Pharmacokinetics - What you should know

Question 1

What are the 4 factors which influence the fate of a drug in the body?

Answer 1

Size of molecule
pH
lipid solubility
ionisation of drug

Question 2

What are the 9 major routes of drug administration?

Answer 2

Oral; IV; IM; Subcut: Intrathecal (epidural); Inhalation (NEB); Epithetial; Subling: Rectal

Question 3

What is Oral administration, giving an example?

Answer 3

Via the mouth and GI tract

Most drugs; Aspirin, paracetamol, ibuprofen

Question 4

What is IV administration, giving an example?

Answer 4

Injected directly into the bloodstream:
Anaesthetic - Thiopentone
Analgesic - Morphine sulphate
Antiemetic - Ondansatron

Question 5

What is IM administration, giving an example?

Answer 5

Injected into the muscle

Adrenaline

Question 6

What is Intrathecal administration, giving an example?

Answer 6

Injected into the subarachnoid space of the spine

Epidural - Bupivacaine in labour

Question 7

What is Inhalation administration, giving an example?

Answer 7

Absorbed via the lungs
Analgesic - methoxyflurane
Bronchodilators - Salbutamol

Question 8

What is Epithelial administration, giving an example?

Answer 8

Applied to membrane such as the skin
HRT - oestrogen patches
Nicotine patches

Question 9

What is Sublingual administration, giving an example?

Answer 9

Under the tongue, absorbed by vasculature

Vasodilators - Glyceral Trinitrate (GTN)

Question 10

What is Rectal administration, giving an example?

Answer 10

Applied via the rectum

Suppository - anti-inflammatory drugs for IBD

Question 11

Factors affecting absorption from the GI tract

Answer 11

Ionisation and lipid solubility of the drug
pH of the GI contents
Metabolism drug during absorption
Surface area for absorption
GI motility
First pass metabolism

Question 12

Outline the concept of drug distribution

Answer 12

After absorption, it will distribute through body and enter tissues in varying amounts.
Fluid compartments are separated by membrane barriers
Distribution is dependant on lipid solubility and pH of body fluids.

Question 13

How is distribution dependant on lipid solubility and pH of body fluids?

Answer 13

Higly lipid-soluble drugs distribute widley throughout body (Tricyclics)
Lipid-insoluble drugs will be distributed in plasma and intistitial fluids.

Question 14

Define the term ‘volume of distribution’ and how it is calculated.

Answer 14

The degree of distribution of a drug in the body. Vd=Q/C
Q= total amount of drug in the body (mg/kg)
C= [plasma] mg/L

Question 15

What is volume of distribution used for?

Answer 15

To determine where the drug will be distributed
Low level (.5) will store throughout the body tissue
Very high level (> total body fluid) stored in the fat

Question 16

How does protein binding affect distribution?

Answer 16

-Degree of binding alters distribution
highly bound drugs will stay in the circulation (warfarin)
-It is Reversible
introduction of new highly bound drug will reduce original
-Prevent metabolism
prolong retention time in body

Question 17

What is the importance of drug Metabolism?

Answer 17

• Has chemical changes which affect drug
• Most result in loss of pharmacological activity
• May result in; Increased activity; change in activity; produce toxic metabolite
• Increases drug solublity, making it easier to excrete
• Mainly done by hepatocytes.

Question 18

Describe Phase I metabolic reactions

Answer 18

• Molecular structure changes
• Oxidation, reduction, hydrolosis reactions
• Forms more reactive product

Question 19

Describe Phase II metabolic reactions

Answer 19

• Conjugate formed between drug and Phase I metabolite

Question 20

What are examples of Conjugates?

Answer 20

Glucuronic acid
Sulphate
Amino Acids
Methyl Groups
Acetyl Groups

Question 21

What are the Metabolic actions of Pro-drugs?

Answer 21

• Inactive in initial form
• Metabolised to anactive form
• • Usually Phase I reaction

Question 22

Give an Example of a pro-drug

Answer 22

Enalapril - vasodilator

Hydrolysed into active form “enalaprilat”

Question 23

What are the effects of drug-induced changes in rates of drug metabolism?

Answer 23

• Induce or inhibit production of enzymes in liver.
• Alters rate that drugs are metabolised
• Alter therapeutic effects
• Toxicity of metabolites enhanced