polyrnyxin ointment d. Saturated magnesium sulfate e. 10 per cent aluminum chloride solution

14. Nystatin is of greatest clinical usefulness in treating a. viral infections b. fungal infections c. s irochetal infections d. {acterroides infections e. penicillin resistant gram positive infections

(b) Nystatin is the prototypic n n t ~ rignl agetit, t l~lls (b) is f" the nrost obvious 1st choice, nrrd e min nates (0). ( d ) 0 5 require an antibiotic, not an antifitngal

42. Which of the following drugs chelates with calcium?

b. a. PO ET ymyxin hromycin B c. Tetrac cline d. Penici&n G e. Chlorarnphenicol

43. Which of the following is NOT characteristic of tetracycline antibiotics?

a. Absorption is impaired when taken with antacids b. They redispose to monilial su erinfection c. They Lrrn a stable complex wit! the developing tooth

matrix d. They have a low tendency for sensititation, but a high

therapeutic index e. They are effective substitutes for penicillin prophylaxis

agalnst infective endocarditis

Answer is (el- A aiir, tile inrportntlt hrnse 61 tlre question isrtot(heyI just Wayrre ntlR~nrt11). Obz~ioasly the fnct tllnt you will renrenrber nborrt tetmcylittes is t h t they cair discolor teeth itr tlte fetris ruherr tnketr by tite mother duritrg preprnncy. But doir 't circle tllnt ntrszr7er because (a) is also characteristic o\ tetmcyclitres (tliey are tite nrost likely of nll the airtibiotics to u t t se superitrfectioir), ntrd is nit nnnoybrg side effect iir ndriits resultiir fronr nlterntioir of tite ornl, gnstrrc ntrd itrtestiiml f7ora. 7% renl nitswer is (e). Tetmcycliires nre trot the drug of clroice or pro hvhxis ngnrirst iirfectirle etrdocndit is. T l i s rs A h to st reptococcnl iirfectioir. 15- 20% of rotcp A str~ptococci are resistntrt to tetrncyciires, but rtorre nre resistnrrt to petricilliir or e ytlrronrycirr. Recerr tl n noir-streptococcnl itrdrrced slrkcrr f e bnctrrinl etrdcnrditis lvrs beerr idetrtr ied, especinlly iir jtizrrrile periodorrtitis y t i en t s . &e cnrisntizje bncteririnr is rrof srlsceptible to peiricillitl or erythronlycirl. It nlny be ltecessn y to trcnt predisposed patieirts with tetrncyclitre for n fcz~f weeks, n~rd then follow this zoitir n corrrse of pcrricillirr or eytlrronlvcilt. Renrenrber t1mt these drrlgs nre nrrtngorristic to enclr otllcr ntrd tlrrls cnrr't be rrsed co~rcr~rreirtly. Perricillitl is n bnctericidnl drrtg zuilicir kills or destroys nlicroorgnrrisnts by itrter erirrg roith the sytrtlresis or frrrrctiorr o tlrc cell zunll, ce f 1 nrenrbrnrre or both. Tlrrls it is n~ost e ~ c t i z r ngnirrst bncterin timt nre nrriltiplyiirg. Tetrncyclitre is n bncteriostntic nrrtibiotic tllnt ncts by itl/ribitirr~ the grozuth nrrd nrltlti licntiorr of orgntrisnrs by irtlribitirrg proteir~ sytrtltesis [V birtdb~ relrrsibly to the 30 5 srrb~itrit of t h bncterinl rihosonre. brerr iite two types nre ghrrr togetlrer, tlreir effcctiz~etrcss is ~lesntcd or rdliced.

Antibiotics, Drug Interactions

44. The concurrent administration of penicillin G and probenecid results in

a. Increased metabolism of penicillin G. b. Increased renal excretion of robenecid c. Decreased renal excretion ofpenicillin G d. Decreased bactericidal effect of penicillin G e. Increased excretion of probenead in the feces

'1. Interaction between penicillin and probenicid is best described by which of the following mechanisms?

ition at the receptor site b. a.mmp't acce eration of drug biotransformation c. alteration in the acid-base balance d. alteration in the rate of renal clearance

Thris pntieltts zoitlr reirnl disense tr?ill slroul ltiglr blood levels of peiricillirt. Sinrilnrlv, probeiricid, n riricos~iric ngeirt (n drug wlriclr teirds ti, eitlrnirce tlte excretiotr of uric ncid by rdlrcirrg rerrnl tltbtrlnr trnrts or1 ntednnisnts), reduces the reml clenrnitcr o/ peitici6iirs. A t d yo11 zuorrdered why we Imd tlrose lectrires oil pi~nrnlncokinet ics!

45. When broad-spectrum antibiotics are administered with coumarin anticoagulants, the anticoagulant action may be

a. Reduced because of enhanced hepatic drug metabolism b. Reduced because of increased protein-binding c. Increased because of reduction of vitamin K sources d. Increased because of decreased renal excretion of the

an ticoagulant

46. The thera utic effectiveness of which of the followin drugs w i l l g most affected by concomitant ingestion o k antacids?

a. Cephalexin b. Erythromycin c. Tetracycline d. Sulfisoxazole e. Penicillin V

Alrswer is (dl- perricilliir is nletnbolized iir the liver, but it rapidly disnppears onr tlte blood drie to rnpid chrntrce by the ~ t r y s . 90 6 o is excreted by trtbrthr secretior~.

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

Cardiovascular Drugs

This cate ory covers a lot of drugs and a lot of questions. They can%e categorized as:

1. Questions asking about which drug from a list might be used to treat a certain condition:

hypertension:

I ) Diuretics such as the high ceilin diuretic, furosemide; 2) Beta-blockers such as propran801 or the

cardioselective beta blocker metoprolol; 3) Alpha-1 blockers such as prazosin, 4) Centrally acting adrenergic drugs such as methyldopa

or clonid ine 5) Neuronal blockers such as guanethidine (reserved for

severe hypertension) 6) Angiotensin converting enzyme inhibitors such as

Captopril

angina: Nitro lycerin, sometimes propranolol, calcium channel bkockers such as verapamil

arrhvthmias: 3) Lidocaine (ventricular arrhythmias), 2) Phenytoin (to reverse digitalis induced arrhythm-ias),

- 3) Quinidine (supraventricular tachyarrhythmias, a trial fibrillation), m e r a p a m i l (sEprye;tritu~; tachyarrhythmias, ~aroxvsmal tachvcar la atria brilla at ion), - 5 ) ~ i g i t a l i s (at ;ial fibrillation, paroxysmal tach cardia) 6) $ropranolol (paroxysmal tachycardia)

Congestive heart failure: Glycosides such as digitalis, digoxin, ACE inhibitors such as captopril

2. The second major category of questions concerns mechanism of action of the various agents:

Antiahythmics: Remember problem is that the heart beats irregularity

a. Type 1A agents such as quinidine: acts by increasing the refractory period of cardiac muscle

b. Type 1B agents such as lidocaine decrease cardiac excitability

c. When digitalis is used for atrial fibrillation it acts by decreasing the rate of A-V conduction

Antian ina drugs: problem is insufficient oxygen to meet demanck of myocardium

a. Nitro lycerin increases oxygen supply to the heart by a %Ired vasodilatory action on the smooth muscle in coronary arteries

b. Propranolol reduces oxygen demand by preventing chronotropic responses to endogenous epinephrine, emotions and exemse.

c. Calcium channel blockers decrease oxygen demand by reducing afterload by reducing peripheral resistance via vasodilation

Antihypertensives: Remember, most drugs have the ultimate effect of reducing peripheral resistance via vasodilation

ACE inhibitors: Captopril blocks the enz me which converts angiotensin I to an iotensin 11. &e latter is a potent vasoconstrictor (alministration of angiotensin will result in an elevation of blood pressure).

Adrenergic Agents:

a. Prazosin: selective alpa-1 blocker, inhibits binding of nerve induced release of NE resulting in vasodilation

b. Methyldopa: acts centrally as a false neurotransmitter stimulating alpha receptors to reduce sympathetic outflow resulting in vasodilation

c. Clonidine: selective a onist stimulates alpha- 2receptors in the C N ~ ~ O reduce sympathetic outflow to peripheral vessels resulting in vasodilation

d. Pro ranolol: nonselective beta blocker reduces car iac output and inhibits renin secretion

e. Metoprolol: selective beta-1 blocker, reduces cardiac output

Diuretics: decrease the renal abso tion of sodium, thus resulting in fluid loss and a rxuction in blood volume. This decreases the work the heart has to pump. Also have weak dilatory action. Types of diuretics which may be mentioned include:

a. Thiazides: chlorothiazide

b. Highceiling or loop acting: furosemide

c. Potassium sparing: spironolactone

Corrgestive henrt failure drugs:

a. Cardiac lycosides such as digitalis or digitoxin are effective fecause they have a positive inotropic effect, increasin the force of contraction of the myocardium. &is is achieved by an inhibition of Na+, K+ ATPASE leading to increased calcium influx. Digitalis therapy reduces the compensate changes that are associated with congestive heart x i lure such as increased heart size, rate, edema, etc.

Drug-co~rdition questions

1. Quinidine is principally used to treat a. Hypertension b. Angina pectoris c. Congestive hear failure d. Supraventricular tachyarrhythmias

( d ) try elimination. H ertension ( (a) ) is treated priniarily with betn b g k e r s such as propranolol. Angina is primarily treated wi th rritroglycerirt, while digoxirt (dr 'tnlis) is the drug of choice for congestive heart ai ure. Quinidine is classed as an arrtrarrthymic drug f f' (Ty 1-blocks sodium clmnnels). It reduces autonraticity

an responsiveness and incruses refractoriness. It also has an antimitscnrinic action preventing the bradycardin tlrnl follows vagnl slimulntiori.

2. Quinidine is used to treat a. Hypertension

b. An6ina pectoris c. Atrial fibrillation d. Ventricular fibrillation e. Congestive hear failure

3. Verapamil is most efficacious in the treatment of a. Atrial fibrillation b. Atrial tachycardia c. Ventricular tachycardia d. Catecholamine-induced arrhythmias

4. Which of the follot\ing d m s is most useful in treating or

a. Digitalis 9 preventing angina pectoris.

b. Quinidine c. Propranolol d. Procainamide e. Pentobarbital

5 . Each of the follo~\*ing drugs can be used in the prevention and treatment of angina pectoris EXCEPT

a. Digitalis b. Propranolol c. Nitro lycerin d. ~ s o s o i i d e dinitrate e. Pentaerythritol tetranitrate

All of the followin drugs are useful in the treatment of hypertension EX~EIT

a. Ephedrine b. Reserpine c. Methyldo a d. Thiazide cfiuretics

7. Digitals is useful in the treatment of which of the following conditions?

a. Atrial fibrillation b. Congestive heart failure c. Paroxysmal atrial tachycardia d. All of the above

8. All of the following dru s are useful in the treatment of cardiac arrhythmias E ~ C E M

a. Di italis b. ~ i j o c a i n e c. Phenytoin d. Procainamide e. Aminophylline

(el

9. The drug of choice for initial therapy for mild hypertension is

a. Reserpine b. Guanethidine c. Phenobarbital d. Chlorothiazide e. Alpha-methyldopa

10. Which of the following antihypertensives are usually reserved for treatment of severe hypertension?

a. Sedatives and reserpine b. Thiazide diuretics and reserpine c. Sedatives and thiazide diuretics d. Guanethidine and ganglionic blocking agents

11. Which of the following beta-adrener ic receptor blocking

a. Nadolol 5 agents is thought to be cardioselective.

b. Timolol c. Metoprolol d. Propranolol

Meclrarr ism of Actio~r Questions

At1 tiarrlr y tlrmics

12. Antiarrhythmic dru s, such as quinidine, suppress certain cardiac arrhythmias%y

a. Stimulating the beta-adrenergic receptor b. Suppressing cardiac ATP-ase activity c. Increasing ectopic pacemaker activity d. Increasing the refractory period of cardiac muscle

13. Most d m s s useful in the treatment of cardiac arrhythmias act primarily b

a. Blocking Arkin ' fibers b. Blocking the alpffa-adrenergic receptor c. Suppressing SA nude impulse formation d. Causing a positive inotropic effect e. Increasing the refractory period of cardiac muscle

14. The most im rtant harmacologic action of drugs that suppress car r iac a n i! ythmias is

a. Blockade of the va s nerve !?= b. Stimulation of car iac ATP-ase activity c. Blockade of t he Beta-adrenergic receptor d. Stimulation of the beta-adrenergic receptor e. Increased refractory period of cardiac muscle

15. Lidocaine produces its antiarrhythmic effects by a. Increasing AV conduction b. Decreasing cardiac excitability c. Increasing cardiac conduction velocity

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharnlacology, Tufts Medical School

d. Increasing spontaneous pacemaker activity

It?) nrrliythnrins nre defiled ns nrry nbtrornmlity of t l u trornrnl sittris rhytlrnr of tlw lwnrt dtre to disense or itr 'linl itrdlicul dnnlnge to t l u inlpube cotdsctitrg systenrs. !%$ nlso restilt from tlre dez)elopnutr t oj ectopic pncenrnkers or nbtrornrnl pncenrnker rltytlrnrs. Dnigs srrclr ns lidocnitre nre used to ~rornrnlize these rlrytlrnrs. Liiocnitre, n locnl nrlestlretic, depresses cardinc excitnbility, ntlswer (b). Tlle refrnctory period of cnrdinc nrriscle is itrcrensed, tllris slowing tlre henrl dowtr. All of the otller nltertrntizpes givetr wolild exncerbnte tlre nrrlrytllnrin.

16. When di6italis is used in atrial fibrillation, the therapeutic objective is to

a. Abolish cardiac decompensation b. Inhibit va a1 impulses to the heart c. Decrease fhe rate of A-V conduction d. Increase the rate of cardiac repolarization e. Produce a decrease in the rate of atrial contraction

Arttiartgirla Drugs

17. Nitroblycerin dilates the coronary arteries in angina pectoris by

a. Decreasing the heart rate reflexly b. Increasins the metabolic work of the myocardium c. Direct action on smooth muscle in the vessel walls d. Increasin the effective refractory period in the atrium e. lock in^ fet a-adrenergic receptors

18. Propranolol is of value in treating angina pectoris because it

a. Has a direct action on vascular smooth muscle b. Blocks autoregulatory mechanisms in the heart c. Inhibits oxygen metabolism in cardiac cells d. Provides relief within seconds of an acute anginal

attack e. Prevents chronotropic re nses to endogenous

epinephrine emotions an exercise

ACE Inhibitors

19. Administration of angiotensin results in a. Anti-inflammato effects b. Antihistaminic ezects c. Increased blood pressure d. Increased heart rate e. A sedative effect

20. The primary antihypertensive effect of captopril (Capoten ) is due to accumulation of

a. Serotonin b. Angiotensin I c. Angiotensin Ifl d. Bradykinin metabolites

( d ) Cnpto ril is ntr arrgiotetrsiotr-cotrz~ertirrg eirzynre itrhiFitor ! L t blocks t l u actiz~atiotr o atrgiotetrsiqtr I to nngrotensrotr 11. Tfre decrensed hroo~cotrcenrrnrrotr of ntrgiotetrsiotr 11 recirices blood pressrire, becnrise nngiotarsiotr 11 is n potetlt z~nsocottstrictor. Wrlis (c ) is rurotrg, nccunrulntiotr of atrgiotetrsiotr I is tlte lisrinl tffect. Cnpto ril also nrniritarns lowered B P b y elevntitrg braykininb in the blood by blockitrg its nlctnbolisnr. W ~ I ~ S ( d ) is wrotr , brndykitrirr nlctnbolites do not accrrnrlilnte. However, t f u key says this is t l u r i Rt atrsmer. Most eople pick (b), wlriclt I tbitlk is pro%nbly t h closest to

Keitrg correct, utlless t l q didtrpt nlean to lit nlctnbolites after bradykitritr. Atrgiotetrsion I accurnukes, blit it ims tro effect otr blood pressure.

21. Administration of angiotensin results in a. A sedative effect b. Increased heart rate c. Increased blood ressure d. Antihistaminic eRects e. Anti-inflammatory effects

Mecltanisnr of Actiort

Diuretics

22. Which of the following is NOT characteristic of the thiazide diuretics?

a. Increase renal excretion of sodium and chloride b. Increase renal excretion of potassium c. Increase the toxicity of digitalis d. Exacerbate existing diabetes e. Cause hypoMemia f. Cause hypoglycemia

23. The most useful diuretic drugs act by a. Increasing the glomerular filtration rate b. Decreasing the renal reabsorption of sodium c. Decreasing the renal excretion of chloride d. Increasing the renal reabsorption of potassium e. Increasing the secretion of antidiuretic hormone

24. Which of the following drugs act by inhibiting renal reabsorption of scdium?

a. Urea b. Chlorothiazide c. Theophylline d. digitalis glycosides e. Procainamide

Cardiac Glycosides

Digoxin exerts its positive inotropic effect by a. Activation of adenylcyclase b. Inhibition of hosphodiesterase c. An agonist effect of - m e tors d. lnhib~tion of Na+, K+ A ~ A s E leading to increased

calcium influx e. Decreasing the amount of calcium available for

excitationtontraction coupling

(dl Answer is (d)- Renlentber, cnrdinc glycosides strclr ns digoxirr nre used irr tlle trenfntertt of cortgestive hurt fatlure, tohiclt is tlle fnilitre of tlle llenrt to fiirtctiott adequately as n pitntp nnd tliiis ntnilttnitt n1t adeqiinte circulatiorr. Cnrdinc glycosides nre tltougltt to act by alterirrg calciunt ion mozjenrent, toitlt n desired eject of d iitcreasiirg the force of coritrnctiort of tlre nryocnr ttinr (e.8. tlle iitotropic effect). Wltile sezrernl of tlre alteritntives iirzrolz~e cnlcittnt, tlte wny digoxirt does it is vin (dl, inltibitiolt of Nn+, K+ ATPnsc, restrltittg i l l ntt irtcrense of cnlciltnr iolt iltfllix irtto tlle cnrdinc ul ls , nlid n srrbseqirerrt errlrnitcenreltt of the colttrnctile nteclutrtisnt. (n) is the Tony epirrepltrilte works.

