29: Drug Action on Nicotinic Receptors

Question 1

Explain the process of ACh signaling.

Answer 1

ACh diffuses across the synaptic cleft and binds to cholinergic receptors on the postsynaptic membrane.

Question 2

Name the two different types of cholinergic receptors.

Answer 2

Nicotinic receptors and muscarinic receptors.

Question 3

Describe the characteristics of nicotinic receptors.

Answer 3

• respond to ACh and nicotine
• ionotropic ligand-gated ion channels
• excitatory
• fast synaptic transmission
• brain, autonomic ganglia, adrenal medulla, and neuromuscular junction

Question 4

Describe the characteristics of muscarinic receptors.

Answer 4

• respond to ACh and muscarine
• metabotropic G-protein coupled receptors
• excitatory OR inhibitory
• slow metabolic response
• brain, heart, and smooth muscles

Question 5

Rank the binding affinity to nicotinic receptors of ACh, nicotine, and muscarine.

Answer 5

Question 6

Rank the binding affinity to muscarinic receptors of ACh, nicotine, and muscarine.

Answer 6

Question 7

Describe signal transduction process of nicotinic receptors.

Answer 7

• form pores through the cell membrane of the post-ganglionic nerves by conformational change after activation by ACh or nicotine.
• Control influx of Na+, K+, or Ca2+ at synapses.
• Trigger membrane depolarization
• mediate the fast transmission of nerve impulses

Question 8

Explain the structure of nicotinic receptors.

Answer 8

• 5 membrane domains
• 17 subunits
• 2 ligand binding sites must be occuplied to activate the receptor

Question 9

What are the two subtypes of nicotinic receptors? Give examples.

Answer 9

Nn: neuronal type
* brain: (a7)5 or (a4)2(b2)3
* autonomic ganglia: (a3)2(b4)3
* adrenal medulla gland

Nm: muscular type
* neuromuscular junction in skeletal muscle: a1ga1b1e

Question 10

Explain the difference of ACh binding sites for Nn and Nm nicotinic receptors.

Answer 10

Nn: neuronal type
* ACh binding sites at interface of a/b and a/a

Nm: muscular type
* ACh binding sites at interface of a/g and
a/e or a/d

Question 11

Explain the physiological reaction of nicotinic receptor activation in the brain.

Answer 11

In brain - regulate neurotransmitter release from nerve terminals (neuronal development, learning and memory formation, and reward).
* synaptic excitation

Question 12

Explain the physiological reaction of nicotinic receptor activation in the PNS (autonomic ganglia).

Answer 12

In PNS - transmit outgoing signal from the pre- to post-synaptic cells within the SNS and PNS.
* excitatory depolarization

Question 13

Explain the physiological reaction of nicotinic receptor activation in the adrenal medulla.

Answer 13

In the adrenal medulla - release catecholamines (epinephrine and norepinephrine) into the bloodstream in preparation for fight/flight reactions.
* excitatory depolarization

Question 14

Explain the physiological reaction of nicotinic receptor activation in the neuromuscular junction.

Answer 14

In the neuromuscular junction of skeletal muscle - primary receptors in muscle for motor nerve-muscle communication (for muscle contraction).
* excitatory depolarization

Question 15

List the nicotinic receptor agonists.

Answer 15

• acetylcholine
• nicotine
• choline
• succinylcholine
• lobeline
• varenicline
• cytisine

Question 16

What is the pharmacological use of nicotine?

Answer 16

A stimulatory alkaloid found in tabacco products that is often used for the relief of nicotine withdrawal symptoms and an aid to smoking cessation.

Question 17

What is the pharmacological use of varenicline?

Answer 17

Partial agonist at nicotinic receptor Nn - aid for smoking cessation.

Question 18

What is the pharmacological use of cytisine?

Answer 18

A strong agonist for the nicotinic receptor Nn - used for treatment of tobacco smoking cessation.

Question 19

What is the pharmacological use of lobeline.

Answer 19

treatment in addictions

Question 20

What is the pharmacological use of succinylcholine?

Answer 20

An agonist of muscular nicotinic Nm receptors as a depolarizing neuromuscular blocker - used as a short-term muscle relaxation agent in anesthesia and intensive care.

Question 21

Name some nicotinic receptor antagonists: ganglionic blockers Nn.

Answer 21

• Hexamethonium
• Pentolinium
• Benzohexonium
• Pentamine
• Chlorisondamine
• Mecamylamine
• Pempidine
• Trimetaphan

Question 22

Name some nicotinic receptor antagonists: neuromuscular blockers Nm.

Answer 22

• Rocuronium
• Rapacuronium
• Vecuronium
• Pancuronium
• Atracurium
• Doxacurium
• Cisatracurium
• Tubocurarine

Question 23

Explain the function of the ganglionic blockers.

Answer 23

• block nicotinic receptors for outgoing signals to be transmitted from the presynaptic to the postsynaptic cells within the ganglia of the ANS.
• block both sympathetic (excitatory) and parasympathetic (inhibitory) stimulation of the heart.
• Nn receptor antagonist

Question 24

Explain Hexamethonium’s drug action on nicotinic receptors.

Answer 24

Neuronal nicotinic receptor antagonist
* therapeutic indication: hypertension

Question 25

Explain the function of neuromuscular blockers.

Answer 25

• block ACh transmission at the neuromuscular junction via their anatagonist action on the Nm receptors
• cause paralysis of skeletal muscles

Question 26

Explain Rocuronium’s drug action on muscarinic nicotinic receptors.

Answer 26

Muscarinic nicotinic receptor antagonist
* therapeutic indication: anesthesia and paralysis

Question 27

Answer 27

Question 28

Answer 28

Question 29

Answer 29

Question 30

Answer 30