lecture 1 - clearance Flashcards
define pharmacokinetics and its two main properties
pharmacokinetics describes what the body does to a drug or simply how a drug ‘moves’ around the body
- clearance (CL)
- volume of distribution (V)
define pharmacodynamics and its two main properties
Pharmacodynamics describes what a drug does to the body. This is commonly assessed using dose-response or dose-effect curves.
- maximum effect (Emax)
- concentration producing 50% of the maximum effect (C50)
parameters of pharmacokinetics
absorption
distribution
metabolism
elimination
define clearance
describes the relationship between concentration and the rate of elimination of a drug from the body (units = L/h)
rate out = CL x Concentration
define maintenance dose rate and its equation
at steady state: the rate out = rate in
it can be predicted if the target concentration and drug clearance is known
Rate out (mg/h) = CL x Concentration
what is the relationship between BF and clearance
BF determines the size of the clearance, CL cant be bigger than the BF rate
what is the largest organ responsible for CL and what is its mechanism
the liver
main clearance mechanism is enzyme metabolism (but some drugs are also excreted unchanged in bile)
name two drugs with rapid clearance and explain why
Glyceryl trinitrate (treats angina)
- very unstable molecule
- breaks down in many tissues of the body
- CL not limited by BF to a single organ
Morphine
- metabolised extensively in the liver & blood clearance approaches liver BF
- extensively extracted from the blood as it passes through the liver
name two drugs with medium clearance and explain why
gentamicin (infections)
- eliminated mainly by GFR
- therefore CL = 6L/h
digoxin (heart treatment)
- cleared by both GFR and metabolism in liver
name two drugs with slow clearance and explain why
theophylline (asthma)
- mainly metabolized in the liver
- low CL in relation to BF
- only small fraction extracted as blood passes thorough
Warfarin
- very slow by liver metabolism
Classification of clearance and give an example for each
- constant
- concentration dependent
- flow dependent e.g. morphine
describe when the elimination process is called mixed order
when CL depends on drug concentration
describe when the elimination process is called first order and linear
when CL is constant
most drug metabolism can be approximated by a first order process because concentrations are small in relation to the Km
!st order Rate out = CL x Conc
what changes should be made if a patient with heart failure is given morphine
morphine CL is dependent on BF
patients with HF will have reduced BF, therefore CL will be low
this means the maintenance dose should be reduced
describe maintenance dose equation
MDR = CL x target conc
