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REVISED - Summer, 2010; * = appeared one time on COMLEX; ** = appeared > one timeChecked by Dr. Tjioe
Basic Pharmacokinetics
*Half-life (T1/2)
Volume of distribution (VD)
Plasma concentration of a drug at a given time Cp
Clearance (CL)
First pass effect
Bioavailability (F)
Steady state
Metabolism
* Phase I
Different steps of Phase I Oxidation, reduction, hydrolysis
*
Prepared by four former LECOM students who are now Osteopathic doctors: Siamak Kazemi, Tom Mertz, Mohamad Sobh and Rahul Sood All four are pharmacists; two were pharmacy majors in college and two had their R.Ph. Degree
Time it takes for amount of drug to fall to half of its value; this is a constant in first order kinetics (majority of drugs)
Relates the amount of drug in the body to the plasma concentration
The ratio of the rate of elimination of a drug to its plasma concentration
The elimination of drug that occurs before it reaches the systemic circulation
The fraction of administered dose of a drug that reaches systemic circulation
When the rate of drug input equals the rate of drug elimination
This step of metabolism makes a drug more hydrophilic and hence augments elimination
Inducers of Cytochrome P450 (CYP450) Barbiturates, phenytoin, carbamazepine, and rifampin
Page 2
*
Products of Phase II conjugation
First order kinetics
Zero order kinetics
Loading dose (Cp*(Vd/F))
Maintenance dose (Cp*(CL/F))
Pharmacodynamics
Affinity
Selectivity of a drug for its receptor Specificity
Potency
Maximum response achieveable from a drug * Efficacy
Full agonist
Ability to produce less than 100% of the response Partial agonist
Competitive antagonist
Noncompetitive antagonist
Inhibitors of CYP450 Cimetidine, ketoconazole, erythromycin, isoniazid and grapefruit
Glucuronate, acetic acid, and glutathione sulfate
Type of kinetics when a constant percentage of substrate is metabolized per unit time
Drug elimination with a constant amount metabolized regardless of drug concentration
Target plasma concentration times (volume of distribution divided by bioavailability)
Concentration in the plasma times (clearance divided by bioavailability)
Strength of interaction between drug and its receptor
Amount of drug necessary to elicit a biologic effect; refers to the drug's strength
Ability of a drug to produce 100% of the maximum response regardless of the potency
Ability to bind reversibly to the same site as the drug and without activating the effector system
Class of drugs with ability to decrease the maximal response to an agonist
Page 3
* Thyroid and steroid hormones
* Insulin
Dose which is lethal to 50% of the population
Window between therapeutic effect and toxic effect Therapeutic index
Term for a high margin of safety High therapeutic index
Term for a narrow margin of safety Low therapeutic index
Antidotes and agents used in drug overdose
Antidote used for lead poisoning Dimercaprol, EDTA
Antidote used for cyanide poisoning Nitrites
Antidote used for anticholinergic poisoning Physostigmine
** Atropine, pralidoxime (2-PAM)
Antidote used for iron salt toxicity Deferoxamine
Antidote used for acetaminophen (APAP) toxicity * N-acetylcysteine (Mucomyst)
A hormone whose mechanism of action (MOA) utilizes intracellular receptors
A hormone whose MOA utilizes transmembrane receptors
Class of drugs whose MOA utilizes ligand gated ion channels
Benzodiazepines and calcium channel blockers
Median effective dose required for an effect in 50% of the population
ED50
Median toxic dose required for a toxic effect in 50% of the population
TD50
LD50
Antidote used for organophosphate/anticholinesterase poisoning
Page 4
Dimercaprol
Penicillamine
Antidote used for heparin overdose ** Protamine
Antidote used for warfarin toxicity *
** Aminocaproic acid
Antidote used for methanol and ethylene glycol Ethanol or fomepizole
Antidote used for opioid toxicity * Naloxone (IV), naltrexone (PO)
Antidote used for benzodiazepine toxicity * Flumazenil
Antidote used for tricyclic antidepressants (TCA) Sodium bicarbonate
Antidote used for carbon monoxide poisoning 100% O2 and hyperbaric O2
Antidote used for digitalis toxicity
Esmolol
Antidote for methotrexate toxicity Leucovorin
Antidote for beta-blockers and hypoglycemia Glucagon
Magnesium sulfate
Antidote for hyperkalemia
Antidote for arsenic, mercury, lead, and gold poisoning
Antidote used in poisonings: copper (Wilson's disease), lead, mercury, and arsenic
Vitamin K and Fresh frozen plasma (FFP)
Antidote for tissue plasminogen activator (t-PA), streptokinase
Digibind (also need to d/c digoxin, normalize K+, and lidocaine if pt. Is arrhythmic)
Antidote used for beta agonist toxicity (eg. Metaproterenol)
Antidote useful for some drug induced Torsade de pointes
sodium polystyrene sulfonate (Kayexalate)
Page 5
Antidote for salicylate intoxication Alkalinize urine, dialysis
Cancer Chemotherapy
Log-kill hypothesis
Pulse therapy
Rescue therapy
Allopurinol
5-flouracil (5-FU)
Prednisone
Side effect of Mitomycin SEVERE myelosuppression
MOA of cisplatin Alkylating agent
Common toxicities of cisplatin Nephro and ototoxicity
6-mercaptopurine (6-MP)
** Allopurinol
* Dexrazoxane
* Bleomycin
Constant proportion of cell population killed rather than a constant number
Treatment with cancer chemotherapy at high doses every 3-4 weeks, too toxic to be used continuously
Toxic effect of anticancer drug can be lessened by rescue agents
Drug used concurrently with toxic anticancer agents to reduce renal precipitation of urates
Pyrimidine analog that causes "Thymine-less death" given with leucovorin rescue
Drug used in cancer therapy causes Cushing-like symptoms
Analog of hypoxanthine, needs HGPRTase for activation
Interaction with this drug requires dose reduction of 6-MP
May protect against doxorubicin toxicity by scavenging free radicals
Blows DNA (breaks DNA strands), limiting SE is pulmonary fibrosis
Page 6
Testicular cancer
Regimen used for non-Hodgkin's lymphoma
Regimen used for breast cancer
Mechlorethamine
Cyclophosphamide
Vincristine
**Paclitaxel (taxol)
Cisplatin
Carboplatin
L-asparaginase
Bleomycin+vinblastine+etoposide+cisplatin produce almost a 100% response when all agents are used for this neoplasm
ABVD regimen used for HD, but appears less likely to cause sterility and secondary malignancies than MOPP
Adriamycin (doxorubicin) +bleomycin, vinblastine +dacarbazine
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab
CMF (cyclophosphamide, methotrexate, and fluorouracil) and tamoxifen if ER+
Alkylating agent, vesicant that causes tissue damage with extravasation
Anticancer drug also used in RA, produces acrolein in urine that leads to hemorrhagic cystitis
Prevention of cyclophosphamide induced hemorrhagic cystitis
Hydration and mercaptoethanesulfonate (MESNA)
Microtubule inhibitor that causes peripheral neuropathy, foot drop (eg. ataxia), and "pins and needles" sensation
Interact with microtubules (but unlike vinca which prevent disassembly of tubules), it stabilizes tubulin and cells remain frozen in metaphase
Toxicities include nephrotoxicity and ototoxicity, leading to a severe interaction with aminoglycosides
Agent similar to cisplatin, less nephrotoxic, but greater myelosuppression
Converts asparagine to aspartate and ammonia, denies cancer cells of essential AA (asparagine)
Page 7
Interferon alpha
Flutamide (Eulexin)
** Tamoxifen
Aromatase inhibitor used in breast cancer Letrozole, anastrozole
Toremifene (Fareston)
Some cell cycle specific anti-cancer drugs
Some cell cycle non-specific drugs
*Odansetron, granisetron
Produces disulfiram-like reaction with ethanol Procarbazine
Octreotide
Somatrem
Sermorelin
Used for hairy cell leukemia; it stimulates NK cells
Anti-androgen used for prostate cancer
Anti-estrogen used for estrogen receptor + breast cancer
Newer estrogen receptor antagonist used in advanced breast cancer
Bleomycin, vinca alkaloids, antimetabolites (eg., 5-FU, 6-MP, methotrexate, etoposide)
Alkylating agents (eg., mechlorethamine, cyclophosphamide), antibiotics (doxorubicin, daunorubicin), cisplatin, nitrosourea
Anti-emetics used in association with anti-cancer drugs that are 5-HT3 (serotonin receptor subtype ) antagonists
Nitrosoureas with high lipophilicity, used for brain tumors
Carmustine (BCNU) and lomustine (CCNU)
Endocrine drugs: hypothalamic and pituitary hormones
Somatostatin (SRIF) analog used for acromegaly, carcinoid, glucagonoma and other GH producing pituitary tumors
Somatotropin (GH) analog used in GH deficiency (dwarfism)
GHRH analog used as diagnostic agent
Page 8
Leuprolide
Ganirelix
* Bromocriptine
Hormone inhibiting prolactin release * Dopamine
** Cosyntropin
* Desmopressin (DDAVP)
SE of OCs ** Increased thromboembolic events
Thyroid and anti-thyroid drugs
** L-thyroxine (T4)
Cytomel
Anti-thyroid drugs
Thioamide agents used in hyperthyroidism
*PTU
PTU (propylthiouracil) MOA*
Iodide salts
GnRH agonist used for infertility or different types of CA depending on pulsatile or steady usage respectively
GnRH antagonist with more immediate effects, used for infertility
Dopamine (DA) agonist (for Parkinson's disease), used also for hyperprolactinemia
ACTH analog used for diagnosis of patients with corticosteroid abnormality
Synthetic analog of ADH hormone used for diabetes insipidus and nocturnal enuresis
Most widely used thyroid drugs such as Synthroid and Levoxyl contain
T3 compound less widely used
Thioamides, iodides, radioactive iodine, and ipodate
Methimazole and propylthiouracil (PTU)
Thioamide less likely to cross placenta, inhibits peripheral conversion of T4 to T3 in high doses, and should be used with extreme caution in pregnancy
