Mechanisms of drug action

Question 1

Phamacology 2 areas

Answer 1

Pharmacokinetics

Pharmacodynamics

Question 2

Pharmacokinetics

Answer 2

effect of body on drug - absorption etc.

Question 3

Pharmacodynamics

Answer 3

Effect of drug on body - mechanisms of action

Question 4

Drug

Answer 4

A chemical substance that interacts with a biological system to produce a physiological effect

Question 5

Drug target sites

Answer 5

Receptors
Ion channels
Transport systems
Enzymes

NOTE: they are all proteins

Question 6

Target sites - receptors

Answer 6

• proteins within cell membranes (usually, apart from steroid receptors = located in nucleus)
• activated by neurotransmitter or hormone
• defined by agonists and antagonists
• 4 types of receptors

Examples:
Acetylcholine (agonist)
Atropine (antagonist)

NOTE: agonist and antagonist only refers to receptors

Question 7

Target site - ion channels

Answer 7

• selective pores - allow transfer of ions down electorchemical gradients
• 2 types: 1. Voltage-sensitive (e.g. VSCC), 2. Receptor-linked (e.g. nAChR (nicotinic acetylcholine receptor))

EXAMPLES:
LAs (local anaesthetics)
Calcium channel blockers

Question 8

Target site - transport systems

Answer 8

• transport against concentration gradients (glucose, ions, NTs)
• specificity for certain species
• examples: Na+/K+ ATPase, NA ‘uptake 1’

Examples:
Tricyclic anti-depressants (TCAs)
Cardiac glycosides

Question 9

Target site: enzymes

Answer 9

• catalytic proteins (increase rate of reactions)
• drug interactions:
  
  1. Enzyme inhibitors (e.g. anticholinesterases (neostigmine)
  2. False substrates (e.g. methyldopa)
  3. Prodrugs (e.g. chloral hydrate —> tricholoroethanol)

NOTE: unwanted effects (e.g. paracetamol)

Question 10

‘Non-specific’ drug action

Answer 10

Physiochemical properties

 - Antacids
 - Osmotic purgatives (draws water into the gut)

NOTE: plasma protein binding (PPB)

Question 11

Drug-receptor interactions

Answer 11

Agonist (ACh; nicotine)
Antagonist (atropine; hexamethonium)
‘Potency’ of a drug depends on:
     - affinity
     - efficacy (‘intrinsic activity’)
           => conformational change of receptor
Full agonist
Partial agonist
     => antagonist activity
Selectivity
Structure-activity relationship
     - ‘lock and key’
     - agonist —> antagonists
     - pharmacokinetics

Question 12

Antagonists

Answer 12

Affinity but no efficacy
2 types of receptor antagonist
1. Competitive (e.g. atropine, propranolol)
=> same site as agonist
=> surmountable
=> shifts D-R curve to right
2. Irreversible (e.g. hexamethonium)
=> binds tightly or at different site
=> insurmountable

Slide 10 [pic]

Question 13

Which of the following statements is most accurate:

1. A partial agonist will always have a higher efficacy than a full agonist
2. Agonists have higher affinities than antagonists
3. Full agonists that are selective for a given receptor will have the same efficacy
4. Antagonists possess better efficacy than their respective agonists
5. Competitive antagonists will preferentially occupy the relevant receptor in the presence of agonist

Answer 13

3

Question 14

A drug acting as an inhibitor at a particular drug target site prevents the removal of neurotransmitter from the synapse. Which type of drug target is this drug acting on?

1. Receptor
2. Voltage-sensitive ion channel
3. Receptor-linked ion channel
4. Transport protein
5. Non-proteinaceous target

Answer 14

4