Block 1 Pharmacodynamics

Question 1

5 major signaling mechanisms

Answer 1

Intracellular rec, transmembrane rec, tm cytokine rec, lig-gated ion channels, GPCR & second messengers

Question 2

Intracellular receptor drugs

Answer 2

Steroid hormones, thyroid hormone, vit D

Question 3

TM enzyme receptor drugs

Answer 3

Insulin, EGF

Question 4

TM cytokine receptor drugs

Answer 4

Growth/diff regulators, GH, erythropoietin, interferon

Question 5

Ligand-gated ion channel drugs

Answer 5

NT-mimetics like Ach, 5-HT, GABA, glutamate

Question 6

GPCR & second messenger drugs

Answer 6

Sympathomimetic drugs

Question 7

Gs receptor substrates and MOA

Answer 7

b-adrenergic, glucagon, 5-HT, histamine

Inc AC = inc cAMP

Question 8

Gi receptor substrates and MOA

Answer 8

a2-adrenergic, ACh (musc), opioids, 5-HT

Dec AC = dec cAMP

Question 9

Gq receptor substrates and MOA

Answer 9

ACh (musc), bombesin, 5-HT

Inc PLC = inc IP3, DAG, Ca2+

Question 10

Epinephrine

Answer 10

alpha-receptor agonist

Question 11

Albuterol

Answer 11

beta-receptor agonist

Question 12

Morphine, hydrocodone

Answer 12

Opioid analgesic, Gi-R agonist

Question 13

Atenolol

Answer 13

B-blocker (b-receptor antagonist)

Question 14

Tamoxifen

Answer 14

ER antagonist (nuclear) for breast cx

Question 15

ACE inhibitor

Answer 15

Enzyme inhibitor for heart failure & HTN

Question 16

Statins

Answer 16

HMG-CoA reductase enzyme inhibitor for hypercholesterolemia

Question 17

Ca-channel blocker

Answer 17

Ion channel blocker for HTN & angina

Question 18

SSRI

Answer 18

NT inhibitor for depression

Question 19

Potency

Answer 19

Concentration of drug required to produce particular effect

Question 20

Median effective dose (ED50)

Answer 20

Dose that produces 50% of maximal response

Question 21

Median lethal dose (LD50)

Answer 21

Dose that causes death in 50% of subjects

Question 22

Therapeutic index (TI)

Answer 22

Ratio of LD50 to ED50, higher TI = safer, smaller risk of OD

Question 23

Dose-response relationship

Answer 23

Relationship between concentration of drug at receptor site and magnitude of response

Question 24

Graded dose-response curve vs. quantal dose-response curve

Answer 24

G: tracks percent of maximum response versus dose
Q: tracks percent of subjects with response versus dose

Question 25

How does dose-response curve change in presence of competitive and non-competitive antagonists?

Answer 25

Comp: increase dose required for ED50, no change in max effect Non: increase dose more than comp and decrease max effect

Question 26

Tolerance

Answer 26

Same dose of drug given repeatedly loses effect, greater doses needed to provide same effect *CNS or hormone-affecting drugs must be tapered over time

Question 27

Tachyphylaxis & example

Answer 27

Acute tolerance - oxymetazolone (Afrin) for nasal congestion

Question 28

Pharmacodynamic tolerance & example

Answer 28

Down regulation of receptors (dec synth) - morphine

Question 29

Pharmacokinetic tolerance & example

Answer 29

Up regulation of metabolic enzymes (inc synth) - carbamazepine (Tegretol) for seizure control *Up regulates P450 = inc met of self and other drugs

Question 30

Stereoisomer variation example

Answer 30

S-warfarin is 5x more active than R-warfarin & is metabolized by CYP 2C9 instead of CYP 1A2, 3A4

Question 31

Pharmacogenetics vs. pharmacogenomics

Answer 31

Genetics: study of genetic basis for variation in drug response Genomics: use of tools to assess multigenic determinants of drug response

Question 32

Extensive, intermediate, poor, and ultra rapid metabolizers

Answer 32

Ex: normal, homozygous for WT CYP450 allele Int: hetero for WT and variant allele Poor: homo for variant Ultra: multiple copies of WT allele

Question 33

Example of variations in CYP450 metabolism

Answer 33

~20% Asians are poor 2C19 = no Dilantin b/c inc toxicity and drug intxn risk 7-10% whites poor 2D6

Question 34

Adverse drug reaction categories & dose-response relationship of each

Answer 34

Allergic (none), toxic (dose-dep), ideosyncratic (unable to predict, genetically based), alteration of biological or metabolic system

Question 35

Example of ADR by altering biological or metabolic system

Answer 35

Alteration of bacterial floor by antibiotics | Inhibition of vitamin absorption or synthesis

Question 36

Drug synergism

Answer 36

Use multiple drugs to increase effect vs. increasing dose Ex: multiple antibiotics or HIV meds Response: potentiation > summation > individual > antagonism