Inhibits thyroid hormone synthesis by blocking iodination of the tyrosine residues of thyroglobulin
Can be effective for short term therapy of thyroid storm, but after several weeks of therapy causes an exacerbation of hyperthyroidism
Page 9
**Thyroxine
Radioactive iodine
Ipodate
Beta-blockers such as propranolol
Iron deiodinates thyroxine
Estogens increase maternal TBG
3 zones of adrenal cortex and their products
Pneumonic for 3 zones of adrenal cortex GFR
Glucocorticoids
Short acting glucocorticoids
Intermediate acting glucocorticoids
Long acting glucocorticoids Betamethasone and dexamethasone
Mineralocorticoids
Dose may need to be increased during pregnancy or with Ocs due to increased TBG in plasma
Permanently cures thyrotoxicosis, patients will need thyroid replacement therapy thereafter. Contraindicated in pregnancy
Radio contrast media that inhibits the conversion of T4 to T3
Block cardiac adverse effects of thyrotoxicosis such as tachycardia, inhibits the conversion of T4 to T3
Vitamins containing iron should NOT be taken simultaneously with levothyroxine because
Thyroxine dose may need to be increased in hypothyroid patient during pregnancy because
Adrenocorticosteroid and adrenocortical antagonists
Glomerulosa (mineralocorticoids), fasciculata (glucocorticoid=GC), and reticularis (adrenal androgens)
Used for Addison's disease, Congenital Adrenal Hyperplasia (CAH), inflammation, allergies, and asthma (as a local inhalation)
Cortisone and hydrocortisone (equivalent to cortisol)
Prednisone, methylprednisolone, prednisolone, and triamcinolone
Fludrocortisone and deoxycorticosterone
Page 10
Some side effects of corticosteroids
*
5-7 days
Inhibitors of corticosteroids biosynthesis
Dexamethasone suppression test
Aminoglutethimide
Ketoconazole
Mifepristone
* Spironolactone
Common SE of spironolactone ** Gynecomastia and hyperkalemia
Gonadal hormones and inhibitors
Estrogen
Clomiphene and tamoxifen
Common SE of tamoxifen and raloxifene Hot flashes
**Raloxifene
Osteopenia, impaired wound healing, inc. risk of infection, inc. appetite, HTN, edema, PUD, euphoria, psychosis, stria, thinning of skin
Period of time of therapy after which GC therapy will need to be tapered
Used for Cushing's syndrome (increased corticosteroid)
Inhibits conversion of cholesterol to pregnenolone therefore inhibiting corticosteroid synthesis
Antifungal agent used for inhibition of all gonadal and adrenal steroids
Antiprogestin used as potent antagonist of GC receptor
Diuretic used to antagonize aldosterone receptors
Slightly increased risk of breast cancer, endometrial cancer, heart disease (questionable), has beneficial effects on bone loss
Antiestrogen drugs used for fertility and breast cancer respectively
Selective estrogen receptor modulator (SERM) used for prevention of osteoporosis and prophylaxis in women with risk factors for breast cancer
Page 11
*Diethylstilbestrol (DES)
Estrogen mostly used in oral contraceptives (OC) Ethinyl estradiol and mestranol
Anti-progesterone used as abortifacient Mifepristone (RU-486)
Combination oral contraceptives (OC)
Oral contraceptive available in a transdermal patch Ortho-Evra
* Testosterone
Anabolic steroid that has potential for abuse
Cyproterone acetate
Drug is used with testosterone for male fertility ** Leuprolide
What do alpha cells in the pancreas produce? Glucagon
What do beta cells in the pancreas produce? Insulin
Where are beta cells found in the pancreas? Islets of Langerhans
What do delta cells in the pancreas produce? Somatostatin
* C-peptide
Non-steroidal estrogen agonist causes clear cell adenocarcinoma of the vagina in daughters of women who used it during pregnancy
Constant low dose of estrogen and increasing dose of progestin for 21 days (last 5 days are sugar pills or iron prep)
Converted to more active form DHT by 5 alpha-reductase
5 alpha-reductase inhibitor used for benign prostatic hyperplasia (BPH) and male pattern baldness
Finasteride (Proscar and Propecia respectively)
Nandrolone, oxymetholone, and oxandrolone
Anti-androgen used for hirsutism in females
Pancreatic hormones, antidiabetics, and hyperglycemics
Product of proinsulin cleavage used to assess insulin abuse
Page 12
Exogenous insulin contains * Little C-peptide
Endogenous insulin contains Normal C-peptide
Lispro (Humalog), aspart, glulisine
Regular (Humulin R)
Long acting insulin * Ultralente (humulin U)
Glargine (Lantus), detemir
Major SE of insulin Hypoglycemia
GLUT 2
GLUT 4
Examples of alpha-glucosidase inhibitors (AGI) Acarbose, miglitol
MOA of AGI's
SE of AGI's
Acarbose
* Nateglinide
Very rapid acting insulin, having fastest onset and shortest duration of action
Rapid acting, crystalline zinc insulin used to reverse acute hyperglycemia
Ultra long acting insulin, has over a day duration of action
Important in synthesis of glucose to glycogen in the liver
Important in muscle and adipose tissue for glucose transport across muscles and TG storage by lipoprotein lipase activation
Act on intestine, delay digestion and absorption of glucose formed from digestion of starch and disacchrides
Flatulence (do not use beano to tx), diarrhea, abdominal cramps
Alpha-glucosidase inhibitor associated with elevation of LFT's
Amino acid derivative, active as an insulin secretagogue
Page 13
MOA of nateglinide
Biguanide Metformin
Drugs available in combination with metformin Glyburide, glipizide, and rosiglitazone
MOA of metformin
Vascular effects of metformin
Most important potential SE of metformin Lactic acidosis
Incidence of hyoglycemia with metformin None
Meglitinide class of drugs Repaglinide
MOA of repaglinide
First generation sulfonylurea
Second generation sulfonylurea Glyburide, glipizide, glimepiride, etc.
MOA of both generations
Hypoglycemia
Chlorpropamide
Thiazolidinediones
Insulin secretagogue - closes ATP-sensitive K+ channel
Decreases hepatic glucose production and intestinal glucose absorption; increase insulin sensitivity
Decreased micro and macro vascular disease
Insulin release from pancreas; faster and shorter acting than sulfonylurea
Chlorpropamide, tolbutamide, tolazamide, etc.
Insulin release from pancreas by modifying K+ channels
Common SE of sulfonylureas, repaglinide, and nateglinide
Sulfonylurea NOT recommended for elderly because of very long half life
Pioglitazone, Rosiglitazone, Troglitazone (withdrawn/d from market)
Page 14
Reason troglitazone was withdrawn from market Hepatic toxicity
MOA of thiazolindinediones
SE of Thiazolindinediones
Glucagon
Drugs used in bone homeostasis
Available bisphosphonates
MOA of Bisphosphonates Inhibits osteoclast bone resorption
Names of three bisphosphonates available IV Pamidronate, zoledronate, ibandronate
Uses of bisphosphonates
Major SE of bisphosphonates Chemical esophagitis
Etidronate
**
* Calcitonin (salmon prep)
Stimulate PPAR-gamma receptor to regulate CHO and lipid metabolism
Edema, mild anemia; interaction with drugs that undergo CytP450 3A4 metabolism
Hyperglycemic agent that increases cAMP and results in glycogenolysis, gluconeogenesis, reverses hypoglycemia, also used to reverse severe beta-blocker overdose and smooth muscle relaxation
Alendronate, etidronate, risedronate, pamidronate, tiludronate, and zoledronic acid
Osteoporosis, Paget's disease, and osteolytic bone lesions, and hypercalcemia from malignancy
Bisphosphonates that cannot be used on continuous basis because it caused osteomalacia
Used for prevention of postmenopausal osteoporosis in women
Estrogen (HRT-Hormone replacement therapy)
Increase bone density, also being tested for breast CA prophylaxis
Raloxifene (SERM-selective estrogen receptor modulator)
Used intranasally and decreases bone resorption
Page 15
Calcium
Vitamin D
Disease caused by excess ergot alkaloids St. Anthony's Fire
Autocoids
Zollinger-Ellison Syndrome
Drug that causes contraction of the uterus * Oxytocin
Distribution of histamine receptors H1, H2, and H3*
Prototype antagonist of H1 and H2 receptors *
1st generation antihistamine that is highly sedating ** Diphendydramine
1st generation antihistamine that is least sedating Chlorpheniramine or cyclizine
2nd generation antihistamines *
Major indication for H1 receptor antagonist Use in IgE mediated allergic reaction
hydroxyzine (Atarax)
Used especially in postmenopausal women, dosage should be 1500 mg
Vitamin given with calcium to ensure proper absorption
Drugs with important actions on smooth muscle
Endogenous substances commonly interpreted as histamine, serotonin, prostaglandins, and vasoactive peptides
Syndrome of hypersecretion of gastric acid and pepsin usually caused by gastrinoma; it is associated with severe peptic ulceration and diarrhea
Smooth muscle; stomach, heart, and mast cells; nerve endings, CNS respectively
Diphenhydramine and cimetridine, respectively
Fexofenadine, loratadine, and cetirizine
Generation of antihistamine that has the most CNS effects
First generation due to being more lipid-soluble
Antihistamine that can be used for anxiety and insomnia and is not addictive
Page 16
H1 antagonist used in motion sickness
Sedation
* Cimetidine
Clinical use for H2 blockers
Receptors for serotonin (5HT-1) are located
**
Sumatriptan
H1 blocker that is also a serotonin antagonist Cyproheptadine
Agents for reduction of postpartum bleeding ** Oxytocin, ergonovine and ergotamine
Agents used in treatment of carcinoid tumor **
***
Dolasetron
Dimenhydrinate, meclizine, and other 1st generation
Most common side effect of 1st generation antihistamines
Lethal arrhythmias resulting from concurrent therapy with azole fungals (metabolized by CYP 3A4) and these antihistamines which inhibit the 3A4 iso-enzyme.
