Principles of Pharmacology 2 L2

Question 1

Competitive reversible antagonists

Answer 1

• Competes with the agonist for the same binding site,
  or binds to an adjacent site that overlaps
• both bind reversibly
• binding is mutually exclusive
• competitive antagonism is surmountable
• maximal effect is still possible

Question 2

Irreversible competitive antagonists

Answer 2

• Compete with agonist for same binding site BUT binds irreversibly
• Presence of antagonist decreases number of available receptors
  ↓decreases maximal response

Question 3

Non - Competitive Antagonist

Answer 3

• A non-competitive antagonist binds at a different binding site
• prevents the effect of agonist, without preventing its binding
• effect of non-competitive antagonist is insurmountable
  i.e. it cannot be overcome by ↑[agonist]

Question 4

Concentration Ratio definition

Answer 4

• the ratio of the concentration of an agonist that produces a specified response (e.g. EC50) in the presence of an antagonist, with the agonist concentration that produces the same response in the absence of antagonist
• EC50 agonist in presence of antagonist / EC50 agonist alone

Question 5

Allosteric modulators

Answer 5

• Ligands that bind to a distinct (allosteric) site on the receptor
  
  • this is different from the agonist binding site
• Ligand binding either increases or decreases the action produced by agonist

Question 6

Negative allosteric modulators

Answer 6

decreases functional response

Question 7

Positive allosteric modulators

Answer 7

increase in functional response

Question 8

Allosteric effects on receptors

Answer 8

• GABA A receptor
• the benzodiazepine receptor
  (or binding site)
• BZ agonists increase the affinity of the GABA site for GABA and thereby increase channel opening

Question 9

Allosteric antagonist

Answer 9

e.g. betacarbolines at the GABAA receptor

• bind (reversibly) at a distinct site from the agonist and decrease affinity of agonist binding site for agonist
• reduce likelihood of agonist binding

Question 10

Channel blockers

Answer 10

e.g. phencyclidine (PCP) at the NMDA receptor

• bind inside the channel and prevent the passage of ions
• binding of channel blockers tends to be enhanced by receptor activation
  
  • use dependence

Question 11

Physiological antagonists

Answer 11

e.g. acetylcholine and adrenaline in the heart

• produce opposite effects on a tissue
• produce a non-selective suppression of the response

eg. Beta adrenoceptor agonist – prevents bronchoconstriction by producing relaxation

Question 12

Desensitisation

Answer 12

• Prolonged or repeated exposure to an agonist reduces the response to that drug

e.g. opiate drugs of abuse, like heroin (µ opioid receptor agonists)
effects through inhibition of 2nd messenger (adenylyl cyclase)
prolonged agonist exposure → upregulation of 2nd messenger
→ increased [agonist] required to produce same level of inhibition

e.g. inactivation of nicotinic receptors
receptor driven into an ‘inactivated’ state