PK and PD General principles

Question 1

Name an example of a Physical mechanism of action by drug.

Answer 1

Activated charcoal (adsorbs substance and prevents absorption)

Mannitol (osmotic activity)

Question 2

Name 2 examples of Chemical mechanism of drugs.

Answer 2

Antacids (neutralizes gastric acids)
Chelating agents (inactivates toxic metals)

Question 3

Drugs that bind R have affinity for receptor and Intrinsic activity, what does this mean?

Answer 3

Affinity - ability to bind R

Intrinsic activity - ability to change something on R

Question 4

Drugs are classified based on Affinity and IA. What does Agonists, antagonists, inverse agonists and partial agonists have?

Answer 4

Agonist: + Affinity, + IA

Antagonist: +Affinity, - IA

Inverse agonist: + Affinity and Negative IA

Partial agonist: +Affinity, sub-maximal IA

Question 5

Name example of Inverse agonist.

Answer 5

Bicuculline (binds GABA-A receptor and stimulates neurons instead of inhibiting them).

Question 6

What is definition of drug action and drug effect?

Answer 6

Action - conformational change caused

Effect - biological function as consequence of drug

Question 7

DRC that has a parallel shift means…?
DRC that has change in height of curve means…?
Change on slope of curve means…?

Answer 7

Changes in Potency of drug
Change in Efficacy of drug
Steep slope (small change in drug causes dramatic response), flat slope (large changes in dose to get some results)

Question 8

Give an example of Synergism between drugs.

Answer 8

Levodopa + Carbidopa

Question 9

Give 2 examples of Physiological antagonism.

Answer 9

1. Epinephrine + Histamine with respect to smooth muscle

2. Steroids + Insulin with respect to blood sugar

Question 10

A right parallel shift in DRC means _____ was used.

Answer 10

Competitive antagonist

Question 11

A decrease in efficacy in DRC can be caused by___, ___, ___.

Answer 11

Non-competitive antagonist
Partial agonist
Irreversible antagonist

Question 12

Explain Tachyphylaxis.

Answer 12

Rapid desensitization produced by repeated small/frequent doses of drug, rendering it ineffective.

Question 13

Spare receptors are said to exist when ____>____.

Answer 13

EC50 > Kd

Question 14

Drugs that undergo First pass metabolism will ____ their Bioavailability.

Answer 14

decrease BA

Question 15

Bioavailability (F) is ___ for IV drugs and ___ for other routes.

Answer 15

100%

<100%

Question 16

____ binds plasma proteins, meaning 99% of drug stays in plasma.
___ (anti-malarial drug) doesn’t bind plasma proteins, which means >99% will go inside tissues.

Answer 16

Warfarin

Chloroquine

Question 17

Drugs that bind plasma proteins ____ their Vd (volume of distribution).

Answer 17

Decrease Vd

Question 18

Phase I metabolism makes drug more hydrophilic, name some reactions.

Answer 18

OXIDATION
reduction
hydrolysis
cyclization
decyclization

Question 19

Phase II metabolism adds conjugates to drug, name some reactions

Answer 19

ACETYLATION
GLUTATHIONE CONJUGATION 
Glucoronidation (MC in body)
Sulfating
Methylation

Question 20

Name CYP inducers.

Answer 20

Rifampin
Barbiturates
Phenytoin
Alcohol

Question 21

Name CYP inhibitors.

Answer 21

Cimetidine

Grapefruit juice

Question 22

How does CYP induction/inhibition affect Pro-drugs.

Answer 22

CYP inducers –> increase concentration of active drug

CYP inhibitors –> decrease concentration of active drug

Question 23

P-glycoproteins expel drugs from intestinal mucosa to lumen, increasing excretion. Name 2 examples of P-gp inhibitors.

Answer 23

Verapamil

Grapefruit juice

Question 24

Renal excretion depends on ___, ___, ___. Name factors they are affected by.

Answer 24

glomerular filtration (size dependent)

tubular reabsorption (ionization dependent, NON-IONIZED/lipid soluble substances are reabsorbed)

tubular secretion (Indépendant of PP binding, lipid solubility)

Question 25

Alkalization of urine can be achieved by… in treatment of Barbiturate or Aspirin poisoning.

Answer 25

Sodium bicarbonate

Acetazolamide

Question 26

Acidification of urine can be achieved by…in treatment of Morphine or Amphetamine poisoning.

Answer 26

Ammonium chloride
Vitamine C
Cranberry juice

Question 27

Probenecid affects concentration of Penicillin by affecting its ___.

Answer 27

Tubular secretion

Maintains it in blood for longer, increasing [ ].

Question 28

Probenecid ___ the effectiveness of diuretics (e.g. Furosemide).

Answer 28

Decreases effectiveness.

Diuretics work by binding pumps in tubular lumen, if maintained in blood, can’t act on their targets.

Question 29

Zero order drugs (ex. Alcohol) get excreted as ______ per unit time.
First order drugs get excreted as _____ per unit time.

Answer 29

constant amount

constant fraction (%)

Question 30

Clearance of drug predicts rate of elimination. If Cl=GFR means ____, Cl > GFR means _____, Cl < GFR means ____.

Answer 30

no active secretion or absorption
Drug has reabsorption
Drug has secretion

Question 31

How many half lives are required to eliminate >97% of drug?

Answer 31

5 t1/2

Question 32

How many doses does it take to achieve Css (constant steady state) of drug in body?

Answer 32

5 or more doses