Pharmacokinetics

Question 1

State the five stages of the journey of a drug through the body.

Answer 1

Administration 
Absorption 
Distribution 
Metabolism 
Excretion 
(Voiding)

Question 2

What is the difference between enteral and parenteral administration?

Answer 2

Enteral – using the GI tract

Parenteral – everything except the GI tract

Question 3

What are the advantages of intravenous administration?

Answer 3

It gives rapid systemic exposure and a high bioavailability

Question 4

State the two ways in which drug molecules move around the body.

Answer 4

Bulk Flow Transfer – in the bloodstream it will move in bulk to the tissues
Diffusion Transfer – molecule by molecule over short distances

Question 5

State six methods by which drugs can cross lipid membrane barriers.

Answer 5

Passive diffusion (most common – pH PARTITION HYPOTHESIS)

Facilitated diffusion

Active transport (more important in drug excretion)

Pinocytosis (phagocytosis-mechanisms – liposomes)

Filtration (small water soluble molecules)

Paracellular transport (around cells, often overlooked

Question 6

Chemically what are most drugs?

Answer 6

Weak acids or weak bases

Question 7

Which factors affect the ratio of ionized to non-ionized drug?

Answer 7

pKa of the drug

pH of the environment

Question 8

Describe and explain the difference in absorption of aspirin in the stomach and the small intestine.

Answer 8

Aspirin has a pKa of 3.4 The stomach has a pH of around 1, as this is lower than the pKa of aspirin, the aspirin equilibrium is shifts to unionised, which is rapidly absorbed.

Eventually, aspirin reaches the small intestines which has a higher pH than the pKa of aspirin, shifting equilibrium to ionised, slowing down aspirin absorption.

Question 9

What is ion trapping?

Answer 9

Some ionized aspirin will enter the systemic circulation, which is an aqueous environment. As it is ionized it is unable to move into the tissues.

Question 10

State four factors affecting drug distribution.

Answer 10

Regional blood flow
Extracellular binding (plasma-protein binding)
Capillary permeability
Localisation in tissue

Question 11

In which state can albumin bind to drugs? Ionized or non-ionized?

Answer 11

Both

Question 12

State three types of capillary.

Answer 12

Continuous
Fenestrated
Discontinuous

Question 13

Give a broad example of localization of a drug in tissue.

Answer 13

Lipophilic drugs tend to localise in fatty tissues e.g. brain and testes

Question 14

What are the two main routes of drug excretion?

Answer 14

Kidneys (main route)

Liver

Question 15

What types of molecule tend to get excreted via the biliary route?

Answer 15

Large molecule weight molecules

The liver allows concentration of large molecular weight molecules that are very lipophilic

Question 16

Via what form of molecular movement do most drugs tend to get excreted into urine?

Answer 16

Active secretion

Question 17

What happens to drug-protein complexes at the glomerulus?

Answer 17

Too large to enter filtrate

Question 18

Where does active secretion of acids and bases occur in the nephron?

Answer 18

Proximal convoluted tubule

Question 19

What can happen to lipid soluble drugs in the proximal and distal convoluted tubules?

Answer 19

Reabsorption

Question 20

Why might treatment with I.V. sodium bicarbonate increase aspirin excretion?

Answer 20

IV sodium bicarbonate will increase blood pH,
increasing ionised aspirin at equilibrium, raising water solubility so the kidneys can excrete more of it and less aspirin is reabsorbed in the proximal and distal tubules .

Question 21

What is the main purpose of the active transport systems that secrete drugs into bile?

Answer 21

They are meant to be for the active transport of glucuronides and bile acids into the bile but drugs can hitch a ride on this mechanism

Question 22

What is a potential problem with biliary excretion of xenobiotics?

Answer 22

Enterohepatic cycling – it can become reabsorbed and return to the liver via the enterohepatic circulation
leading to drug persistence.

Question 23

Define bioavailability.

Answer 23

The proportion of the administered drug that is available within the body to exert its pharmacological effect

Question 24

Define apparent volume of distribution.

Answer 24

The volume in which a drug appears to be distributed – an indicator of pattern of distribution

Question 25

Define biological half-life.

Answer 25

The time taken for the concentration of a drug (in blood/plasma) to fall to half its original value

Question 26

Define clearance.

Answer 26

The volume of plasma cleared of a drug per unit time

Question 27

Define First-Order kinetics.

Answer 27

Rate of drug excretion is proportional to the concentration of drug remaining within the body (most drug removal is this.)
T1/2 = Vd x log(2)/Cl
Vd = volume of distribution
Cl = clearance

Question 28

Define Zero-Order kinetics.

Answer 28

Constant amount of drug removed from body per unit time, implying that the enzymes responsible for drug removal are saturated.