26. Digitoxin is effective in the treatment of cardiac failure because it

a . 1s primarily a diuretic b. Reduces the ventricular rate c. Decreases abnormal cardiac rhythms d. Produces peripheral vasoconstriction e. Has a positive cardiac inotropic action

27. The primary action of therapeutic doses of digitalis on cardiac muscle is an increase in

a. Force of contraction b. Ventricular excitability c. Refractory period of the atrial muscle d. Refractory riod of the ventricular muscle e. ate of con$ktion of impulse to the muscle

28. The beneficial effects of di italis in congestive heart failure result in part from the fact &at di italis causes

a. A decrease in end-diastolic v i u m e b. A decrease in enddiastolic pressure c. An increase in stroke volume and cardiac output d. A decrease in central venous pressure e. A decrease in rate of the hear where tachycardia exists

i. (a), (b) and (c) ii. (a)and (c)only iii. (c) and (d) iv. (el only v. All of the above

29. The cardiac glycosides will reduce the concentration of which ion in an active heart muscle?

a. Sodium b. Bromide c. Calcium d. Chloride e. Potassium

30. Which of the following ions augments the inotropic effect of digitalis? < M i u m

b. Lithium c. Calcium d. Chloride e. Magnesium

31. In the treatment of congestive heart failure, digitalis glycosides generally decrease all of the followng EXCEPT

a. Edema b. Urine flow c. Heart size d. Heart rate e. Residual diastolic volume

(El

32. The mechanism of action of prazosin, an antihypertensive agent is to

a. Block beta-adrener ic receptors b. Inhibit formation ofangiotensin I1 c. Inhibit nerve-induced release of nore inephrine d. Stimulate central inhibitory alpha-a8energic receptors e. Inhibit the postsynaptic action of norepinephrine on

vascular smooth muscle

(el

33. Which of the following owes a significant amount of its antihy ertensive effect to a central action?

a. d t h y l d o p a b. Metoprolol c. Hydralazine d. Propranolol e. Guanethidine

(a) All o these dru s are used to trent h pertensiott, but J nct by dierent nrecfaiiisnts. (n), nletltyl opa. is t l ~ drug witlr central actiolr- it alters CNS cotttrol o blood pressure b acting on cardioregulnto an d vasomotor s stems o/!'lu brain b stinrulatittg &ha2 receptors bl t L brain stem. ~ l o n i z n e is the usual drug t h t is ittvolved in this particular question. (b) metropolol is a selectively blocks beta-2 receptors in the heart to reduce cardiac output. (c) hydralazine has a direct action on vasculnr smooth muscle to reduce h ertension via vasodilntion. (d ) propranolol blocks g a receptors i f 1 tltr heart, while (e) guanethidine prevents the release and causes depletion o catecholamines taken u p into storage ! vesicles and is re eased like a false transmitter. It does trot cross the blood-brain barrier.

34. Which of the following drugs is thought to reduce arterial blood pressure by activatin alpha receptors in the vasomotor center of the mefulla?

a. Prazosin

Prepared by M.L. Thompson, Ph. D., Dqt. Of Pharmacology, Tufts Medical School

b. Clonidine c. Propranolol d. Guanethidine e. Chlorothiazide

35. Propranolol (Inderal ) can be useful in the treatment of hypertension because it blocks

a. Alpha-1 adrenergic rece tors b. Sodium reabsorption in &e kidney c. The release of renin from juxta lomerular cells

l? d. The release of norepinephrine om nerve terminals e. The reflex tachycardia seen with the use of other

antihypertensives

i. (a)and(b) ii. (a) and (d) iii. (b), (c) and (d) iv. (c), (d) and (e) v. (c) and (el only

(v ) Aiiszc~er is (el- Yori sltorrld intnredintely rccogitize tlmt proprnirolol is the prototypic beta-ndreirergic receptor blocker, tlrrts nity nirszoer zoitlr nlter~rntirje n ((n) nird 2 ) is rc1roitg. Sinrilnrfty, d is wroitg ns well-propmitolo1 i s n conrpetitir~e betn- receptor blocker- it lrns iro efect oil NE relense. Airother d r l q used for hyperteitsion, Cloitidiite, acts z~in this nrecltnirtsnr by stinrlrlntiirg nlplm-2 nlrtoreceptors. Tllrrs (b) , 3, nird 4 nre zoroirg. This lenrjes ( e ) ns tlle o ~ i y possible right nirsrcyer. lirdeed, nside front blockiitg betn-l receptors, blockiirg of reiriir relense is tltorrght to be the other nrecltnlrisnr rolwreby betn-blockers nlter hyperteirsioir.

36. One of the proposed mechanisms of the antihypertensive effect of beta-adrenergic receptor blocking agents is

a. Sedation b. A diuretic effect c. An antirenin effect d. A vagal blocking effect e. An increase in cardiac output

Selective beta-1 adrenergic agonists will produce which of the following effects?

a. Glycogenolysis b. Increased cardiac output c. Decreased diastolic pressure d. Decreased peripheral resistance e. Relaxation of bronchial smooth muscle

Miscellaneous Side Effect Questions

38. Ototoxicit with deafness may encountered occasionally in patients ta&ng which of the following diuretic agents?

a. Osmotic b. Thiazide c. Mercurial d. Highceiling

Iiiglt-ceililtg dirrretic. How the llell nre yo11 srrpposed to renrenrber all of this stuff???

39. S m toms of digitalis toxicity include all of the following E&&

a. Extrasystoles b. Nausea and vomiting c. Yellow-green vision d. A-V conduction block e. Decreased P-R interval

40. Administration of which of the following drugs increases the likelihood of a toxic response to digitalis?

a. Diazepam b. Lidocaine c. S ironolactone d. &lorothiazide e. Acetylsalicylic acid

(dl Clriort!rinzide is n dirtretic rolriclr crrnses potnssirrnl loss or irypohlenrin. This resrtlts irr p t e r perretrntioir of digitnlis iirto the nryocnrdirtnl, nird t rrrs potelttinl toxicity.

41. Which of the following cardiac depressants is contraindicated in a patient with cardiac arrhythmia?

a . Lidocaine b. Quinidine c. Phenytoin d . Propranolol e. Procainamide

(d) All o t h e nre used to trent nr thnrins, bltt proprn~to f ol is probnbly tlle nrrswer %urtse it cnrr sonretinles resrtlt iit colrgetioe Irenrt failrtre.

( d ) ntrstoer is (d) - strni ht ntentorizntiolt- denpress is typicnlly nssocinted zuitf rrse of etlrncryrtic n c d , n loop or

Analgesics- NSAIDS: 1. Mechanism of action questions rebarding analgesic,

antipyretic and effects on bleeding:

Anal esic effects: aspirin inhibits the synthesis of -+gaK Antipyretic effects: aspirin inhibits PG synthesis in the

hypothalamic temperature regulation center

Bleeding time: inhibit synthesis of thromboxane A2 preventing platelet synthesis

2. A 2nd type of question has to d o with pharmacological or toxic effects of aspirin: ou get to ick which of the list is or is not associated wit{ aspirin. Phera utic effects of aspirin include pain relief, antipyretic eRLts, antirheumatic and anti-inflammatory effects. Adverse or toxic effects include all of the following: occult bleeding from the GI tract, tinnitus, nausea and vomiting, acid-base disturbance or metabolic acidosis, decreased tubular reabsorption of uric acid, salicylism, delirium, hypcnrentilation, etc.

3. A third type of question focuses on the difference between 1) as irin and acetaminophen, 2) aspirin and other anti- iniammatories like prednisone, and 3) between aspirin and ibuprofen:

1) Acetaminophen lacks anti-inflammatory activity, is hepatotoxic, and does not cause GI upset

2) Anti-inflammatories like prednisone, hydrocortisone, triamcinolone etc. are steroids and d o not act

rimarily by PC inhibition 3) rbuprofen causes much less GI irritation

Freque~ttly asked questions on NSAIDS

4. The thera eutic effect of the salicylates is explained on the basis of tRe ability of the drug to

a. Activate autonomic reflexes b. Uncouple oxidative phosphorylation c. Inhibit the synthesis of prostaglandins d. Competitively antagonize prostaglandins at the receptor

site

5. The mechanism of the antipyretic action of salicylates probably results from

a. Inhibition of prostaglandin synthesis in the CNS affecting h thalamic temperature regulation

b. inhibition %radykinin in the periphery leading to sweatin5

c. Depression of oxidative enzymes leading to decreased heat production

d . Suppression of cholinergic mediators in the hypothalamus

e. Stimulation of norepinephrine in the hypothalamus

6 . The antipyretic action of salicylates is explained in part by a. Analgesia leadin to sedation b. Increased blood l o w through the hypothalamus c. Cutaneous vasodilation leading to increased heat loss d. Depression of oxidative processes leading to decreased

heat production

7. The locus of action of aspirin's central antipyretic effect is the

a. Brain stem b. Hypothalamus c. Basal ganglia d. Limbic system e. Cerebral cortex

( b ) Answer is (b)- ntentorizatiort questioit- renlentber nttt ipyresis ntealts ntrtifever. Tentpernfltrc regtrlotiort certter is irt the llypotllnlnntus.

8. A patient who has been taking large uantities of aspirin might show increased postoperatiire bqeeding because aspirin inhibits

a. Synthesis of thromboxane A2 and prevents platelet aggregation

b. Synthesis of prostacyclin and prevents platelet aggregation

c. S thesis of prostaglandin and prevents production of b G d latelets

d . Thromiin and prevents formation of the fibrin network e. G.I. absorption of vitamin K and prevents synthesis of

blood clotting factors

(a) Attszuer is (0)- T1t.e rst fnct yorr nrust renrenlber is tlln f nspiritt prezjettts P atelet ng regntiort- this lintits your c io ius to (n) ntt Rib) . TI^ Rope to coti/u= air ty usirtg prostac~litr, but of cottrse yott krtozu t wt t rrs ts wrort inrnzedintely, the ri ht tuord is prosta larrdirt, ns irt ( c f but yotr ltazw alren t y elinrinatd tlwt cfoice bemuse i f doent't metrtiott rezpentiort o plntelet aggregntion. Tltlrs, azen i f ou l d i r ' t rentent b er tlmt throntboxnrte A2 induces pbte$t aggre ation, and nspirirr blocks lltis nctioit, you colrld et t%e answer b y elintinnt ioit. ( d ) is how heparitr works, w h e (e) is how co~rnwriw works.

9. Anti-inflammatory agents, such a s aspirin, interfere with hemostasis by

a. Activating antithrombin b. Preventing vasoconstriction c. Inhibiting thrombin generation d. Inhibiting platelet aggregation e. Inhibiting polymerization of fibrin

10. Which of the followin6 anti-inflammatory agents does NOT act primarily by inhibiting activity of prostaglandin synthetase?

a. Diflunisal b. Ibuprofen c. Triamcinolone d . Oxyphenbu tazone e. Acetylsalicylic acid

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

11. A nonsteroidal, anti-inflammatory a ent that appears to produce fewer gastrointestinal disturtances than high does of as irin is

a. Ku rofen b. ~ r o k n e c i d c. Pentazocine d. Acetaminophen e. Phenylbutazone

d. Anti-inflammatory action e. Antirheumatic action

i. (a), (b) and (c) ii. (a), (c) and (d) iii.(a), (d) and (e) iv. (b), (c) and (d) v. (b), (d) and (e)

(n) yoti mi 111 be tenrpterl to nttszoer ncetnnri~roplrerr, berxrrse it &estrlt cntrse GI rrpset, k i t renrenrher it is nlso 17. All of the followin are pharmacoIo ic or toxicoIogic not artti-inflnntnrntoy. Tlle alrszoer is ibriprofeit. properties of acetykalicylic acid EXEEPT

a. Tinnitus

12. Prolonged use of which of the followin6 drugs does NOT cause a predisposition to gastric irritation and bIeeding?

a. Phenytoin b. Ibuprofen c. Indomethacin d. Phenylbutazone e. Acetylsalicylic acid

(n) Arrszoer is (a)- n t i s is n strniglrt dr~r iderttyicntion qrrestiolt. Artsz~~ers 2-5 nre nll ~~orr-steroi&l nrttiirt nntntntory drtr s zolliclt cnrrse gnstric irritntiotr nltd h f redilrg due to tfeir el ects or1 prostnglnrtdirr sytthcsis ill tlte nrricosnl zon I 101 tlre gtrt. # 3 is nrr nltti- cotr z~ulsnltt -its ntnjor side ellect t llnt oflerr npenrs ns n

riestiolr olr bonrds is tlw prodlrctior~ ojgiirgtz~nl Ilyperplns in.

13. Each of the followin a ents has been associated with gastric irritation E X ~ E ~ T

a. Aspirin b. Alcohol c. Ibuprofen d. Indomethacin e. Acetaminophen

14. Which of the followin is NOT produccd by excessive doses

a. Delirium Y of acetyIsalicylic acid.

b. Tinnitus c. Hypothermia d. H perventilation e. d t abo l i c acidosis

15. All of the following areeharmacologic and toxicologic properties of aspinn EX E M

a. Tinnitus b. Analgesia c. Salicylism d. Antipyresis e. Suppression of the immune response

16. Therapeutic effects of aspirin include a. Analgesia b. Tranquiliza tion c. Pyret~c action

b. Analgesia c. Antipyresis d. Methemoglobinemia e. Inhibition of prostaglandin synthesis

18. All of the following are possible effects of aspirin EXCEPT a. Reduction of fever b. Shortening of bleeding time c. Suppression of inflammatory response d. Bleeding from the gastronintestinal tract e. Increase in the renal excretion of uric acid at high doses

19. Of the followin aspirin does NOT cause a. Occult blf&ng b. Nausea and vomiting c. Acid-base disturbance d. Suppression of the cou h reflex e. Decreased tubular realsorption of uric acid

( d ) Atrswer is (d)- (n) & (b) are tlre nznjor side effects oj aspirilr (restrltiltg Jrom tlre irthibitiott o j prostngln~rdirt syrrtltesis) lor the nrajority 01 people, and orte rensort lor the poptrlnrity 01 nspirilr nlterrrntives suclr ns ncetnntillopltert nrld ibtrprolert, wlriclt produm tllese elects to n lesser extertt. # 3 & 5 nt nlso be seen Lllowilr lnrger doses 01 nspirin. ( Z i s not see11 with nspirin.$ut rs n nmjor tlrernpelitic use o/ narcotic opiates slrclr as codeirte. I guess t l q nre hopin tlmt you will get tlre elects 01 codeitre nlrd nspirilr nlixeif u , srrrce the t w are ole11 compnred and coetrastd ns nrograte pnirt re1 iezpers.

20. Which of the following is NOT true about acetaminophen? a. Is a non-prescription drug b. Is cross-aller enic with aspirin c. Possesses bok analgesic and antip ic effects r d. May induce methemo lobinemia at 'gh doses e. May be the pharmaAogically active form of

acetophenetidin (phenacetin)

21. Which of the following is NOT true regarding acetaminophen?

a. It has antipyretic properties b. It may induce methemo obinemia R' c. It can be combined wit codeine d. It has anti-inflammatory properties

e. It is not cross-allergenic with aspirin

22. The most prominent acute toxic effect associated with acetaminophen use is

a. Hemorrhage b. Renal necrosis c. Hepatic necrosis d. Gastric ulceration e. Respiratory alkalosis

( c ) Renlentber, ncetnnrirto hert (tylerrol) is nrt aspirirt alternntioc. Alterrtntiz~es 1: 4, 5 nre side e ects of aspirirr- type dru s. Tlle populnrity of acetantittop 1 l e r r as nrt aspirin a$ferrlntive is becnrrse the irtcidertt of srcch effects wrtli tliis drug is z)ery low. However, becnrtse ncetnnrirtoplmr cnrt rtrrdergo biotrartsfornlntiort to n toxic irrternredinte, hepatic nrrd rertnl rrecrosis llnve beerr reported, especinlly nfter very ltiglr doses. (c) , lrepntic necrosis is tlre nrost prontirrertt.

23. LYhich of the follois- in^ anti-inflammator agents does NOT act primaril by inhibiting the activity o?cyclooxygenase? ? a. Ibu ro en

b. ~ifkunisal c. kednisone d. Indomethacin e. Phenylbutazone

( c ) Arrszuer is (c)- (n) , 2 , 4 , nruf 5 nre NSAIDS tltnf red~tce

Analgesics - morphine 1. One of the most frequently asked questions concerns

mixed-agonist-anatagonists (MAA) - they ask you to identify which drugs out of a list of 5 is an MAA. The one they usually exptxt you to know is pentazocine, but sometimes nalbuphine.

2. Additional drug identifications they always ask involve knowing that naloxone is an antagonist used to treat . overdose, and that methadone is used in detoxification of morphine addicts.

3. Some uestions ive you a list of pharmacological effects and a 2 you to ijentify which is not an effect of morphine. Morphine roduces respiratory de ression, euphona, sedation, 4s horia, analgesia, an d' constipation. The substitution tEey often make is diarrhea for constiipation.

4. The last most frequent1 asked type of uestion regarding 2' opiates concerns over ose of toucity. I n overdose morphine causes coma, miosis, and respiratory depression. Sometimes they ask the mechanism of respiratory

depression: loss of sensitivity of the medullary respiratory center to carbon dioxide.

Frequently asked questiorzs on morphine:

5. Occurence of which of the followin is LEAST

a. Vomiting 8 characteristic of narcotic ingestion.

b. Diarrhea c. Urinary retention d. Bronchiolar constriction e. Increase in intracranial pressure

( b ) Atrswer is (b)- Agnitz, the key word i s l e e Nnrcotics, in tlle form of pnregoric (tirrctrrre of opium), and Lontotil (lopernmide) are over the cortrlter ornl preparatiorts for tlle trentnlertt of diarrllen. Opintcs act ort receptors irt tlle grit to prodrrce corrstipntiorr. Tltrts ( b ) is obzjiorlsly wrorrg. All of tlle other nrrszuers nre side effects of opinte ndnrtrtistratiorl.

6. Therapeutic doses of mor hine administered intramuscularly may p r J u c e

a. Constipation b. Euphoria c. D sphoria d. d n t a l clouding e. Decreased response to pain

i. (a) and (b) only ii. (a), (b) and (d) iii .(a), (d) and (e) iv. (c), (dl and (e) v. All of the above

7. Which of the folIowing drugs acts to suppress the cough reflex?

a. ASA b. Codeine c. Meperidine d. Acetaminophen e. Phenyibutazone

8. Which of the following are pharmacologic effects of mor hine?

a. %espiratory depression b. Eu horia c. ~ J a t i o n d. Constipation e. Dysphoria

- i. (a), (b) and (c) ii. (a), (b) and (d) iii.(a) and (e) iv. (c), (dl an2 (el v. All of the above

Prepared by M.L. l lo i~~pson, Ph. D.. Dept. Of Pharmacology, Tufts Medical Scl~ool . .

9. Morphine causes vomiting by a. A direct irritant action on the astric mucosa b. Stimulation of the nodose gan %on of the \ laps nerve c. Stimulation of the medullary cjernorece tor trig er zone d. Direct stimulation of the gastrointestina!muxukture

10. The decrese in ventilation caused by mro hine, mepridine and some of the related opioids depends cRiefly upon

a. Depression of cortical activity b. Penpheral blockade of chemoreceptor impulses c. An Increase in carbon dioxide concentration in the

blood d. Blockade of afferent autonomic impulses from the lungs e. Loss of sensitivity of the medullary respiratory center

to carbon dioxide

( e ) Atrsr~ver is (el- nrcnrori:ntiort. Dotr't befooled b (0)- t l w drugs nrc salRtbrg, but this lvls lrotlrilrg to 2 zoitlr t l u decrense in respirntoy mte.

11. Small doses of barbiturates and morphine depress respiration primarily by

a. A arasym athomlnetic action b. 1nRibiting tRe ~ e r i n e - ~ u e u e r reflex c. Rendering the aortic chemoreceptor system insensitive

to 0 2 d. Rendering the respiratory center less sensitive to

changes in C02 e. A specific effect at myoneural junctions of phrenic and

intercostal nerves

( d ) Atlsz~ier is (dl- 1 toM yorr this ilr nry lcctirrc olr nrorplritre-if yorr nriss this yorr '11 lrrrrt nry fcelitlgs.

