Cholinergics - 8/21/15 (Scrogin) Flashcards by Stephen Murata

Name 2 classes of cholinergic receptors

Muscarinic (GPCR)

2. Nicotinic (ligand gated ion)

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How many transmembrane polypeptides compose nicotinic receptors?

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Nicotinic receptors are permeable to what ions?

K+ and Na+

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Nicotinic receptors are located on what cell types?

Nn type: POST-ganglionic cells

Nm type: skeletal muscle

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Which system, sympathetic or parasympathetic, is activated by nicotinic agonists?

Both, simultaneously

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Nicotine stimulates what type of receptors, specifically

Nn in autonomic ganglia, and CNS

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What’s nicotine used for

smoking cessation

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What is the MOA of succinylcholine

Blocks Nm receptors in the NMJ, causing depolarization block

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Succinylcholine - Rx?

relaxation for intubation or ECT

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Succinylcholine - 2 contraindications?

familial hyperthermia

skeletal muscle myopathies

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Name 4 quaternary nitrogen analogs

Acetylcholine
Methacholine
Carbachol
Bethanechol

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Acetylcholine - what receptors?

Nicotinic and muscarinic

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Acetylcholine - clearance?

BOTH acetyl and plasma-cholinesterase

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Acetylcholine - Rx?

No therapeutic use - metabolized to fast

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Methacholine - clearance?

acetylcholinesterase, slowed hydrolysis (longer t1/2 than acetylcholine)

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Methacholine - receptors?

Muscarinic - smooth muscle, glands, heart

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Methacholine - Rx?

Diagnose asthma

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Methacholine - Tx?

Bronchiolar constriction

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Methacholine - contraindication?

B-blockers

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Carbachol - clearance?

More resistant to acetylcholinesterase

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Carbachol - receptors?

Both muscarinic and nicotinic activity

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Carbachol - Rx

miotic agent

Reduces intraocular pressure after cataract surgery

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Carbachol - SE?

excessive muscarinic/nicotinic activation

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Bethanochol - clearance

resistant to acetyl- and plasma cholinesterase

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Bethanochol - receptor selectivity?

Muscarinic only (GI and urinary bladder)

Bethanochol - Rx?

Post-op urinary retention Post-partum urinary retention Neurogenic bladder atony

Can quaternary amine drugs cross the BBB

No they're charged

Bethanochol - contra?

peptic ulcer asthma bradycardia

Muscarine poisoning causes profound

sympathetic activation

Muscarine poisoning - antidote?

Atropine - muscarinic antagonist

Pilocarpine - receptor selectivity?

pure muscarinic

Pilocarpine - BBB?

Yes, crosses (tertiary amine). Appreciable CNS effects

Pilocarpine - Rx?

dry mouth (radiotherapy) Sjogren's syndrome Open glaucoma Closed-angle glaucoma

Pilocarpine - Contra?

B-blockers (exacerbates slowed conduction)

Cholinesterase inhibitors act INDIRECTLY as

cholinergic agonists

2 types of endogenous cholinesterases:

1. Acetylcholinesterase | 2. Plasma-cholinesterase (aka butyryl-cholinesterase)

Where is butyrylcholinesterase localized

plasma

What hydrolyzes exogenous cholinergics?

butyrlcholinesterase (plasma cholinesterase)

Name 3 reversible cholinesterase inhibitors

1. Neostigmine 2. Edrophonium 3. Donepazil

Neostigmine - BBB?

Poor penetration of BBB

Neostigmine - MOA

inhibits acetylcholinesterase; stimulatory effect at Nm

Neostigmine - Rx

Reverse neuromuscular blockade | eg. MS

Neostigmine - SE

Excessive ACh stimulation at peripheral muscarinic and Nm

Neostigmine - contra

intestinal obstruction

Edrophonium - MOA?

Inhibits cholinesterases, stimulates nicotinic R

Edrophonium - pharmakodynamics?

Rapid onset of action. Short duration of action.

Edrophonium - Rx?

1. Diagnosis of myasthenia gravis | 2. Differential btwn myasthenia gravis progression and cholinergic crisis (excessive ACh)

Edrophonium - SE?

Bradycardia

Edrophonium - Tx?

Neuromuscular block promoting muscle weakness (mistaken for MS progression)

Physostigmine - BBB?

Crosses it

Physostigmine - clearance?

plasma cholinesterase (long time though)

Physostigmine - Rx?

Counteract delirium via excess anticholinergic activation

Physostigmine - SE?

too much ACh at N and M receptors

Physostigmine - contra?

Asthma, cardiac insufficiency, gut obstruction

Donepezil - Rx

Alzheimer's

Donepezil - MOA

Reversible inhibitor of acetylcholinesterase in CNS

Donepezil - BBB?

Crosses BBB

Found in insecticides and nerve gas

organophosphates

Organophosphate - MOA

irreversible inhibitor of cholinesterase's - the complex "becomes a stable complex with time"

Two antidotes for organophosphate poisoning (cholinergic crisis)

Atropine | 2-PAM

Name an organophosphate that is used to produce long term mitosis for open angle glaucoma

Echothiophate

What is a parsympatholytic agent?

Muscarinic antagonist

At high doses, muscarinic antagonists can

block nicotinic cholinergic receptors at autonomic ganglia

Atropine - name 5 Rx

1. Allay the urgency and frequency of micturition 2. relieve hypermotility of colon and hypertonicity of the small intestine 3. organophosphate poisoning antidote 4. indue mydriasis and cycloplegia (paralysis of ciliary muscle) 5. reverse vagal bradycardia

Scopalamine Rx?

1. Minimize secretions before surgery | 2. Treat chemo-induced nausea/emesis

Glycopyrrolate Rx?

Prevents overstimulation of gut during reversal of neuromuscular blockade.

Name 3 muscarinic antagonists

A. Atropine B. Scopalamine C. Glycopyrrolate

How do Atropine poisoning patients present?

"Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone"

Edrophonium half life?

10 minutes

Pralidoxime (2-PAM) half life?

75 min

Pralidoxime (2-PAM) - MOA?

PERIPHERAL AchE reactivator

Pralidoxime (2-PAM) - Rx?

Resp. muscle weakness from organophosphate poisoning

Physostigmine - MOA?

reversible AChE inhibitor

What would you give for delirium from anticholinergic drugs, or glaucoma?

Physostigmine, a reversible AChE inhibitor

What would you give to diagnose myasthenia gravis, or to reverse neuromuscular block?

Edrophonium, an AChE inhibitor

What would you give for open angle glaucoma?

Echothiophate, an irreversible AChE inhibitor with a VERY LONG half life.

What would you give for excessive secretions b4 surgery, hypertonic gut, organophosphate poisoning, bradycardia?

Atropine, a muscarinic antagonist

What would you give, for motion sickness, or to reduce secretions during surgery?

Scopalamine, a muscarininc antagonist (like atropine, except longer T1/2)

What drug would you give, with a shorter half-life than echothiophate, to reverse neuromuscular blockade and reduce secretions?

Glycopyrrolate, a muscarinic receptor antagonist

Pilocarpine - half life?

1 hr