Pharmacokinetics Flashcards
What is the definition of pharmacokinetics?
Study of movement of a drug into and out of the body
What the body does to the drug
What sorts of things can effect drug pharmacokinetics?
Renal function, liver function, GI function, CV function, disease, alcohol intake, pregnancy etc
What is the mnemonic for the pharmacokinetic process?
ADME
Absorption
Distribution
Metabolism
Elimination
Explain the difference between initial plasma concentrations of drugs that are given orally vs given IV
IV drugs - immediate peak plasma concentration
Oral drugs - takes time to be absorbed first so takes longer to reach peak plasma concentration
What is the therapeutic window?
Range of doses in which a therapeutic response is caused without adverse effects
What is Cmax?
Peak plasma concentration
What is Tmax?
Time in which peak plasma concentration (Cmax) is reached
What is bioavailability?
The fraction of a dose which enters the circulation to have an active effect
What is the bioavailbility for an intravenous bolus?
100% (all enters bloodstream)
Note that for other routes, compare amount reaching the body comartment by that route with IV bioavailability
On a plasma concentration/time graph, what equates to the bioavailability?
Area under the curve
How would you calculate oral bioavailability (F) from a graph?
F = Area under the curve (oral) / Area under the curve (IV)
What factors can affect bioavailability?
Drug formulation, age, whether its being taken with food, vomiting, malabsorption, first pass effect
What is first pass metabolism?
Metabolism that occurs before the drug enters the systemic circulation
Where can first pass metabolism occur?
Liver (via portal system)
Gut lumen
Gut wall
Give an example of a drug that undergoes first pass metabolism in the liver
Propanolol, GTN
Give an example of a drug that undergoes first pass metabolism in the gut
Benzylpenicillin, insulin
What two key factors influence drug distribution?
Protein binding and volume of distribution
What is the effect of protein binding on drugs?
They are inactive and can’t be eliminated; most drugs must be free to have a pharmacological effect
What factors can influence protein binding?
Hypoalbuminaemia (eg malnutrition), pregnancy, renal failure, displacement by other drugs
What is the volume of distribution (Vd)?
A measure of how widely a drug is distributed in body tissues (proportional to half life)
How do you calculate Vd?
Vd = Dose/[Drug]t0
What is half life proportional to?
Volume of distribution
What can tissue distribution be affected by?
Specific receptor sites in tissues, regional blood flow, lipid solubility, disease states, drug interactions
What is a pro drug?
A drug that is metabolised into a pharmacologically active drug
Give an example of an inactive pro drug
Enalaprilat (inactive) to enalapril (active)
What are the main cytochrome p450 isoenzymes?
CYP2D6, 2C9, 2C19, 3A4
Give an example of CYP enzyme inhibition
Cimetidine inhibits a CYP which slows the metabolism of warfarin
What does CYP2D6 metabolise?
Codeine, beta blockers, tricyclics
What is CYP2D6 inhibited by?
Fluoxetine, paroexetine, haloperidol, quinidine
How does age affect drug metabolism?
Metabolism reduced in elderly and children
What is the main route of drug elimination?
Through the kidney
can also be through lungs, breast milk, swear, tears, bile, saliva
Which 3 processes determine the renal excretion of a drug?
Glomerular filtration, passive tubular reabsorption, active tubular secretion
What is an example of a drug that is actively secreted in the nephron?
Penicillin
How does half life relate to clearance?
Inversely proportional
What effect does a reduction in clearance (or GFR) have on half life?
Increases half life
What is 1st order kinetics?
Rate of elimination is proportional to drug level - constant fraction of drug eliminated in unit time
What is zero order kinetics?
Rate of elimination is a constant
Why do most drugs exhibit zero order kinetics at high doses?
Because the receptors/enzymes become saturated
Which drugs are more likely to result in toxicity: first order or zero order?
Zero order - fixed rate of elimination per unit time
What is steady state?
The situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination.
In practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started.
How many half lives are required to reach steady state?
4-5 half lives
- from CpSS it also takes 4-5 half lives to eliminate most of the drug
What is a loading dose?
An initial higher dose of a drug - used in acute cases, in drugs with long half life
Give an example of a drug that usually requires a loading dose
Digoxin
How do you calculate loading dose?
LD = Vd x target concentration of drug
What is half life proportional to in terms of clearance?
t1/2 = 1/Clearance (GFR)