12. Which of the following are pathognomonic symptoms of narcotic overdose?

a. Miosis, coma and depressed respiration b. Mydriasis, coma and smooth muscle spasms c. Mydriasis, coma and de ressed respiration d. Miosis, convulsions anBde ressed respiration e. Mydriasis, convulsions anldepressed respiration

13. The cause of death with opioid intoxication is a. Oxy en apnea b. ~ a r f i a c arrest c. Terminal convulsions d. Circulatory collapse e. Respiratory depression

(e) - agaitr, n nrenrorizatiotr questiotr.. Wlzat lvlppetrs is tllat opioids decrense the response o respirato cetrters itr tlre braitrstem to t l r cnrbotr dioxide tensiotr o7the blood, artd also depresses pontine and medrtlln y cetrters regulating respirato y freqrtetrcy. Opioids do not cause oxygot r(pttca, (&I), t h y co l~ be co~~tu tb ive , hu f 110t fernrirral y so ((c)), Il nre stnbiJizirrg otr tlre lzenrt ntrd sonle are actrrnlly u J i t 1 opelr-lmrt s s r ery ((b)) , artd t l q no not cause circrr,ntoy collnpsc ((41

14. Which of the following is an opioid that has both agonistic

i n

and antagonistic activities? a. Cdeine b. Methadone c. Naloxone d. Meperidine e. Pentazocine

(el This is an exanrple of the type of qrrestiolr wllere tlre drug clnss is girjen. Yort are asked to trot otrly irletrtifi a drrtg from tile list as beit18 fronr titis clnss, but addrtroltally tllat it has tlle roperties titat are give11 i l l f l u questiotr tlvlt distbrgtris! it from tlre other drugs o the class tlzat are listed as altenratives. In this exanlpk, tllere is orrly orre drug wlriclr nreets this criteriorr. All are drugs wlrich act via opiate receptors, but 3 are agotrists ((a), (b), (d l ) , I is atr alrtagottist orrly ((c)). (e ) pelrtnzocitre is the olrly drrrg which lurs botlr types ofactio~r, atld is tlre otre drrcg left b y tlre process of elrmitmt iolr.

15. A heroinde endent atient should NOT tw given nalbuphine h u b a i n ffor pain because

a. It has no analgesic properties b. It may produce respiratory depression c. As a mixed agonist-antagonist, it can elicity withdrawal

d. r"? he i6h abuse potential of nalbuphine may add to the patient s problems

16. A patient while not currently taking drugs has a history (6 months ago) of narcotic de ndency. Which of the following analgesics should be avoi& in this patient?

a. Aspirin b. Pentazcine

Z P$KZK,"K;' e. Acetaminophen f. None of the above

17. Which of the following statements does NOT characterize pentazocine?

a. It is equianalgesic with codeine b. It is a partial opioid antagonist c. Its abuse otential is less than that of heroin d. It may infuce dysphoria and mental aberrations e. It is effective only on parenteral administration

18. The antagonist of choice in the treatment of opioid overdosage is

a. Naloxone b. Nalorphine c. Pentazocine d. Levallorphan e. Propoxyphene

19. Which of the folowing is a complete anta onist of the opioid receptor and the atent of choice in t i e treatment of narcotic overdose?

a. Naloxone

b. Nalorphine c. Cyclazocine d. Levallor han e. None of &e above

20. Methadone is used in detoxification (drug withdrawal) of patients physically dependent on morphine because methadone

a. Precipitates withdrawal reactions b. Antagonizes the depressant actions of morphine c. Will not in itself produce physical dependence d. Withdrawal reactions are less intense and stressful

than those of morphine

( d ) This is nrt exantple of t l ~ kirrd of qrcestiotl tllnt reqltires tlz17t V O I ~ llnzte nlenlonied n fact nbotrt n pnrticltlnr drug, irl tltis knse tlte fnct is (d). Metlrdotre yorr will renxnrber is trot ntl atltngotrist like rlnloxorlc- it is n f~rll a ortist with nrlnlgesic propertks, jrst like nto . fillctl tnkert ornlly it is ,rot elrpllorlc it1 addicts, 11t ncts just like nlo llitle to prodltce tolerntlce arrd pllysicnl dePetldettce.%tldrnrunl is less severe tllntl rurtlr nlorpltitle becnlrse ntetlmdotre Irns n nlllcll lotrger lmlf life. Fncts 1, 2, nrld 3 zootrM be met by ntl nrltngotrtst stlclt ns t~nloxorle, or perllnys ezwl n nlixed ngotrist-nrttngottist slrcll ns perltnzocitle.

21. Which of the followin drugs is currently \\.idely used in treating opioid-depenfent individuals?

a. Codeine b. Methadone c. Alphaprodine d. Pentazocine e. Meperidine

Autonornics:

Clr o l inergics

1. Drug identification type questions that involve mechanism of action. You need to know the following types of facts:

a. atropine, scopolamine, propantheline are competitive muscarinic receptor blockers which sometimes are used to control salivary secretions. An additional fact that often ets asked about atropine has to do with the fact that it%locks vagal reflexive control of heart rate, resulting in tachycardia.

b. physosti ine and neosti ine are reversible antichocesterases that %er in that physostigmine acts both centrally and peripheral1 neostigmine on1

ripherally, but neostigmine also tas some direct Azh E e activity at the neuromuscular junction, in addition to prolonpng the activity of endogenous ACh. They sometimes see use in treating xerostomia.

c. pilocarpine, methacholine, etc. are direct acting cholinergic a onists. May be used for xerostomia.

d. organophospkates and insecticides irreversibly inhibit cholinesterase

e. pralidoxime is an enzyme regenerator used in

organophosphate toxicity f. succinylcholine is a depolarizing neuromuscular

junction blocker, subject to rapid inactivation by plasma pseudocholinestease: it is used to prevent aryngospasm

g. d-tubocurarine is a nondepolarizing neuromuscular junction blocker

h. mecarnylamine and hexamethonium are ganglionic blockers that produce orthostatic hypotension

2. The 2nd type of question has to do with physiological effects of choliner ic stimulation, blockade, or overdose toxicity situations &nd what drug you would give to reverse the toxicity).

a. cholinergic crisis symptoms: bradycardia, lacrimation, salivation, voluntary muscle weakness, diarrhea, bronchoconstriction-treat by giving atropine

b. sco olamine overdose: disorientation, confusion, Ra~lucinations, burning dry mouth, hyperthennia: treat with physostigmine

c. An additional fact that often gets asked about atropine has to do with the fact that it blocks va a1 reflexive control of heart rate, resulting in tachycarbja.

Frequentlg asked questions about Clr o linergics:

Identification and mechanism of action quest ions:

1. Atropine and propantheline exert their effects on peripheral structures by

a. preventing release of acetylcholine b. preventing synthesis of acetylcholine c. enhancing destruction of acetylcholine d. com eteing with acetylcholine for receptor sites e. p J u c i n g physiologic effects opposite to those of

acetylcholine

( d ) - (a) is wrorlg- botltlitrrrnt toxirl does this. (b) is wrortg-lrenricllolinr~rnl works this w n ~ . ( c ) is wrotlg- ACIl is broker1 dowrt alnrost instatltntreolrsly, so it is alnrost inrpossible to enllnnce its destruction. (e ) is wrong-these drugs dotr't have a n y actiotrs of their owtt, t l q just prevent ACh effects by blockilrg receptors: atropirie attd

ropntttheline are postgarlglionic rnuscarinic receptor [lockers-thas ib answer is (d) .

2. Neostigmineproduces its effst by a. de ressing acetylcholinesterase release b. in&biting acetylcholinesterase activity c. increasing the rate of acetylcholine synthesis d. acting like acetylcholine at gan lionic sites

nerve terminals a e. increasing the amount of acetylc oline released from

3. Organo hosphate insecticides and nerve ares inhibit the action of which of the following enzymes?

a. adenylate cyclase

Prepared by M.L. Thontpson, Ph. D., Dept. Of Pharn~acology, Tufts Medical School

b. monoamine oxidase c. phosphdiesterase d. acetylcholinesterase e. carbonic anhydrase

b. is a comri t ive blockin agent c. has no e ect on acetylc olinesterase P; d. is more potent than diiso ropylfluoro hosphate e. is capab e of acting directry on the en$late

4. Drugs which are addictive with or potentiate the effects of acetylcholine include

(a) metacholine

(c) pra idoxime (d) neos t iphe (e) pilocarpine

I. (a), Co), and (c) 2. (a), (c), and (dl 3. (a), (dl and (el 4. (b), (d 1, and (el 5. (c), (dl and (el

10. Which of the following is used to prevent laryngospasm? a. atropine b. epinephrine c. diazepam (Valium) d, neoshgmine (b t igmine ) e. succinylcholine (Anectine)

( e ) W l a t is needed is a skeletnl muscle relaxant. This re uires a dru wiricir acts at the neuromusculnr junctio~r. 07 those listetf only succin icholine ( e ) is it1 this category. (a ) atropba is a ciolitrergic receptor blocker, (h) epi~lephrinc is an adrettergic ngonrst, and (c ) dinzepnnr is n benzodinzepirre, nrld (dl is nrr nnticlrolirlesterase.

(3 1 11. In treating xerostomia, which of the following might be prescribed?

a. atropine 5. \Yhich of the follor\.ing drugs is k s t to administer after b. ephedrine

poisoning by an organophosphate cholinesterase inhibitor? c. neosti mine a. atropine d. scopo!amine b. phen toin e. mecarnylamine c. pralidoxime d. propan teline ( c ) e. phenobarbital

( c ) 12. Which of the following drugs is most likely to dry secretions in the oral cavity?

a. diazepam 6. Which of the following compounds is a ganglionic blocking b. prometazine

agent? a. curarine d. c. physostir ropant ehne b. edrophonium e. c!iphenhyd rarnine C. mecamylarnine d. succinylcholine ( d ) e. gallamine tricthodide

(c ) 13. The most useful drug to induce salivation is one which has properties that are

a. adrenergic 7. Which of the following acts by antagonizing cholinesterase? b. cholinergic

a. atropine c. ganglionic blocking b. muscarine d . adrenergic blocking c. neostigmine e. cholinergic blocking d. p i loca~ine e. acetylc oline (b)

8. When neostipine is administered before acetylcholine, the action of acetylcholine will be

a. blocked b. enhanced and prolonged c. less intense and of shorter duration d. none of the above. The action of acetylcholine is not

affected by neostipine

9. Neostipine can stimulate denervate skeletal muscle because it

a. is a congener of acetylcholine

14. Drugs which are commonly used in the control of excessive salivation include

(a) meprobamate (b) atropine (c) methantheline (d) cudeine (e) chlorpromazine

I. (a) and (b) only 2. (a), (b), and (c) 3. (b) and (c) only 4. Co), (c), and (dl 5. (dl and (el

Questiorzs regarding physiological actiorzs of clz o linergic drugs:

15. Administration of ganglionic blocking agents will result in a. miosis b. diarrhea c. copious salivation d. orthostatic hypotension e. enhanced activity of the parasympathetic nenrous system

19. Based on its known mechanism and sites of action, sco lamine should theoretically be useful in

(acreatment of peptic ulcer (b) providing euphoria and amnesia prior to surgery (c.) relieving bronchoconstriction (d) relieving some of the symptoms of Parkinson disease (e) visualization of the retina

1 .. (a), (b), (dl and (e) 2.. (a), (b), and (e) only 3. (a),and (c) 4. (b) and (e) only 5. All of the above

16. Tach cardia in a patient administered with atropine or scopoLmine results from

a. release of adrenal catecholamines b. blockade of vagus nerve activity c. blockade of the nicotinic cholinergic receptor d. stimulation of the alpha adrenerpc receptor e. stimulation of the beta adrenergic receptor

(b) Artsroer is (bl- Atropirre nlrd scoyohntirte nre nttrscnrirtic clrolirter ic receptor blockers. ]tist krtoroirtg tlmt elinrirrntes nN t f e nlterrmthss except (bl. Blrt yntr sltorrld nlso renrenrber tlrnt lrenrt rnte is k t rrrrder tigltt % reflexizre cort trol: nlry slrddcrr irtcrense irt R ttsltnlly stinrrrlntes bnroreceptors to sard n siptnl to tlre zrn pis trerve to stinrttlate tlte llenrf to sloro rt bnck dorurr. 111s reflex is cholitrergicnlly ntedinted, nrtd toil1 be blocked by cltolirrer 'c blockers suclt ns atropirtc. Ezperr uyltert giver1 irt the ngerrce of higlter tlrnrr rrornrnl lrenrt rnte, ntropirre will block the trornml cltolirrergic corrtrol ozper the lrenrt, lenvitrg tlte syntpntlretic systent ilt clmrge zoitlr n restt ltrrtg tncltycndin.

17. All of the following are possible effects of cholinomimetic drugs except

a. mydriasis b. bradycardia c. increased peristalsis d. stimulation of sweat glands e. increased secretion by bronchial glands

(n) Atrswer is (0)- Tlte first tlrirtg yorr lmrle to krtoro is tllnt n cholit~onrintctic dru is orte rulric'lr nrinrics tlte nctiort of ncetylclrolit~e, tlre ett&notls ttettrotmrantitter it1 tlze parasyntpntlletic or cholitter 'c ttervorrs systen~. Tlle ncron rn for ren~enrberhg t E effects of cholitlergic stinitryatioti is SLLILI, or fitcreased salilmtion. lncrintation, defeation, arrd rrrittntiotl. The henrt is the exceptiotr it1 that activity or ltenrf rate is decren,d (brndycardia)- thtts sitrce tlre questiotr nsks or ntt efect wllicll does trot occur with chol~ner 'c stin111 atiott, t 1 tat lenves (n) as tlle otlly possibility. h80sis. not mydrinsis, occrrrs witlr clrolitrergic st imulntiotr.

18. A para1 zing dose of succinylcholine initially elicits a. ~ N J d e ~ r e s s i o n b. CNS depression c. decreased salivation d. muscle fasiculation e. extrapyramidal reactions

Questions regarding toxicity of clzo linergic drugs:

20. Symptoms of r isoning by an organophosphate onsecticide include all of t e followin except:

a. skeletal muscle fasicu ation b. excessive salivation

B c. bronchoconstriction d. hot, dry skin e. diarrhea

All of the followin6 symptoms are associated with neostipine poisoning except

a. diarrhea b. salivation c. convulsions d. bonchiolar constriction e. skeletal muscle paralysis

22. Symptoms of atropine poisoning in man include (a) decreased intraocular pressure (b) burning dry mouth (c) nausea, vomiting and diarrhea (d) h rthermia (e) oxostat ic hypotension

1. (a) and (c) 2. (b) and (d) 3. (b), (d), and ( 4 4. (d) and (e) 5. All of the above

23. The most likely signs or symptoms of overdosage with atro ine are

a, ENS excitation and tachycardia b. intestinal cramps and diarrhea c. skin rash and cutaneous itching d. ptyalism and increased sweating e. constriction of the pupils and blurring of vision

Prepared by M.L. Thompson, Ph. D., D q t . 01' Phannacolop~, Tufts Medical School

.4. Disorientation, confusion and hallucinations resulting from an overdose of scopolamie are most efficaciuosly treated by administering

a. atropine b. levodo a c. acety~c~o1ine d. phsostigmine

23. The immediate cause of death from irreversible cholinesterase inhibitors is

a. shock b. convulsion c. cardiac arrhythmia d. respiratory aralysis e. dehydration ! o m vomiting and diarrhea

( d ) Arrswer is (d ) - rolrile sonle 01 tllese nre irldeed associnted wit11 orgnrr oplrospllnte toxicity, tlle inln~edinfe cartsc oJ deotll is drte to ( d ) , wlricll results Jronr the sfinrrtbtio~r oJ ?licofirric recqttors n f the rrelironr~lscrllnr jrlrrctio?r resrlltirlg i ~ t pnrnlysis oJ skeletnl nrllscles.

26. Each of the follo~\.ing is a symptom of cholinergic crisis exce t

a. gradycardia b. lacrimation c. vasoconstriction d. extreme salivation e. weakness of voluntary muscles

Adrenergics: 1. Drug identification type questions that involve mechanism

of action. You need to know the following types of facts:

a. Receptor blockers: alpha or beta adrenergic drugs such as prazosin or propranolol act by competitive inhibition of postjunctional adrenergic receptors

b. Drugs which inhibit the action of adrenergic nerves: i. Reserpine: depletes NE by inhibiting reuptake ii. Guanethidine: inhibits the release of catecholamines iii. Alpha methyldopa: acts centrally as a false

neurotransm~tter which ets taken u into storage vesicles and released wih NE, thus !ecreasing sympathetic activity

iv. Clonidine: stimulates alpha2 receptors in CNS with a resulting decrease in sympathetic outflow

c. Indirect acting drugs: amphetamine, tyramine, and ephedrine act by stimulating the release of stored NE

2. Physiological action questions: Many of these questions involve actions of epinephrine in the presence of either an alpha or beta blocker, such as: a. "Epinephrine reversal": in the presence of an alpha

blocker (usually they ive prazosin, but drug such as chlorpromazine may a 9 so be given) epi causes decrease in blood pressure rather than increase because beta

mediated vasodilation predominates b. vagal reflex: injection of a pressor dose of NE ma

result in decreased heart rate d u e to activation o r baroreceptors which stimulate va a1 reflex to reduce heart rate. Vagal reflex is b l o c k d b y atropine

Thus you must be familiar with the effects of alpha or beta receptor stimulation or block. The most important ones to remember are:

a. Alpha-1 receptor stimulation: vasoconstriction, urinary retention, mydriasis

b. beta rece tor stimulation: increased heart rate (Bl), bronchochation (BZ), vasodilation (B2)

c. Alpha-1 block: vasodilation d. beta block: decreasd heart rate (Bl),

bronchoconstriction (B2)

3. They usually throw in a question regarding the use of levodopa in the treatment of Parkinson's: remember, Parkinson's is DA deficiencv in brain. Remedv is to increase DA in brain. 1njeAed DA doesn't crdss BBB, but levodopa, a precursor to DA does cross BBB. Carbidopa is given with levodopa to block dopa decarboxylase activity in periphery, which in the absence of carbidopa, converts the levodo a to DA in the periphery, decreasin the amount of l evo~opa that ends up in the brain. You ayso need to remember that levodopa is sympathornimetic, and will produce sym athetic stimulation in the peripher).. Development of agnormal facial movement, nausea and vomiting, cardiac arrthymias, and mental disturbances are all associated with levodopa therapy.

Adrenergics - Mechanism of Act ion

4. Alpha or beta-adrenergic blocking drugs act by a. Inhibiting s nthesis of norepinephrine. b. Increasing tKe metabolism of norepinephrine c. Competitive inhibition of postjunctional adrenergic

receptors d. A local anesthetic effect on the adrenergic nerve

terminal e. Depleting norepinephrine ffom adwnergic nerve

terminals

5. A mechanism for the antiadrenergic action of guanethidine is a. Inhibition of d o a decarboxylase b. Inneased rate ofmetabolism of norepinephrine c. De letion of norepinephrine from the nerve terminals d . sugstitution for norepinephrine and subsequent action

as a false transmitter e. Uncouplin of the action potential from the

n o r e p i n e p k e release mechanism

6 . Which of the followins statements most accurately describes the effectiveness of act~on of methyldopa?

a. It causes marked cardiac slowing b. It directly relaxes vascular smooth muscle

c. It causes rapid depletion of norepinephrine from adrenergic nerve terminals

d. It causes formation of a false transmitter which is released at vascular smooth muscle

e. I t produces a false transmitter, the effect of which is primarily at central nuclei

7. The mechanism of action of reserpine is to a. Inhibit monoamine oxidase b. Inhibit catechol-O-methyltransferase c. Block the assage of the nerve action potential in the

ost angEonic nerve fibers d. Etabfiize the axon terminal membrane thus preventing

release of norepinephrine

action of norepinephrine at beta-adrenergic receptors? - a. Atropine b. Naloxone c. Propranolol d. Phcntolamine e. Hexarnethoniurn

12. Pretreatment with reserpine prevents a response to which of the following agents?

a. Amphetamine b. E ine hrine c. PRen$ePhrine d. Isoproterenol d. Norepinephrine

(a) reserpitte causes depletion of NE front storage sites, tlttrs it cattttot be r e l e n d by an1 letantine. All of t l e others listed act postsyttnptical~.