Terfenadine and astemizole (have been removed from the market)
H2 blocker that causes the most interactions with other drugs
Acid reflux disease, duodenal ulcer and peptic ulcer disease
Mostly in the brain, and they mediate synaptic inhibition via increased K+ conductance
5HT-1d agonist used for migraine headaches Sumatriptan, naratriptan, and rizatriptan
Triptan available in parenteral and nasal formulation
Ketanserin cyproheptadine, and phenoxybenzamine
5HT-3 antagonist used in chemotherapeutic induced emesis
Ondansetron, granisetron, dolasetron and alosetron
5HT-3 antagonist that has been associated with QRS and QTc prolongation and should not be used in patients with heart disease
Page 17
DOC to treat chemo-induced nausea and vomiting ** Odansetron
Nitroprusside
Uterine contractions
SE of ergot alkaloids Hallucinations resembling psychosis
Ergot alkaloid used as an illicit drug * LSD
Dopamine agonist used in hyperprolactinemia * Bromocriptine
Bradykinin and histamine
*Bradykinin
* Capsaicin
Prostaglandins that cause abortions *
Drug that selectively inhibits COX 2 Celecoxib and rofecoxib
Inhibitor of lipoxygenase * Zileuton
Major SE of zileuton Liver toxicity
Zafirlukast and montelukast
Drug used in ergot alkaloids overdose, ischemia and gangrene
Reason ergot alkaloids are contraindicated in pregnancy
Peptide causing increased capillary permeability and edema
Mediator of tissue pain, edema, inactivated by ACE, and may be a contributing factor to the development of angioedema
Drug causing depletion of substance P (vasodilator)
Prostaglandin E1 (misoprostol) PGE2, and PGF2alpha
Difference between COX 1 and COX 2 COX 1 is found throughoutthe body and COX 2 is onlyin inflammatory tissue
Inhibitor of leukotrienes (LTD4) receptors and used in asthma
Page 18
* PGE1
Approved for use in severe pulmonary HTN PGI2 (epoprostenol)
Prostaglandin used in the treatment of impotence * Alprostadil
Irreversible, nonselective COX inhibitor Aspirin
Class of drugs that reversibly inhibit COX NSAIDS
Arginine
MOA and effect of nitric oxide *
Long acting beta 2 agonist used in asthma Salmeterol
Muscarinic antagonist used in asthma * Ipratropium
MOA action of cromolyn * Mast cell stabilizer
Pentoxifylline
inhibit phospholipase A2
*
Antimicrobials
MOA of quinolones ** Inhibit DNA gyrase
Used in pediatrics to maintain patency of ductus arteriosis
Primary endogenous substrate for Nitric Oxidase Synthase
Stimulates cGMP which leads to vascular smooth muscle relaxation
Methylxanthine derivative used as a remedy for intermittent claudication
MOA of corticosteroids
SE of long term (>5 days) corticosteroid therapy and remedy
Adrenal suppression and weaning slowly, respectively
Page 19
MOA of penicillin
Drug used for MRSA * Vancomycin
Vancomycin MOA ** Blocks peptidoglycan synthesis
Type of resistance found with vancomycin Point mutation
Meningitis prophylaxis in exposed patients * Rifampin
*
Two toxicities of aminoglycosides nephro and ototoxicity
DOC for Legionnaires' disease Erythromycin
MOA of sulfonamides * Inhibit dihydropteroate synthase
Methicillin, nafcillin, and dicloxacillin
*** Amoxicillin
Cephalosporins
PCN active against pseudomonas Carbenicillin, piperacillin and ticarcillin
Drug causes teeth discoloration Tetracycline
MOA of tetracycline
Block cell wall synthesis by inhibiting peptidoglycan cross-linkage
Technique used to diagnose perianal itching, and the drug used to treat it
Scotch tape technique and mebendazole
Penicillins active against penicillinase secreting bacteria
Cheap wide spectrum antibiotic DOC for otitis media
Class of antibiotics that have 10% cross sensitivity with penicillins
Antibiotic causing red-man syndrome, and prevention
Vancomycin, infusion at a slow rate and antihistamines
Decreases protein synthesis by inhibiting 30S ribosome
Page 20
Chloramphenicol
Clindamycin
** Metronidazole
Treatment of resistant pseudomembranous colitis ORAL vancomycin
Anemia caused by trimethoprim * Megaloblastic anemia
Cartilage damage
* Metronidazole
*
Metronidazole SE if given with alcohol Disulfiram-like reaction
Common side effect of Rifampin * Red urine discoloration
MOA of nystatin
Neurotoxicity with isoniazid (INH) prevented by Administration of Vit. B6 (pyridoxine)
Toxicity of amphotericin Nephrotoxicity
Gynecomastia
Topical DOC in impetigo Topical mupirocin (Bactroban)
DOC for influenza A * Amantadine
Drug that causes gray baby syndrome and aplastic anemia
Drug notorious for causing pseudomembranous colitis
DOC for tx of pseudomembranous colitis
Reason fluoroquinolones are contraindicated in children and pregnancy
DOC for giardia, bacterial vaginosis, pseudomembranous colitis, and trichomonas
Treatment for TB patients (think RIPE) Rifampin, Isoniazid, Pyrazinamide, and Ethambutol
Bind ergosterol in fungal cell membrane
SE seen only in men with administration of ketoconazole
Page 21
DOC for RSV * Ribavirin
DOC for CMV retinitis Ganciclovir
SE for ganciclovir Neutro, leuko and thrombocytopenia
Nevirapine, amprenavir
* Protease inhibitors
Antivirals that are teratogens Delavirdine, efavirenz, and ribavirin
Antivirals associated with neutropenia
HIV med used to reduce transmission during birth AZT (zidovudine)
Drug used for African sleeping sickness Suramin
Drug used in Chagas disease Nifurtimox
Cephalosporins able to cross the BBB
Cephalosporins NOT able to cross the BBB Cefixime (3rd) generation
Drug used for N. gonorrhea in females * Ceftriaxone
Cephalosporin causes kernicterus in neonates Ceftriaxone or cefuroxime
SE of INH Peripheral neuritis and hepatitis
Aminoglycoside that is least ototoxic Streptomycin
Anti-viral agents associated with Stephen Johnson syndrome
HIV antiviral class known to have severe drug interactions by causing inhibition of metabolism
Ganciclovir, zidovudine, saquinavir, and interferon
Cefuroxime (2nd) generation, Ceftazidime, Ceftriaxone
Page 22
Drug used in exoerythrocytic cycle of malaria Primaquine
Minocycline
Drug of choice for leprosy
DOC for herpes and its MOA *
* Sulfonamides
MOA of erythromycin
* sulfamethoxazole/ trimethoprim
Lactam that can be used in PCN allergic patients Aztreonam
SE of imipenem Seizures
Anti-viral with a dose limiting toxicity of pancreatitis Didanosine
Sedative Hypnotics
Common side effect of hypnotic agents Sedation
Tolerance
Additive CNS depression
Benzodiazepines used to promote sleep Temazpam, trizolam, flurazepam
Benzodiazepine used for anxiety Alprazolam
Non-benzodiazepine used as an anxiolytic Buspirone
Oral antibiotic of choice for moderate inflammatory acne
Dapsone, rifampin and clofazimine combination
Acyclovir; incorporated into viral DNA and chain termination
Anti-microbials that cause hemolysis in G6PD-deficient patients
Inhibition of protein synthesis at the 50s subunit of ribosome
Anti-biotic frequently used for chronic UTI prophylaxis
Occurs when sedative hypnotics are used chronically or at high doses
The most common type of drug interaction of sedative hypnotics with other depressant medications
Page 23
Non-benzodiazepine used for sleep Zolpidem
* REM is decreased
Neurologic SE of benzodiazepines Anterograde amnesia
Reason benzos are used cautiously in pregnancy * Ability to cross the placenta
Main route of metabolism for benzodiazepines Hepatic
* Flumazenil
Diazepam
Clonazepam
Alprazolam and Clonazepam
Midazolam
DOC for status epilepticus Diazepam
Chlordiazepoxide and Diazepam
Major effect of benzodiazepines on sleep at high doses
Benzodiazepine that undergo extrahepatic conjugation (which are useful in older or hepatically impaired)
Lorazepam, oxazepam, and temazepam
MOA for benzodiazepines increase the FREQUENCY of GABA-mediated chloride ion channel opening
Antidote to benzodiazepine overdose (antagonist that reverses the CNS effects)
Benzodiazepine with useful relaxant effects in skeletal muscle spasticity of central origin
Benzodiazepine that has efficacy against absence seizures and in anxiety states, such as agoraphobia
Benzodiazepines that are the most effective in the treatment of panic disorder
Benzodiazepine that is used for anesthesia
Longer acting benzodiazepines used in the management of withdrawal states of alcohol and other drugs
Page 24
Barbiturates
Acute intermittent porphyria
Liver enzyme INDUCTION
Barbiturates MOA
Barbiturate used for the induction of anesthesia Thiopental
Others
Site of action for zaleplon and zolpidem
Zolpidem, zaleplon
Buspirone
Buspirone
Alcohols
*Ethanol
Agent with zero-order kinetics Ethanol
Rate limiting step of alcohol metabolism Aldehyde dehydrogenase
Agents having active metabolites, long half lives, and a high incidence of adverse effects
Diazepam, Flurazepam, chlordiazepoxide, and clorazepate
Barbiturates may precipitate this hematologic condition
Barbiturates decrease the effectiveness of many other drugs via this pharmacokinetics property
Increase the DURATION of GABA-mediated chloride ion channels
Benzodiazepine receptor BZ1 (although do not have a benzodiazepine ring structure)
