pharma slide 01

8/14/2019 pharma slide 01

1/9

.,;.!.,

Definitions

.function, and does no t create a newfunction.Pharmacology: The science of drugs.It is the knowledge of history, source,physical and chemical properties,absorption, distribution,biotransformation, excretion, actions atherapeutic uses of drugs (or toxic effeon microbes),

Two aeneral principlesttt e v ~ r ystudent should always r Jmember

1. All substances can u ~ d e f certainconditions be toxic. ' '

2. All dietary supplements and allsubstances promoted as health-enhancing should meet the samestandards of efficacy and safety.

lDefinitionsMedical (or Clinical) Pharmacology: Is thescience that deals with the use of drugsfor diagnosis, prevention and treatment ofhuman disease.

Toxicology: Is that aspect ofpharmacology which deals with adverseeffects of drugs and the toxic effectsproduced by household, envb,nmentaland industrial chemicals. [poisons arealso drugs, why?)


2/9

Definitions Pharmacotherapeutics: Is the useof drugs in the prevention andtreatment of disease ( or themedical uses of drugs).

Chemotherapeutics: Is the use ofdrugs to stop the growth or killmicroorganisms or cancer cells

DefinitionsIdiosyncratic drug response:Unusual response, infrequently observed inmost patients. Usually caused by geneticdifferences in metabolism of drug, or byimmunologic mechanisms including allergicreactions. Tolerance:Is a decrease in the responsiveness to thedrug with continued drug administration. Tachyphylaxis:Similar to tolerance but m9!e rapid.

Definitions Ph?rmacogenomics: Thebetween the individual'smakeup to his/her responspecific drugs (entire gen Pharmacogenetics: Intervariation in drug responsdue to genetic influencesgene).

Areas of Pharmaco Pharmacodynamics:

Is what the drug does to twhich includes the biocheand physiological effectsdrug, including the mechaaction, interaction with reas well as the adverse eff.J - ' -


3/9

Areas of Pharmacology Areas of PharmacoPharmacokinetics:Is what the body does to the drug.Deals with absorption, distribution,biotransformation and excretion ofdrugs.

1. Absorption: Is the movement of drugmolecules from the site ofadministration into the circulation.

2. Distribution: Is the movemenmolecules from the circulatioand between different parts o3. Biotransformation: Is conversdrug from one chemical strucanother by the action of metaenzymes (metabolism)4. Excretion: Is the movement omolecules out of the body.

DNg inthe systemic circulationI DI&tribullonPharmacokinetics & Pharmacoharmacokinetics & Pharmacodynamics

Dosage formIDisintegrationIDissolutionIAbSOrption

Drug in the systemic circulation

1\

Drug in tissues of distributionJOlstrlbutionDrug in elimination organs

J Excretion I"'.t.bolismKidney Uver Pharm


4/9

'f

1!, ~ Drug Receptors

A receptor is a component of the cell thatinteracts with a drug and init iates a chain ofevents leading to drug's action.Receptors are responsible fo r selectivity ofdrug action.Receptors determine the quantitativerelationship between drug concentration andpharmacological effect.Receptor function can be modified byagomsts and antagonists. Antagonistsint'lrfere with the ability of the agonist toactivate the receptor.i

13

Drug ReceptorMost receptors are 'protelns:

1. The best characterized drug receptors aregulatory proteins, which mediate theendogenous chemical signals such asneurotransmitters, autacoids and hormo2. Some receptors Include enzymes that cInhibited by drugs. (dihydrofolate reductrimethoprim).3. Some receptors are transport proteins (ATPase and digitalis).4. Some receptors are structural proteinscolchicine).

Signaling MechanismsFive basic transmembrane signalingmechanisms are well understood:

1. A lipid-soluble chemical signal crosses theplasma membrane and acts on an intracellularreceptor.2. The signal binds to the extracellular domain of atransmembrane protein, thereby activating anenzymatic actiVity of its cytoplasmic domain.3. The signal binds to the extracellular domain of atransmembrane receptor bound to a proteintyrosine kinase, which it activates.4. The signal binds to and directly regUlates theopening of an ion channel. "5. The signal binds to a cell-surface receptor linkedto an effector enzyme by a G protein.