8. Am hetamineactsby a. gromoting storage of the mediator b. Causing a rapid release of the mediator c. Causing a slobv depletion of the mediator 13. Each of the followin dru s is considered to be a direct- d. Combining with a receptor substance on the effector cell acting c a t e c h o l a m i n e % ~ ~ f ~ ~ e. Interfering with the response of the receptor to the a. Epinephrine

mediator b. Amphetamine c. Isoproterenol

(b) d. Norepinephrine

9. Which of the following characterizes the mechanism of action on levodopa?

a. It acts through a direct anticholinergic action b. It stimulates s ecific Ldopa receptors in basal ganglia c. It replenishes t ie otherwise deficient dopamine in

atients with parkinsonism d. increases concentrations of norepinephrine in the

brain to counterbalance an otherwise overactive cholinergic system

10. Which of the following combinations of agents would be necessary to block the cardiovascular effects produced by the injection of a syrnpathomimetic drug?

a. Atropine and prazosin b. Atropine and propranolol c. Prazosin and propranolol d. Phenoxybenzamine and curare e. Amphetamine and propranolol

(c) - The itljectiorr of a synlpathominletic (e.g. a drtrg which acts like N E ) stinlulates both alpItn and beta receptors. Alplta receptor st imulatiott produces z~asoconstrictioir, ittcrensed s stolic and diastolic

ressure and reflex tachycarjia. These effects cat1 be !locked by a1 ha nttd beta rec tor blockers. the otlly alternatiw t%t lists both a,, &ha fprarosin) and beta

ro rarrolol) blocker is (c). Atropi~te is n muscarinic ?' cho f'. lnergic ) receptor blocker tltnt would accelerate tlte Ireart, the opposite effect tlrat you watrt, thtrs (a) atld 2 are wrottg. Phenoxybetlznntine is at1 a1 ltn blocker, but curare is a nicotbic rec tor blocker, not geta receptor- tlrlrs (d ) . As f ~ r T 5 , an1 Ietan~itle is at1 itldirect acthtg synlpnt is wro"f ronlin~tic, t ~ o t a R locker, thlrs (el is wrorlg.

11. Which of the following drugs competitively blocks the

Effects

14. After pretreatment with hentolamine, intravenous adrninlstration of e inepKrine should result in

a. Relaxation orbronchial smooth muscle b. Positive chronotropic and inotropic effects c. S lanchnic vasoconstriction d. &lation of skeletal muscle vascular beds e. Secretion of a mucoid viscous saliva

i. a, and b only ii. a, b and d iii. a, d and e iv canddonly v. c, d and e

(ii) plmltolamine is art alpltn blocker, thus the it1 hrine will stimulate beta receptors primarily, witlt

t te e ects listed in option (ii) 7'7 15. Which of the following changes produced by intravenous

administration of epinephrine result from stimulation of beta-adrenergic receptors?

a. Respiratory inhibition b. Cardiac acceleration c. Dilation of the upil d. Increased systoyic pressure e. Decreased diastolic pressure

i. a, band c ii. a, b and d iii. band e iv. c, d and e

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

v, c and e only

16. M'hich of the following is NOT an action of epinephrine when administered intravenous1 in a high dose? r T a. Increases liver 61 cogeno ysis

b. Causes bronchi0 ar constriction c. Produces a rise in b l o d pressure d. Evokes extrasystoles in the heart e. Prduces restlessness and anxiety

"Epinephrine reversal" of blood ressure can best ke demonstrated by injecting epinepRrine intravenously afier pretreatment with

a. Prazosin b. Atropine c. Propranolol d. Neostigmine e. Isoproterenol

(n) epitleplrritre is n poteltt stinrlrlntor of botlr nlplln ntrd bctn receptors. Itlject ro11 of epi risltnlly cnrtses n rise it1 blood presslrre dric to I ) nryocnrdinl stinllthtiotr tlmt illcreases vetttricrtlnr cotttrnctiott, 2 ) ntr itlcrense it1 llenrt rate, atrd most inrportnrlt, 3 ) z~nsocotlstrictiotl dlre to nlplm receptor st in~liht iot i . However, blood flotu to skeletnl ntrtscles is itlcrensed drie to ozclerflil betn-2 receptor vnsodibtor actiott tltnt is or16 pnrtinlly colitlterbnlntlced b n z~nsocottstrictor nctiott ott tlre nlplln receptors tlmt nre ayso presettt it1 tlre z~nsclrlnr bed. Wlretl gizwtl 61 tile presetlce of nlr nlpltn blocker, betn-reccptor n d i n t e d zmsodihtiott is more prottoritrced, tlle totnl pcriplternl resistatrce is decrensed ntrd tlle n m t t blood pressrire fnlls. This decrense it1 blood pressttre is cnlled 'epitreplrrrtle reversnl". Tlle otrly nlplla-blocker listed is prnzositt, atlszuer (n). Atroprrle ts n cllolittergic nr~tscnrittic reccptor blocker, proprnttolol is n betn-blocker, treostipritte is n cl~olitresternse itrllibitor, ntrd isoyroteretrol 1s n predonritrntely betn receptor ngottist.

18. Each of the following is a predictable adverse effect of drugs that block the sym athetic nervous system EXCEPT

a. Gastrointestinal Js turbance b. Postural hypotension c. Nasal congestion d. Urinary retention e. Miosis

19. In ion of a pressor dose of norepinephrine may result in a g r e a s e d heart rate because of a. Activation of barorece tor reflexes b. Direct stimulation of a&ha receptors c. Direct stimulation of beta-1 receptors d. Direct stimulation of beta-2receptors e. Direct stimulation of muscarinic receptors

(n) Atrswer is (n)- alterttntives 2-4 nll itrcrense lrenrf mte, while N E ltns 110 e f i c t at ntuscnrinic receptors ((e)), wlliclr nre specific for clrolitrergic drrtgs.

20. Alpha-adrenergic agonists are used in combination with local anesthetics to

a. Stimulate myocardial contraction b. Reduce vascular absorption of the local anesthetic c. Increase the rate of liver metabolism of the local

anesthetic d. Increase the concentration of the local anesthetic at its

receptor site e. Anta onize the vasodilating effects of the local

aneshet ic

i. (a), (b) and (c) ii. (b), (c) and (d) iii . (b), (d) and (e) iv. (c), (d) and (e) v. (d) and (e) only

( i i i ) Anstuer is (c)- Alplra-adretrergic ngotlists srtclr ns epirreplrrine produce vnsocotrstrictron, which worrld acconrplislt botlr "b" atrd "en. # 3 is the otrly altentntive tllat itrcllides both b ntrd e tlrlis yotr dotr't Itnve to know ntrythitlg else. "a" atid "c" nre'fnlse. Vnsocotrstrictors nre itrclride r r r locnl ntrestltetic repnrntiotrs to ( I ) prolottg nrrd brcrense tlw d 111 of nttestf,&in retabrhl tlre ntrestlletic irt t E nren i t r j e c t ~ , (3 reduce t i e toxic efect of tlle drlig b y delnyitrg its absorptiott itrto tlre getrernl circlilntiotr attd (3) to retlder tlte nren of ittjectiotr less henrorrlrngic.

21. Administration of an otherwise effective pressor dose of epinephrine could cause an "e inephrine reversal" in a patient taking which of the foKowlng drugs?

a. Reserpine b. Propranolol c. Am hetamine d. ~ h L r ~ r o m a z i n e e. Lithium carbonate

( d ) CPZ is n potnrt alplla blocker like prnzositt.

22. Of the following sympathomimetic agents, the most potent bronchodilator is

a. Amphetamine b. Norepinephrine c. Phenylephnne d. Iso roterenol e. h4eLoxamine

( d ) Atls~uer is (d)- W l a t is t teded for brottclrodilatiotr is relaxntiott of brottdtial smootli nrrtscles. This is accontplislud wi th beta2 receptor stimulatiotr. Isoproterenol is the on1 drug listed wi th poterrt betn2 nctiorr. (a ) stimulates a$hn receptors in the C N S , (b) NE stimrtlates alphn and beta1 receptors ntore than beta2, (c) pherryleplrrine is a n alplm receptor agonist, while (e) methoxnmine is a vasocotrstrictor that stinrulates alpha receptors preferentially.

Administration of which of the following d ru s would produce vasomnst riction of the gingival vessef s?

a. Levonordefrin b. Phentolarnine c. Epinephrine d. Propranolol e. Phenylephrine

i. (a) and (b)

ii. (a) and (c) only iii. (a), (c) and (el iv. (b), (dl and (el v. (b) and (dl only

24. Carbidopa, a dopadecarbxylase inhibitor, is often used in the treatment of arkinsonism because it

a. Potentiates t i e central action of dopamine b. Potentiates the central action of norepinephrine c. Decreases the pen heral metabolism of levcdopa d. Inhibits the peripReral stimulatory fibers from the

central nervous system e. Increases the permeability of the blood-brain barrier to

levcdopa

Of the followin one of the most effective treatments currently availagle in the US. for most patients suffering from parkinsonism involves oral administration of

a. Dopamine b. Amantadine c. Benztropine d. Levcdopa alone e. Levodopa plus carbidopa

26. Levcdo a therap for Parkinson disease may result in each of the foiowing eiects EXCEPT:

a. Development of abnormal, involuntary movements, especially in the face b. Extreme sensitivity to sympathomimetic drugs c. Exacerbation of an acute psychosis d. Nausea and vomiting e. Extreme sedation

27. Adverse effects of levodopa include: a . Arrh thmias b. Psyc{otic disturbances c. Nausea and vomiting d. Abnormal involuntary movements

i. (a), (b), and (c) ii. (a), (b) and (d) iii. (a), (c) and (d) iv. (b), (c) and (dl v. All of the above

(v ) Arrswer is (e)- Lerrodopn is t ixpr in lnrydru used to t r u t pnrkinson's diunse, which results from afirormally low levels o d o amine in the braiti. Leoodopa, or L- D O P A is t L L r e d precursor of do amine (which cnn't be used hecnrrse it doesn't cross the hood brairr harrier- L- D O P A does and is converted to D O P A it1 the brain) is ztsai to incrense dopnmine irz the brain. All of tlte efects are es tab l i s id side effecis of L - D O P A therapy, thus the arrswer is (e) . Abrtornrnl involurrta y rnovenlerrts (AlMS) nre tite most prevalerrt atrd troublesome "extrapymnridal" side effects, typicnlly involving the orofncinl nrusarlnture. Nnusen nnd vonrrtitrg nre seetr duritrg tire first piuse of tizernpj but tolernr~ce develops to tlzese effects. Tire psyclrot zc effects nre nrrrclr less prevaletrt ,

seer1 iir or11 a snlnll perccrrtnge of pntie~rts. lrrcrensed irr cideirce o/Ynrrllythnrhs is also a problenr. Letjodopn nlso serrsitizes the iteart to epitteplrrirre irrdrtced arrltytiznrins.

General Principles of Drug Action

Remember this section of the course? This is where we defined a bunch of terms that described how drugs interact with receptors to produce their effects. Most of you yawned and thought "What the hell do we need to know this stuff for - just tell us about antibiotics!" Well the Great Board Gods want you to know some of this stuff - that's why I put it in the course. Your apologies are graciously accepted, as always!

I . A pharmacologic agonist is a chemical substance that a. Binds to a specific receptor and produces a response b. Elicits a pharmacologic response without binding to a

receptor c. Possesses the property of affinity but not of intrinsic

activity d. Exhibits no activity except to oppose the effect of an

antagonist

2. When comparing drugs with respect to intensit&of res rnse , the drug that produces the greatest maximum e ect is t e one with the highest

a. Affinity b. Potency c. Efficacy d . Therapeutic index

3. If dru has a greater efficacy than drug B, then drug A a. I! more toxic than dru B b. Has a greater affinity for the receptor than drug B c. Has a reater margin of safety than drug B d. Is capa%le of producing a greater maximum effect than

drug B

4. A drug with a high L D g and a low ED50 has a a. High therapeutic index and is, therefore, very dangerous b. High therapeutic index and is, therefore, relatively safe c. Low therapeutic index and is, therefore, very dangerous d. Low therapeutic index and is, therefore, relatively safe

5. The ratio of the median lethal dose ( L D s ) to the median effective dose (EDSO) is the

a. Morbidity index b. Mortality index c. Anesthetic ratio d. Therapeutic index

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

6. The therapeutic index of a drug is the ratio of a. The effective dose to the toxic dose b. Half the toxic dose to half the effective dose c. The maximum tolerated do= to the minimum effective

dose d. The lethal dose for 50% of animals to the effective dose

for 50% of animals

The phenomenon in which two drugs produce op effects on a physiologic system but do not act at t K Z K e rece tor site is

a. $otentiation b. Chemical Antagonism c. Competitive antagonism d. Physiologic antagonism e. Noncompehtive antagonism

8. Epine hrine anta onizes the effects of histamine by a. Reventing tRereleaseofhistamine b. Acting on the central nenpous system c. Producing physiologic actions opposite to that of

histamine d. Competitively blocking histamine at the cellular

receptor site

(c) epi~r hrirte ncts ns n plrvsiolopc nittngo~rist. It ,roirspec&nlly n,ttngorrizes lristnnri~te by exertirtg its oro~t distilrct effects, for exnnt le, t~nsocorrslrictioit, brorrcltodilntiorr, n~rd decrensJG1 ntotility. It does wot reverse tlte e fect o ltistnntitte by blockirrg nt n specific receptor ((d){ RS td antilristnntilres. It does ,rot prar,rt the reknse of lristnnri~te ns does n drtt sriclt ns cronrolvn ((n), by prezwrrtbr nlnst cell degrnlrrrkliort). A,rsirler (b) is ,rot rclmnat, wf i le (n) is tlre nteclm,risnt o ncfiort for cronrolylt, tolriclr idribits nrnst cell dcgrn~rri I ntiolr..

9. Interaction between nitroglycerin and epinephrine is what type of antagonism?

a. Allosteric b. Physiologic c. Biochemical d. Competitive e. Pharmacologic

(b) A~tswer is (b)- epilreplrriue uforild stinttilate nlplrn adrenergic recqptors to produce vasoco~tstrictio~r, wltereas nit rog ycerin relaxes z~ascrtlnr sntooth nruscle. n t t i s the two drttgs wottld lmve o oshrg actiotts. H o w w r , tlte nclions m e p r ~ d u c 8 y the drrtgs acthr or1 differetrt meclmttisnrs; tritroglyceritt does not act at a&lm receptors as does epin rine. If it did, tlte interadio~r wottM be conrpetittz~e. 1" 11 this case tlte i~tternctiolr is vin competiirg physiological effects.

10. When the combined action of two drugs is greater than the sum of their individual actions, this is

a. Induction b. Synergism c. Idiosyncrasy d. Hypersensitivity e. Cumulative action

11. In which of the follorrrinp airs of drugs is the pharmacolo ic activity o t e first drug diminished or anta onized%y the second drug?

a. histamineepinephrine b. Penicillin-erythromycin c. Morphine-naloxone d. Procaine-sulfanilamide e. Aspirin-phenylbutazone

i. (a), (c) and (dl ii. (a), (c) and (e) iii.(b) and (d)

v. iv. (d) (c) OnllY on y

12. Which of the following responses is least predictable in occurrence?

a. Toxicit b. ~ ide-efLts c. Idiosvncrasv d. ~ a c h b h ~ l d x i s e. Therapeutic effects

(c) A~rsroer is (c)- Idiosy~~crntic renctioirs nre selreticnlly deternti~red nbirornlnl respolrses to n drttg. Tlrev nre tlre nrost rt~r redictable in occrtrrettce becatise t l e ietreticnlly- b n d d6ererrce resportsible for sltclr a reactio~r to n drug nrny ,tot beconte evtdnrt until tlte drti is take11 for tlre first time by the patietrt. Typically, t& effect is orte of nb~tornlal seirsitizlity to a drti , suclr thnt a tlternpetittc effect is presetrt at doses nttic% lower tlln~t ttornlally ttsed, wltile tlte nornlnl dose ntay result i ~ t a toxic reactiotr. At1 exnnrple is tlte respolrse to sticciirylcholi~re i l l patieuts witlt ntvpical plnsnrn cltoli~testernse. Tltese pntiettts don't nretnbolize srtcci~r~lcltolitre nt tlte sane rate, n~rd tlrtis sltoro n prolo~rgeddnt nctiorr nlrd itrcrensed se~rsitizlity to tlte drrtg. Tlte otlter aier,mtizJes nre typicnlly relnted to tlte dose of the drtig and becntise tlte nlnjority of t l e populntio~r do tot possess all atypicnl ge~tettc bnsis for tlre respolrse to tlte drug, the effects are predictnble gizjetr tlte dose alrd krrowledge of wlwt the drrig does.

13. Idiosyncrasies to drugs are'related to

a. b. Pies enetic factors c. A e of the patient d. Afl of the above

14. Two drugs, A and B, have the same mechanism of action. Drug A in a dose of 5 mg. produces the same magnitude of

nse as drug B in a dose of 500 mg. Which of the EEwing statements is correct:

a. Drug A is less toxic b. Drug A is more efficacious c. Drug A is 100 times as potent d. Drug A has a shorter duration of action e. Drug A is a better drug to use when a maximal response

is desired

15. According to the theory that agonists and antagonists occu y the same receptor site, an effective antagonist should g exhi it

a. High intrinsic activity and high affinity b. Low intrinsic activity and low affinity c. High intrinsic activity and low affinity d. No intrinsic activity and high affinity

16. All of the following statements are true regardin the occu ation theory of drug-receptor interaction &CEPT:

a. h e affinity of a drug is dependent on its intrinsic activity

b. The maximum effect of a drug occurs when all receptors are occupied

c. An antagonist has affinity for the receptor but not intrinsic activity

d. The ma itude of the effect of a drug is proportional to the num%r of receptors cxcupied

e. It follows the law of mass action

17. The occupational theory of drug-receptor interaction states that

a. The ma itude of the drug response is proportional to the numKr of receptors cxcupied

b. A partial agonist has intrinsic activity but no affinity for the receptor site

c. An antagonist dru has affinity but no intrinsic activity d. The rate at which t i e drug-receptor complex associates

and dissociates determines drug efficacy e. The degree of drug action is dependent on the law of

mass action

i. (a), (b) and (c) ii. (a), (c) and (el iii. (b), (c) and (dl iv. (b) and (e) v. (c), (d) and (el

Sedatives

This category consists of mostly questions regarding benzodiazepines and barbiturates, and requires you to know the differences between the two types of drugs in terms of mechanism of action, therapeutic actions and adverse side effects and toxicities. Here's a capsule review:

Benzodiazepines:

1 .Examples: diazepam, chlordiazepoxide, etc. 2.Mechanism of action: modulate the activity of the

inhibitory neurotransmitter, GABA 3.Advanta es vs. barbs: less addiction potential, less

profounfi CNS depression, larger therapeutic index, less respiratory depression

4.Other points to remember: A)many BDZs form active metabolites; B)N injection of diazepam can cause irritation such as thrombophlebitis due to the solvent the BDZ is dissolved in.

