Pharmacokinetics

Question 1

List major routes for drug administration

Answer 1

Dermal (P)
Sublingual (P)
Intramuscular (P)
Subcutaneous (P)
Intraperitoneal (P)
Inhalation (P)
Intravenous (P)
Ingestion (E)
Rectal ('E')

Question 2

What is the difference between enteral and parenteral administration?

Answer 2

Enteral = Gastro-intestinal administration

Parenteral = absorption is usually rapid, and drugs bypass the G-I tract, thereby avoiding presystemic metabolism to reach systemic circulation

Question 3

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

Answer 3

1. Bulk flow transfer i.e. in the bloodstream

2. Diffusional Transfer i.e. molecule by molecule over short distances

Question 4

State the main ways in which drugs cross lipid membrane barriers

Answer 4

• Simple diffusion
• Diffusion through aqueous pores
• Carrier mediated transport
• Pinocytosis

Question 5

Finish the sentence: most drugs are either …… or ……

Answer 5

Weak acids or weak bases

Question 6

Identify the factors that affect drug absorption

Answer 6

1. Non-polar substances (drug in non-ionised form) penetrate lipid membranes freely, and vice versa; pKa of a drug and local pH determines the non-ionised fraction of drug
2. Smaller molecules diffuse more easily across membranes than larger molecules
3. Lipid solubility (intrinsic property) measured in terms of a partition coefficient

Question 7

State exactly how pH affects drug absorption

Answer 7

Acidic drugs are increasingly ionised with increasing pH, while basic drugs are increasingly ionised with decreasing pH

10^[pKa-pH] = [AH]/[A-] = [BH+]/[B]

Question 8

What is ‘ion-trapping’ in the context of aspirin?

Answer 8

Aspirin in the systemic circulation will be mostly of the ionised form and hence is trapped as it is less able to cross lipid membranes.

Question 9

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

Answer 9

I.V. sodium bicarbonate increased blood pH => more ionised aspirin => aspirin is more water-soluble and less lipid-soluble => kidneys can more easily excrete it and less aspirin can be reabsorbed at PCT/DCT

Question 10

Identify the factors influencing drug distribution

Answer 10

• Regional blood flow
• Extracellular binding (Plasma-protein binding)
• Capillary permeability (continuous, fenestrated, discontinuous; blood brain barrier has tight junctions)
• Localisation in tissues (Lipophilic drugs tend to localise in fatty tissues despite 2% blood supply)

Question 11

What are the two main routes of drug excretion?

Answer 11

• Kidney (mainly) - active secretion at PCT vs reabsorption (especially for lipid soluble drugs)
• Liver

Question 12

Describe how biliary excretion works

Answer 12

It involves active secretion (coupled with bile acids and glucuronides) of drug molecules or their metabolites from hepatocytes into the bile. The bile then transports the drugs to the gut to be excreted.

Question 13

What is meant by enterohepatic cycling?

Answer 13

Deconjugating enzymes cause drug/metabolite, excreted into gut (via bile), to be reabsorbed and taken back to liver => drug persistence.

Question 14

Define bioavailability

Answer 14

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

Question 15

Define ‘apparent volume of distribution’

Answer 15

The volume in which a drug appears to be distributed

- an indicator of the pattern of distribution

Question 16

Define biological half-life

Answer 16

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

Question 17

Define clearance

Answer 17

The volume of blood plasma cleared of a drug per unit time