Test 2 Lecture 5

Question 1

What are the 2 overall types of cholinergic receptors?

How many different ones are there?

Answer 1

G protein-linked (muscarinic receptors) and ligand-gated ion channels (nicotinic

receptors) .
- 5 (3 w/known fcn)

Question 2

Where are muscarinic receptors found?

Answer 2

Smooth muscle, cardiac muscles, most
exocrine glands, sweat glands, in blood vessels of the major vascular beds, and at cortical and subcortical sites in the CNS

Question 3

The nicotinic receptors are pentomeric (five) transmembrane polypeptides, the subunits of which form a selective channel permeable to what 2 ions?

Answer 3

Na+ and K+

Question 4

Where are nicotinic receptors found?

Answer 4

Plasma membranes of parasympathetic and sympathetic postganglionic cells in the autonomic ganglia (Nn-neuronal) and on the membranes of SkM (Nm-muscle). Neuronal nicotinic receptors (Nn) are also expressed in cortical and subcortical nuclei in the brain.

Question 5

Nicotinic receptors are present on postganglionic cells of both the symp and parasymp nervous systems. What does this mean that nicotinic agonists can do, physiologically?

Answer 5

Nicotinic agonists can activate both the sympathetic and parasympathetic systems simultaneously.

Question 6

What are the effects of stimulating muscarinic receptors?

Answer 6

• Activates myenteric plexus
• Decreases HR (*M2)
• Contracts circular ciliary m.
• Bronchoconstriction
• Contracts GI smooth m.
• Contracts bladder detrusor m. (micturition)
• Stimulates secretions from GI tract, eccrine sweat glands, tear glands, salivary glands

Question 7

Generally, what type of drug is succinylcholine?

Answer 7

Muscle relaxant (Blocks Nm–see future lectures)

Question 8

What’s another name for muscarinic agonists?

Answer 8

Parasympathomimetics

Question 9

What receptor types does ACh bind?

Why doesn’t it have a therapeutic use?

Answer 9

• Nitotinic and muscarinic

- Because it’s rapidly hydrolyzed by plasma and actylcholinergic esterases

Question 10

What classification of drug is methacholine?
What are its effects?
Indications?
Toxicity?
Contraindications?

Answer 10

• Quaternary nitrogen analogue (hydrolyzed more slowly than ACh)
• Effects: Primarily muscarinic
• Indications: to dx bronchial hyperactivity in pts suspected of having asthma
• Tox: bronchiolar constriction
• Contra: in pts given beta-blockers (beta-blockade)

Question 11

What classification of drug is carbachol?
What are its effects?
Indications?
Toxicity?
(No contraindications)

Answer 11

• Quaternary nitrogen analogue (resistant to hydrolysis by ACh-esterase
• Effects: Both muscarinic and nicotinic
• Indications: topical miotic agent for ocular surgery and glaucoma
• Tox: excessive muscarinic activation
  i.e., bronchoconstriction, reduced cardiac
  conduction

Question 12

What classification of drug is bethanechol?
What are its effects?
Indications?
Toxicity?
Contraindications?

Answer 12

• Quaternary nitrogen analogue (hydrolyzed more slowly than ACh)
• Effects: Muscarinic only (*less CV effects–less M2 activity)
• Indications: post-op urinary retention neurogenic bladder atony
• Tox: bradycardia (even w/less M2 activity), bronchoconstriction
• Contra: asthma, peptic ulcer (stomach secretions can cause ulcers), bradycardia

Question 13

What drug class is muscarine in?
What receptor does muscarine bind?
Why isn't it used clinically?

How is muscarine poisoning treated?

Answer 13

• Tertiary amine muscarinic agonists (has quaternary nitrogen structure)
• Muscarinic
• Too potent; no ester moiety so resistant to breakdown

Tx w/atropine, a muscarinic antagonist

Question 14

What classification of drug is pilocarpine? (Does it cross BBB? 1/2-life?)
What are its effects?
Indications?
Toxicity?
(No contraindications)

Answer 14

• Non-selective muscarinic receptor agonist (crosses BBB; 1/2-life ~1 hr)
• Effects: Activates all muscarinic receptors
• Indications: dry mouth and neck from radiotherapy, also open angle glaucoma, acute and chronic angle-closure glaucoma
• Tox: excess muscarnic activation (slowed AV conduction), hypotension, excessive salivation and bronchoconstriction

Question 15

What’s the difference b/w open- and closed-angle glaucoma?

Answer 15

Open-angle glaucoma (chronic glaucoma) is what the majority of glaucoma pts suffer from. Aqueous fluid does not drain well out of the eye, potentially causing dmg to the optic n.

Closed angle glaucoma (acute glaucoma) is an emergency. This occurs when the iris bows forward and completely blocks fluid access to the trabecular meshwork. The pressure builds up in a positive feedback loop, the patient has excruciating eye pain, and vision is lost quickly. (Use pilocarpine to help)

Question 16

What type of drugs are cholinesterase inhibitors classified as?

Answer 16

Indirectly-acting cholinergic agonists

Question 17

Name the 2 classes of cholinesterases.

