S2.1 Pharmacokinetics Flashcards
What is pharmacokinetics?
What the body does to the drug
ADME
Absorption is affected by bioavailability, what is bioavailability?
The fraction of a dose which finds its way into a body compartment, usually circulation.
It is affected by absorption, and first pass metabolism
Outline drug distribution
A drugs ability to dissolve in the body.
Affected by blood flow, lipophilicity and hydrophilicity.
Once in circulation, many drugs are bound to proteins e.g albumin. Only free drugs have a pharmacological effect
What is volume of distribution?
Measure of how widely a drug is distributed in body tissues.
Small Vd=confined to plasma and ECF, large Vd=distributed throughout tissues.
How does half-life relate to volume of distribution?
Half-life is proportional to Vd, longer half-life means greater distribution.
Outline drug metabolism
Occurs in the liver via phase 1 and 2 enzymes, which increase ionic charge and eventually form water soluble products which are easily eliminated.
Outline phase 1 metabolism
Carried out by CP450 which involves redox reactions. CP450 mainly present in liver and metabolise toxins such as carcinogens and pesticides.
Outline phase 2 metabolism
Carried out by hepatic enzymes which catalyse sulphation and methylation.
What is the affect of CYP450 inducers and inhibitors?
CP450 induction shall reduce plasma levels of a drug, CP450 inhibition shall increase it.
Outline drug elimination
Main route is through kidney and is determined by GFR, tubular reabsorption and secretion.
What is clearance?
Rate of elimination of a drug from the body (usually =GFR)
Half-life is inversely proportional to clearance so a reduction shall increase T1/2.
T1/2 = (0.7 x Vd)/Cl
What is the difference between 1st and zero order kinetics?
1st Order kinetics – Linear: Rate of elimination is proportional to drug conc.
Zero Order kinetics – Non-linear: rate of elimination is a constant.
Most drugs initially exhibit first order, then zero order kinetics at high doses.
Zero order drugs are more likely to result in toxicity as small dose changes can produce large increments in plasma conc.