Good hypnotic activity with less CNS SE than most benzodiazepines
Agent that is a partial agonist for the 5-HT1A receptor
Drug of choice for generalized anxiety disorder, NOT effective in acute anxiety
Agent that is metabolized to acetaldehyde by alcohol dehydrogenase and microsomal ethanol-oxidizing system (MEOS)
Page 25
*MEOS
Enzyme that metabolizes acetaldehyde to acetate Aldehyde dehydrogenase
Agents that inhibit acetaldehyde dehydrogenase
Disulfiram
*
Ethanol
Agent that is the antidote for methanol overdose Ethanol, fomepizole
Fomepizole
Anti seizure Drugs
Most frequent route of metabolism Hepatic enzymes
Sodium channel blockade
MOA for benzodiazepines and barbiturates GABA-related targets
MOA for Ethosuximide Calcium channels
MOA for Valproic acid at high doses
System that increases in activity with chronic ethanol exposure and may contribute to tolerance
Disulfiram, metronidazole, certain sulfonylureas and cephalosporins
Agent that inhibits alcohol dyhydrogenase and its clinical use
FOMEPIZOLE – used to prevent formation of toxic metabolites from methanol and ethylene glycol ingestion
Agent used in the treatment of alcoholism, if alcohol is consumed concurrently, acetaldehyde builds up and results in nausea, headache, flushing, and hypotension
The most common neurologic abnormality in chronic alcoholics
Peripheral neuropathy (also excessive alcohol use is associated with HTN, anemia, and MI)
Agent that is teratogen and causes a fetal syndrome
Drug that inhibits alcohol dehydrogenase and is used in ethylene glycol exposure
Mechanisms of action for Phenytoin, Carbamazepine, Lamotrigine
Affect calcium, potassium, and sodium channels
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* Valproic acid and Phenytoin
DOC for febrile seizures Phenobarbital
Drugs of choice for absence seizures * Ethosuximide and valproic acid
Drug of choice for myoclonic seizures * Valproic acid
Drugs of choice for status epilepticus
Drugs that can be used for infantile spasms Corticosteroids
Carbamazepine
* Gabapentin
Phenytoin
SE of phenytoin *
Carbamazepine
Valproic acid
Serum ammonia and LFT's
Drugs of choice for generalized tonic-clonic and partial seizures
IV diazepam for short term (acute) treatment; phenytoin for prolonged therapy
Anti-seizure drugs used also for bipolar affective disorder (BAD)
Valproic acid, carbamazepine, phenytoin and gabapentin
Anti-seizure drugs used also for Trigeminal neuralgia
Anti-seizure drugs used also for pain of neuropathic orgin
Anti-seizure agent that exhibits non-linear metabolism, highly protein bound, causes fetal hydantoin syndrome, and stimulates hepatic metabolism
Gingival hyperplasia, nystagmus, diplopia and ataxia
Anti-seizure agent that induces formation of liver drug-metabolism enzymes, is teratogen and can cause craniofacial anomalies and spina bifida
Agent that inhibits hepatic metabolism, is hepatotoxic and teratogen that can cause neural tube defects and gastrointestinal distress
Laboratory value required to be monitored for patients on valproic acid
Page 27
SE for Lamotrigine Stevens-Johnson syndrome
SE for Felbamate
Valproic acid
Carbamazepine may cause Agranulocytosis
General Anesthetics
MOA of general anesthetics
Nitrous oxide
Inversely related to potency of anesthetics
Halothane and methoxyflurane
Most inhaled anesthetics SE Decrease arterial blood pressure
Inhaled anesthetics are myocardial depressants Enflurane and halothane
Inhaled anesthetic causes peripheral vasodilation Isoflurane
Nitrous oxide
Aplastic anemia and acute hepatic failure
Anti-seizure medication also used in the prevention of migraines
Anti-seizure drugs used as alternative drugs for mood stabilization
Carbamazepine, gabapentin, lamotrigine, and valproic acid
Most are thought to act at GABA-A receptor - chloride channel
Inhaled anesthetic with a low blood/gas partition coefficient
Minimum alveolar anesthetic concentration (MAC)
Inhaled anesthetics metabolized by liver enzymes which has a major role in the toxicity of these agents
Inhaled anesthetic that may sensitize the myocardium to arrhythmogenic effects of catecholamines and has produced hepatitis
Halothane
Inhaled anesthetic, less likely to lower blood pressure than other agents, and has the smallest effect on respiration
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Methoxyflurane
Nitrous oxide
Desflurane
* Dantrolene
IV barbiturate used as a pre-op anesthetic Thiopental
Benzodiazepine used adjunctively in anesthesia Midazolam
*Flumazenil
Ketamine
*Fentanyl
Neuroleptanesthesia
Propofol
Local Anesthetics
MOA of local anesthetics (LA's)
Fluoride released by metabolism of this inhaled anesthetic may cause renal insufficiency
Prolonged exposure to this inhaled anesthetic may lead to megaloblastic anemia
Pungent inhaled anesthetic which leads to high incidence of coughing and vasospasm
DOC for malignant hyperthermia that may be caused by use of halogenated anesthetics
Benzodiazepine receptor antagonist, it accelerates recovery from benzodiazepine overdose
This produces "dissociative anesthesia", is a cardiovascular stimulant which may increases intracranial pressure, and hallucinations occur during recovery
Opioid associated with respiratory depression, but is used in high risk patients who may not survive full general anesthetia
State of analgesia and amnesia produced when fentanyl is used with droperidol and nitrous oxide
Produces both rapid anesthesia and recovery, has antiemetic activity and commonly used for outpatient surgery, may cause marked hypotension
Block voltage-dependent sodium channels
Page 29
This may enhance activity of local anesthetics Hyperkalemia
This may antagonize activity of local anesthetics Hypercalcemia
Vasodilation
Cocaine
Tetracaine and bupivacaine
These LA's have surface activity Cocaine and benzocaine
CNS toxicity
Cocaine
LA causing methemoglobinemia Prilocaine
Skeletal Muscle Relaxants
Neuromuscular blocking drugs
Nondepolarizing type antagonists
Almost all local anesthetics have this property and sometimes require the administration of vasoconstrictors (ex. Epinephrine) to prolong activity
Local anesthetic with vasoconstrictive property, favored for head, neck, and pharyngeal surgery
Longer acting local anesthetics which are less dependent on vasoconstrictors
Most important toxic effects of most local anesthetics
Commonly abused LA which has cardiovascular toxicity including severe hypertension with cerebral hemorrhage, cardiac arrhythmias, and myocardial infarction
Structurally related to acetylcholine, used to produce muscle paralysis in order to facilitate surgery or artifical ventilation. Full doses lead to respiratory paralysis and require ventilation
These drugs strongly potentiate and prolong effect of neuromuscular blockade (NMB)
Inhaled anesthetics, especially isoflurane, aminoglycosides, and antiarrhythmic
These prevent the action of Ach at the skeletal muscle endplate to produce a "surmountable blockade," effect is reversed by cholinesterase inhibitors (ex. neostigmine or pyridostigmine)
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Tubocurarine
Mivacurium
Pancuronium
Atracurium
Succinylcholine
Cholinesterase inhibitors
Spasmolytic drugs
Spasmolytic drugs
Facilitates GABA presynaptic inhibition Diazepam
GABA agonist in the spinal cord Baclofen
Similar to clonidine and may cause hypotension Tizanidine
* Dantrolene
Agent used for acute muscle spasm Cyclobenzaprine
*Drug induced Parkinsonism
Agent with long duration of action and is most likely to cause histamine release
Non-depolarizing skeletal muscle antagonist that has short duration
Skeletal muscle agent that can block muscarinic receptors
Skeletal muscle agent that undergoes Hofmann elimination (breaks down spontaneously)
One depolarizing blocker that causes continuous depolarization and results in muscle relaxation and paralysis, causes muscle pain postoperatively and myoglobinuria may occur
During Phase I these agents worsen muscle paralysis by succinylcholine, but during phase II they reverse the blockade produced by succinylcholine
Agents acting in the CNS or in the skeletal muscle, used to reduce abnormally elevated tone caused by neurologic or muscle end plate disease
DOC for malignant hyperthermia by acting on the sacroplasmic reticulum or skeletal muscle
Drugs Used in Parkinsonism & Other Movement Disorders
Irreversible condition resulting from the use of antipsychotics, reserpine at high doses, and MPTP (by-product of illicit meperidine analog)
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L-dopa
Carbidopa
"On-off-phenomenon"
Levodopa
Bromocriptine
Pramipexole and ropinirole
Amantadine
Selegiline
Entacapone and Tolcapone
Benztropine
Agent effective in physiologic and essential tremor Propranolol
Agent used in drug therapy of Parkinson's instead of Dopamine which has low bioavailability and does not cross the BBB
