Principles

Question 1

Km

Answer 1

Inversely related to the affinity of the enzyme for its substrate.

The greater the K, lower the affinity

Question 2

Lineweaver-Burk plot

Answer 2

X intercept = -1/Km

Y intercept = 1/Vmax

Question 3

Enzyme inhibition

Answer 3

competititve inhibitor: reduces potency

non competitive inhibitor: reduces efficacy

Question 4

Volume of distribution

Answer 4

Vd=amount of drug in the body/plasma drug concentration

Vd of plasma protein-bound drugs can be altered by liver and kidney disease (reduced protein binding, increased Vd)

Vd = low (4-8L), blood, large/charged molecule, plasma protein bound

Vd= mid, ECF, small hydrophilic molecules

Vd= high, all tissues, small lipophilic, esp if bound to tissue proteins.

Question 5

Half life

Answer 5

t1/2= 0.7x Vd/CL

Question 6

Clearance (CL)

Answer 6

Relates the rate of elimination to the plasma concentration.
Clearance may be impaired with defects in cardiac, hepatic, and renal function.

CL=rate of elimination of drug/plasma drug concentration
CL=Vd x Ke (elmination constant)

Question 7

Dosage calculation

Answer 7

Cp= target plasma concentration

Loading dose =Cp x Vd/F
Maintenance dose = Cp x CL/F

In renal or liver disease, maintenance dose decreases and loading dose is unchanged.

Time to steady state depends primarily on t1/2 and is independent of dosing frequency or size.

Question 8

Zero order elimination

Answer 8

Capacity limited elimination

Phenytoin, ethanol, and aspirin (at toxic concentration) “PEA=round shaped like 0 in zero order”

Question 9

First order elimination

Answer 9

Flow-dependent elimination

Constant FRACTION of drug eliminated per unit time

Question 10

Weak acids

Answer 10

Phenobarbital, MTX, aspirin

Trapped in basic environment, so treat with bicarb

Question 11

Weak bases

Answer 11

Amphetamine

Trapped in acidic environment, so treat with ammonium chloride

Question 12

Urine pH and drug elimination

Answer 12

Ionized species are trapped in urine and cleared quickly.

Neutral forms can be reabsorbed

Question 13

Drug metabolism: phase I

Answer 13

reduction, oxidation, hydrolysis with cytochorme p450
usually yields slightly polar water soluble metabolites (often still active)

GERIATRIC patients lose phase 1 first

Question 14

Drug metabolism: phase II

Answer 14

Conjugation: glucoronidation, acethylation, sulfation
“Geriatric patients still have GAS”

Usually yield very polar, inactive metabolite, then renally excreted.

Slow acetylators have greater side effects from certain drugs because of reduced rate of metabolism.

Question 15

Efficacy

Answer 15

Maximal effect of drug

High efficacy drugs are analgesic, antibiotics, antihistamine, and decongestions.

Partial agonists less efficacy than full agonists.

Question 16

Potency

Answer 16

Amount of drug needed for a given effect
Increase potency, increased affinity for receptor

High potent drugs: chemo, antiHTN, antilipid.

Question 17

Therapeutic index

Answer 17

median lethal dose/median effective dose

TILE = therapeutic indenx =LD50/ED50

Safter drugs with high TI valuves.

Drugs with low TI: digoxin, lithium, theophylline, and warfarin.

Therapeutic window: measure of drug safety. Range of minimum effective dose to minimum toxic dose.

Question 18

CNS AND PNS

Answer 18

Parasympathetic: M AchR: cardiac and smooth muscle, gland cells, nerve terminals

Sympathetic: M AchR: sweat glands

Sympathetic: NE alpha beta: cardiac and smooth muscle, gland cells, nerve terminals

Sympathetic: D1: renal vasculature, smooth muscle

Somatic: N AchR: skeletal muscle

All use N Ach R for pregangionic.

Question 19

ACH receptor

Answer 19

Nicotinic Ach: and Na/K channels, found in autonomic ganglia or neuromusclar junction.

Muscarininc Ach: G coupled proteins. 5 subtypes