Clinical pharmacology Flashcards
Pharmacokinetics vs pharmacodynamics
- Pharmacokinetics is what the body does to the drug. covers absorption, distribution, metabolism and elimination of the drug
- Pharmacodynamics is what the drug does to the body.
Formulas for absolute bioavailability
Formula 1
F= AUC(ORAL) / AUC(IV)
Formula 2
Bioavailability = 1 – Hepatic extraction ratio
Best measure of overall exposure to a drug
AUC
Relative bioavailability formula
F= AUC(ORAL) / AUC(REFERENCE)
What is Hepatic extraction ratio
Proportion of drug that passes through the liver that is metabolized
= 1 – bioavailability
How to target loading dose
Loading dose = Vd x target plasma concentration
Clearance definition
Cl = Rate of elimination/Concentration
High affinity albumin binding drugs
acidic drugs
- salicylic acid,
- warfarin,
- phenylbutazone,
- penicillins and
- sulphonamides
Relevance of protein biding on drugs?
unbound fraction of the drug that is available for physiological/pharmacological processes:
– Interaction with receptors
– Metabolism
– Renal excretion
formula for renal clearance of drug depending on protein binding of the drug
CL(renal) = CL(d/t renal secretion) + fraction unbound x GFR
Loading dose calculation
Vd x Css
time to reach 97% of steady state?
5 half lives
Formula for half-life (with Vd and Cl)
T1/2 = 0.693 x Vd/Cl
Effect of ionisation of drug pharmacokinetics
less lipid soluble/ less able to cross membranes
What is linear kinetics?
first order kinetics of drug - constant amount cleared per unit time
therapeutic index formula
tachyphylaxis
Initially a high response occurs to a given plasma concentration but the response to the same plasma concentration decreases rapidly with time. (eg amphetamines, cocaine)
hysteresis loop occurs when tolerance to a drug occurs rapidly.
hysteresis loop
when tolerance to a drug occurs rapidly
Effect of drug efficacy from competitive inhibition
Effect of drug efficacy from NON-competitive inhibition
Phases of clinical trials
Phase I First time in man
Phase II Proof of concept
Phase III Large scale efficacy
Phase IV Postmarketing
Phases of clinical trials
Phase I First time in man
Phase II Proof of concept
Phase III Large-scale efficacy
Phase IV Postmarketing
Steps in biotransformation of a drug (by liver)
- phase I reactions: hydroxylation, oxidation, reduction and hydrolysis
- phase II reactions (conjugative):
sulphation, glucuronidation, acetylation, methylation, glycylation, glutamylation - phase III, transport processes:
transmembrane solute transporters