This is combined with L-dopa, inhibits DOPA decarboxylase (active only peripherally) which allows lower effective doses of L-dopa and allows for fewer SE's (GI distress, postural hypotension, and dyskinesias)
Clinical response that may fluctuate in tx of Parkinson's dx
Anti-Parkinson's drug which increases intraocular pressure and is contraindicated in closed angle glaucoma
Ergot alkaloid that is a partial agonist at D2 receptors in the brain, used for patients who are refractory or cannot tolerate levodopa, causes erythromelalgia
Non ergot agents used as first-line therapy in the initial management of Parkinson's
Enhances dopaminergic neurotransmission SE's include CNS excitation, acute toxic psychosis and livedo reticularis
Inhibitor of MAO type B which metabolizes dopamine, used adjunct to levodopa or as sole agent in newly diagnosed patients
Inhibitors of catechol-O-methyltransferase (COMT), used as adjuncts in Parkinson's dx and cause acute hepatic failure (monitor LFT's)
Agent decreases the excitatory actions of cholinergic neurons. May improve tremor and rigidity but have LITTLE effect on bradykinesia. Atropine-like side effects
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Agents used in Huntington's Disease
Agents used in Tourette's dx Haloperidol or pimozide
Chelating agent used in Wilson's disease Penicillamine
Antipsychotics
MOA of neuroleptics Dopamine blockade
*
Antipsychotics that reduce positive symptoms only Older antipsychotics
* Risperidone
Atypical antipsychotic causing high prolactin levels * Risperidone
Olanzapine
Haloperidol
Drug used in neuroleptic malignant syndrome * Dantrolene
Tetrabenazine (amine depleting drug), Haloperidol (antipsychotic)
Extrapyramidal dysfunction is more common with these agents, which block this subtype of dopamine receptor
Older antipsychotic agents, D2 receptors
Side effects occuring in antipsychotics that block dopamine
Hyperprolactinemia, menorrhea, galactorrhea, confusion, mood changes, decreased sexual interest, and weight gain
Newer atypical antipsychotics that also improve some of the negative symptoms and help acute agitation
Olanzapine, aripiprazole, and sertindole
Antipsychotic used in the treatment of psychiatric symptoms in patients with dementia
Newer atypical antipsychotic used for bipolar disorder, known to cause weight gain, and adversely affect diabetes
Agent more frequently associated with extrapyramidal side effects that can be treated with benzodiazepine, diphenhydramine or muscarinic blocker
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Muscarinic blockers
* Thioridazine
Haloperidol
Thioridazine
**Clozapine
* Clozapine
Anti-psychotics available in depot preparation Fluphenazine and haloperidol
Reduced seizure threshold
Orthostatic hypotension and QT prolongation
Increased risk of developing cataracts Quetiapine
Lithium
Major route of elimination for Lithium * Kidneys
*Lithium toxicity
Theophylline
Agents may exacerbate tardive dyskinesias (may be irreversible and there is no treatment)
Antipsychotic having the strongest autonomic effects
Antipsychotic having the weakest autonomic effects
Only phenothiazine not exerting antiemetic effects, can cause visual impairment due to retinal deposits, and high doses have been associated with ventricular arrhythmias
Agent having no effect on D2 receptors, blocks D4, reserved for resistant schizophrenia, and can cause fatal agranulocytosis
Anti-psychotic not shown to cause tardive dyskinesia
Low-potency typical antipsychotics and clozapine
Low potency phenothiazines and ziprasidone
Patients being treated with lithium, who are dehydrated, or taking diuretics concurrently, could develop
Drug increases the renal clearance hence decreases levels of lithium
Page 34
Lithium is associated with this congenital defect
DOC for bipolar affective disorder * Lithium
Concern using lithium Low therapeutic index
SE of lithium *
Antidepressants
Norepinephrine and serotonin
2 to 3 weeks
Elderly patients
Well-tolerated and are first-line antidepressants SSRI's, bupropion, and venlafaxine
Monamine oxidase inhibitors
Hypertensive crisis
Serotonin syndrome
Tricyclic antidepressants (TCA)Tricyclic antidepressants (TCA)
Three C's associated with TCA toxicity
Cardiac anomalies and is contraindicated in pregnancy or lactation
Tremor, sedation, ataxia, aphasia, thyroid enlargement, and reversible diabetes insipidus
Example of three antidepressants that are indicated for obsessive compulsive disorder
Clomipramine, fluoxetine and fluvoxamine
Neurotransmitters affected by the action of antidepressants
Usual time needed for full effect of antidepressant therapy
Population group especially sensitive to side effects of antidepressants
All antidepressants have roughly the same efficacy in treating depression, agents are chosen based on these criterion
Side-effect profile and prior pt response
Monoamine oxidase inhibitors (MAOI) Most useful in patients with significant anxiety, phobic features, hypochondriasis, and resistant depression
Condition will result from in combination of MAOI with tyramine containing foods (ex. wine, cheese, and pickled meats)
MAOI should not be administered with SSRI's or potent TCA's due to development of this condition
Sedation is a common side effect of these drugs, they lower seizure threshold, uses include BAD, acute panic attacks, phobias, enuresis, and chronic pain and their overdose can be deadly
Coma, Convulsions, Cardiac problems (arrhythmias and wide QRS)
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Tertiary amines
Amitriptyline
TCA used in chronic pain, enuresis, and ADD * Imipramine
Doxepin
Clomipramine
Nortriptyline, Desipramine
Side effects seen with tricyclic antidepressants
Heterocyclics Amoxapine
Maprotiline
Venlafaxine
Venlafaxine
Trazodone
Nefazodone
*
Bupropion
Mirtazapine
Agents having higher sedation and antimuscarinic effects than other TCA's
TCA used in chronic pain, a hypnotic, and has marked antimuscarinic effects
TCA with greatest sedation of this group, and marked antimuscarinic effects, used for sleep
TCA used in obsessive compulsive disorder (OCD), most significant of TCA's for risk of seizure, weight gain, and neuropsychiatric signs and symptoms
Secondary amines that have less sedation and more excitation effect
Muscarinic blockade (dry mouth, constipation); weak alpha-1 block (orthostatic hypotension); weak hisamine block (sedation)
Antidepressant associated with neuroleptic malignant syndrome
Antidepressant associated with seizures and cardiotoxicity
Antidepressant having stimulant effects similar to SSRI's and can increase blood pressure
Antidepressant inhibiting norepinephrine, serotonin, and dopamine reuptake
Antidepressant also used for sleep that causes priapism
Antidepressant which is inhibitor of CYP450 enzymes and may be associated with hepatic failure
Heterocyclic antidepressants least likely to affect sexual performance, used for management of nicotine withdrawal, SE's include dizziness, dry mouth, aggravation of psychosis, and seizures
Antidepressant with MOA as alpha 2 antagonist, has effects on both 5-HT and NE, blocks histamine receptors, and is sedating
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SE of mirtazapine
Selective serotonin reuptake inhibitors (SSRI)
Side effects frequently seen with SSRIs CNS stimulation; GI upset
Antidepressants with no effect on BP, no sedation SSRIs
Fluoxetine
SSRI indicated for premenstrual dysphoric disorder Fluoxetine (Sarafem)
SSRI less likely to cause a withdrawal syndrome Fluoxetine
Opioid Analgesics & AntagonistsAscending pathways
*
Postsynaptic Mu receptors
* Miosis and constipation
Meperidine
Opioid Analgesics
Strong opioid agonists
Opioids used in anesthesia Morphine and fentanyl
Liver toxicity, increased serum cholesterol
Except for these agents all SSRI have significant inhibition of CytP450 enzymes
Citalopram and its metabolite escitalopram
SSRI with long T1/2 and can be administered once weekly for maintenance, not acute tx
Some of SSRIs' therapeutic effects beside depression
Panic attacks, social phobias, bulimia nervosa, and PMDD (premenstrual dysphoric disorder), OCD
Inhibit synaptic activity of primary afferents and spinal cord pain transmission neurons
Activation of these receptors close Ca2+ ion channels to inhibit neurotransmitter release
Presynaptic mu, delta, and kappa receptors
Activation of these receptors open K+ ion channels to cause membrane hyperpolarization
Tolerance to all effects of opioid agonists can develop except
All opioids except this agent (which has a muscarinic blocking action) cause pupillary constriction
SE of these drugs include dependence, withdrawal syndrome, sedation, euphoria, respiratory depression nausea and vomiting, constipation, biliary spasm, increased ureteral and bladder tone, and reduction in uterine tone
Morphine, methadone, meperidine, and fentanyl
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* Methadone
