Drug pharmokinetics

Question 1

Where are most drugs absorbed

Answer 1

GI tract

Question 2

Discuss the factors that affect absorption from the GI tract

Answer 2

Motility - speed of absorption will affect speed of drug reaches site of action
Food - can enhance or impair rate of absorption
Illness- Malabsorption, migraine reduces the rate of stomach emptying

Question 3

What site is the most common site of action for drugs

Answer 3

Small intestine

Question 4

Why is the C.dif drug absorbed

Answer 4

The lining of the bowel is inflammed

Question 5

What physio- chemical factors that affect transfer of drugs across the cell membrane

Answer 5

Molecular size and shape
Degree of ionisation
Lipid solubility

Question 6

Do ionised drugs cross the cell membrane

Answer 6

NO

Question 7

What is the degree of ionisation highly dependent on

Answer 7

pH of the environment (gut)

Question 8

Do un-ionised drugs cross the cell membrane

Answer 8

yes - distribute until equilibrium is reached

Question 9

Define bioavailabilty

Answer 9

Amount of drug that reaches circulation and is available for action

Question 10

What factors affect bioavailabilty

Answer 10

Slow release formulation
Ability to pass membrane
GI effects - illness/ food
First pass metabolism
Route of administration

Question 11

Describe Tmax

Answer 11

The time taken for concentration the peak
Higher rate of absorption = faster conc. peak
Dose wont alter

Question 12

Describe Cmax

Answer 12

Increasing drug dose increases peak concentration

Question 13

Define AUC (area under curve)

Answer 13

Amount of drug which reaches the systemic circulation

Question 14

Define therapeutic range

Answer 14

Measure of the range at which a drug is safe and active
Above - toxic
Below - inactive

Question 15

Define drug distribution

Answer 15

The reversible transfer of a drug between the blood and the extra-vascular fluids and tissues of the body

Question 16

Describe the medical importance of the first pass metabolism

Answer 16

Metabolism of drug prior to reaching the systemic circulation
Can limit the oral route
Can be altered by other drugs or disease

Question 17

What structures are involved in the first pass metabolism

Answer 17

Gut lumen (acid, enzymes)
Gut wall (metabolic enzymes)
Liver (heapatic enzymes)

Question 18

How do plasma proteins affect the binding of drugs

Answer 18

Only unbound drugs are biologically active

Question 19

What does plasma protein binding depend on

Answer 19

Renal failure
Malnourishment / low protein
Pregnancy
Other drugs

Question 20

What are the most common plasma proteins drugs bind to

Answer 20

albumin and alpha-1-acid glycoprotein

Question 21

What is the lipid; water partition coefficient?

Answer 21

Ratio of dissolved drug in lipid and water phase in contact

Question 22

In terms of lipid solubility, what must drugs be to cross the membrane?

Answer 22

in solution and lipid soluble

Question 23

What factors affect the therapeutic range of a drug

Answer 23

Volume of distribution, Clearance, Half life

Question 24

Describe the Volume of Distribution

Answer 24

the volume in which the drug would be uniformly distributed to produce the observed blood concentration
Higher Vd- Greater ability to diffuse across the membrane
Low Vd - Drug will stick to proteins

Question 25

What should the volume of distribution theoretically be?

Answer 25

42 L

Question 26

Describe clearance

Answer 26

the theoretical volume of fluid from which a drug is completely removed over time Measure of elimination in ml/min

Question 27

How do renal and hepatic functions affect the clearance of a drug

Answer 27

renal - concentration and urine flow | hepatic - metabolism and biliary excretion

Question 28

What will happen if the liver and kidney are failing?

Answer 28

Drug will build up leading to toxicity

Question 29

Describe half-life of a drug

Answer 29

the time taken for the drug concentration in the blood to decline to half original value t1/2 = 0.693Vd/C (depends on Vd and C) Longer half life -> toxicity

Question 30

What does the half life of a drug help to know

Answer 30

How often to administer a drug to achieve optimal plasma concentration

Question 31

What is the primary organ of excretion

Answer 31

Kidney

Question 32

Describe glomerular filtration (most important excretion route)

Answer 32

Glomerular filters all unbound drugs of correct size, charge and shape If mutated - reduced drug clearance (filters around 190L a day)

Question 33

Describe the main method of excreting protein bound cationic and anionic drugs

Answer 33

Active tubular secretion - drugs are actively secreted into the proximal tubule

Question 34

Describe the passive tubular reabsortption of weak un-ionised drugs

Answer 34

As filtrate moves down renal tube, the drug present is concentrated. Passive diffusion down conc. gradient allows drug to move back into circulation Occurs in distal tube + collecting duct

Question 35

Define drug metabolism

Answer 35

Biochemical modification of pharmaceutical substances by living organisms, usually through specialised enzymatic activity

Question 36

Where does most drug metabolising occur and by which enzymes

Answer 36

Liver - cytochrome p450

Question 37

Describe the effects of bile secretion on drug activity

Answer 37

Drugs passively or actively secreted into bile for excretion Many drugs then reabsorbed into the circulation (entero-hepatic circualtion) Continues until drug is metabolised in liver until excreted by kidney

Question 38

List the factors which affect drug metabolism

Answer 38

``` Other drugs!! (herbal - enzyme inhibitors) Genetics Hepatic blood flow Age, ethnicity and gender Pregnancy Rate of first pass metabolism ```

Question 39

Which sex is more prone to drug toxicity?

Answer 39

Women

Question 40

How does age affect drug metabolism

Answer 40

Young - reduced enzyme activity and renal function | Old - Low weight, reduced renal activity, often on multiple drugs due to chronic disease

Question 41

What age range has the greatest metabolizing rate

Answer 41

Teenagers

Question 42

Describe the process of drug metabolising

Answer 42

Makes lipid soluble/ non polar compounds into water soluble/ polar compounds to be excreted Can activate to form pro-drugs

Question 43

Describe the reactions involved in the Phase 1 Metabolism and what they do

Answer 43

Hydrolysis, Oxidation and reduction Expose polar groups to provide an active site for phase 2 cytochrome p450 - oxidative

Question 44

Outline the phase 2 metabolism and conjugation

Answer 44

Molecule from phase 1, endogeneous to body donates segment to the foreign molecule Conjugation - increases water solubility, enhancing excretion