Barbif ura fes:

1. (a) question in occurrence about barbs is always regarding thiopental. Remember, thiopental's action is terminated by redistribution of the dru out of the brain-it enters the brain rapidly and exits rapi y, thus quick onset and short duration of action.

di

2. (b) question wants you to remember that barbs are not analgesic - this is usually in the form of a list of actions and they want you to indicate which is not true.

3. Questions about toxicity - a. Barbiturate overdose kills you because of

respiratory depression b. Barbs are contraindicated in a patient with

intermittent orphyria - barbs enhance po r~hy r in synthesis an$ thus will aggravate the disease

Sedatives

1. Diaze am is preferred to a barbiturate as an antianxiety agent gecause diazepam

a. Produces no sedation b. Has less addiction potential c. Is a very short-acting drug d. Is substantially less expensive e. Does not potentiate the action of CNS depressants

2. Benzodiazepines produce their antianxiety effects by modulatin which of the following neurohumors?

a. GAB! b. Glycine c. Doparnine d . Acetylcholine e. Norepinephrine

3. Benzodiazepines exert their main effect on a. Neuromuscular junctions b. Peripheral reflex synapses c. Central GABAergic neurons d. Central serotonergic neurons e. Central adrenergic nerve endings

(c) Answer is (c)- memorizntiorr- BDZ8s birrd to sites on the GABA receptor.

4. All of the followin pertain to general anesthesia induced by thio ntal E X C E ~ :

a. E s t induction b. Decreased secretions

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufb Medical School

c. Low therapeutic index d . Short duration of anesthesia e. Predisposition to laryngospasm

( b ) Bnrbittlrntes nre problentntic ns nttestltetics becnlrsc t l q often ittd~rce excessiae snlizntiort nrtd brortchinl secrettorr, tistinlly reqrtirirtg tlte tise of ntr nrtticltolirtergic drri to be adnrirtistered to redttce tllese secretiorts. Tlrtis (b) fins to be tlte jalse stntentertt.

31. Which of the following factors contributes to the short duration of action of a single dose of thiopental?

a. rapid biotransformation b. rapid accumulation in body fat c. high lipid solubility of the undissociated form d. ability to enter and leave the brain tissue rapidly

(dl is correct - tltioperttnl is tlle clnssic exnntple nlzunys giver1 o a drug wltose dltrntiort of ncliort is deterntitterl by redistrr 5 utiort nuwy front its site o/ nctiort irt tlle brnirt to less well perfiised ttssiles. Tltey lenzw otlt t l ~ e zvord redistribrltiott front tlte nrtsruer to cort/tlsc yorl -tlley btoro tltis is tlte rony yo11 lenrtted it.

3. Speed of recovery from short-acting anesthesia with thiopental de nds chiefly on the rapidity of

a. Renal t u c l a r secretion b. He atic degradation of the thiopental group c. ~existribution from the brain to skeletal muscle d. Reverse diffusion across the blood-brain barrier e. None of the above

6 . The action of the ultrashort-acting barbiturates is terminated primarily by the process of

a. Oxidation b. Redistribution c. Renal excretion d. Plasma protein bindin e. Conjugation with sulkte

7. Which of the following is NOT characteristic of barbiturates?

a. Possess anticonvulsant properties b. Possess significant analgesic properties c. Possess serious drug dependence potential d. Vary in degree of lipid solubility and hypnotic potency

8. The cause of death from acute barbiturate poisoning is a. Convulsions b. Liver damage c. Renal failure d. Respiratory failure e. Cardiovascular depression

9. Which of the following adverse effects is most commonly associated with administration of an intravenous barbiturate?

a. Hypotension b. Renal failure c. Hepatic necrosis d. Nausea and vomiting e. Respiratory depression

10. Im ortant steps in the treatment of barbiturate poisoning incide:

a. Maintainin an open airway b. Increasing t i e input of afferent stimuli c. Maintaining respiration d. Administemg a narcotic antagonist e. Administering a central nervous system stimulant

i. (a) and (b) only ii. (a), (b), (c) and (el iii.(a) and (c) only iv. (b) and (e) only v. (d) only

11. \Yhich of the following are true regarding barbiturates? a . Significant1 elevates pain thresholds b. Are metaboKzed by the liver c. Are classified according to duration of action d. Depress all levels of the CNS e. Cause death by cardiovascular depression

i. (a), Cb) and (c) ii. (a) and (d) iii.Cb), (c) and (d) iv. Cb) and (el v. (c), (dl and (e)

(iii) Artswer is (c)- Bnrbitlirntes nre ttot nrmlgesics, tlttis nrry nnswer witlt "a" srlclt ns (n) cart be elinritrnted.. "b" is true, tltlis tlle arrswer ntrtst contniri "b" as one of tile nlterrrntives, tltris (d ) aitd (e) are eliniiimterl.. "c" is also trtre, barbiturates nre alwnys clnssified nccorditig to dtirntioir of actiorr (tltiopeittnl- ultra-short actiitg; plrertobnrbitnl-loit -uctirtg, etc.). Tltis eliniinntes # 3 so tlle nitsruer ntust k (f). Of course, ori should lmve been nble to rnpidly elintirtnte a r t s w s (c! 4, arrd 5 because bnrbrtrlrntes cartse dentlt by respirntory depressiotr, trot cnrdioz~nsculnr depressiort.

12. Barbiturates are contraindicated in a dental patient with: a. Emphysema b. Hy rtension c. LJngaPosed severe pain d. Acute intermittent porphyria

i. (a), (c) and (dl ii. (a) and (d) only iii.(b) and (c) iv. (b) only

( i ) Answer is (a)- "d" is the absolute contraiirdicatiotr for barbiturate use, sitrce these drugs stinlulate t k syntltesis o ertzynles involved in the s y n t k s i s of porphyritrs and t I rus will a g p a w t e this d i m . Tlrus the answer must coirtairt "d' , eliminating (c) and (d). Sittce both (a) ntrd (b) difler only by alternative c, that is the second fact you must h o w . Barbiturates are not annlgesics, but d n t i v e s . Witetr pain is present, they nmy evert nrake tile pairr

ziyorse, resrrltifrg i ~ r nrozrsnl, rnge ntrd perllnps delirilrnr it1 tlre pntietrt. Tlrlrs, "c" wolrld seen1 to be n pretty stro~lg co~rtrni~tdicntio~l, nrnki~rs (n) tlze right nfrs1rver.

13. If diazepam (Valium ) is to be iven intravenously, it is recommended that a lar e vein ke used in order to

a. Hasten the onset o k action b. k e a s e the risk of thrombophlebitis c. Offset the vasoconstrictor qualities of diazepam d. None of the above

(b) (b) is correct. This is one oj tlze adverse side efiects oj IV diazepnnr. None o j tlre otlrer nlter~~ntiz~es npply.

14. The most important therapeutic measure to be taken in a case of barbiturate poisoning is to

a. Alkalinize the urine b. As irate stomach contents c. Aiminister a CNS stimulant d. Assure adequate res iration e. Administer osmotic guretics

Psychopharmacology: Antidepressants and Antipsychotics

Antipsychotics questions are usually about phenothiazines and usually about chlorpromazine. They ask for: a. Mechanism of antipsychotic action: blockade of dopaminergic sites in the brain b. Major side effects: i) anticholinergic effects, ii) extrapyramidal stimulation resulting in tardive dyskinesia

2. Antidepressant questions are usually about tric clic antidepressants such as imiprarnine or amitriptyine- usually of the t ... which of the followin is used to treat depression? ... fGs are the most commonf used antidepressant medication, but remember tlat MA0 inhibitors such as tran lwromine or phenylene are also used. 2nd eneration dlugs are fluoxetineand trazodone. The drug I8 the cpestions may ask for: a. Mechanism of action: blockade of amine reuptake or alterations of receptor number b. Side effect: anticholinergic or atropine side effects

3. The last type of uestion, again a dru LD asks that you remember that lit 1 ium is the drug of cioioice for the manic phase of manic depression.

Antipsyclzotics - Meclzanisnr of Action

1. Which of the following are pharmacologic properties of

antips chotic drugs? . a. d e y block the dopamine receptor b. They affect the hypothalamic temperature regulation

c. G E a u s e emesis d. They are synergistic with LSD e. They cause hypertension

i. (a) and (b) only ii. (a), (b) and (c) iii.(b), (c) and (d) iv. (c), (dl and (e) v. (dl and (el only

2. The anti sychotic effects of the phenothiazines arc probably the resug of

a. Release of serotonin in the brain b. Release of norepinephrine in the brain c. Blockade of do aminergic sites in the brain d. Prevention of tKe release of norepinephrine from brain

neuron terminals e. Increase in the dopamine content of the cerebral cortex

3. The antipsychotic effects of phenothiazines result from a. Release of serotonin in the brain b. Release of norepinephrine in the brain c. Blockade of do aminergic sites in the brain d. An increase in tRe doparnine content of the cerebral

cortex e. Prevention of the release of norepinephrine from brain

neuron terminals

4. Chlorpromazine and related drugs are thought at a d by block~ng which of the following receptors? a. Adrenergic b. Muscarinic c. Dopaminergic d. Central serotonin

( c ) Answer is (c)- Clrlorpronlazine is the rototypic phenothiazble, an antipsychotic drug u d i n t p t r a t nlent 01 schizophrenia. O t l w ntrtips chotzc drugs used jor thls purpose are haloperidol anhhioridazine. These drugs act via dopaminergic receptors.

Side Effects

5. Which of the following is an irreversible side-effect resulting from long-term administration of phenothiazines?

a. Sedation b. Xerostomia c. Infertility d. Parkinsonism e. Tardive dyskinesia

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufk Medical School ,

6 . Tardive dyskinesia is a neurolo ica1 sideeffect of which of 9 the following classes of drugs. a. Alcohols b. Tricyclic antidepressants c. Barbiturate antiepileptics d. Phenothiazine antipsychotics e. Monoamine oxidase inhibitors

( d ) Tardizw dyski~tesin is atr irrezjersible cotrditiolr tlrnt consists of irtzjolurrtn nrovenrerrt of skeletnl nrttscles, n cottditiort whiclr mny?e u e t t followbrg prolorrged use of drugs. This is typicnlly n dopnnriirergic nledinted effect. Tlle llerzothinztrre ant;psyclrotics nre tlle ottly drrigs 1 i s t J w h i c h nct vin dopantine. T l u otlrers, s u c l ~ ~ ns tricyclics nrtd M A 0 itrlribitors nffect ndretter PC tra~tsntissiott, bnrbittimtes act zjin GABA, ns oes nlcollol.

7. \Yhich of the following drugs are most likely to cause extrapyramidal stimulation? a. Antibiotics b. Salicylates c. Barbiturates d. Phenothiazines e. Benzodiazepines

( d ) - Extmpymntidnl side effects nre the nrnjor side e fects of n~rtipsycllotic nredicntiott nttd itrclude darkirtsotr-like effects ns rue11 ns tnrdiis dyskit~esin (from dez~elopnlerrt of sripersettsitirjity reslr lt itlg front clt rot1 ic blocknde of doynnrtr~e receptors in bnsnl gnrrglinl- nbtrornrnl mpid nltertrntittg ntoz~enrerrts of totrglre nrtd perioral areas, fncinl grinrncitt , etc. Pllettotlrlnrirlcs nre the ortly ntttipsyc,totrc nrlrgs i s t e n .

8. Phenothiazine derivatives do NOT produce a. Jaundice b. Xerostomia c. Gingival hyperplasia d. Postural hypotension e. Symptoms of parkinsonism

( c ) A~rswer is (c)- # 3 sltouM stntrd orrt irtrnrulintel~ beulise this is alnrost nlwnvs nletttiotted ns n side elect of dilarrtitt, wlticlr is )rot n plle;rothinrirle, but ntr nrlti- co~tvtilsnnt. Pllettothinzitte deriz)ntiz~es nre nrrtipsyclrotic dru s sudr as hnloperidol (Hnlcyort) or clrlo ronmzttte u s d i n the treatment o disorders such as sc%zo lrrenia. Yolr slrould rentenrber t f rnt t l u ntost troublirtg sic!! cffect o these drugs is t l ~ prodtidiort of tnrdive dyskinesra a t d t1* arkinsotlian-like extrapyramufal disorders. Thus t 5 is e k i n a t d . A s rr rule tltese drugs k v e anticltoliner ic and anti-a1 lta adretter ic side effects, wluc t wou * + eliminate xerostonrtn, an postural hypotension (due to an an ti-ad renergic depressant elfect on both vasomotor centers and the autonomic rtervotis systent) as possible answers. Iaundice is a less fre tient side e ect than tlte e x t r a ~ r a m i d n l syn~ptoms , am! ofterl rese B t s from art allergrc readiotr to tllese drrigs. n t u s the arlswer is (c).

b. Photosensitivity c. Excessive salivation d. Anticholinergic effects e. Antiadrenergic effects

AIZ tidepressants

10. The drug most commonly 4 to treat severe mental de ression is a. L i u m b. Imi rarnine c. ~ h P o r romazine d. ~ r a n ~ b r o m i n e e. Dextroamphetamine

( b ) this qrlestiott is obviorisl ront tlle enrly 80's; you would see a different list o#u s todny, so review your sylbbris otr antidepressnnts. ~ 0 % ~ you wotrld probnhly see sonrethirrg like prozac. Trnrt Icypromirte is tlle ottly o t h r nntidepressnttt listed (~li%rpronmzitre is nrr nttti sycltotic used to trent scltizoplrrettin), brrt is ntt M A 0 inhtkitor. n ~ s e are 2nd cltoice dn igs drce to side effects.

11. Which of the following drugs is most effective as an antidepressant? a. Diazepam b. Reserpine c. Amitriptyline d. Chlorpromazine e. Hydroxyzine

Meclzanisnr of action

Which of the following is most likely to be the major mechanism of action of the tricyclic antidepressants? a. Enhanced release of acetylcholine b. Inhibition of neuronal synthesis of norepinephrine c. Potentiation of serotonin synthesis in nervous tissue d . Stimulation of reuptake of norepinephrine from the

s naptic cleft e. dockade of the reuptake of amine neurotransmitters

released into the synaptic cleft

Side Effects

13. Tricyclic antidepressants have a rominent side effect that most nearly resembles the usuafpharmacological action of a. Codeine b. Atropine c. Ephedrine d. Pro ranolol e. ~ e K a c h o l i n e

9. All of the followin actions are associated with the use of ch lorpromazine%~c~IT: a. Jaundice Antimanics

14. Which of the follo\vins drugs has its primary use in the treatment of the manic phase of depressive psychosis? a. Lithium b. Reserpine c. Imipramine d. Am hetarnine e. ~hPor~romazine

13. Lithium carbonate is particularly effective in treating a. Parkinsonism b. Hypertension c. Schizophrenia d. Acute anxiety e. Manic-depressive psychosis

16. The current drug of choice for treatment of the manic phase of manic-depressive psychosis is a. Lithium b. Caffeine c. Reserpine d. Irniprarnine e. Amphetamine

Anti-inflammatory Drugs:

In general, you need to remember that

1. These are corticosteroids or glucocorticoids and that they suppress the immune system m addition to their antiinflammatory activity. Thus latent infections such as tuberculosis may go systemic or opportunistic infections such as Candidiasis may become more of a problem

2. Side effect profilejastric ulcers, immunosuppression, acute adrenal ins ficiency, osteoporosis, hyperglycemia, redistribution of body fat

Frequently asked questions on anti- inflammatory drugs;

1. Which of the following statements is NOT true regarding the adrenal corticosteroids? a. Cause retention of sodium and fluid b. Decrease activity in lymphoid tissue c. Heighten the immune responw to antigens d. Can roduce a diabetes-like syndrome with high blood

leveL e. Are therapeuticall beneficial when administered r orally, parenteral y or topically

b. Candidiasis c. Tuberculosis d. Peptic ulcers

i. (a), (b) and (c) ii. (a), (b) and (d) iii. (b), (c) and (d) iv. (c) and (d) only v. All of the above

(v ) Artswer is (e)- Corticosteroids nre antiirtflnntnmto y drugs used topically, orally attd pnrertterallv. However, they suppress the imnilrne systent of the body. Tltey lrave beat btown to cause peptic ulcers, as well as nlask tlze syntptorns of an ulcer, and perforntion arrd lzemorrlmge m y result. Thus "dm has to be in the answer, eliminating (a). Because they are immunosuppressive, they would obviotrs make an AIDS pt ient , w to already has a conrprontised intmurte s stenr, worse. Sintrlarl , laterrt tubercnlosis could also & reuctivnted. 711~s Y Jarid (dl car1 be elirnirtated. Use of corticosteroids in irtlzalers or astltnta, while adrpantageous in rcducirrg the side e k c t s res~tltirtg front s stenttc ndntirlistrntiort, hns led to nn itrcrensc irr prob&nts witlt Cattdidinsis, so "b" lras to he it1 the nnszuer. (e) is tlle orlly arrswer tlmt nteets all tllese req~tirenlerrts.

3. Which of the following does NOT result from prolonged treatment with steroids? a. Gastric ulcer b. Osteoporosis

d. c- Hpglycemia yocardial atro hy e. Redistribution orbody fat

4. Glucocorticosteroids are useful as secondary treatment of anaphylaxis because they a. Inhibit the production of antibodies b. Prevent the union of antigen with antibody c. Prevent the release of histamine from sensitized cells d. Su ress the inflammatory response to cell injury e. 1n;iit the release of serotonin from vascular storage

sites

(d) Arlswer is (dl- Glucocorticoids such as ltydrocortisone are classed as antiirtfirnrnntories, irtl~ibitirtg e v e y step of the inflantntatoy process.- tltus ( d ) is the correct answer. The otlzer alternatives are single steps along the pathway, that are handled by otlter drugs that are more selective than glucocorticoids.

5. Adrenal steroids are used successfully to treat all of the following conditions EXCEPT a. Gastric ulcers b. Addison disease c. Lupus erythernatosus d. Rheumatoid arthritis e. Aphthous stomatitis

2. Which of the follohin conditions contraindicate use of corticosteroids in a ental patient? a. AIDS

i

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

General Anesthetics: 1. Questions always come u p re arding factors that influence i? the rate of induction. Remem er that onset of anesthesia is

inversely proportional to solubility of the anesthetic in the blood. The more soluble the agent is in blood, the more must be given to reach critical tension in the brain.

2. A second set of questions has to do with adverse side effects of various general anesthetics. Halothane is associated with hepatotoxicity.

3. Some questions are based on the pro ressive depression of CNS function leading to anesthesia %at characterized older anesthetic agents. Remember the 4 stages of anesthesia:

Stage I: analgesia Stage Il: delirium Stage In: sur ical anesthesia Stage lV: mdul la ry paralysis

Frequently asked questions:

1. Signs and stages of anesthesia are most likely to be seen ~\.ith a eneral anesthetic that has a a. $w potenc b. Slow rate ofYinduction c. Low Ostwald coefficient d . High oil-water solubility coefficient e. High tissue-blood partition coefficient

2. All of the followin influence the rate of induction during anesthesia EXC~PT: a. Pulmonary ventilation b. Blood su ply to the lun s c. ~ e m o ~ l o % l n content of &e blood d . Concentration of the anesthetic in the inspired mixture e. Solubility of the anesthetic in blood (blood-gas

partition coefficient, Ostwald coefficient).