Opioid available trans-dermally * Fentanyl
*Morphine
Meperidine
Moderate opioid agonists *
Propoxyphene
Partial agonist or mixed antagonists Buprenorphine
* Naloxone
* Naltrexone
These agents are used as antitussive Dextromethorphan, Codeine
These agents are used as antidiarrheal Diphenoxylate, Loperamide
Drugs of AbuseInhalant anesthetics NO, chloroform, and diethyl ether
Organic nitrites
Steroids
Opioid used in the management of withdrawal states
Opioid that can be given PO, by epidural, and IV, which helps to relieve the dyspnea of pulmonary edema
Use of this opioid with MAOI can lead to hyperpyrexic coma, and with SSRI's can lead to serotonin syndrome
Codeine, hydrocodone, and oxycodone
Weak opioid agonist, poor analgesic, its overdose can cause severe toxicity including respiratory depression, circulatory collapse, pulmonary edema, and seizures
Partial opioid agonist, considered a strong analgesic, has a long duration of action and is resistant to naloxone reversal
Opioid antagonist that is given IV and had short DOA
Opioid antagonist that is given orally in alcohol dependency programs
Toxic to the liver, kidney, lungs, bone marrow, peripheral nerves, and cause brain damage in animals, sudden death has occurred following inhalation
Fluorocarbons and Industrial solvents
Cause dizziness, tachycardia, hypotension, and flushing
Causes acne, premature closure of epiphyses, masculinization in females, hepatic dysfunction, MI, and increases in libido and aggression
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*
IV administration
* Overdose of opioids
Abstinence syndrome
Treatment for opioid addiction
* Naloxone
Sedative-HypnoticsSedative-Hypnotics action
CNS depressants
"Date rape drug" * Flunitrazepam (rohypnol)
The most important sign of withdrawal syndrome Excessive CNS stimulation (seizures)
Treatment of withdrawal syndrome involves
These agents are CNS depressants *
Stimulants Caffeine
Nicotine
Readily detected markers that may assist in diagnosis of the cause of a drug overdose include
Changes in heart rate, blood pressure, respiration, body temperature, sweating, bowel signs, and pupillary responses
Opioid Analgesics Most commonly abused in health care professionals
Heroin, morphine, oxycodone, meperidine and fentanyl
This route is associated with rapid tolerance and psychologic dependence
Leads to respiratory depression progressing to coma and death
Lacrimation, rhinorrhea, yawning, sweating, weakness, gooseflesh, nausea, and vomiting, tremor, muscle jerks, and hyperpnea are signs of this syndrome
Methadone, followed by slow dose reduction
This agent may cause more severe, rapid and intense symptoms to a recovering addict
Reduce inhibition, suppress anxiety, and produce relaxation
Additive effects when Sedative-Hypnotics used in combination with these agents
Common mechanism by which overdose result in death
Depression of medullary and cardiovascular centers
Long-acting sedative-hypnotic or a gradual reduction of dose, clonidine or propranolol
Ethanol, Barbiturates, and Benzodiazepines
Withdrawal from this drug causes lethargy, irritability, and headache
W/D from this drug causes anxiety and mental discomfort
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Treatments available for nicotine addiction *
Chronic high dose abuse of nicotine leads to
Amphetamines
Amphetamine agents
These agents are congeners of Amphetamine DOM, STP, MDA, and MDMA "ecstasy"
Cocaine "super-speed"
HallucinogensPCP
Removal of PCP may be aided
*
Marijuana
Direct-Acting Cholinomimetic AgonistsMuscarinic agonists or parasympathomimetic
*Bethanechol
Pilocarpine
Cevimeline
Patches, gum, nasal spray, psychotherapy, and bupropion
Psychotic state, overdose causes agitation, restlessness, tachycardia, hyperthermia, hyperreflexia, and seizures
Tolerance is marked and abstinence syndrome occurs
Dextroamphetamines and methamphetamine
Overdoses of this agent with powerful vasoconstrictive action may result in fatalities from arrhythmias, seizures, respiratory depression, or severe HTN (MI and stroke)
Most dangerous of the currently popular hallucinogenic drugs, OD leads to nystagmus, marked hypertension, and seizures, presence of both horizontal and vertical nystagmus is pathognomonic
Urinary acidification and activated charcoal or continual nasogastric suction
THC is active ingredient, SE's include impairment of judgment, and reflexes, decreases in blood pressure and psychomotor performance occur
Cholinoreceptor-Activating & Cholinesterase-Inhibiting Drugs
This agent has greater affinity for muscarinic receptors and used for postoperative and neurogenic ileus and urinary retention
Only direct acting agent that is very lipid soluble and used in glaucoma
This agent used to treat dry mouth in Sjögren's syndrome
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Edrophonium
Neostigmine
Physostigmine
Treatment of myasthenia gravis Pyridostigmine
OrganophosphatesAntiglaucoma organophosphate Echothiophate
Long acting cholinesterase inhibitors
Scabicide organophosphate Malathion
Metrifonate
Toxicity of organophosphate:
*
Respiratory failure
The most toxic organophosphate Parathion
Atropine
Pralidoxime
Prototypical drug is atropine Nonselective Muscarinic Antagonists
* Benztropine, trihexyphenidyl
Treatment of motion sickness * Scopolamine, meclizine
Indirect-Acting ACh Agonist, alcohol, short DOA and used in diagnosis of myasthenia gravis
Carbamate with intermediate action, used for+A1170 postoperative and neurogenic ileus and urinary retention
Treatment of atropine overdose and glaucoma (because lipid soluable). Enters the CNS rapidly and has a stimulant effect, which may lead to convulsions
Associated with an increased incidence of cataracts in patients treated for glaucoma
Organophosphate anthelmintic agent with long DOA
DUMBELSS (diarrhea, urination, miosis, bronchoconstriction, excitation of skeletal muscle and CNS, lacrimation, salivation, and sweating)
The most frequent cause of acute deaths in cholinesterase inhibitor toxicity
Treatment of choice for organophosphate overdose
This agent regenerates active cholinesterase and is a chemical antagonist used to treat organophosphate exposure
Cholinoreceptor Blockers & Cholinesterase Regenerators
Treat manifestations of Parkinson's disease and EPS
Page 41
Produce mydriasis and cycloplegia *
Bronchodilation in asthma and COPD * Ipratropium
Reduce transient hyper GI motility Dicyclomine, methscopolamine
Oxybutynin, dicyclomine
Toxicity of anticholinergics
Another pneumonic for anticholinergic toxicity
Infants
Contraindications to use of atropine
Nicotinic Antagonists
Severe hypertension
Reversal of blockade by neuromuscular blockers Cholinesterase inhibitors
Succinylcholine
Pralidoxime, atropine
SympathomimeticsPneumonic for beta receptors *
This is the drug of choice for anaphylactic shock * Epinephrine
Atropine, homatropine,C1208 tropicamide
Cystitis, postoperative bladder spasms, or incontinence
block SLUD (salivation, lacrimation, urination, defecation
"dry as a bone, red as a beet, mad as a hatter, hot as a hare, blind as a bat"
Atropine fever is the most dangerous effect and can be lethal in this population group
Infants, closed angle glaucoma, prostatic hypertrophy
Limiting adverse effect of ganglion blockade that patients usually are unable to tolerate
Tubocurarine is the prototype, pancuronium, atracurium, vecuronium are newer short acting agent, produce competitive block at end plate nicotinic receptor, causing flaccid paralysis
Nondepolarizing Neuromuscular Blockers
Only member of depolarizing neuromuscular blocker, causes fasciculation during induction and muscle pain after use; has short duration of action
Chemical antagonists that bind to the inhibitor of ACh Estrace and displace the enzyme (if aging has not occurred)
Cholinesterase regenerators, pralidoxime
Used to treat patients exposed to insecticides such as parathion
You have 1 heart (Beta 1) and 2 lungs (Beta 2)
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Amphetamines
Phenylephrine
Reduce aqueous secretion
Albuterol
Salmeterol
Beta1 agonists
*
Alpha1 agonists
Reduce the loss from area of injection
Midodrine
Terbutaline
Epinephrine
Epinephrine
Dopamine
Phenylisopropylamines that are used legitimately and abused for narcolepsy, attention deficit disorder, and weight reduction
Alpha agonist used to produce mydriasis and reduce conjunctival itching and congestion caused by irritation or allergy, it does not cause cycloplegia
Newer alpha 2 agonist (apraclonidine and brimonidine) treat glaucoma by acting to
Short acting Beta 2 agonists that is drug of choice in treatment of acute asthma but not recommended for prophylaxis
Longer acting Beta 2 agonist is recommended for prophylaxis of asthma
These agents increase cardiac output and may be beneficial in treatment of acute heart failure and some types of shock
