Pharmacokinetics I

Question 1

Define adsorption

Answer 1

Movement of a drug from its site of administration into the blood

Question 2

How are most drugs absorbed?

Answer 2

By passive absorption, some drugs need carrier mediated transport

Question 3

Describe the rate of diffusion by small molecules and lipid soluble non-ionised drugs

Answer 3

Small molecules diffuse more rapidly than larger

Lipid drugs are absorbed faster

Question 4

What are the different absorption processes?

Answer 4

Gastric emptying, colonic transit, via small intestine

Question 5

Describe the effects of gastric emptying

Answer 5

Biological variability, greater motility with increased absorption, drugs taken with food to prevent gastric irritation

Question 6

Describe the causes of gastric emptying

Answer 6

Increase in large liquid volumes, physical activity, emotional state
Decrease in ingestion of food, physical inactivity, depression

Question 7

Describe what factors affect oral absorption

Answer 7

Drug chemical stability, motility/mixing in GI, type of food, passage across GI, blood flow to GI

Question 8

What is the law of mass action?

Answer 8

Rate of ADME of drug occurs is proportional to its concentration in the body

Question 9

Describe the first order process in terms of drug absorption

Answer 9

Rate of drug absorption is proportional to amount remaining to be absorbed

Question 10

What is absorption half-life?

Answer 10

Time needed to increase plasma drug concentration by 50%

Question 11

What is elimination half-life?

Answer 11

Time needed to reduce plasma drug concentration by 50%

Question 12

Describe plasma membrane permeation of cells by drugs

Answer 12

Direct diffusion through lipid - Ionisation
Carrier-mediated transport - Uphill transport, Finite number of receptors leads to saturation/competition between drugs for transport
Diffusion through aqueous pores
Pinocytosis

Question 13

Describe the effects of ionisation in terms of oral drugs

Answer 13

Mouth - Neutral
Stomach - Acid
Intestines - Alkaline
Many drugs are weak electrolytes so ionise to greater/lower in terms of pH
Degree of lipid solubility determined by ionisation

Question 14

Describe the characteristics of GI tract

Answer 14

Oesophagus: pH5-6
Stomach: pH2-6 (fasting), pH1.5-2 (presence of food)
Small intestine: pH6-6.5 (duo/jej), pH7-8 (ileum)
Colon: pH5.5-7

Question 15

Describe the factors affecting absorption in terms of oral drugs

Answer 15

Passive transfer relies on ionisation/lipid solubility of drugs
Non-ionised forms soluble in membrane lipids to cross
Strong bases poorly absorbed
Strong acids fully ionised

Question 16

Describe the physiochemical properties of drugs

Answer 16

Too hydrophilic, unable to pass through membrane lipids

Too lipophilic, not soluble enough to penetrate intercellular media

Question 17

What does ionisation depend on?

Answer 17

pH of the aqueous environment and drug dissociation constant

eg strong acid low pka vv

Question 18

Describe aspirin in the body

Answer 18

Stomach: Aspirin unionised so lipid soluble/diffusible
Enters gastric epithelial cells, its ionised/localised there
Metabolised tp salicylic acid in body
pH 7.4: Highly ionised stays in extracellular fluid

Question 19

Describe aspirin in overdose cases

Answer 19

Removal of salicyclic acid helped make urine more alkaline so aspirin’s more ionised so stays lipid insoluble, passes into urine

Question 20

Describe amfetamine

Answer 20

Acidifying urine increases elimination

Question 21

What is bioavailability?

Answer 21

Fraction of drug dose that reaches blood stream in an active form

Question 22

What is bioavailability affected by?

Answer 22

First pass effect
Metabolism in gut wall
Hepatic disease
Drug formulation

Question 23

Describe what bioavailability is dependent on

Answer 23

Amount of drug absorbed
Route of administration
Food intake
Disease
Drug interactions

Question 24

Describe the extent of absorption

Answer 24

Due to bacterial metabolism in small intestine

Issue in elderly where bacterial overgrowth is pathological condition

Question 25

Describe the interactions with drug-food

Answer 25

Ca2+ in milk causes chelation of tetracyclines
Sub of protein for fat/carbs increase drug oxidation
Formation of lipid pockets causes dissolution of hydrophobic drugs reducing absorption

Question 26

Describe delay absorption in terms of oral drugs

Answer 26

75% of oral drugs should be absorbed 1-3hrs