3. The rapidity of onset of anesthesia with an inhalation anesthetic agent is primarily related to its a. Molecular wei ht b. Degree of bloo% solubilit c. Temperature in the gas pLase d. Interaction with preoperative drugs

that the most resistant part of the central nervous system is the a. S inal cord b. d d u l l a oblongata c. Cerebral cortex (motor area) d . Cerebral cortex (sensor area)

6. General anesthetics can do all of the following EXCEPT: a. Produce delirium b. Stimulate medullary centers c. Produce a state of unconsciousness d. Reduce perception of painful stimuli e. Decrease excitability of the motor cortex

7. In ~ene ra l anesthesia, the last part of the CNS to be depressed is the a . Medulla b. Cerebnun c. Midbrain d. Cerebellum e. Spinal cord

49. General anesthesia with halothane is commonly preceded by administration of atropine to

inhibit vagal overactivity commonly caused by halothane

induce muscular relaxation by blocking cholinergic receptors

c. reduce salivation and bronchial secretions caused by halothane

d. all of the above.

Ausroer is (c)- illis is i l ~ e clnssic clitriul use of atropitle and oue yorr slrolrld ltnzle conlnritfed to menrory. Atropitre does )rot induce nrlrsclrlnr rehxatio~r- iltnt worrld be a ttettronrrisc~tlnr jrrrtctiott blocker srrclr ns curare, thus (b) ntrd ( d ) nre wrong. #! might colrfirx yotr. Atropirre is used to ozjerride vn a1 nctizjity, but tlmt is trot tlie reasorr it is givett before hlotlmt1e.

Questions regarding antihistamines generally want ou to know what H1 and H2 antihistamines are u s d f o r :

H1 antihistamines are useful for: .

4. Which of the following forms of drug toxicity is associated with the halogenated hydrocarbon general anesthetics? a. Liverdama e b. ~ ~ o c a r d i a k a t r o ~ h ~ c. Peripheral neuritis d. Severe hypertension

5. The behavior of patients under general anesthesia suggests

1. Treating dermatologic manifestations of an allergic response. (ex. chlorpheniramine)

2. Preoperative medication for sedation, antiemetic properties, anticholinergic effects. (ex. promethatine)

3. For controlling the symptoms of parkinsonism (ex. d iphenhydramine)

H2 antihistamines such as cimetidine are used to reduce gastric

acid secretion (ex. cimetidine)

.. Which of the followin d r u ~ s is useful in treating dermatologic mani estations of an allergic response? a. Diazepam

P b. Atropine c. Hexylresorcinol d. Chlorpheniramine e. Phenoxybenzamine

(d ) Anstuer is (e)- Tlze inrplid drug clnss is atrtihistnnrirres. 0 tlle drugs gizpetl orrly 2, (c), ntrd (e) nre nnt ilristnnritres. Ti here nre two chsses o ant ilristnnrirres, d HI and H2. H2, represetrted by cinreti itle, nre used to treat ulcers not skirr conditions. HI atrt ilristnntirres nre used to trent nllergic renctiotrs, ntrd chlorplrerrirnnritre is nrr HI drrig. Thlrs tlle atrswer is ( e l

2. Cimetidine is used therapeutically to a. Stimulate respiration b. Protect against anaphylaxis c. Decrease gastric acld secretion d. Hasten excretion of barbiturates e. Dilate smooth muscles of the bronchioles

3. Gastric acid secretion has been shown to be most effectively reduced with the use of a. Adrenal steroids b. Anticholinergic drugs c. Serotonin antagonists d. HI-histamine receptor antagonists

4. Drug-mediated inhibition of Hz-histamine receptors is most useful in treating a. Asthma b. Anaphylaxis c. Contact dermatitis d. Gastric h peracidity e. Localizedlallergic reactions

5. Which of the following antihistamines is most commonly used as reo erative medication? a. RlecPuine b. Cyclizine c. Promethazine d . Dimenh yd rina t e e. Chlorpheniramine

6. Use of diphenh drarnine (Benadryl ) in controlling the symptoms o?pzrkinronism is based upon which of the following effects? a. Anticholinergic b. Local anesthetic c. Adrenergic-blockin d. CNS depressant on Phe midbrain e. Stimulant to doparninergic nerves in the basal ganglia

(n) Renlenlber tllnt Parkirrsorrisnr is oj D A il l tlle brairl, nrld is clrrrerrtly arrd mrbidopn. However, prior to tllese, ntrt drugs ruere tkeftrst drrigs folrrrd to be jor trentnletrt o this disense, in tllat clroliner 'c ntl dopanritrergic lrncts b,teracf itr tlze braitt, a n f t h u s reducing cholinergic activity vin anticl~olitlergic drugs inrproves or enhatrces dopnminergic fxr nctiotr, sug estitrg otre is inhibitory to f l u otlzer. Drugs witlr atrticltoitrergic actizjity are often still tlle first drug tried. Atltilristanrine drugs suclr ns diphetlhydramine oftett h z j e strottg atrtrclrolitrergic act izpity, wlliclr nccounts for their eflectivetress in drying nasnl secretiotls associated with a cold. Therejore, the answer is (a). (e) is there to confxtse you, but don't be. Diphenlrydranritle does not stinrlrlate dopanrinergic nerves in the bnsal ganglia. Ad retrergic blockers ( (c) ) do see sonre use in tlle treatntent of Pnrkitrson's, but d i lletllr drnnlitre has no adretrergic blockitrg act izjit . &pherl~yirnnritre does l law t l u act iorrs git~etr itr (b) atrX(d), but tllese nre 11ot respotrsible jor its ejFcacy itr Parkitlson's..

41. The mechanism of action of HI antihistamines is a. M A 0 enzyme inhibition b. competitive antagonism c. physiologic antagonism d. noncom~titive antagonism e. inhibition of release of bound histamine

(b) Atrszoer is (b)- nlenrorizntiotr - HI ntltillistnnlitres are conrpetitizpe histanlitre receptor blockers. Mnny stlrdetlts nrrswer (e), brtt this is tlle nrecltnrrisnr ojnctiotr o j cronrol 11. ( c ) nlso dratus sonle arrswers, birt is wrorrg- epitrepfritle is tlle pl~ysiological ntltngotrist oj histnnritre.

Miscellaneous questions from a variety of categories that are not asked quite

as frequently as the ones above: 24. Which of the followin drugs is often used to treat Fs tri eminal neuralgia.

a. cfonazepam b. carbamazepine c. acetazolamlne d. succinylcholine

Answer is (b)- This is a memorization question. Carbamazepine, as well as phenytoin, are the ?in drugs used to treat trigeminal neuralgia. Clona a m zs a betlzodiaupine, succinylcholine is a d e p x r i z i n g neurontuscular blockin agent, while acetazolanttne is an ant icotrvulsant like ca%anxuzepine.

1. The use of epinephrine for local hemostasis during surgery might result in a. hypo~lycemia b. cardiac arrthymia c. an acute asthma attack d. a drastic drop in blood pressure e. any of the above

The answer is (b), Cardiac arrthynrias are the main bad side effect o j epinephrine as a vnsoconstrictor. Epi

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

slinrrrhles bollr nlplrn n~rd heh receyIors. Betn recqwtors nre forrird iir tlre l ~ ~ r t nird stinrrrlntioir of betn receptors iircrenses lrenrt mte, force of coirtmctioir, cnrdinc orttprrt n~d oxyserl iliiliznfiort. ( R ) is rurorlg, epi elezmfes blood glrrcose. (c) is wron - betn stinrulntroit iit snrootlr ntlrscle nird broitclti cnrrses f roircltodilntioit, n~rd is tltrrs n drrtg of cltoice for ncrrte nstlrnrntic nttncks. (d ) is obzliorrsly wroitg- n decrense iir blood pressure wortld itot resrtlt front adreilergic stintulatioil, iitcrensed blood pressrtre is tlre rrtle.

4. The highest risk associated with use of oral contraceptives is a. hepatic necrosis b. permanent sterility c. cancer of the breast d. cancer of the uterus e. thromboembolic disorders

Tlle two nrn'or side effects nre srtspected cnrciiro eiricity nitd tlte teiideitcy to produce tkronrboentbolisnts. f i w r fiorctioir cnii be nltered brrt this is rez~ersible. Resenrclr lrns f n iM to prove tlre l i~ tk betweeit estrogeit nild brenst cnitcer, nird reprodlrctiz~e firirctioir ezleirtlmlly retrtrits ~tpoit cessntioir of tllernpy. Tlle nirswer nccordiirg to tlre gods of tlre testiirg bonrd is (e). Anteit.

#9. Factors common to all forms of drug abuse include a. miosis b. tolerance c. physical dependence d. psychological dependence e. any of the above

The niiswer is (dl . Miosis ( (n) ) is n clroliirergic effect t picnlly observed zuitlr opintes. Cocniire doesit't cnltse txis ki id of cflect for exnnrple. (b), tolemirce, is conmtoir to nrnit drugs sltclt ns o intes, bnrbitrrrntes nnd sdntizjes, but h s trot becir clenrb denroitstrnted for nll nbltsed drrtgs. (c) , pltysicnl depeitdeitce, is ltsrrnlly tlrorrglrt to be true 011ly for ntorphiite, nlcolrol, c#iite, nird perllnps cocatire.

27. Alcoholic eu horia results from a. increadactivity of the cerebellum b. increased activity of the cerebral areas c. increased activity of the spinal synapses d. decreased activity of the medulla centers e. removal of inhibitory activity of x e cortex

Anszuer is (e)- Alcolrol iithibits the CNS , thus elintiitntiirg (a), (b), nnd (c), lenviirg the choice betweeir 4 and 5. Alcohol hns beeir postrtlated to inhibit G A B A elfects, the ntajor inltibito transmitter in the CNS , especrnlly iit the cortex. Thus ( 3 i s t h answer.

28. Sulfon 1 ureas cause insulin secretion by a. aAnergic simulation b. cholinergic stimulation c. direct st~mulation of pancreatic beta cells

Airszoer is (c)- nlenroriznt ioir- nlplln ngoir ists decrense iirsulin release, betn ngonists iitcrense it. Thus becarrse both of these nre adreitergic stinrulatioi1, (a) cail't be the airswer. (b ) - nlltscnriiric ngoirists iircrense iirsulilr relense, brtt tlris is not tlte nlecltairtsnt o sulfoitylureas. They cnrtse iirsuliir r e h s e hj (c), nir d are tlle primary ornl

37. If a patient requiring an extraction reports that he is on dicoumarol therapy, the laboratory test most valuable in evaluating the surgical risk is a. clotting time b. bleeding time c. sedimentation rate d. complete blood cell count e. plasma prothrombin time

Airswer is (e)- Dicortnrnrol is an oral anticoagulant. Thus tlle risk iir air extrnctioir is thnt the patient may bleed excessively, or thnt a serious iilteraction witlr a drttg t h t yo11 might require in your nlanagemeitt of the atieirt, such as barbiturates or salicylates may occur. fou may net4 to adjust the anticoagulant activity to withiit a safe range for stt rgicnl p r o d u r e s . Since dicou mnrol prez)etrts blood clotting by prezreittiitg the conz~ersioir of Vitamill K to prothronrbin, (el is tlle oirly appropriate test.

42. A drug has a half-life of 4 hours. If 2 gms are given every 4 hrs what will be the amount in p s in the body immediately after the third dose? a. 1.5 b. 2.0 c. 3.5 d. 4.0 e. 6.0

Airswer is (c)- 2 t nt 0 ltr, at 4 ltrs 112 fronr rst 6 iiljectioir is goite, g u i l t I gnr iit tlte body air yort iilject 2 nrore for n totnl after i re secoitd iirjectioit of 3. At tlre third dose, 112 of 3 is goile, h o b r g 1.5 pot yrt iirject 2 nrore for a total of 3.5 intntediately riper tlle t rird dose.

43. LVhich of the following combinations represents acceptable agonist-antagonist pairs in antidotal therapy? a. morphine-naloxone b. dicoumarol-protarnine c. warfarin-phenylbu tazone d. carbon monox~de-carbon dioxide

(n) slrorrld be inrnredintely obviorts- go iro furtlzer, do trot pnss go, do not collect $200. (b ) is wrong-Protnmiile is air ni~tngoirist of lwpariil, not dicounrnrol. (c): plleitylbutnwire eillzailces the toxicity of wnr nrirr by displaciirg it front lasnla protein birtdiilg sites. (d): ltyperbnric oxae i t wor t i be a useful treat nteit t for carboit nloitoxide porsoitiitg, ?lot C 0 2

46. The various insulin reparations useful in the treatment of diabetes mellitus %ffer primarily in a. locus of action b. mechanism of action c. mode of transformation d. onset and duration of action e. none of the above

Answer is (d)- remember, diabetes medicatioits cait be or anized into 3 groups based on their onset and duration ofiction: 1 ) ast-actii, : insuliit injection, 2 ) internrediate I . 8 . actiitg: Isop lane rnsu rn suspetrsion, and 3) lottg acting: protanrille zinc insulin suspeirsioit

48. Displacement of a drug from protein binding sites is expected to increase the a. drug effect observed b. duration of drug effect

c. dose required for a given effect d. none of the above

tised iit a cnse of adreitnl nrdtilln iits~ifficieircy.

52. In Fig. 1, three different doses of drug A are tested for activity. In Fig. 2, three doses of drug B are tested for activit in the same test system. In Fi .3, three doses of drug Kare tested in the presence of t t e high dose of drug B. Based upon the responses seen, which of the follotving statements best describe drugs A and B? a. drug A is a partial agonist; dru B is an antagonist b. drug A is an antagonist; drug #is a partial agonist c. drug A is an agonlst; drug B is an antagonist d. drug A is a agonist; drug B an partial agonist e. drug A is an agonist; drug B is neither an agonist or an

antagonist

(5) sorry cnlr't reproduce the f i lire. Brit 1 tllillk t l q give yoli n copy of this exnnt, dotl't t$?lf ,lot, look this u trl P yotir course syllabtis. You still lmz~e yorir colirse syl nbtis, dort't you?Artstuer is (e)- drug A depicts n dose respottse curzje for a bill ngorlist- tlte typicnl signtoidnl dose resporlse curz)e goiitg front 0-100% resporlse, tlllis (b) is elintinnted fronl furtller cortsideratiort. Tlle dose res orlse ctirve or drug B is Ft-iro resportre nt nll. Drtig B t i i s catt 't 6 e a pnrtinl ngoitist, tulticit nrenrts (d) is wrottg. It ntrist eitller be nn arttngortist or iteitller nrt ngorrist or nrrtngortist in tlris systent. Tlte fact tlrnt it doesrl't secnt to alter tlre dose respottse c1irz)e for Drtig A irl Fig. 3 iirdiurtes it cnrt't be ntt atttn ortist- t:le clirzJe wotiM be sintilnr Lt slmpe except shlffld to the right. Tlre nrtsiuer is tlrtis (el.

56. In an addisonian crisis (hypoaldosteronism) resulting from stress from a minor dental procedure, the patient should be treated immediate1 with a. 0.5 ml norepineplrine b. 5 mg. prednisolone acetate c. 1 % triamcinolone acetonide d. 0.5 ml, 1:1000 epinephrine e. 2 ml(100 mg) hydrocortisone hemisuccinate

Answer is (el- Addison's disuse resrrlts from ailure of tile adrennl cortices to roduce adrertocortical / tormortes sucit as aldosterone. ~Pdosterone is a mirteralocorticoid that controls sodiunr retention aitd potassiunl excretion. Lack of aldosterone results it1 electrolyte imbalnnces, with tlre major problem being hyponat remta (sodium loss). Similar sym toms may also be seen when a patient is withdrawn ;om chronic adrenal steroid therapy. Due to depressed adreital function, patients cart 't respottd to stressful situatiotts (such as dental procedures) adequately, artd art adrertal crisis ntay occur. Tile recommertded treatment is (el, I00 nlg of ltydrocortisotte ilemisuccirlnte. Of the other corticostero~ds giuelt, ire dose giver1 for rdnisoloite ((b)) is too low, while triamcirtoEne lncb arty e ects ort soditrnt reterttion. NE nnd Epi would not be u s!J irr titis situntiotr- t l q ntigitt be

59. Drug A inhibits the biotransformation of Drug B. The duration of action of drug B in the presence of drug A will usually be a. shortened b. prolonged c. unchanged

Answer is (b)- uslinlly biotraits ornlatiort results it1 a ntore wnter soluble, ntore readi f y excreted form of tlze pareilt drug. lit ntost ca.se.5 tltis rnactivates tlre drug, but tlrere are some except ioits whiclt inzjolue tlre formation of ntetabolites with activir ( d i n ~ a n r ) or wllot an innctive prodrug is given (levo opa) w tch becontes active after the first step in tlle biotraitsformatiorr pathway (DOPA) sonletimes are asked in questions of tilts form.

61. In which of the following groups of drugs is there the most consistency in chemical structure? a. diuretics b. antiepileptics c. local anesthetics d. general anesthetics e. nonbarbiturate sedatives

Artswer is (c)- Rentenlber that lour1 ntresthetics nre eitller esters or nntides. A11 of tlw other nlterilntizjes dizjerge widely ir l tlleir structures.

64. Cimetidine is administered to a. aid in slee ing b.relieve a s t h a c. inhibit gastric secretion d. relieve cold and flu symptoms

Artswer is (c)- Rentember, cinletidirte or "Taganret" is ait HZ nrttiltistnmine nre used tllera euticnlly to irlhibit gnstric secretioit ((c)) iit cases o$pTtic ulcer. This is its otlly clirtical rise. Yori migltt see it trt a questiotr regardin drug nutabolisnr- it is also a poteitt iitlttbitor of tlle m i x d fr!nctiorr oxidase drug metabolirirtg ettzynte systent in the Itver. The other alterrtntives are to coirfuse you because YOU probably at least renrentber tlmt it is ail antiltistamirte, but ori don't kitow tlre differerrce betweert HI artd H2 nrtt Xistantines.

65. Which of the following anticancer drugs can be classified as an antimetabolite? a. cisplatin b. lomustine c. vincristine d. methotrexate

Aitswer is (d)- I would guess (d ) because its the only one I've e w r heard of, aird since this wasn't covered in class you mi ht be one to guess it also. Wow, we ot it ri ht! B Actual y, i fyou look the others up, (a) b. (bfare al&latirtg agents, (c) ts an alkaloid derived from plants. (d) is a folate antagonist, which acts as an antimetabolite. Just for your future edification, most cancer chemotherapy dru s cause cell death by p ecting the abilit of cells to divid. 6r The drugs thus rnhr rt oite or more pLses of the cell cycle or prevent a cell in Go (the nortdividing phase) from entering into the cycle of cell division. Arttimetabolttes may act iit 2 ways ( I ) by incorporntion . into a nletabolic pathwny and formation of a false

Prepared by M.L. Thompson, Ph. D., Dept. Of Pharmacology, Tufts Medical School

nrdnbolite wlriclr is 1rotr c~rctiolrnl or ( 2 ) by irrlribitiolr of tlte cntnlytic jlrirctiorr o ! nn e~rzynre or elizynte systent. Metltotrexnte is nrr exnnrple of n cell cvcle spectfic nltfinretnbolite ttrnt i~lfribrts D N A sy~rt)resis dlrrrlrg tlre S phnse. Viircristitle ncts d~rrirlg the nritotic plmse

66. Which of the following hormones acts to elevate blood concentration of iomc calcium?

b. a. gluca%? parat yroid c. aldosterone d. thyrotropin e. thyrocalcitonin

Answer is (b)- maintaining the concentration of Ca++ in extracellular fluid by re ulating the deposition and mobiliza Son of calcium from bone, absorption from the GI tract, excretion etc. is the main function of

arathyroid hormone. Thyrocalcitonin is another name k r calcitonin. They hope to confuse you because there is a correlation between calcitonin and calcium, except that calcium concentrations regulate the synthesis and release of calcitonin. Gluca on is a pancreatic hormone that stimulates glucose prJuction, thyrotropin is there to confuse you with parath oid hormone, and aldosterone regulates Na+ cvels not Ca++.

