Pharm 101

eesohbel's version from 2015-08-06 16:56

Enzyme kinetics

Question Answer
Kminversely related to the affinity of the enzyme for its substrate
lower Kmmeans higher enzyme affinity
Vmaxdirectly proportion to enzyme concentration
slope in lineweaver-burk plotKm/Vmax
y intercept in lineweaver burke1/Vmax
x intercept in lineweaver burk1/-Km
increased y intercept in lineweaver burklower Vmax
further to the right the x-intercept (closer to zero)greater Km and lower the affinity
reversible competitive inhibitors and Kmincreased Km and therefore decrease potency
irreversible competitive inhibitors and Vmaxdecrease Vmax and therefore decrease efficacy
noncompetitive inhibitors and Vmaxdecrease Vmax and therefore decrease efficacy
distinguishing feature for noncompetitive antagonistsED50 is unchanged, but Emax decreases


Question Answer
low volume of distribution drug typecharged molecules
low volume of distribution compartmentblood
medium volume of distribution drug typesmall hydrophilic molecules
medium volume of distribution compartmentECF
high volume of distribution drug typesmall lipophilic molecules
high volume of distribution compartmentall tissues including fat
Sublingual administrationUseful for drugs with high-first pass metabolism like nitroglycerin, since hepatic metabolism is bypassed
First order velocityVelocity of reaction is directly proportional to the concentration of substrate; the more substrate there is, the faster the reaction occurs
Zero order kineticsReaction velocity is completely independent of substrate concentration; the only way to speed up the reaction would be to add more enzyme so that there are more binding sites for the substrate
First order eliminationConstant FRACTION of drug is eliminated per unit time; most drugs
Zero order eliminationConstant AMOUNT of drug is eliminated per unit time; PEAs are shaped like zeros: Phenytoin, Ethanol, Aspirin (Straight line graph). Negative slope
what happens to maintenance dose and loading dose in renal or liver diseasemaintenance dose decreases and loading dose is unchanged
Phase I reactionsHydrolysis, Oxidation, Reduction
Phase I metabolitesSlightly polar, water-soluble, active
Phase II reactionsMethylation, acteylation, glucuronidation, sulfation (conjugation rxns)
Phase II metabolitesNonpolar (do not cross cell membranes readily), inactive, easy to excrete in urine
1 half live amount eliminated50%
2 half lives amount eliminated75%
3 half lives amount eliminated87.5%
4 half lives amount eliminated93.75%
5 half lives amount eliminated100!
3.3 half lives amount eliminated90%
weak base drugsamphetamines. treat overdose with ammonium chloride
weak acid drugsphenobarbital, methotrexate, aspirin, TCAS. tread over dose with bicarbonate


Question Answer
CL(0.7 x Vd)/t1/2
t1/2(Vd x .7)/CL
Vd(amount of drug given in IV form)/[drug in plasma]
CL rate of elimination of drug/[drug in plasma]
LD Css x Vd
MDCss x CL

Efficacy versus Potency

Question Answer
left shifting of EC 50increases potency
Full agonistsoccupy receptors to cause maximal activation; intrinsic activity = 1
Partial agonistscan occupy receptors but cannot elicit a maximal response. intrinsic activity = <1
Competitive antagonists Shift the dose-response curve for the agonist to the RIGHT increasing Km; more agonist is required to elicit a response; Vmax unchanged
Noncompetitive antagonistsSame Km; Lower Vmax
agonist with competitive antagonistshifts curve to the right decreased potency, no change in efficacy.
examples of agonist with competitive antagonistbenzo plus flumanezil
agonist with non competitive antagonistshifts curve down decreased efficacy.
examples of agonist with non competitive antagnoistNE plus phenoxybenzamine
partial agonistdecreased Vmax
Safer drugs have highertherapeutic indexes
drug with lower therapeutic indexesdigoxin, lithium, theophylline and warfarin


Question Answer
competitive antagonistshifts curve to right and decreases potency
noncompetitive antagonistshifts curve down (decreases efficacy). Cannot be overcome by increasing agonist substrate concentration.
partial agonist alonedecreases efficacy.

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