Pharmacodynamics Flashcards
Pharmacodynamics
-concentration and effect relationship
-actions of drug on body
-receptor interaction
-efficacy, toxicity (dose-response)
-mech of therapeutic and toxic effects
PK PD venn diagram
-PK: dosage regimen
-both: drug exposure
-PD: effects
Importance of PK/PD
-relate patterns of response to drug admin following dosing
-rationale for drug design/selection/dosage regimen
-aid in design of protocols to view in vivo effects
Exposure
-any dose or drug input to the body or various measures of acute or integrated drug concentrations in plasma or other biological fluid
Reponse
-measure of pharmacologic observation
-desired vs harmful
Effect
-change in response from one time to another
-gonna use interchangably with “response” tho
Relating exposure to effect
-exposure: time vs concentration
-effect: % effect vs time
-combined: % effect vs concentration
Drug-receptor interactions
-form drug-receptor complex
=initiate response
Drug action is mediated by
-free drug concentrations
Effect equation
do i need to know??
Graded response
-continuous scale
-measured in single biologic unit (person)
-relates dose to INTENSITY of effect
Quantal response
-all or nothing effect
-measured in more than one individual
-relates dose to FREQ of effect
Graded dose-response relationship
-inc curve over time until it hits max
Clinical stress testing
-dobutamine for pt that cannot get on treadmill for cardiac stress test
-synthetic cholamine to assess inc in heart rate
-inc dose inc HR
Concentration-effect relationship (parameters)
-Emax: peak effect
-EC50: concentration for half max effect
Emax
-max effect
-NOT concentration units
EC50
-CONCENTRATION units
-concentration for half max response
Receptor parameter
-% receptors bound vs dose
-Bmax and kd
Doxorubicin
-cardiotoxin
-chemo
-quantal response
-heart either fails or it doesnt
-put population data together to get an individual graph
-how much can we give someone before they develop heart failure
Clinical quantal
-50mg per treatment * 8 treatments = 400mg lifetime dose
Efficacy (Emax)
-max effect
-Emax
Potency
-sensitivity to drug
-EC50
Agonist vs partial vs antagonist
-agonist: max effect
-partial: part effect
-antagonist: no effect
When an antagonist is added to an agonist
-make agonist less POTENT
-shifts curve right
Effect of kidney disease on PD
-Na secretion effect on plasma log
-dec response
-gonna need to inc dose or freq
effect of disease on PD
-effect response
Linking concentration to response
-GRAPHS HUH
-slide 45
Response vs time
-predicts response will decline linearly
-one-compart
-linear log-dose relationship
-dec in effect is impact by k (PK) and m (PD)
What happens to time course of response if k is increased
-Slope declines more quickly
-Eo unchanged
-m unchanged
-time course changed due to change in PK
What if dose is changed?
-slope same
-y-intercept diff
what could cause a change in m?
idk
Non-compartment PK/PD modeling
-PK: Cmax, AUC, fu
-PD: Cmax/MIC, AUC/MIC, t>MIC (time above MIC)
graph graph graph
slide. 50
PD models
-linear
-Emax
-Sigmoid Emax
Linear model
-Effect = Eo (intercept) + S(slope)*C(concentration)
Log-linear model
-effect = Eo + S * logC
Emax model
E=(Emax*C)/(EC50+C)
Sigmoid Emax model
E = (Emax * C^h)/(EC50^h + C^h)
-h is constant
-high h is gonna be steeper slope
-EC50 stays same
Ketamine example
-sigmoidal model
-S ketamine more effective
Direct effect model
-peak concentration happens around the same time as peak response
Dysequilibrium in concentration-effect relationship
-peak effect is NOT at same time as peak concentration
=LOOP
hysteresis loop
-delay in response causes graph to loop
Potential reasons for delay in response
-delay in drug reaching effect site/biophase
-production of active metabolite that produces response similar to parent
-up-regulation of receptor response or sensitixation
-indirect effect