Answer 17

1. Acetylcholinesterase

2. Butyrylcholinesterase (pseudocholinesterase)

Question 18

The accumulation of ACh resulting from cholinesterase inhibition occurs at all
cholinoceptive sites, resulting in the following effects: (4)

Answer 18

1. muscarinic actions at autonomic effector targets
2. nicotinic actions at autonomic ganglia
3. nicotinic actions at motor end plate
4. muscarinic and nicotinic actions in CNS

Question 19

What classification of drug is neostigmine?
What are its effects?
Indications?
Toxicity?
Contraindications?

Answer 19

• Quaternary nitrogen (thus, doesn’t cross BBB), reversible ACh-esterase inhibitor
• Effects: Direct stimulation of Nm receptors (nicotinic receptors at SkM endplate)
• Indications: myasthenia gravis, reversal of non-depolarizing neuromuscular blockade
• Tox: muscarinic and nicotinic excess
• Contra: intestinal obstruction

Question 20

What classification of drug is edrophonium? (relative 1/2-life?)
What are its effects?
Indications?
Toxicity?
Contraindications?

Answer 20

• Reversible ACh-esterase inhibitor
• Effects: Activates Nm receptors directly
  (*Rapid onset, 1/2-like ~10 min)
• Indications: dx of myasthenia gravis, differential diagnosis of too little or too much AChE inhibitor in rx of myasthenia gravis
• Tox: muscarinic and nicotinic excess
• Contra: intestinal obstruction

Excessive cholinesterase inhibition can cause neuromuscular block, resulting in muscle weakness which can mimic and be mistaken for myasthenia gravis progression.

Question 21

What classification of drug is physostigmine?
What are its effects?
Indications?
Toxicity?
Contraindications?

Answer 21

• Reversible ACh-esterase inhibitor
• Effects: (crosses BBB; ~2hr duration)
• Indications: antidote for muscarinic antagonist poisoning
• Tox: convulsions, respiratory and CV depression
• Contra: asthma, CV dz, intestinal obstruction

Question 22

What classification of drug is donezepil?
What are its effects?
Indications?

Answer 22

• Reversible ACh-esterase inhibitor
• Effects: in the CNS (inhibits only ACh-esterase)
• Alzheimer’s dz

Question 23

What types of drugs are organophosphates?

What are they used for, commercially?

Answer 23

• Irreversible inhibitors of cholinesterases

- Insecticides, nerve gas (P’lated enzyme becomes stable w/time and therefore extremely toxic)

Question 24

What are the toxic sx of organophosphates?

Answer 24

DUMBBELS (lacks an “L”)

• D: diarrhea
• U: urinary freq and incontinence
• M: miosis
• B: *bradycardia
• B: *bronchorrea (^ secretions)
• E: emesis
• L: lacrimation
• S: Salivation

Question 25

What are the 4 steps in tx of organophosphate poisoning?

Answer 25

1. Ventilation 2. Suction of tracheal secretions 3. Anti-muscarinic agent (atropine) 4. Reactivation of acetylcholinesterase with Pralidoxime Chloride (2-PAM) (might be too late)

Question 26

What classification of drug is echothiophate? Indications? Relative 1/2-life?

Answer 26

- Irreversible acetycholinesterase inhibitor (used clinically) - long-term miosis in the treatment of open angle glaucoma - Very long 1/2-life

Question 27

What's another name for muscarninc antagonists?

Answer 27

Parasympatholytic agents

Question 28

What classification of drug is atropine? Indications? (5) (no contraindications)

Answer 28

- Competitive muscarinic antagonists - Indications: 1. organophosphate poisoning (insecticides + nerve gas), 2. induction of mydriasis and cycloplegia- paralysis of eye ciliary mm. (though long duration of action), 3. reverse bradycardia of vagal origin, 4. reverse GI hypermotility, 5. bladder spasms (urgency) associated w/cystitis - Tox: "see atropine poisining"

Question 29

``` What classification of drug is scopolamine? What are its effects? Indications? Toxicity? (no contraindications) ```

Answer 29

- Competitive muscarinic antagonists - Indications: N/V associated w/motion sickness or chemotherapy, used in prep for surgical anesthesia to minimize secretions - Tox: anti-muscarinic actions (see atropine poisoning), effects may be long-lived, especially in adults

Question 30

What classification of drug is glycopyrrolate? Indications? Toxicity?

Answer 30

- Competitive muscarinic antagonists - Indications: used to protect against excessive muscarinic effects of cholinesterase inhibitors during reversal of neuromuscular blockade, pre-operative anti-salilogogue - Tox: can cause heat stroke due to inability to sweat in heat

Question 31

What are the sx of atropine poisining? (just have relative understanding)

Answer 31

- CNS: nervousness, confusion, hallucinations, muscular coordination and weakness, inappropriate laughter, psychosis - PNS: dry mouth, difficulty swallowing, thirst, hot/dry/flushed skin, dilated pupils, blurred vision/photophobia, tachycardia, ^ BP, micturition difficulty, resp collapse

Question 32

What classification of drug is pralodozime (2-PAM)? What's its ~ 1/2-life? Indications?

Answer 32

- Peripheral AChE reactivator - ~75 min 1/2-life - Respiratory muscle weakness in organophosphate poisoning