KINETIC/DYNAMICS CUDDYSTUDY Flashcards
(30 cards)
Give a definition for pharmacokinetics and pharmacodynamics and sketch an illustration that supports your
definitions.
Pharmacokinetic is the bodys effect on the drug while pharmacodynamics is the drugs effect on the body.
The graphic should include absorption to the systemic system, elimination by kidneys/liver, distribution to tissues. The pharmodynamics should include…
Be able to identify the differences between full, inverse and partial agonists.
full results in max efficacy, inverse results in decreased efficacy and partial results in positive efficacy but not max. partial can displace full.
Given a plot with ≥2 drugs, be able to rank order the drugs from least to most potent
most potent would be on the left for a graded dose response graph
Given a plot with ≥2 drugs, be able to rank order the drugs from highest to lowest efficacy
on a graded graph it would be the one that is shortest and plateus the lowest on y axis
Be able to define and interpret the concept of therapeutic index
therapeutic index is the ratio of lethal dose to the effective dose. large is desired for drug risks.
Be able to define and distinguish between a graded and quantal dose-response curve
graded is sigmoidal with response vs dose
quantal is bell shaped with frequency vs dose and has a cumulative percent
Know the difference between potency and efficacy and be able to illustrate it using a drug concentration –
response plot
potency is a relative term comparing the dose required for one drug compared to another drug for a given effectiveness (ask what dose?). efficacy refers to what kind of response is achieved given one drug (ask how high?)
Give a definition for therapeutic index (TI) and be able to apply the TI concept
Therapeutic index is the ratio of lethal dose to effective dose. High Ti is clinical more safe.
Be able to define and distinguish between drug tolerance and drug tachyphylaxis
Drug tolerance is a hyporeactivity to drugs due to chronic exposure whereas tachyphylaxis is an acute tolerance of drugs meaning that quick hyporeactivity occurs and then resets when not given. tolerance is much longer to develop and get rid of.
Be able to identify the differences between reversible and nonreversible antagonists – give two examples of
each
reversible can be outcompeted by agonist while irreversible cannot. examples: Alpha blocker are Aspirin for non reversible binding to platelets.
Give a definition of a drug which obeys first-order kinetics and give one example – recognize 1st order from a log concentration versus time plot.
Most drugs so adderol. 1st order will be a log and have a straight line down with slope=ke with con vs. time. The steeper the ke the lower the halflife
Be able to explain what factors influence the renal clearance of a drug (at least three factors)
filtration - Large protein bound drugs don’t filter
secretion- protein bound weak acids and some bases
reabsorption - lipid soluble unionized
Be familiar with the cytochrome P 450 system as it applies to drug-drug interactions. Know and understand the important generalizations covered in class and within the PowerPoint
Cytochrome P 450 are major group of enzymes involved in drug metabolism (and endogenous metabolism).
Generalizations:
- some substrates are inhibitors of SAME enzyme
- some inhibitors affect >1 isozyme
- some substrates are metabolized by >1 isozyme
- doses magnitude matter ( one inhibitor at one dose may not inhibit another enzyme)
- isomers in racemic mixtures tend to metabolized by different p450s
IMPORTANT Be able to estimate drug half-life and volume of distribution from a drug concentration –time plot
half life = 0.693 ( Vd/Cl) (also half life = 0.693/ke)
Pick a point and half the y axis value and then draw two lines straight down and get the hours.
Be able to predict steady-state drug concentration given drug half-life and the concentration achieved after a
single initial dose (the drug accumulation concept)
essentially if drug given with accumulation is the same as half life simply double the peak plasma con and the half life concentration to get steady state values
Be able to define the first-pass concept and be able to distinguish a low first-pass drug and a high first-pass drug
First pass ONLY is relevant for oral administration and it refers to the liver metabolizing drug before it can reach the systematic circulation greatly reducing concentration. It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, pethidine, cannabis, cimetidine, lidocaine, and nitroglycerin. F is a measure.
Be able to define what is meant by bioavailability and bioequivalence
Bioavailability relates to extent and rate that a drug is able to reach the systematic circulation while bioequivalence is lack of significant difference in rate and extent between two drugs then they can be considered bioequiv
Be able to define and calculate absolute and relative bioavailability
Absolute bioavailability = Fraction of drug administered which becomes systemically available. Comparing an oral dose to and an intravenous dose of a drug. Bioavailability = AUC PO/AUC IV = F = fraction of the dose that is systemically avaliable
Relative bioavailability = AUC PO Test/ AUC PO standard. Asks Is there a significant difference in the test and standard?
Know what is meant by Phase I (nonsynthetic) and Phase II (synthetic) drug metabolism
Refers to drug biotransformation: Phase I is the non synthetic or preparatory meaning that it is an endogenous natural metabolism of drug. Phase II is synthetic meaning that exogenous metabolizers are introduced to help terminate the drug. SUMMARY: make the drug water soluble.
Knowing half-life, be able to estimate the time required to reach steady-state and the time required to eliminate
drug from the body (50%, 75%, 75% etc)
half life= 0.693/ke=0.693(Vd/Cl)
time to reach steady state
time required to eliminate drug from body
Know the differences and be able to apply the concept of hepatic enzyme induction and hepatic enzyme
inhibition
so hepatic enzyme inhibition is going to keep the liver from clearing drug as easy thus ke will be greater and thus halflife increases. more common in clinical
hepatic enzyme induction will enhance liver function so ke will be steeper and halflife will decrease
What is meant by “F” and how does it influence the size or an oral and IV loading dose and maintenance dose
F is the extent of absorption or amount of drug entering body. IT is an Inverse relationship so if F halfs then Loading dose and maintenance dose doubles.
Be able to calculate maintenance dose given clearance, target plasma concentration and F.
maint dose= (Cpss x Clearance) / F
Be able to calculate loading dose given Vd, target concentration and F.
LD= Cpa x Dv / F