These agents decrease blood flow or increase blood pressure, are local decongestants, and used in therapy of spinal shock (temporary maintenance of blood pressure which may help maintain perfusion
Shock due to septicemia or myocardial infarction is made worse by
Increasing afterload and tissue perfusion declines
Epinephrine is often mixed with a local anesthetic to
Chronic orthostatic hypotension can be treated with
Beta 2 agonist used to suppress premature labor, but cardiac stimulatory effects may be hazardous to mother and fetus
Sympathetic agent which stimulates heart rate and can dilate vessels in skeletal muscle at low doses
Mast cells to reduce release of hisamine and inflammatory mediators
Agent used in shock because it dilates coronary arteries and increases renal blood flow
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Dobutamine
Ephedrine
Alpha 1 agonist toxicity * Hypertension
Beta 1 agonist toxicity
Beta 2 agonist toxicity Skeletal muscle tremor, tachycardia
The selective agents loose their selectivity at high doses
Adrenoceptor BlockerPhenoxybenzamine
Phentolamine
*Prazosin, terazosin, doxazosin
Tamsulosin
Yohimbine
Beta-Blocking Drugs
*
Labetalol and carvedilol
Pindolol and acebutolol
Agent which stimulates cardiac contractile force more than rate with little effect on total peripheral resistance
Long acting sympathomimetic, sometimes used to improve urinary continence in children and elderly with enuresis
Sinus tachycardia and serious arrhythmias
Nonselective alpha-blocking drug, long acting and irreversible, and used to treat pheochromocytoma. Blocks 5-HT, so occasionaly used for carcinoid tumor. Blocks H1 and used in mastocytosis
Nonselective alpha-blocking drug, short acting and reversible, used for rebound HTN from rapid clonidine withdrawal, and Raynaud's phenomena
Selective Alpha 1 blocker used for hypertension, BPH, may cause first dose orthostatic hypotension
Selective Alpha-1A blocker, used for BPH, but with little effect on HTN
Selective Alpha 2 blocker used for impotence (controversial effectiveness)
SelectiveB1 Receptor blockers that may be useful in treating patients even though they have asthma
Acebutolol, atenolol, esmolol, metoprolol
Combined alpha and beta blocking agents that may have application in treatment of CHF
Beta blockers partial agonist activity (intrinsic sympathomimetic activity) cause some bronchodilation and may have an advantage in treating patients with asthma
Page 44
*
Timolol
Esmolol
This beta blocker is the longest acting Nadolol
These beta blockers are less lipid soluble Acebutolol and atenolol
Propranolol
Beta blockers
Beta blockers
Pilocarpine, carbachol, physostigmine
Epinephrine, dipivefrin
Apraclonidine, brimonidine
These Beta blockers decrease aqueous secretion *
Acetazolamide
This agent cause increased aqueous outflow Prostaglandin PGF2a
Antihypertensive AgentsInhibit angiotensin-converting enzyme (ACE) * ACE inhibitors
Captopril and enalapril (-OPRIL ending) are * ACE inhibitors
SE of ACE inhibitors * Dry cough, hyperkalemia
This beta blocker lacks local anesthetic activity (a property which decreases protective reflexes and increases the risk of corneal ulceration) and used in treating glaucoma
This parenteral beta blocker is a short acting (minutes)
This beta blocker is highly lipid soluble and may account for side effects such as nightmares
Clinical uses of these agents include treatment of HTN, angina, arrhythmias, chronic CHF, and selected post MI patients
Toxicity of these agents include bradycardia, AV blockade, exacerbation of acute CHF; signs of hypoglycemia may be masked (tachycardia, tremor, and anxiety)
Glaucoma (all agents topical except for diuretics)
Cholinomimetics that increase outflow, open trabecular meshwork, and cause ciliary muscle contraction
Nonselective alpha agonists that increases outflow, probably via the uveoscleral veins
Selective alpha agonists that decreases aqueous secretion
Timolol (nonselective), betaxolol (selective)
This diuretic decreases aqueous secretion due to lack of HCO3- ion. Causes drowsiness and paresthesias, alkalinization of the urine may precipitate calcium salts, hypokalemia, acidosis
Page 45
ACE inhibitors are contraindicated in * pregnancy and with K+
Losartan and valsartan block * Angiotensin receptor
Angiotensin receptor blockers do NOT cause * Dry cough
Agents that block L-type calcium channel Calcium channel blockers
CCB contraindicated in CHF * Verapamil
CCB with predominate effect on arteriole dilation Nifedipine
SE of CCB * Constipation, edema, and headache
* Beta-blockers
B-blockers that are more cardioselective Beta-1 selective blockers
Cardioselective Beta 1-blockers * Atenolol, acebutolol, and metoprolol
Beta-blockers should be used cautiously in
Propranolol
SE of beta blockers*
Alpha 1selective blockers *
Phenoxybenzamine
For rebound HTN from rapid clonidine withdrawal Phentolamine
* Tamsulosin (Flomax)
SE of alpha blockers*
Clonidine, and methyldopa
SE of methyldopa Positive Comb's test, depression
Agents that reduce heart rate, contractility, and O2 demand
Asthma (bronchospastic effects), diabetes (block signs of hypoglycemia) and peripheral vascular disease
Non-selective Beta-blocker also used for migraine prophylaxis
Bradycardia, SEXUAL DYSFUNCTION, decrease in HDL, and increase in Triglycerols (TG)
Prazosin, terazosin and doxazosin (-AZOSIN ending)
Non-selective Alpha1blockers use to treat pheochromocytoma
A1a-selective blocker with no effects on HTN used for BPH
Orthostatic hypotension (especially with first dose) and reflex tachycardia
Presynaptic Alpha 2 agonist used in HTN, and acts centrally
Page 46
Methyldopa is contraindicated in *
SE of clonidine Rebound HTN, sedation, dry mouth
Direct vasodilator of arteriolar smooth muscle Hydralazine
SE of hydralazine * Lupus-like syndrome
Minoxidil
SE of minoxidil Hypertrichosis
IV Drug used Hypertensive Crisis Nitroprusside
Nitroprusside vasodilates Arteries and veins
Toxicity caused by nitroprusside and treatment
DiureticsCarbonic anhydrase inhibitor Acetazolamide
Diuretic used for mountain sickness and glaucoma * Acetazolamide
SE of acetazolamide
*
MOA of loop diuretics inhibits Na+/K+/2Cl- cotransport
Site of action of loop diuretics * Thick ascending limb
SE of loop (furosemide) diuretics *
Ototoxicity
Loops lose and thiazide diuretics retain * Calcium
MOA of thiazide diuretics Inhibit Na+/Cl- cotransport
Site of action of thiazide diuretics * Work at early distal convoluted tubule
Geriatrics due to its CNS (depression) effects
Arterial vasodilator that works by opening K+ channels
Cyanide toxicity treated with sodium thiosulfate
Paresthesias, alkalization of the urine (which may ppt. Ca salts), hypokalemia, acidosis, and encephalopathy in patients with hepatic impairment
Hyperuricemia, hypokalemia and ototoxicity
Aminoglycosides used with loop diuretics potentiate adverse effect
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Sulfonamides
SE of thiazide (HCTZ) diuretics *
Potassium sparing diuretics inhibit * Na+/K+ exchange
Diuretic used to treat primary aldosteronism * Spironolactone
SE of spironolactone *
* Mannitol
ADH agonist used for pituitary diabetes insipidus * Desmopressin (DDAVP)
Used for SIADH Demeclocycline
SE of demeclocycline
Antiarrhythmic agents
*Sodium channel blockers
SE of procainamide * Lupus-like syndrome
Limiting side effect of Quinidine * Prolongs QT interval
Other side effects of Quinidine
Major drug interaction with Quinidine Increases concentration of Digoxin
* Amiodarone
DOC for digoxin induced arrhythmias Phenytoin
SE of phenytoin Gingival hyperplasia
Class II antiarrhythmics are B-blockers
Class of drugs that may cause cross-sensitivity with thiazide diuretics
Hyperuricemia, hypokalemia and hyperglycemia
Gynecomastia hyperkalemia, and impotence
Osmotic diuretic used to treat increased intracranial pressure
Antidiuretic hormone (ADH) agonist and antagonist
Bone marrow and teeth discoloration for children under 8 years of age
MOA of class I A (eg. Procainamide), class IB (eg. Lidocaine), and class IC (eg. Flecainide) antiarrhythmics
Thrombocytopenic purpura, and CINCHONISM
DOC for management of acute ventricular arrhythmias
Class of anti-arrhythmics that has a pro-arrhythmic effect (CAST trial), therefore are used as last line agents
Class IC (flecainide, propafenone, moricizine)
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Sotalol
Side effect of sotalol prolongs QT and PR interval
Esmolol
Anti-arrhythmics that decrease mortality B-blockers
MOA of class III antiarrhythmics Potassium channel blockers
Amiodarone
Prolonged half-life, up to six weeks
Antiarrhythmic effective in most types of arrhythmia Amiodarone
SE of Amiodarone
MOA of class IV antiarrhythmics Calcium channel blockers
* Torsades de pointes
Agent to treat torsades de pointes Magnesium sulfate
Drug used supraventricular arrhythmias Digoxin
Adenosine
Adenosine's MOA
Anti-arrhythmic with 15 second duration of action Adenosine
