Block 1 Pharmacodynamics Flashcards
5 major signaling mechanisms
Intracellular rec, transmembrane rec, tm cytokine rec, lig-gated ion channels, GPCR & second messengers
Intracellular receptor drugs
Steroid hormones, thyroid hormone, vit D
TM enzyme receptor drugs
Insulin, EGF
TM cytokine receptor drugs
Growth/diff regulators, GH, erythropoietin, interferon
Ligand-gated ion channel drugs
NT-mimetics like Ach, 5-HT, GABA, glutamate
GPCR & second messenger drugs
Sympathomimetic drugs
Gs receptor substrates and MOA
b-adrenergic, glucagon, 5-HT, histamine
Inc AC = inc cAMP
Gi receptor substrates and MOA
a2-adrenergic, ACh (musc), opioids, 5-HT
Dec AC = dec cAMP
Gq receptor substrates and MOA
ACh (musc), bombesin, 5-HT
Inc PLC = inc IP3, DAG, Ca2+
Epinephrine
alpha-receptor agonist
Albuterol
beta-receptor agonist
Morphine, hydrocodone
Opioid analgesic, Gi-R agonist
Atenolol
B-blocker (b-receptor antagonist)
Tamoxifen
ER antagonist (nuclear) for breast cx
ACE inhibitor
Enzyme inhibitor for heart failure & HTN
Statins
HMG-CoA reductase enzyme inhibitor for hypercholesterolemia
Ca-channel blocker
Ion channel blocker for HTN & angina
SSRI
NT inhibitor for depression
Potency
Concentration of drug required to produce particular effect
Median effective dose (ED50)
Dose that produces 50% of maximal response
Median lethal dose (LD50)
Dose that causes death in 50% of subjects
Therapeutic index (TI)
Ratio of LD50 to ED50, higher TI = safer, smaller risk of OD
Dose-response relationship
Relationship between concentration of drug at receptor site and magnitude of response
Graded dose-response curve vs. quantal dose-response curve
G: tracks percent of maximum response versus dose
Q: tracks percent of subjects with response versus dose
How does dose-response curve change in presence of competitive and non-competitive antagonists?
Comp: increase dose required for ED50, no change in max effect
Non: increase dose more than comp and decrease max effect
Tolerance
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
Tachyphylaxis & example
Acute tolerance - oxymetazolone (Afrin) for nasal congestion
Pharmacodynamic tolerance & example
Down regulation of receptors (dec synth) - morphine
Pharmacokinetic tolerance & example
Up regulation of metabolic enzymes (inc synth) - carbamazepine (Tegretol) for seizure control
*Up regulates P450 = inc met of self and other drugs
Stereoisomer variation example
S-warfarin is 5x more active than R-warfarin & is metabolized by CYP 2C9 instead of CYP 1A2, 3A4
Pharmacogenetics vs. pharmacogenomics
Genetics: study of genetic basis for variation in drug response
Genomics: use of tools to assess multigenic determinants of drug response
Extensive, intermediate, poor, and ultra rapid metabolizers
Ex: normal, homozygous for WT CYP450 allele
Int: hetero for WT and variant allele
Poor: homo for variant
Ultra: multiple copies of WT allele
Example of variations in CYP450 metabolism
~20% Asians are poor 2C19 = no Dilantin b/c inc toxicity and drug intxn risk
7-10% whites poor 2D6
Adverse drug reaction categories & dose-response relationship of each
Allergic (none), toxic (dose-dep), ideosyncratic (unable to predict, genetically based), alteration of biological or metabolic system
Example of ADR by altering biological or metabolic system
Alteration of bacterial floor by antibiotics
Inhibition of vitamin absorption or synthesis
Drug synergism
Use multiple drugs to increase effect vs. increasing dose
Ex: multiple antibiotics or HIV meds
Response: potentiation > summation > individual > antagonism
