Pharmacodynamics - part 1 Flashcards
(43 cards)
Pharamcokinetics includes:
Absorption
Distribution
Metabolism
Excretion
These factors take a dose of drug and determine the drug concentration in target organ over time.
Pharmacodynamics includes:
Receptor binding
Signal transduction
Physiological effect
These factors use the drug concentration in target over time to determine the mechanism + magnitude of drug effect.
What is the therapeutic window?
The drug concentration above lack of effect (therapeutic failure) and below side effects (drug excess).
While over the counter drugs have a _________ therapeutic window, prescription drugs have a ________ therapeutic window.
Larger; narrow
The side effects/toxicity a drug can exert and pass the therapeutic window may be due to:
1) Same mechanism/action as the therapeutic effect but HIGHER INTENSITY
2) Same mechanism/action but NON-TARGET TISSUE
3) Different mechanism than the therapeutic effect
In simpler terms, PD is how the ________ affects the _________, while Pk is how the __________ affects the ________.
substance; organism
organism; substance
What are three methods a xenobiotic can make use of to induce changes in the organism?
1) Xenobiotic-receptor interactions (agonism, antagonism, inhibition, etc)
2) Physical actions (osmotic activity, effects of membrane)
3) Chemical actions (antacids, chelating agents, pro/antioxidants)
2/3 not as specific like 1.
As a mechanism of action, a drug typically exerts effects on the molecular level, which induces cellular changes, leading to tissue/organ changes that affect the whole organism (systemic).
Briefly use these terms to describe the effects of Nifedipine, Verapamil, Diltiazem (Ca2+ ion blockers).
Usually calcium ions go and bind to calmodulin which causes contraction in tissues/organs, leading to an increased blood pressure.
This xenobiotic:
Molecular: blocks calcium ion channels
Cellular: calcium can no longer bind to calmodulin
Tissue/organ: contraction is inhibited
Systemic: blood pressure decreases
What is a dose-response relationship?
The relationship between the concentration of a xenobiotic at the receptor site (in vitro) or in the dose/blood (clinic) and the magnitude of response.
Concentration is in reference to bioavailability (in blood or SOA).
What are the two types of dose response relationships?
1) Graded (continuous; describe the effect of various doses of a drug on an individual)
2) Quantal (all-or-none; respond or not - show the effect of various doses of a drug on a population of individuals)
A graded dose response is the relationship among dose/concentration, target/receptor “activation”, and the ____________ of the response.
The response elicited with each dose is plotted against the _____ dose/concentration and can be described as ______ _______________.
Magnitude
Log; % of Maximal Response
A quantal dose response is the relationship among dose/concentration and the ________ of the response.
The response elicited with each is plotted against the _____ dose and can be described as _________________.
Frequency
log; % of population
Responses generated with increasing dose of a drug/toxin described as the cumulative % of subjects exhibiting a defined all-or-none effect.
Match the following terms to their definition:
1) Emax
2) ED50
3) Tmax
4) TD50
5) LD50
A) MEDIAN EFFECTIVE DOSE the dose that produces 50% of the Emax
B) MEDIAN TOXIC DOSE - the dose that produces 50% of the Tmax
C) MEDIAN LETHAL DOSE - if the effect is death, ED50 is referred to as LD50.
D) the maximal response produced when the targeted interaction is saturated (all receptors occupied)
E) the maximum toxic response
Emax: the maximal response produced when the targeted interaction is saturated (all receptors occupied)
ED50: MEDIAN EFFECTIVE DOSE - the dose that produces 50% of the Emax
Tmax: the maximum toxic response
TD50: MEDIAN TOXIC DOSE - the dose that produces 50% of the Tmax
LD50: MEDIAN LETHAL DOSE - if the effect is death, ED50 is referred to as LD50.
(T/F) LD50s are calculated and expressed relative to a population; Quantal relationship (yes/no).
True!
What is NOEL? What is NOAEL?
NOEL: no observed effect level
NOAEL: no observed adverse effect level
In a graded dose response, first there is _______ and then a _________ and then the _______ effect.
Where is NOAEL?
NOEL; threshold, maximal
NOAEL is between the threshold and the maximum effect where ED50 is.
Some drugs can have a threshold and some do not. What is the difference between the two?
Having a threshold means that the patient can tolerate the drug for a little without a response. It is after crossing that threshold where the effects start showing.
Without a threshold, the patient is not able to tolerate without a response. The response is present right away.
Describe potency: how it is expressed, how it is determined, what it is related to, etc.
Potency is generally expressed as EC50 (dose that produces 50% of the maximal effect).
It is determined by the affinity of the xenobiotic for its target. A drug with high affinity requires lower dose to occupy more receptors.
Potency is inversely related to ED50; a drug with ED50 of 5 mg is 10x more potent than a drug with ED50 of 50mg.
Efficacy is the _________ response produced by a drug.
A full agonist has a ________ efficacy.
An antagonist has a ________ efficacy.
Maximal
Maximal; partial agonists have below 100-50%.
No
Drugs can have the ______ efficacy but a _______ potency or vice versa.
same; different
more potent drug; less dose needed to reach 50% of the max efficacy
less potent drug: more dose needed to reach 50% of the same max efficacy
What is IC50?
The concentration of an inhibitor where the response is reduced by half.
The smaller the IC50 (less drug to inhibit more), the greater the potency of the drug.
What is the slope in graded dose response curves?
High slope means ________ concentration sensitive; a ________ therapeutic window.
Low slope means _______ concentration sensitive; a _________ therapeutic window.
The change in response per unit dose/plasma concentration.
HIGHLY: narrow (small changes = big differences)
MIDLY; broader (OTC drugs)
(T/F) In the slopes of graded dose response curves, a high slope drug means individual variation is less important, while a low slope drug means individual variation more import.
False!
High slope: individual variation important; need for personalized dose titration
Low slope: individual variation less import; common dosing schedules
Suppose drug A has a slope of 1.0, drug B has a slope of 1.5, and drug C has a slope of 0.5 in a graded dose-response curve.
Which drug is most likely to be an OTC drug?
Which drug is least likely to be an OCT drug?
Drug C (lowest slope) most likely to be an OTC drug.
Drug B (highest slope) least likely to be an OTC drug.
The higher the slope, the higher the sensitive to dose. Less drug = more changes. Therapeutic window narrow.
