Pharmacology II Flashcards
most FDA approved drugs target which aspect of your body?
proteins
which proteins do drugs target?
receptors (agonist, antagonist, and inverse agonist), ion channels, enzymes, and carriers
agonist drugs mimic/block the effects of the endogenous agonists
mimic
antagonist drugs mimic/block the effects of the endogenous agonists
block
Kd
dissociation constant; concentration of drug for which 50% of receptors are occupied; direct reflection of affinity for the drug
x-axis
usually drug concentration
hill-langmuir equation
Y = [D]/ (Kd + [D]) Y (fraction bound to receptor) D = drug
the lower the Kd the more potent/efficacy the drug has
potent
potency
how much drug is needed for reaction
How would increased potency affect kd and affinity?
lower Kd = higher affinity
How would decreased potency affect kd and affinity?
higher kd = lower affinity
Does efficacy and potency correlate?
they do not necessarily correlate; there are drugs that can be more effective at lower potencies and vice versa
why does receptor occupancy not necessarily affect effectiveness?
signal amplification allows a smaller number of receptor occupancy for a larger reaction
receptor reserve
receptors that can bind agonist but do not have to to reach maximal effect
two types of antagonist drug molecules
competitive and noncompetitive
competitive antagonist
compete for the same spot as the endogenous molecule; binds reversibly
two types of non-competitive antagonist
- reversible 2. irreversible
how does a competitive antagonist affect the potency and efficacy?
decrease in potency same efficacy
how would a non-competitive antagonist affect potency and efficacy?
decrease in efficacy
full agonist
elicits the maximal response from its receptor
partial agonist
elicits sub-maximal response form its receptor
neutral antagonist
decreases endogenous agonist but has no effect itself
inverse agonist
inhibits the basal activity of a receptor in the absence of endogenous agoinist; can also be competitive antagonist and block the effects of endogenous agonists
inverse agonist and competitive antagonist examples
- metoprolol: cardio- hypertension 2. losartan: cardio- hypertension 3. famotidine- GI- histamine blocker 4. naloxone- neuro- emergency treatment for heroin/opiod overdose 5. risperidone GI- histamine blocker
dose-response curves are useful for describing effects that are continuous/quantal
continuous ex. pain, blood pressure, anxiety
what does a does curve mean when the variable is quantal?
the curve shows the % of patients; uses a curve to describe a population
therapeutic window
the dosage of drug from the minimum therapeutic effect to the minimum toxic does
Therapeutic index (TI)
TD50 (toxic drug concentration where 50% is bound to receptor)/ ED50 (effective drug concentration where 50 % is bound to the receptors) or LD50 (lethal) / ED50
higher or lower therapeutic index is better?
higher
Why would the sape of a dose-response curve be different for therapeutic versus toxic effects?
different receptors may accound for therapeutic and toxic effects
How is the therapeutic index affected if different receptors are used for therapeutic and toxic effects?
TI would grossly overestimate the safety of the drug
certain saftey factors (CSF)
LD1 (lethal dose one)/ TD99 (therapeutic effect 99)
higher is better
If you have drug A = 10 and drug B = 5 what is the overall synergy effect?
> 15
If you have drug A = 10 and drug B = 5 what is the overall additive effect?
15
If you have drug A = 10 and drug B = 5 what is the overall antagonist effect?
< 15
potentiation
when drug A has a therapeutic effect and drug B does not have any therapeutic effect but helps increase the therapeutic affect of drug A
example of potentiation
cephlasporin/penicillin and probenecid
tolerance/desensitizaton
reduced effect with continued use of drug over a period of time
tachyphylaxis
short-term tolerance/desensitization leaving durg less effective shortly after given due to desensitizatoin
casues of desensitization
- receptor inactivation - uncoupling from signaling cascade
- receptor internalization via endosomes
- receptor down regulation via lysosome and break up
how does tolerance/desensitization affect the dose response curve?
could decrease potency and eventually decrease eficacy
