Session 9: Pharmacokinetics

Question 1

4 factors/questions about drug administration

Answer 1

1 Is drug getting to the patient? - Pharmaceutical process

2 Is drug getting to the site of action? - Pharmacokinectic process

3 Is drug producing the desired pharmacological effects? - Pharmacodynamic process

4 Is the pharmacological effect producing a therapeutic effect? - Therapeutic process

Question 2

ways a drug can be administered - the form and site

Answer 2

form: liquid, tablet (if tablet its rate of action is dependent on the rate of dissolution)

Site: local (eg skin, eye, inhaling), systemic - enteral (sublingual, oral, rectal) or parenteral (inhaled, SC/IC/IV injection, transdermal)

Question 3

Define oral bio-availability and how it is affected

Answer 3

proportion of a dose given orally (or any route other than IV) that reaches the systemic circulation in an unchanged form

measured by amount or rate of availability: amount is measured by area under curve of blood drug level against time and is affected by GI absorption (food, disease) and 1st pass metabolism

-rate is measured by peak height and rate of rise of drug level in blood, and is affected by pharmaceutical factors and the rate of gut absorption

Question 4

therapeutic ratio

Answer 4

max. tolerated dose/min. effective dose
ie. lethal dose in 50% of population/effective dose in 50% of population

Question 5

vol. of distribution

Answer 5

total amount of drug in the body divided by drug blood plasma concentration

a theoretical volume into which a drug has distributed assuming it dissolved instantaneously

Question 6

protein binding interactions

Answer 6

many drugs bind to plasma proteins - the free level of drug is the one that exerts the effect

Object drug (Class I): dose is much lower than the number of albumin binding sites

Precipitant drug (Class II): dose is higher than the number of albumin binding sites and displaces the object drug

eg warfarin is displaced by sulphonamide, aspirin, phenytoin

Question 7

Orders of kinetics

Answer 7

1st order: metabolism is proportional to drug concentration - straight line is produced when plotted on a LOGARITHMIC scale

0 order: RATE of decline of plasma drug level is constant, straight line is made when plotted against normal (non log) plasma conc.s, steady state will be reached w/in 5 half lives of the drug

1st order gives a predictable therapeutic response, 0 order gives therapeutic response that may suddenly escalate when elimination mech.s become saturated eg alcohol

Question 8

describe metabolism of drugs by liver

Answer 8

Phase I: reactive group is added to or exposed on the molecule - some drugs are already reactive and can bypass Phase I (eg morphine), common rxns here are oxidation, reduction and hydrolysis, requires an enz. system called cytochrome p450 (CYP) and a high energy cofactor (NADPH), these CYP enz.s are inducible and inhibitable (ie. can be stim. or inh. by other molecules)

Phase II: conjugation w/ a polar (hphi) molecule to form a water-soluble complex, glucuronic acid is most common molecule, sulphate ions and glutathione are also used, requires a high energy cofactor -UDPGA

both of these act to increase the solubility of a drug to permit the passage in the circulation and glomerular filtration

Question 9

describe elimination of drug by kidneys

Answer 9

glomerular filtration

only free drug is filtered through glomerulus, drugs can be actively secreted by tubule eg penicillin, urine pH can determine quantity of drug excreted

for weak acids eg aspirin: making urine alkaline ionises drug -> cannot move across pm -> stays in tubule lumen and is passed out in the urine

the opposite is true for weak bases eg amphetamine