Pharmacokinetics

Question 1

Define T max

Answer 1

Time the drug takes to reach its max conc

Question 2

Define C max

Answer 2

Max conc of drug in the plasma

Question 3

Define bioavailability

Answer 3

Fraction of a dose which finds its way into a body compartment (usually circulation

IV = 100%

Other routes compare against IV)

Question 4

How is bioavailability (F) calculated?

Answer 4

F = AUC oral / AUC IV

Question 5

What factors affect bioavailability?

Answer 5

Drug formulation

Age

Food: lipid-soluble > water-soluble

Vomiting/malabsorption

First pass metabolism

Question 6

Define first pass metabolism

Answer 6

Any metabolism occurring before the drug enters the systemic circulation

Occur in = gut lumen, gut wall, liver

Question 7

Recognise the main routes of drug administration in to the body

Answer 7

Oral

IV

IM

PR

SL

Dermal

Question 8

What key factors effect drug distribution?

Answer 8

Protein binding

Volume of distribution

Question 9

Briefly outline the factors affecting drug-protein binding

Answer 9

Hypoalbuminaemia

Pregnancy

Renal failure

Displacement by other drugs

Question 10

How can adding another drug affect protein binding?

Answer 10

Drug B may bind more highly = displaced drug A = higher [free drug A]

Question 11

What is volume of distribution?

Answer 11

measure of how widely a drug is distributed in body tissues

Vd = dose / [drug]t0

Question 12

Describe CYPs

Answer 12

Genetically dependent

Role = oxidation, dealkylation, reduction, hydrolysis

Can be influenced by enzymes inducing/inhibiting drugs

CYP450 - mainly present in liver

Question 13

Outline the factors affecting drug Metabolism

Answer 13

Race – CYP 2D6 absent in 7% caucasians

Age – reduced in older/children

Sex

Species

Clinical or physiological condition

Question 14

What are the phases of drug metabolism?

Answer 14

Phase 1 = chemical changes, CYP450

Phase 2 = conjugation, increased solubility, allows excretion

Question 15

What factors effect drug excretion

Answer 15

Age

Glomerular filtration

Passive tubular reabsorption

Active tubular secretion

Question 16

Describe clearance

Answer 16

Ability of body to excrete drug

T ½ is inversely proportional to Cl

Question 17

How is drug half life calculated?

Answer 17

T1/2 = Vd / Cl

= proportionally equal to Vd

= inversely proportional to Cl

Question 18

Describe 1st order kinetics = Linear

Answer 18

Rate of elimination is proportional to drug level

Constant fraction of drug is eliminated in unit time

Half life can be determined

Question 19

Describe Zero order kinetics = Non-Linear Kinetics

Answer 19

Rate of elimination is a constant

Zero order drugs are more likely to result in toxicity = small dose changes may produce large increments in [plasma]

DRUG MONITORING ESSENTIAL

Question 20

Appreciate how Steady State therapeutic levels in plasma (CpSS) are reached

Answer 20

4-5 half lives required to reach steady state

Question 21

How are loading doses are employed to reach CpSS more rapidly

Answer 21

Used when pt require effective dose quickly

Very high first dose which sets the dose level appropriately

Question 22

How is digoxin toxicity treated?

Answer 22

Inject something that binds digoxin = inactive and gets eliminated