Vasodilators and treatment of anginaMOA of sildenafil (Viagra)
***
Drugs used in the management of angina
Antiarrhythmic that exhibits Class II and III properties
Used intravenously for acute arrhythmias during surgery
Class III antiarrhythmic that exhibits properties of all 4 classes
Specific pharmacokinetic characteristic of amiodarone
Cardiac dysfunction, photosensitivity, skin (blue smurf syndrome), Pulmonary fibrosis, thyroid and corneal deposits
Life threatening cardiac event that prolong QT leads to
DOC for paroxysmal supraventricular tachycardia (PSVT)
Activattion on an inward K+ current and inhibition of Ca++ current resulting in marked hyperpolarization
Inhibits phosphodiesterase-5, enhancing effects of nitric oxide-activated increases in cGMP
Aspirin, Nitrates, CCB, and Beta blockers
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Aspirin reduces mortality in unstable angina by Platelet aggregation inhibition
MOA of nitrates*
Nitrate used for acute anginal attacks Nitroglycerin sublingual tablets
Nitrate used to prevent further attacks
Nitrate free intervals are needed due to Tolerance
SE of nitrates
CCB are DOC for Prinzmetal's angina
Classic
Drugs used to treat CHFMOA of Cardiac glycosides (eg. digoxin)
Digoxin is used in Atrial fibrillation and CHF
Digoxin toxicity can be precipitated by Hypokalemia
Antidote for digoxin toxicity Digibind
Amrinone and milrinone
SE of amrinone Thrombocytopenia
Beta 1 agonists used in acute CHF Dobutamine and dopamine
Diuretics work in CHF by Reducing preload
Beta blockers work in CHF by
Peptide drug used to treat CHF Nesiritide (BNP)
SE of nesiritide Excessive hypotension and kidney failure
Relax vascular smooth muscle, at low doses dilate veins and at high doses dilate arterioles
Oral and transdermal forms of nitroglycerin
Postural hypotension, reflex tachycardia, hot flashes, and throbbing headache due to meningeal artery dilation
Beta blockers are used for which type of anginal attack
Indirectly increase intracellular calcium and cardiac contractility by inhibiting Na+/K+ ATPase
Phosphodiesterase inhibitors that increase mortality and have been found to have NO beneficial effects
Reducing progression of heart failure (never use in acute heart failure)
MOA of nesiritide Increasing sodium excretion and decreases arterial and venous tone
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Carvedilol
Nesiritide (Natrecor)
Drugs used in coagulation disordersVitamin K dependent anticoagulant * Warfarin (PT)
Warfarin is contraindicated in Pregnancy
Anticoagulant of choice in pregnancy Heparin
Heparin (PTT) increases activity of * Antithrombin 3
Route of administration of warfarin Oral
Routes of administration of heparin IV and IM (only LMW)
SE of both warfarin and heparin Bleeding
SE of heparin
Alternative anticoagulant used if HIT develops Lepirudin
Antidote to reverse actions of warfarin Vitamin K or fresh frozen plasma
Antidote to reverse actions of heparin * Protamine sulfate
MOA of aspirin Irreversibly blocking cyclooxygenase
Aspirin, metoprolol
SE of Aspirin * GI bleeding
Ticlopidine
SE for ticlopidine Neutropenia and agranulocytosis
Effective in preventing TIA's Clopidogrel and ticlopidine
Dipyridamole
Abciximab, tirofiban and eptifibatide
Agent used in CHF that is a selective alpha and nonselective beta blocker
Agent used in acutely decompensated CHF resembling natriuretic peptide
Heparin induced thrombocytopenia (HIT)
Agent used to treat MI and to reduce incidence of subsequent MI
Antiplatelet drug reserved for patients allergic to aspirin
Prevents thrombosis in patients with artificial heart valve
Block glycoprotein IIb/IIIa involved in platelet cross-linking
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MOA of thrombolytics *
Thrombolytics are used for * Pulmonary embolism and DVT
Thrombolytic that can cause allergic reaction Streptokinase
Tissue plasmin activator
SE of tPA Cerebral hemorrhage
Antidote for thrombolytics Aminocaproic acid
Agent to treat hypochromic microcytic anemias Ferrous sulfate
Chelating agent used in acute iron toxicity Deferoxamine
Agent for pernicious anemia * Cyanocobalamin (Vit B12)
Vitamin B12
*Folic acid
* Erythropoietin
Interleukin 11 (oprelvekin)
AntihyperlipidemicsDrugs decrease intestinal absorption of cholesterol Bile acid-binding resins
Cholestyramine and colestipol are Bile acid-binding resins
MOA of lovastatin (STATIN) inhibits HMG COA reductase
Pregnancy
Degradation of fibrin clots and are administered IV
Thrombolytic used for acute MI and ischemic (non hemorrhagic) CVA
Agents used in anemias and hematopoietic growth factors
Agent used for neurological deficits in megaloblastic anemia
Agent used for megaloblastic anemia (but does NOT reverse neurologic symptoms) and decrease neural tube defects during pregnancy
Agent used for anemias associated with renal failure
Agent used neutropenia especially after chemotherapy
G-CSF (filgrastim) and GM-CSF (sargramostim)
Treatment of patients with prior episodes of thrombocytopenia after a cycle of cancer chemotherapy
Major nutritional side effect of bile acid-binding resins
Impair absorption of fat soluble vitamin absorption (A,D,E,K)
HMG CoA reductase inhibitors are contraindicated in
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* Inhibit Cytochrome P450 3A4
SE of HMG COA reductase inhibitors Rhabdomyolysis and Hepatotoxicity
* LFT's
Decreases liver triglycerol synthesis * Niacin
SE of niacin * Cutaneous flush
Aspirin
Fibrates (gemfibrozil) increase activity of * Lipoprotein lipase
Most common SE of fibrates Nausea
Fibrates are contraindicated in Pregnancy
Rhabdomyolysis
Ezetimibe (Zetia)
NSAIDS and DMARDSMOA of NSAIDS
Difference between aspirin and other NSAIDS
Four main actions of NSAIDS
Agent used for closure of patent ductus arteriosus * Indomethacin
SE of salicylates Tinnitus, GI bleeding
NSAID also available as an ophthalmic preparation Diclofenac, ketoralac
NSAID available orally, IM and ophthalmically Ketoralac
Ketoralac
MOA of drug or foods (grapefruit juice) that increase statin effect
Monitoring parameter to obtain before initiation of STATINS
Cutaneous flush and be reduced by pretreatment with
Concurrent use of fibrates and statins increases risk of
New class of drugs that works by inhibiting absorption of intestinal cholesterol and can be given concurrently with the Statins
inhibit prostaglandin synthesis by inhibiting cyclo-oxygenase (cox)
Aspirin irreversibly inhibits cyclooxygenase
Anti-inflammatory, analgesia, antipyretic and antiplatelet activity
Aspirin is contraindicated in children with viral infection
Potential for development of Reye's syndrome
NSAID that is used for acute condition, such as pre-op anesthesia and has limited duration (<5 days) of use due to nephrotoxicity
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Newer NSAID that selectively inhibits COX-2 Celecoxib
COX 2 inhibitors may have reduced risk of Gastric ulcers and GI Bleeding
Pre-existing cardiac or renal disease
Acetaminophen only has * Antipyretic and analgesic activity
SE of acetaminophen Hepatotoxicity
Antidote for acetaminophen toxicity * N-acetylcysteine
DMARDs are slow acting drugs for * Rheumatic disease
Initial DMARD of choice for patients with RA Methotrexate
Methotrexate
Causes bone marrow suppression Methotrexate
SE of penicillamine Aplastic anemia and renal toxicity
Interferes with activity of T-lymphocytes Hydroxychloroquine
Anti-malarial drug used in rheumatoid arthritis (RA) Hydroxychloroquine
SE of hydroxychloroquine Retinal destruction and dermatitis
MOA of Leflunomide (newer agent)
Adalimumab, infliximab and etanercept
Anti-rheumatic agent also used for ulcerative colitis Sulfasalazine
Anti-rheumatic agent also used for Chron's disease Infliximab
Drugs used in GoutNSAID used in gout * Indomethacin
COX 2 inhibitors should be used cautiously in pts with
Drugs-Modifying Anti-Rheumatic Agents (DMARDS)
Drug ofter used in combination with TNF - alpha inhitors for RA
Inhibiting dihydroorotate dehydrogenase which leads to decreased pyrimidine synthesis, decreased T cell proliferation and decreased antibody production by B cells
Proteins that prevent action of tumor necrosis factor alpha (TNF-alpha)
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NSAID contraindicated in gout Aspirin
MOA of colchicine (used in acute gout)
SE of colchicine Kidney and liver toxicity, diarrhea
Probenecid and sulfinpyrazone
* Xanthine oxidase
InsulinsRapid acting insulins that do not self-aggregate **
Peakless ling acting insulin ** Insulin glargine
Cardiac drugs
Adenosine
Selective inhibitor of microtubule assembly
Agent used to treat chronic gout by increasing uric acid secretion and excretion
Allopurinol treats chronic gout by decreasing uric acid production by inhibiting
lispro insulin, aspart insulin, glulisine insulin
DOC for paroxysmal supraventricular tachycardia; has high efficacy and short duration of action