lecture 38 - metabolism and excretion - PoD

define clearance

theoretical volume of plasma from which the drug would be completely removed from over a period of time measured in ml/min

Define the half life of a drug

the time needed to remove half the drug from the body

prolongation of half life

increase plasma levels leading to toxicity due to reduced clearance and large Vd

to achieve a therapeutic effect, how must some drugs be given

chronically - more than one dose

how long does it take for a drug to stabilise

4-5 half lives

what may be necessary to get drug levels into therapeutic range

loading dose

what factors can prolong half life

age

pregnancy

malnourishment

hypoproteinaemia

liver disease and failure

renal impairment and failure

heart disease and failure

what is drug elimination made up of

metabolism and excretion

where are drugs metabolised

liver

where are drugs excreted

kidneys

reduced glomerular filtration rate

reduced clearance which can lead to prolongation of half life and toxicity

what does drug excretion depend on

glomerular filtration

active tubular secretion

passive tubular reabsorption

biliary secretion

phase 1 metabolism

Oxidation, reduction, hydrolysis

- increases polarity of compounds and provides active site for phase II

what drugs are excreted

water soluble

what drugs are reabsorbed

lipid soluble

what are cytochrome P450 enzymes responsible for

drug metabolism

- CYP3A4

- CTP2D6

- CYPIA2

phase 2 metabolism

conjugation

- increases water solubility

- enhances excretion of metabolised compound

- deactivates drug

what factors can affect metabolism of drug

age

hepatic blood flow

pregnancy

ethnicity

genetics

liver disease

sex

enzyme induction

involves increased enzyme synthesis to increase activity

- can take weeks

- biotransformation

enzyme inhibition

quick

reversible or irreversible binding to an enzyme