1-> J""


5/9

Drug Receptcr InteractionDefinitions:

Agonist: A d"ug that binds to andactivates the receptor to bring about thepharmacological effect.1. A full agonist produces maximalpharmacological response with fullreceptor occupancy.2. A partial agonist produces less thanmaximal (lower) pharmacologicalresponse with full receptor occupancy. Itis also calleq partial antagonist.

Drug Receptor InteractionB

1.0

0.8 Partial agonist_ Full agonist0.6

0.4&!0.2 -

0. 0 _ ~ . S 0 = - - - ' - - - - ~ 8 ; - - - " - - - - - - ' ; ; 6 : - - - - - ' ' - - - - 'log (Full agonist or partial agonist)

Drug Receptor Inte1 .0 r - - - - - - - - - - -

I,II: EC50i / .

Drug concentrat ion

Drug Receptor Inter Antagonis t: A drug that bindreceptor but does not activatprevents the agonist from bireceptor and prevents its actthe generation of pharmacolIt can be either reversible orcompetitive or noncompetitivSome antagonists are calledagonists". They reduce recepbelow basal levels observedabsence bound ligand (drug)


6/9

Drug Receptor Interaction Drug Receptor Inter Competitive Antagonist

In the presence of a fixedconcentration of agonist, increasingthe concentrations of a reversiblecompetitive antagonist progressivelyinhibit the agonist response; highantagonist concentrations preventresponse completely.

Conversely, suffic::ilntly higconcentrations of agonist ccompletely overcome the egiven concentration of the Because the antagonism iscompetitive, the presence oincreases the a ~ o n i s t concrequired for a given degreeresponse, and so the agoniconcentration effect curvethe right.

Drug wi th non-competitive,D,ug ~ n t a g o n ; ' . ? talone "" _

Drug concentratio

- - - - . . . , , ~

AgonlGt concf'tntrntlon

Agonist -tocompeti l ive antagoni,st

c ' _ C (1 -+- hi ] I K i), /

Drug Receptor InteractionA

\ Q l "Iit.


7/9

.,", Drug Receptor Inter

FIGURE 2 .5I d ~ a l i l e d dosc-rcsoonse cun'li:s of an agonist in tfIE.absence Ie) and lhc presence (b. c. d} of i n c r t : a ~ i n 6 oose-sof ilr'l cquilibnum-eonll'Ctil,\,C antacofllst.

Irreversible Antagonist:Some a n t a ~ o n i s t s bind to than irreversible fashion eithecovalent bond with the recepbinding tightly to it, so that tnot available fo r a ~ o n i s t bindremaining unoccupied recepagonist normally, but mightenough to elicit an adequateThe duration of action of theantagonist is more dependeturnover than antagonist elim

Drug Receptor Inter

- - ~ - - - - - - , A g o ni st . .noncompAl i l

,: EC sa: /

- - - - ~BDrug Receptor Interaction

Another way of noncompetitiveantagonism is binding to thereceptor on a different site thatbinds the agonist, therebypreventing receptor activation bythe agonist without blockingagonist binding. This is also called"allosteric modulation".

Agon is t concen t ra t io


8/9

. !

c:;Q;u'51o.0' i i i

Drugalone

Drug w it hcompeti t iveantagonist '

D r ~ g concentrat ion

FIGURE 2 .6Idealized dose-resixmse CUf\!CS of an agonnos-eoce ia l ;,no tnc Df'escO(",c (b. c. d! 01 inof ;l non-eQuilil>nw!KCmiX'(llive anlCigonis

Drug Receptor InteractionOther mechanisms of drugantagonism:

1. Chemical antagonism: heparin &protamine.2. Physiologic antagonism: Insulinand glucocorticoids effects onblood glucose.

3 1

Spare Recepto Occupation of a receptor bis only the first of many steto bring about the pharmaceffect.The transduction process tdrug occupancy of receptopharmacologic response iscoupling.


9/9

Sometirr,es the effect of the drug is l inearlyrelated to the number of receptor bound.In other cases, the effect increasesdisproportionately to the number ofreceptors occupied by drug.Receptors are said to be "spare" for a givenpharmacoloic response if a maximalresponse is elicited at an agonistconcentration that does not result in ful loccupancy of receptors.-

100%

Effect

0%

Documents

pharma slide 01