67. Disorientation, confusion, and hallucinations resulting from an overdose of scopolamine are most efficaciously treated by administering a. atropine b. levodo a c. acetylcRoline d. physostipine

A~rstver is (d)- scopolnnr i~re is n nrriscnririic receptor blocker sinrilnr to ntropi~re, tlrrls (n) is wrolrg. Lmodopn llns nothi~rg to do zvith tlris qrtestiolr. To corirrternct n conrpdititle nrrlscnrirric receptor block, yo11 Ired to ilrcrense tlte 1ez)els of ngorr is!, ill tlris cnse acet lclioli~re. However, yo11 cn~l ' t gitr AClt becnrise it is brorerr down nlntost i~rstnrrtnneorrsly by ncet lclro1irresternse. The mrswer is to g i t r R drrl wllicb Locks out the B ncet lcholi~resternse, a lowirrg endoge?rousl relensed A c X t o nccrrnrelate to ozrrconv tlle nctiolr o/scopobnrbre. Tlre drug wlriclr will do tlris is plrysostignri~re.

69. Developed hyporeactivity to a drug is a. tolerance b. antagonism c. detoxification d. desensitization

A~rswer is (a)- your clroices are betwee11 toleralrce and desensitiuttion, (n) and (d). T l v latter re/ers to sonte alteration o j receptors that lends to dintrnished respoltse to tlre d r ~ t , and is really a meclmltisnl whereby tolera~lce ntay occur. ?hus the Gods of the Board questio,o have decreed t lut tlre atrswer slull be (a).

77. Absorption of a drug from the intramuscular site of administration may be slowed by a. exercise b. vasoconstriction c. the presence of con estive heart failure d. administering the drug as an insoluble complex

2. b only 3. b, c, and d 4. b and d 5. all of the above

Alrszcler is (c)- "n" cn11't be rigllt becnrtse exercise irtcrenses blood flow throrrglr nnlscles nlrd tlrrcs intproves nbsorption. Thus # I is wroltg. "b" is obviolrsly ri ltt or tlre sante rensotr. "c" worrld also resrtlt i ~ t reduced b B oo d flow so slower nbso Tion worrld also be a problenr. "d" is oftell used for prolovge and steady drug release so it also is true. Tlre attswer nittst thus be (c).

78. Salicylism includes which of the following? a. nausea b. tinnitus c. vomiting d. gastrointestinal bleeding

l . a ,b ,andc 2. a, b, and d 3. a and c only 4. b, c, and d 5. all of the above

A11szc)er is (e)- "Snlict/lisnr" is n niild toxic renctiolr to nspiri~r (ncetylsnlicy~c ncid), rrsunlly occrlrrbtg nfter prololt~ed trentnze~rt toit11 hrpe doses. Nnrrsen, fililrittrs, i~onri thg aird GI bleeding ar; nll synrptonrs of snlicyli.snr. Other ~rotnble side eJIects of nspiri~t tulriclt res~llt from ingestiorr of n si~rgle lnrge dose nre disturbnnces of ncid- base imbalance (acidosis or nlhlosis), fever, h po lycenrin. Remember, aspirin, is iorr traindicnted i~r c i r l Jen srifieri~rg front irrJluenut or chicken pox: aspirirr lms been in~plicaterl itr tlte dezlelopntelrt of Renee's syrrdronte.

82. Which of the following are important criteria for the adequate clinical evaluation of a new drug? a. comparison with a lacebo b. evaluation of side e k t s c. utilization of control groups d. comparison with a standard drug e. double blind experimental design

1. a, b, c, and d 2. a, b, d, and e 3. a, c, dl and e 4. b, c, and e 5. b, d and eonly 6 . all of the above

Atistver is #6- A ginrnte-this is just conrrnon sense.

84. Each of the following a ents has a lon duration of action due to the presence of h e r g e n e r a t d a d h e metabolites EXCEPT a. diazepam b. oxazepam c. flurazepam d. chlordiazepoxide

Answer is (b)- This is a pure memorization questiotl. All of these drugs are benzodiazepines, which typicall have a long duratron of action baause !hey a!e convert K to pharmacologically active metabolttes wrth long half-lives. Oxazeprn, midazolnrn, and lorazepam are exceptions that are not converted to active metabolites. The altswer is

exceptiori- it will rrot precipitnte witldrawnl becarise it is orrly n zucnk niir aritngoriist .

86. Each of the following statements relates to the general aspects of toxicology EXCEPT

a. most drugs exert a single action b. toxicity is both time and dose dependent c. toxicity can be due to overdosage of a drug d. symptoms of toxicity can be anything rangng from

nausea to death e. for some drugs, even a minimal concentration can be

harmful

Ariswer is (a)- If yoir learned airythirrg froni plmrmacology, you should iristaiitly be nble to idortib (0) as tlle correct answer. Tlle coristnrit uest o pltarnmcology s / as a science is to design or iderrfib rirgs t mt lmzpe as narrow or specific rarige of actiorr as possible, but rrot to many sirigle action drirgs hnve been ider i t iw . Alterriatives (c) arrd (b) sliould reniirid yorr of plirases sudr as dose-resporlse curves arid tlteraperrtic index (the ratio o a toxic or letlml dose to a thernperrtic dose, LD50/ED50). A toxic e fect cnrl be brondly defirred ns nriy

B d irrrdesired e ect of tlw rlrg, thrrs # 4 cnri't be tlle exceptiorr. o rirle orrt # 5, tlririk of nerzle gns.

92. The central actions of eth 1 alcohol are not synergistic with 2' which of the following. a. diazepam b. meperidine c. pentobarbital d. chlorpromazine e. methylphenidate

Answer is (el- Tlte cerrtrnl nctioirs of nlcolrol nre depressnrlt. nirrs tlre clioice of correct nrrswer conres dowri to fnrowirig wlliclr of tlte dru s listed is trot n CNS !epressnrit. Ditzepnnr is a berlzo$nzepirle, perrtobnrbitnl is n barbitrrrate. Both nre sedatirig. Meperidirle is nrr opiate, wltile chlorprontnziile is n plrerrotlrinzirre nritips chotic. Both o tllese clnsses of drir s nre also typicn$ saintbig. Ale correct nrtsluer is fe), niethylplleriidnte (Ritnliir). Ritnlirr is nrr itrdirect act irrg s nr ntkoniinretic, arm ncts sinrilnr to nnrplletnnlirre irr tlre

N it is a stinirrlnrrt. 2' 4- 97. A heroin de ndent atient should not be given nalbuphine

(Nubain) E r pain L a u s e a. it has no analgesic properties b. it may produce respiratory depression c. as a mixed agonist-antagonist, it can elicit withdrawal

d . x G x b u s e potential of nalbuphine may add to the patient's problems

Answer is (d)- Nalbuphine is a nrixed agoriist-antagonist tlrnt is anal esically equipoterit with nio lrine (thus # I is ruled out?. However, analgesia is prolZ)uced by its agonistic e ects at kappa o ioid receptors. It has pronotrn~aritagoriistic e g c t s at the mu rec tor, and can be uwd clintwlly to reverse respirato Tepression (b blocking nirr receptors) without a loss &nnl esic e{ets (by stimulntiri kappa receptors). Thus, # 3 is rulcd out. # 4 is not fkely. The nrixed a ortist*ritngoriists were designed to conibine artalgesia w i t i enou 11 antagonistic properties to prevent t W r abusc. fhus, # 3 is the right answer. Typicall these drugs car1 mimic the efiect of nrorphirre hi a drug )ke patierit, but arrtngoriize opiate actiott in a depetident pat rerrt, thus r r e c p a t ing witldrawnl. Of this chss of drugs, butorp rnrio is tlre

99. All of the followin methods of drug biotransformation are % classified as synt etic except: a. N-alkylation b. Odealkylation c. sulfate con'ugation d. g~ucuronide conjugation

Arrswer is (b)- Norrsyrrthetic renctiorrs (plmse I reactiorrsl include the various trarisformatioris of molecular structure: oxidation, reduction, and hydrolysis; tl represerif the first stage of biotransforniatiorr. S rizetic (phase II) rolctions consist of the con -u ation ofdrugs or their nretabolites with nctional *.!he nlturrntives, (c) nrid ( 6" ) are corijugat~ori reactions, arid flirts are wrott because tliey are synthetic reactiorrs. Altenvtive (a? is tricky. It is nude to sound like N - dealkylatiorr, which is a nonsyritlletic or llnse I oxidatizle reaction. Tltere is no reaction urlled N-a$htiori. Tliirs (b), art oxkhtive plmse I rendioii is left ns tlle riglit aiiswer

Prepared by M. L. Thompson. Ph.D., Dept. Of General Dentistry, Tufts Dental School

1993 Board Exam Review Addendum -

1. The therapeutic index (T.I.) of a drug is defined

(E) And yori worrderd wlry 1 nude yoti nreniorize c m like this! Renrenrber, TI is art indicator of t L safety of a dn ig , with safety nefirrd ns n ratio of tlre dose tltnt ruorild h letltnl to 5070 of tlre dose tltnt is e ectizie the grenter t P te differcrtce doses, tlre snfer t l ~ dn ig .

11. Which of the follow in^ classes of dru sf when combined with a narcotic anal esic, is t%e MOST like1 to produce a fataf drug Y interaction.

a. cardiac glycosides b. oral anticoagulants c. tricyclic antidepressants d. oral antidiabetic agents e. monoamine oxidase inhibitors

( E ) Tlris is just n reworded runv of nski~rg tlre nrepeririinc (Denrerol) - M A O ~ (trartylcypronrirre or plrerrylzirre) drrs-drrrg irrternctrorr qriestiorr- tlre roblent is excessrzie respirntory d ressiorr. CLS excitntio,r, 7 colt zpri lsiorrs, typerpyrexin, etc.

19. Aspirin is CONTRAINDICATED with which of the followin drugs?

a. ~oumar in fcournadin) b. Triazolam (Halcyon) c. Barbiturates (Phenobarbital) d. Pentobarbital (Nembutal) c. Methylprednisolone (Medrol)

( A ) aspirirt irtterferes witlt plntelet aggregnt iotr, incrensirrg bleedirrg t inre, wlrile countnrirr is nrt arrticongrilnrrt d n i irrteractior~ would be excessitr b i s i F g

27. Which of the followin barbiturates MOST readil penetrates the hmd-brain barrier?

a. drb i ta l b. Phenobarbital c. Secobarbital d. ThiopentaI e. Pentobarbital

(D) tltnts w h y tlrioperrtnl is l i d ns ari IV irrdtictiorr agent. It is the nrost lipid soluble of tlrose listed arid eriters nrrd leaz~es tlre brairr rnpiiily, qtiickly rerrderirrg tlre patierrt irrrcortsciotrs. Methollexital (Brevitnl), riot listed, is s in~ilnr.

36. Each of the following side effects can occur as a result of systemic absorption of lidocaine EXCEPT one. Which one is the EXCEPTION?

a. increased gastric motility b. tonic-clonic convulsions c. decreased cardiac output d. respiratory depression

( A ) tlre sytemic effects of lidoairre that are problematic are its effects on the cardiovnsculnr system and tlre C N S (irritnl excitatiorr stich as cont)ulsiorrs followed by C N S depressior~ involz~ing collapse of the respiratory artd carioz~sacular systenrs)

39. A 43 year old patient who has mitral stenosis, secondary to rheumatic fever, requests extraction of two eriodontally involved mandibular teeth.%utially, the dentist should

a. premedicate the patient with cephalos por in b. premedicate the patient with amoxicil in c. premedicate the patient with ampicillin and

g en tarnicin d. consult with the patient's physician to

determine the ant~biotic of choice.

( B ) pnticrrt's corzditiorr cnlls for errdocnrditis ro ltylnxis reginrerr, of whiclr anroxicillirr

r s t clzoice, ~irrlcss pntierrt is PCN F nl ergic.

44. Which of the followin is a nonsteroidal anti- inflammatory agent wit! a tendency to produce blood dyscrasias?

a. indomethacin (Indocin) b. Ibuprofen (Motrin) c. Ketorolac (Toradol) d. Acetaminophen e. Aspirin

(n) tlre lnst two nreb't N S A I D S , so tltey carr't be right. Of tlre N S A I D S listed, I less ori are )list supposed to hatie nrr irrcr ex? ible a b ility to nrenrorize arid renrenrber tllat irrdonrethaci1~ is tlie orrl orre tllat does tlris, nrost likely becarise t L otlier have rezrrsible effects orr prostnglnrrdin synt llesis, wltile t h t of r lrdontet llacirr is irreversible.

52. Which of the followin drugs is often administered to treat lik-threatening arrhythmias?

a. quinidine b. lidocaine c. verapa.mil d. propranolol

58. A male patient who is receiving Coumadin thera y presents for an elective extraction. His protrRombin time (m) is prolonged. Which of the following methods is preferred for reducing the PT to an acceptable level?

a. administering vitamin K (Aqua Mephyton) b. Withdrawing Coumadin for two days c. reducing Coumadin to one half the usual

Prepared by M. L. Thompson, Ph.D., Dept. Of General Dentistry, Tufts Dental School

dose for two days d. administering a Coumadin antagonist, such as heparin e. administerin a latelet transfusion to enhance coaguf;ab&ty

62. Each of the following drugs has a significant anti-inflammatory prperty except one. Which one is t h ~ exception?

a. aspinn b. cortisol c. acetaminophen d. ibuprofen e. indomethacin

(c) eer, they keep repentbtg this questiott year n h r yenr after year - i f yori do11 t intnzedintely brow t l s t the nilswer is ncetnntitroplzerr, I loill cnll Mr. Flenrittg attd clwtr e yottr grnde in Plmrnlncology to 011 B "F".

72. A patient has a history of significant cardiovascular impairment. The maximum safe dose of epinephrine that can be administered to this patient is:

a. 1 cc, 1: 50,000 b. 2 cc, 1 : 50,000 c. 1 cc, 1 : 100,000 d. 2 cc, 1 : 100,000

(b) tlre rule is ..04 nrg oj epi nrnx it1 CV pntietlts. TIE ensiest wny to ji lire this oitc I out is to renrenrber oti sltortl il't 'z~e nrore thntt 2.2 carpriles oyxylocnbre wi ty 1:100,000 i - yotrr ristinl cltoicc ns n locnl nttesthetic.?wo cn riles is 3.6 cc. Tlris elinrirmtes o lions ?i!) nrrd (d), sbrce t l q would be snJ hi t ttot nsxinml. Sitrce 1:50,000 is twice ns concet~trnted ns 1 :I 00,000, 1 cc of 1 :50,000 (optiotr (n)) is tlre snnre ns 2 cc oj 1:100,000 so still trot close to nlnx, so (b) hns to be tlze right nttswer. 0 course, ou corrld htpe first renanr berel I:100,0~0 eqtrnls .O1 ntg rr cc, so 1:5O,OOO eqsnls .02 ntg per cc, so (6 wotrld eqrrnl tlre nrnx oj .04 ntg.

75. Which of the following is the current drug of choice for status-e ilepticus?

a. diazepam ( ~ J u m ) b. phenytoin (Dilantin) c. chlorpromazine (Thorazine) d. carbamate~ine flearetol)

(a) nrenrorize, mentonk. AN are anticonvulsatlts, btrt dinzepanr is drug oj choice.

83. Which of the following is an example of an enteral route of administration?

a. oral b. submucosal c. inhalation d. suh taneous e. intramuscular

(a) erlteral ntearts zpin GI tmct-only rorrte listed tlrat goes directly itrto GI tract ;s (a) ornl.

93. Propranolol (Lnderal) exerts its major antian inal effect by

a. dfating coronary arteries b. dilating systemic blood vessels c. increasing cardiac contractility d. stimulating vagal slowing of the heart e. blocking beta-adrenergic receptors of the

heart

(e) my god, i f you don't renzenlber pro ratrolol as the protot pe nonspecific beta aLnerg ic receptor blocrrr, ou shouldn't be taking this test. h angina, t& goal is to reduce the oxygen denrands oj the heart, since it urtr't get etrou It. (a) and (b) are usefir1 actiotts in an na, fut are the wa that ttitro lyceritr a n f u k i u n , clumtrel bcckers w o r l not propmrr 0101, whiclt ncts to decrease urrdiac orrtput ntld coittrnctility (so (c) is obviotisly wrotlg- this is at1 nct iott that is needed itt lrmrt jnilure patietrts, tlot aitgitra)

99. Bradycardia is MOST commonly treated with which of the following drugs?

a. atropine b. epinephrine c. a diuretic d. a potent vasodilator

(n) bradycnrdin is n reflexive slowed lzenrt mte, coittrolled by z q n l ~irprrt to tlre llenrt, nltd is cholitrergicnlly nredinted, whiclt nzeaits you t t d a clrolirrer 'c receptor blocker to reduce the va a f$ fec t . Atropitre is tlze ot1ly drug listed wf ich is a cholinergic agent. T l q tlrrew it1 epinephritte as a tease, because if you brew bradycardin was cnrdinc slowitrg, you nliglrt be tent ted to think epi, which usually speeds up t R hmrt, would be tlre right answer- but you've got to block tlre zrngal ittprrt, epi wotl't work.

103. Which of the following best ex lains why drugs that are hi hly ioruzed ten&o be more rapidly excretedgthan those that are less ionized? The hi hl ionized are

a. less lipid s8ub;e b. less water soluble c. more rapidly metabolized d. more extensively bound to tissue

(n) n o n i n i d forms oj drugs cross membranes more readily and are highly lipid soluble, and tend to get stored in jat tissue from wlzere they are only slowly released. Thus hi hl iotrized drugs, whtch are less lipid sofubye don't get stored in jatty tissue and are subject to more rapid excretion.

110. Which of the followin groups of d ~ g s is CONTRAINDICATED k r patients who have glaucoma?

a. adrenergic b. choliner~ic c. anticholinergic

Prepared by M. L. Thompson, Ph.D., Dept. Of General Dentistry, Tufts Dental School

d. adrenergic blocking

(c) orre o j tlre tlrirrgs yotr lrnd to nrenrorize nbortf n troprrre, tlte prototype nrrticlrolirrergic drrrg wns dorl't use it with ghrrconln pntierrts, ns rt will irrcrease irr t rnocrtlnr pressrrre, mlticlr is nlrendy f l u problenr 7oitlr glnrrconln pntie~lts. Drrr s irr categories (b ) alrd ( d ) nre nctrrnlly r r - d t o trcnt lnrrconrn, so they ore obaiously )tot co?rtrnilt icnted. Obr)iorrsly, (n) 7uorrlrlrr't lrelp either.

l!

