Lecture 1: Clearance

Question 1

Pharmacokinetics links what?

Answer 1

dose and concentration

Question 2

Pharmacodynamics links what?

Answer 2

concentration and effect

Question 3

Clearance is?

Answer 3

relationship between concentration and rate of elimination from the body. Rate out/elimination = Cl x Conc. Is a fixed drug property but does depend person to person UNITS = L/h

Question 4

kidney blood flow? glomerular filtration rate? liver blood flow?

Answer 4

70L/h upper limit for kidney clearance 6L/h for all for all drugs 90L/h upper limit for liver blood flow (via enz. clearance)

Question 5

Clearance classification?

Answer 5

Constant conc dependent flow dependent

Question 6

Constant elimintion

Answer 6

aka first order or linear glomerular elimination is always first order

Question 7

conc dependent elimination

Answer 7

aka mixed order, non linear commonly enz reactions that are saturable, and are described in terms of Vmax and Km-(50% of Vmax). At small conc compared to km it appears first order and at higher concs it appears zero-order. in between these extremes, it is mixed order and is hat most drugs are considered

Question 8

flow dependent

Answer 8

usually associated with flow through the liver, eg. morphine thus CL is decreased in a HF patiens

Question 9

Uses of CL?

Answer 9

maintenance dose rate = CL x Target conc. T(1/2) = (0.7 x V)/(CL)

Question 10

Haemodialysis and haemoperfusion?

Answer 10

Same procedure used for RF Puts blood through a cartridge designed to absorb the drug, can be double that of haemodialysis

Question 11

Examples of very rapid, rapid, medium (x2), slow and very slow CL?

Answer 11

v. rapid = glyeryl trinitrate (150L/h just about anywhere it goes)

rapid = morphine (60L/h in the liver)

medium (x2) = gentamicin (6L/h in kidney GFR)

= digoxin (9L/h in the kidney and liver)

slow =Theophylline (3L/h in the liver)

very slow CL = warfarin (3L/DAY in the liver)