6) Cholinoreceptors

Question 1

Indirect cholinomimetic

Answer 1

• Inhibit acetylcholine esterase enzyme, inhibiting the breakdown of ACh

Question 2

Cholinomimetics

Answer 2

• Drugs with acetylcholine-like effects

Question 3

Cholinomimetics consist of two major groups based on their mode of action

Answer 3

• Directly acting on acetylcholine (Ach)
  receptors
• Indirectly acting through inhibiting the cholinesterase enzyme

Question 4

Acetylcholine (Ach) is an important neurotransmitter whose effects are mediated by two classes of receptors:

Answer 4

• Nicotinic acetylcholine receptors (ion channels)
• Muscarinic receptors (G-protein coupled receptors)
• Five different subtypes of Ach receptors (mAChRs) have been identified (M1–M5)

Question 5

Muscarinic receptors M2 and M4

Answer 5

• Serve as autoreceptors pre-synaptically

- Suppress ACh release and inhibit cholinergic neurotransmission

Question 6

M1, M3, M5, but also M4 mAChRs

Answer 6

• Located postsynaptically

- Facilitate cholinergic synaptic neurotransmission

Question 7

Nicotinic receptor mechanism

Answer 7

• Channel protein selective to sodium and potassium

Question 8

When the nicotinic receptor is activated

Answer 8

• The channel opens
• Depolarization of the cell results in influx of sodium
• Causes excitatory presynaptic potential (EPSP)

Question 9

Effects of muscarinic toxicity

Answer 9

• Miosis
• Bronchoconstriction
• Gastrointestinal/genitourinary excessive activity
• Increased secretory activity
• Bradycardia followed by reflex tachycardia (mushroom poisoning)

Question 10

Effects of nicotinic toxicity

Answer 10

• Paralysis
• CNS toxicity including convulsions
• Stimulation of CNS and ganglion
• Increase blood pressure

Question 11

Enzyme acetylcholinesterase inhibitors

Answer 11

• Bind to the acetylcholinesterase and cause hydrolysis

Question 12

Effects of enzyme acetylcholinesterase inhibitors

Answer 12

• Increase concentration of Ach, half-life, and actions of acetylcholine in synapses where acetylcholine is released physiologically
• Muscarinic and nicotinic toxicities

Question 13

Reversal of muscarinic/nicotinic toxicity

Answer 13

• Atropine (anti-muscarinic)

- Pralidoxime (PAM) reverses (both nicotinic and muscarinic)

Question 14

Indirect-acting cholinomimetic agonists classes

Answer 14

• Carbamate (reversible)
• Organophosphates (irreversible)
• Alcohol (reversible)