Drug receptor interactions

Question 1

What are cholinergic receptors (2)

Answer 1

1. Key receptors in the autonomic nervous system regulated by acetylcholine (ACh)
2. Adrenergic receptor plays a key role in regulating human physiology

Question 2

What are the types of cholinergic receptors (3)

Answer 2

1. Nicotinic – respond to acetylcholine & nicotine
2. Muscarinic – respond to acetylcholine & muscarine
3. Both are activated by acetylcholine and differ in their location and pharmacological function

Question 3

What are the types of natural ligands for cholinergic receptors (3)

Answer 3

1. Acetylcholine
2. Muscarine
3. Nicotine

Question 4

What is the important structure in acetylcholine and muscarine and what are its properties (5)

Answer 4

Quaternary nitrogen
1. aligns molecule to receptor
2. helps receptor binding
3. selectivity
4. hydrophillic, not hydrophobic
5. shape and conformation

Question 5

What are the properties of nicotinic Receptors (2)

Answer 5

1. Coupled directly to ion channels
2. ACh activation = immediate response on nerve and muscle and sensor cells

Question 6

What are the properties of muscarinic Receptors (3)

Answer 6

1. Involved maintaining homeostasis in humans
2. ACh activation = stimulation/inhibition of salivary, sweat glands, secretions and contractions of the gut, tonic action on smooth muscle, vasodilation, bronchial constriction
3. Longer duration of action than nicotinic receptor

Question 7

What are the functional groups present in acetylcholine chloride and what are their functions (5)

Answer 7

1. Quaternary ammonium ion - Provides a positive charge crucial for receptor binding.
2. Ester group - Links the acetyl group to choline, making acetylcholine susceptible to rapid breakdown by acetylcholinesterase.
3. Ethyl linkage - Connects the quaternary nitrogen and ester, providing spatial arrangement.
4. Chloride ion - Balances the charge for stability in the salt form.
5. These groups together allow acetylcholine chloride to function as a neurotransmitter, enabling it to interact specifically with cholinergic receptors in the nervous system

Question 8

What is the purpose of cholinesterase (3)

Answer 8

1. Cholinesterase metabolises acetylcholine
2. This is an enzymatic acylation reaction at the carbonyl group involving a hydroxyl group from serine acting as a nucleophile
3. The enzyme is restored by a hydrolysis reaction

Question 9

How do direct acting and indirect acting agonists work (2)

Answer 9

direct acting - mimic the action of natural hormone

indirect acting - inhibits the enzymes that deactive the hormone, increasing the hormone levels

Question 10

What is carbachol and neostigmine (2)

Answer 10

1. Carbachol is a direct-acting cholinergic agonist that mimics the action of acetylcholine
2. Neostigmine is an indirect-acting cholinergic agent that functions by inhibiting acetylcholinesterase, thereby increasing the level of acetylcholine at cholinergic synapses.

Question 11

Why is neostigmine given orally (3)

Answer 11

1. carbamate ester & quaternary ammonium group = resistant to hydrolysis.
2. The carbamate = more stable than the ester linkage = won’t break down as quickly in the acidic environment of the stomach.

Question 12

Why is Carbachol poorly absorbed orally (2)

Answer 12

1. high polarity
2. low lipid solubility