125. Low dose aspirin therap revents the formation of thromboembos Ey preferentially inhibiting which of the follow~ng?

a. phospholipase A2 in the blood vessel walls

b. prostacyclin synthetase in the blood vessel walls

c. thromboxane synthetase in the platelets d. vitamin K in the liver

(c) plntelct nggrcgn ti011 is coirt rolled by t luo fncfors, prostncyclin, rc*lriclr dccrenscs it, ntrd tlrroniboxnrrc, rcllriclr elrlmrlccs it. Lorc dose nspirirl blocks the lntter, so ( c ) is riglrt, (n) is tlre nleclut~ii_cnl of ncfiolr of corticosferoid dnrgs, ( d ) is the meclmrrisnr of nctioll of nrrtrcongrrlnrrt drrrgs like corrnmdirr.

128. A patient who is receiving an N diazepam sedation has uper eye-lid ptosis (Verill's sign). The dentist should

a. assist respiration immediately b. consider the patient to be adequately

sedated c. place the patient in the Trendelenberg

position d. administer one more increment of diazepam

and proceed with the treatment

(b ) nrcnrorize - tlris is tlre s i p yorr look or to fell t l u pntierrt is adcqrmfeli sednfed!

132. A dentist is considering the use of nitrous- oxide conscious sedation for a patient. However, this t of sedation will be CONTRAINDI?~~EED, should the atient have

a. dental anxiety 5' a history of which of the following.

b. psychotic care c. controlled hypertension

(b )ever1 I you didn't blow tltnt tritroris cart alter t L patie~rt's sense of renlity (tltnt's wlry yotr dorr't give it nlorre irr yorrr office, tlley nriglrt Jnntnsize tllnt yorr lrad olrr way witlt t k n r wlwn you didn't!) by elntinntion (b ) llns to be tlte right nriswer sirrce (a) aird (c) nre irrdicatiorrs for t l u rtse of nitrous

137. The correct total liter flow of nitrous oxide- oxygen is determined by

a. a standard 6 liter er minute flow b. the patient's metagolic oxygen

requirements c. the amount necessary to keep the reservoir

bag 113 to 2/3 full

d. the largest volume that the patient can exchange within one miunte

(c) I didrr't know this- I hope yolr did! I hope sonlcorre tenclres tlris sonrewqlwre irr tlle ctrrricrtlum!

139. Which of the following sympathomimetic agents is the most potent bronchodilator?

a. amphetamine b. norepine hrine c. phenylepkke d. iso rotereol e. met!oxamine

(d ) for bronchodilntiorr yort want R potort beta-2 ndretrer ic receptor a onist- of tlte drugs listed (A is t l u best. %etboxnntbre a d plwrryleplrrine are alplm-1 agorrists, aniplwtnnri~re is an illdirect acting a ouist tlra, cnrrses tlte relense of rrorepirrepfrirre, rulriclr is less poteirt nt betn receptors tllnrr isoprotererrol.

148. Succinylcholine blocks neuromuscular transmission by

a. inhibiting cholinesterase b. inhibiting the central nervous system c. depolarizing the motor endplate of skeletal

muscle d. inducin the formation of cholinesterase at

the end$ate e. blocking release of acetylcholine at the

end plate

(c) See- yorr knew those d n r i list defirritiorrs I nrnde yorr nrenrorize ~ U O J ~ ! conte rn rtseftrl! Nerr ronrrtscrrlnr trnrrsnrissio~r reqrrires the nctiorr of acetylclrolirle at the tricot irr ic receptors orr t l u irertrontrtscrtlar jrrnctiorr endplnfe. TIE two drrigs rlsed clrnically to do this are crrrnre nrrd sltccirrylcholiire. Curare is n nicotiuic receptor blocker, srtccirrylclroline acts to overstinlulate the receptor, tlwreby causirrg its srrbseqrterrt clepolnniatiorr of t l u nacrorr arrd a block of rrrrscle activity. (el is how spider verronls nrld srrnke toxilrs work, trot srtccitrylclroli~re. (n) wortld errlmtrce narronrrrsculnr actiott, arid is actually made use of clirticnlly witlr nrynstllerr in gravis patients. ( d ) isn't possible.

153. Which of the following effects are common to pentobarbital, diazepam, and meperidine?

a. anticonvulsant and hypnotic b. analgesia and relief of anxiety c. sedat~on and ability to produce dependence d. amnesia and skeletal muscle relaxation

(c) tlte only definition which covers all three dru s. (a) applies orrly to pentobarbital, (b) nppf'es only to meperidinr, arrd ( d ) epplics orrly to dinteparn.

154. The onset of action of drug is primarily determined by the rate of

a. excretion

Prepared by M. L. Thompson. Ph.D.. Dept. Of General Dentistry, Tufts Dental School

b. absorption c. distribution d. biotransformation

( b ) obvioztsly - dnig Itns to be obsorbed before nrr of the otller nctiorrs cnrt take plnce. The ot&rs 1~701tld Lternririe dlr rntiorr of nctiort, rrot ortset.

168. Injection of a local anesthetic into an inflammed area usual1 has a less than optimal result. Which of the fofiowing best explains why?

a. the prostaglandins stabilize the nerve mebrane

b. inflammation reduces the availability of the free base

c. the drug will be absorbed more rapidly because of the increased blood supply

d. the chemical mediators of inflammation will present a chemical antagonism to the anesthetic

174. The major effect of a drug is produced by the amount of the drug that is

a. free in plasma b. excreted by the kidney c. detoxified in the liver d. bound to plasma protein

176. A 4 yr old child is shy, timid, and fearful. Which of the following will be MOST appropriate for the restorative appointments for this child?

a. Naloxone b. Nitrous oxide/oxygen c. Promethazine d. Hydroxyzine hydrochloride (atarax) or

hydroxyzine pamoate (Vistaril) in divided doses

e. Meperidine (Demerol), promethazine (Phenergan) and chlorpromazine (Thoraz~ne) combined

177. A primary advanta e of intravenous sedation is which of t i e followin ?

a. fewer side effects fmm the sdation b. slower biotransformation for prolonged

action c. the ability to titrate individualized dosage d. a smooth and more gradaual onset of

sedation

c. it usually converts a drug to its lipid soluble, nonionized form

d. it generally involves alterations of the chemical structure of the drug

191. Which of the following drugs causes the LEAST CNS de ression and impairment of psychomotor s&lls?

a. diazepam b. buspirone c. al razolam d . c&oral hydrate

Test 27/28, 1993

16. A patient who has which of the following conditions is most likely to have postoperative bleeding after multiple extractions?

t g$:?es c. cirrhosis d. rheumatic fever e. chronic bronchitis

42. Local anesthetics aid in reducing the flow of saliva during operative procedures by

a. blocking the cholinergic nerve endings b. blockins innervation to major salivary glands c. blocking efferent parasympathetic nerve pathways d. reducing sensitivity and anxiety during tw th preparation

( d ) locnls don't have actiorls (a), (b) , or (c)!Nerz~ous pnt iertts, however, do salivnte niore.

49. Which of the following combinations of agents would be necessary to block the cardiovascular effects produced by the injection of a sym thomimetic drug?

a. atropine an 8" prazosin b. atropine and propranolol c. prazosin and propranolol d . phenoxybenzarnine and curare e. amphetamine and propranolol

179. Each of the followin is true re arding drug biotransformation E X ~ E P T one. h i c h one is the EXCEPTION?

a. the rate may differ significantly in various animal species

b. it primarily occurs in the liver microsomal enzyme system

74. Accordin to the American Heart Association, which okthe following prophylactic antibiotic regimens is recommended for a 20- kg child who has con enital heart disease?

a. 1.0 gram amoxicl 4 lin orally one hour before the dental medurn and 500 mg 4 times a day g r 2 days postoperatively

Prepared by M. L. Thompson. Ph.D., Dept. Of General Dentistry, Tufts Dental School

b. 1.0 gram enicillin V oral1 one hour

mg orally 6 hours later 2 before g e dental proce ure and 500

c. 1.0 gram amoxicillin orally one hour before the dental procedure and 500 mg orally 6 hours later

d. 3.0 gram amoxicillin orall one hour- before the dental p r o c d ~ r e and 1 .J grams orally 6 hours later

75. When com ared therapeutically to penicillin G, penici~in V has a

a. slower renal excretion b. more reliable oral absorption c. broader antibacterial spectrum d. reater resistance to enicillinase e. P ewer potential for a R ergic reaction

118. Which of the following antibiotics is found at much higher concentrations in crevicular fluid than in serum?

a. clindamycin b. penicillin c. metronidazole d. tetracycline

When administered as oral centrally acting analgesics, which of the following is considered to have the highest dependence liabilit ?

a. J e i n e b. oxycodone (in Percodan) c. propoxyphene (Darvon) d . pentazocine (Talwin)

135. Antibiotics are useful in the treatment of 89. Each of the fol lo~~~ing is i; common side effect which of the following?

of prolon ed tetrac cline thera EXCEPT a. herpangina one. hi& one is tKe EXCEP$&? b. angina pectoris

a. diarrhea c. recurrent apthous stomatitis b. superinfection d. necrotizing ulcerative gingivitis c. photosensitivity d. visual disturbance (d) e. discoloration of newly forming teeth

106. Which of the follorving drugs produces sufficient CNS depression to cause a state of sleep from which one may be aroused?

a. a sedative b. a hypnotic c. an opiate d. an anesthetic

110. To reduce a patient's salivary flow, a dentist has prescribed atropine. As a result of this medication, the patient mi ht experience which of the followng side eaects?

a. sedation b. diarrhea c. bradycardia d. blurred vision e. stomach cramping

136. Audito nerve deafness is associated with the use o?'

a. polymixin B b. chloramphenicol c. amphotericin B d . gen tarnycin

151. The maximal or ceiling effect of a drug is also correctly referred to as the drug's

a. agonism b. potency c. efficacy d. specificity

168. Which of the following a ents found in tobacco products cause aidiction?

a. tar b. formaldehyde c. nicotine d . carbon monoxide

11 2. Of the following local anesthetics, which (c) has intrinsic vasoconstrictive actions?

a. cocaine b. procaine 172. Aller ic reactions to local anesthetics are c. xylocaine d. bupivacaine

c a u A b y a. rapid absorption b. slow detoxification

(a) c. an antigen-antibod y reaction d. improper administration technique

Prepared by M. L. Thompson, Ph.D., Dept. Of General Dentistry, Tufts Dental School

184. Which drug group is the LEAST likely to cause xerostomia.

a. opioids b. antidepressants c. antihistamines d . benzod iazepines e. anticholinergics

36. With an overdose of a cholinergic drug, one to see each of the following ?:i%8?r one, Which one is the

E~CEPTION? a. sweating ,

b. urination c. mydriasis d. bradycardia e. copious serous saliva

187. Currently, the BEST oral sedative drugs for dentistry fall into the class of 42. Ce halos rins are definitely

a. narcotics C~NT&NDICATED for penicillin-allergic b. barbiturates patients who exhibit c. henothiazines a. immediate-type reactions d .!enzodiazepines b. nausea and vomiting with erythromycin

c. any type of reaction to the penicillins (dl

(a)

189. Which of the following best describes the drug-receptor activity of naloxone? 46. Which of the following is a beta-adrenergic

receptor blockin agent used for the treatment Affinity Intrinsic Activity of hypertension. !

a. prazosin (Minipress) a. high high b. clonidine (Catapress) b. low high c. atenolol (Tenomin) c.high none d. hydralazine (Aprezoline) d.none low e. verapamil (Calan)

200. U'hich of the following types of chemical bonding is the least likely to be involved in a 50. In which of the follo~cin categories are drug-receptor interaction? e hedrine, tyramine, antamphetamine

a. covalent bonding c&ssi fied? b. hydrogen bonding a. anticholinesterases c. dipoledipole bonding b. a1 ha-adrenergic blocking agents d. electrostatic bonding c. iniinxt-acting sympathomimetics e. van der Waal's forces d . d ired-act ins parasjm pathomimetics

Test 21/22 1993

After a threshold stimulus, the cell membrane becomes permanently altered. The liberation of which of the followin transmitter substances causes this aqteration?

a. acet lcholine b. cholnesterase c. hydroxycholine d. acetylsalicylic acid

23. Which of the following compounds is used as an antiviral agent?

a. amantadine (Symmetrel) b. novobiocin c. miconazole (monistat) d. amphotericin B

57. Thiazides, which are used in the treatment of hypertension, ma require supplemental administration 07

a. sodium b. chloride c. calcium d. potassium

Which of the followin adverse reactions of

the most serious? P oral contraceptives is t e most common and

a. hypotension b. hepa totoxicity c. uterine neo Iasia d. thromboemgolic disorder e. decreased resistance to infection

80. The supraspinal anal esic activit of rnorphme is rnediatJprimarily tfLough its

Prepared by M. L. Thompson. Ph.D.. Dept. Of General Dentistry. Tufts Dental School

influence upon which opioid receptor subtype?

a. mu b. ka pa e- c. deKa d. sigma e. epsilon

83. Which pair of anesthetics is most likely to show cross-allergenicity?

a. lidocaine-mepivacaine b. prilocaine-tetracaine c. procaine-me ivacaine dP d. rocaine-li ocaine e. fdocaine-benzocaine

(n) yo14 nye lookirlg for nr1 nntide - antiric pntrtrl or nit ester - ester pnirirtg. O i ~ l y fa) nteets this criterioit. procnirte, betrzocnirle nr~d tctrncnirte nre esters, lidocnii~e, prilocnirtc nrtd nleyir~ncniire nre nn~idcs.

107. Thrombophlebitis, which occurs after intravenous administration of diazepam, is usually attributed to which of the folloi\.ing substances in the mixture?

a. benzoic acid b. ethyl alcohol c pro ylene glycol d.. d m metabisulfite

(c) nlenrorite fltis picky little fnct ylense!

170. Each of the following is a harmacolo ic efect of phenothiazines E X ~ E P T one. 8hich one is the EXCEPTION?

a. sedation b. an antiemetic effect c. alpha-adrenergic effect d. potentiation of the action of narcotics e. an anticonvulsant

(e) see, t l q do nsk yo11 q~iestiorrs nbo~c t drugs tltnt yo11 dor~'t t~ornrnlly use eve dny. Actior~s a, c. nrtd d nre 011 ~ lh t icn?;~ trseflil nctior~s o tlle pllertotlriazirres, / wlrrclr yo11 nri rt rentenrber were discussed n t r z r t l ~ e cntegonj of nrrtipsyclrotic drugs. Blrt wnit- Prornetltnzitre (Plrettergan) is used it1 dentistry as n da t i r l e , ofterr itr conrbiiratiotr wit11 Denrerol because it reduces tlte trausea associated witlr the

119. Epinephrine antagonize the effects of histamne bv

a. p ~ ~ p e n h n the release of histamine b. acting on fhe central nervous system

c. producing hysiologic actions opposite to that orhistamine

d. com titively blocking histamine at the ceKlar receptor site

(c) exnctly why I kept asking yo11 oil erlenj exnnr to give nte arr exnn~ple of pl~ysiological atttagonisnt as a drtrg- drug interncfion sestiotr. N does trot act via (0). which is Row chon~olyrr (ltrtal) works. or by ( d ) wlricl~ is how atttilristamrtles work.

121. Which of the following represents the drug- ofchoice in the treatment of candidiasis for an HN-infected patient?

a. acyclovir b. n statin c. A h d. chlorhexidine

( b ) cnitdidinsis is n furl nl irtfcctiort t h t R treecis to be treate with nit nrttifitr~gal ngertt like tlystntitt. (0) ntrd (c) nre ar~tizjirnl drlcgs risen to trent HIV, wlrilc clrlorkexidirte is n nrtt inticrobinl n~olr t I I wnslr

132. A patient presents for treatment of a large fluctuant mass in the submandibular s ace as a result of extension of odontogenic inpection. He has a temperature of 38.5 degrees C (101 degrees F). Initially, the dentist should treat this patient with which of the following?

a. salicylate therapy to reduce the tempera tun?

b. alternate application of heat and cold to the area to improve circulation

c. incision and drainage and a culture for antibiotic sensitivity

d. antibiotic therapy to reduce the swelling and infection

( c ) arrtibiotic t h r a p y wotr8t be very effectiz~e i f yo11 dotr8t itrcise ar~d drnirl first. (rt) arrd (b) are allintioe nctiorrs tlte ntierlt car1 take at Ln t e , not nctions for t L derttist.

146. The only local anesthetic that increases the pressor activity of both epinephrine and norepinephrine is

a. cocaine b. rocaine c. Xibucaine d. lidocaine e. mepivacaine

(a) I q , why do 11 always ask some dumb ~ u e s t iotr like?& about cocaine-lrke vou

uys use it ctlr day it; your oficed &OU k11er no/!f dny onJ ri~mk( cocdif~e 1; an ifidired drl;n ddrenerg/c agonist, acting b y causing relurse o/ adreneric neurotransmitters ns well as blocking their reuptake, thereby prolot? !ng their activity. The ootlvr f drugs rsfrd are just local arrestltetics

Prepared by M. L. Thompson. Ph.D., Dept. Of General Dentistry. Tufts Dental School

flmt dolr't lmtle tlris nctiotr - tlrey jrrsf block sodirrnr itrflrcx i n fo flre lrerrrotr.

155. Corticosteroid therapy for arthritis is contraindicated for a patient who also has which of the following conditions?

a. anemia b. nephritis c. alcoholism d. peptic ulcer e. rheumatic heart disease

( d ) patielrf s usirrg corf icosferoids for arthritis oftelr dct)elop jr lcers becartse these drug block prosfnglnlrdilr nctiorr irr the stomaclr, thereby itrcrensing acid secret ioti wlrile dccrensilrg tlre protect itle nrrrcosnl bnrrier of tlre stonrnclr.

160. Which of the following is the first symptom that is usual1 perceived by the patient being administerdnitrous oxide?

a. nausea b. eu horia B c. gi diness d . tingling of the hands

(dl tlle first tlrrce are nll sigrrs f l a t f l ~ e pntietrt is geft itrg too nril~rclr tritrorrs.

176. Each of the following, EXCEPT one, is a ood reason for using sedation. Which one is tRis EXCEPTION?

a. to allay apprehension, anxiety or fear b. to decrease the amount of local

anesthesia that is required for a given procedure

c. to alleviate stress in a severely meedically compromised patient

d. to accomplish certain prmedures that a practicioner would not normally be able to d o on an anxious patient

( b ) sedntiolr docs not decrcnsc tlre locnl nlrestltetic reqrrircnrclrt, tlle pntielrt tuill still feel pnitr. Sedntitjes, tuitlr tlle exc ti011 of nitrorrs oxide, luzje lro n n z e s i c e ect -bnrbit rrrnte w i n titles nray nrnke t re patient nrore se1rsitit)e to pnrn.

7 179. Which of the following is classified as an

antianxiety drug? a. methohexital b. lorazepam c. haloperidol d. pentazocine e. phen ylpropanolamine

(b ) olily berrzodiazepilres nre nctrrnlly classifid as nntinlrxiety dnrgs, althorrglr other drrcgs, srtclr as opioids lrntw nlrtin~ixiety nctiolis itr addttiolr to their otlrer clinrcnlly rise ul nctiolrs. (b) lorazepanr is tlre o t~ l y B h Z listed. nreflrollexitnl is a barbiturate - tlrese are classified as seatit)cs. Hnloperidol is nlr

ntrtips~cltc~ic, petrtnzocitre art opioirl, ntrd p~re~:;rlpro~nnolnnrilre is n decorrgestattf irrqd itr cold nredicntiorrs.

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