Pharmacodynamics Flashcards
what determines drug half-life?
Vd and clearance of drug
how do you determine the halflife? (what is the equation?)
T1/2= (0.7*Vd/Cl)
what is accumulation factor?
when drug is given repeatedly and cumulate to reach a steady state level, must be considered in calculating loading and maintenance dose
when is 95% of drug cleared?
4.3 half-lives
why is it important to consider potency when dosing a drug?
high potency drugs (ACE inhibitors) will will have a very high effect in the body even after multiple half lives, when dosing you need to know that happens to the effect as the half lives pass (think if the ACE example, 87.5% of drug was gone but it still had 75% effect)
how does half life length impact pharmacodynamic effect?
it doesn’t. they are separate principals
what is an acute effect on drug action?
drug effect occurs within minutes to hours (effect is proportional to concentration)
what is important to consider with delayed effect drugs?
effect takes days or weeks
what might cause a delay in drug action?
delay in distribution, turnover of the enzyme/receptors or accumulation factor needed to reach steady state
what are cumulative effects?
irreversible effects that produce higher drug peak and saturate uptake mechanism (example chemo drugs on DNA biding results in cytotoxic effect)
how does tolerance shift the effect curve?
to the right (sensitivity shifts to the left)
what are steady stat plasma concentrations used for?
calculating loading and maintenance doses
what is the therapeutic window?
plasma concertation between MEC desired and adverse
is the pharmacodynamic effect lost after concentration falls below MEC desired?
not necessarily but it is no longer in the therapeutic window
how do you calculate the loading dose?
Vd*TC/bioavailability
(tc is target concentration)
what kind of drugs can you give once a day therapeutic window wise?
large therapeutic window
what is different about the plasma concentration graph for IV vs oral?
both average to the same but oral has high peaks and low troughs and IV is constant (if you did 3x a day dose might be better but you have to be realistic about what a pt will actually maintain which is why most are one a day when can be)
how do you calculate the dosing rate?
CL*TC/bioavailability
what is an agonist drug?
a chemical that upon binding triggers a response
(endogenous example: hormone, neurotransmitter, cytokines)
(drug ex LDOPA, morphine)
what type of effect is seen by signaling?
short or long term
what is the speed of extracellular signaling?
faster than ones that go into the nucleus to do protein syn
what does receptor occupancy indicate?
magnitude of the effect depends of affinity and intrinsic activity of the drug
what must occur for the effect size to increase?
the numbers of receptors bound with drug must increase or the intrinsic activity must increase
what kind of drugs are full or strong agonists?
those with high biding affinity
what is EC50?
need 50% of concentration to get 50% effect
what is Kd?
where 50% of the binding sites are occupied by the drug
what effect does high Kd have on affinity?
low affinity
(low Kd=high affinity)
a drug at E max is a _____
full agonist
what do graded response curves show?
differences in potency and efficacy of different drugs
what does a shift to the left on a graded response curve indicate?
higher potency (Kd is less)
on the graded response curve what shows the efficacy?
the highest point on the curve
(on slide 66 both have same efficacy in pic 1 but in 2 X is the highest Z is lowest)
higher intrinsic activity means higher ____
efficacy
what are non competitive antagonists?
irreversible antagonists that decrease both efficacy and potency (shift curve down and right)
what do competitive antagonists do?
reversible, shift curve to right, efficacy can be the same if you get enough of the agonist to override the competitive, but does not effect the efficacy of the agonist
what type of antagonist is more common?
competitive (most drugs are comp) because reversibility is so important for safety
what are inverse agonists?
negative intrinsic capability, induces increases in something other than the what is more commonly targeted by agonists
go over slide70 with the allosteric activators and inhibitors graphs
!!!
what is the therapeutic index?
ratio of Lethal dose to effective dose for a given measure of drug safety
what kind of therapeutic index does a safe drug have?
high
(unsafe drugs very low)
how is the effective dose determined?
median effective dose is where 50% of individuals have a therapeutic effect
how is EC50 determined?
drug concentration that produces 50% of max response
How should drugs be dosed?
lowest dose possible to produce acceptable benefit
what are adjunctive drugs?
drugs acting through a different receptor mechanism may allow clinician to lower the initial dose, imp if toxicity of the drug is high (ex use of immunosuppressive agents with glucocorticoid to treat inflammatory disorder)
what is selectivity of drugs?
drug action may increase by manipulating concentration of receptors available in different parts of the buy (taking the drug from a different method)
a quantal dose curve plots :
outcome occurrence in population against he drug dose
how do lipophilic agonists activate responses?
pass through the membrane and bind to nuclear receptors allowing for intracellular signaling and gene transcription
what are ionotropic receptors?
slow ions to traverse the membrane depolarize/hyperpolarize membranes
describe the second messenger system that works through PLC? which G protein is it?
gaq protein, PLC, PIP2, DAG + IP3
DAG: PK-C
IP3: Ca efflux (go signal smooth muscle reaction VASOCONSTRICTION)
describe the second messenger system that works through adenylate cyclase? which G protein is it?
Gas, AC, cAMP, gAMP
(VASODILATION)
what is physiological antagonism?
when you have a drug like a glucocorticoid, raising blood sugar but the body reacts by secreting insulin to stop or reduce those effects
what is pharmacological antagonism?
when you have a drug that blocks another drug
what is buprenorphine?
partial agonist that helps with the withdrawal, gives some euphoria and helps to prevent the pt from using harder drugs because it does not allow them to have the full effect of the drug
what should you consider when considering drug selection?
- is the drug clinically indicated for a particular use. need to provide reason to provide the drug (some use off label if a drug has a desired anterior effect)
- mechanism of action
- adverse effects
- contradictions
(review this slide again for details 85)
