8-21 Cholinergics Flashcards
[M1 Muscarinic Receptors]
A: Molecular Mechanism when activated (3)
B: Activates _______ Plexus—> INC _______ _______
[M1 Muscarinic Receptors]
A: INC IP3 / DAG / Ca+
B: Activates Myenteric Plexus—> INC GI Motility
[M2 Muscarinic Receptors]
A: Molecular Mechanism when activated (3)
B: Effects of Molecular Mechanism
ºPrevents _______ release from _______ nerve terminals by DEC _______ and _______
º _______[INC/DEC] [HR/Contraction/Cardiac Output] by opening ___ channels
[M2 Muscarinic Receptors]
A:
1) Opens K+ channels–> DEC HR/Contraction/Cardiac Output
2) DEC cAMP
3) DEC Ca+
B: [2 & 3] –> Inhibits NorEpi release from sympathetic nerve terminals
A: [M3 Muscarinic Receptors] _______[INC/DEC] IP3, DAG and Ca+.
B: What are the effects of this?
- Contracts ___ muscle (5)
- VasoDilation or vasoconstriction?
- Stimulates Secretions from _____ (6)
[M3 Muscarinic Receptors] INCREASE IP3, DAG and Ca+
Effects:
-Contracts circular ciliary muscle / bronchioles/GI smooth m/ uterine / bladder
- VasoDilation (via NO from endothelium)
- Stimulates secretions of GI tract / sweat glands / tear glands / salivary glands / pancreas / bile
NICOTINE
MOA
NICOTINE
MOA: ACTIVATES Neuronal NICOTINIC RECEPTORS
NICOTINE
Usage / Rx
NICOTINE
Usage / Rx: Reduces Withdrawal Sx associated with Smoking Cessation
SUCCINYLLCHOLINE
MOA
SUCCINYLLCHOLINE
MOA: BLOCKS MUSCULAR NICOTINIC RECEPTORS VIA DEPOLARIZATION –> NEUROMUSCULAR BLOCK!
SUCCINYLLCHOLINE
USAGE / RX (2)
SUCCINYLLCHOLINE
Usage / Rx:
- Emergent Intubation
- Electroconvulsive Shock Therapy
SUCCINYLLCHOLINE
Elimination
SUCCINYLLCHOLINE
Elimination: ButyrlCholinesterase
ACETYLCHOLINE
HALF-LIFE
ACETYLCHOLINE
HALF-LIFE = 150 milliseconds
ACETYLCHOLINE
USAGE / RX
ACETYLCHOLINE
USAGE / RX = NONE!
METHACHOLINE
HALF-LIFE (Longer or shorter than Ach?)
METHACHOLINE
HALF-LIFE = LONGER THAN ACH
METHACHOLINE
TOXICITY
METHACHOLINE
Toxicity: Bronchoconstriction
CARBACHOL
MOA
CARBACHOL
MOA: [Nicotinic and Muscarinic Receptor] Agonist
BETHANECHOL
MOA
BETHANECHOL
MOA: Muscarinic Agonist (specifically of the GI and Urinary Bladder)
BETHANECHOL
USAGE / RX (2)
BETHANECHOL
USAGE / RX: U
- Urinary Retention
- Neurogenic Bladder Atony
BETHANECHOL
CONTRAINIDICATION (3)
BETHANECHOL
CONTRAINDICIATIONS: DO NOT USE IN PT WITH: a)PUD [peptic ulcer dz] b) bradycardia c) asthma
CARBACHOL
USAGE / RX (2)
CARBACHOL
USAGE / RX:
- INDUCES MIOSIS IN OCULAR SURGERY
- REDUCES PRESSURE (via miosis) POST-OCULAR SURGERY
METHACHOLINE
Contraindications
METHACHOLINE
Contraindications: DO NOT GIVE TO PT TAKING BETA BLOCKERS SINCE [BETA 2 AGONIST] IS USED TO REVERSE TESTING
METHACHOLINE
MOA
METHACHOLINE
MOA: Muscarinic Agonist
METHACHOLINE
USAGE / RX
METHACHOLINE
Usage/Rx: Dx of subclinical asthma or test of severe asthma
ACETYLCHOLINE
ELIMINATION
ACETYLCHOLINE
Elimination = Acetylcholinesterase
ACETYLCHOLINE
MOA
ACETYLCHOLINE
MOA= [Nicotinic and Muscarinic Receptor] Agonist
Pralidoxime:
Half-life
~75 mins
Pralidoxime:
Mechanism of Action
Peripheral AchE reactivator
Pralidoxime:
Rx
Respiratory muscle weakness in organophosphate poisoning
[Tx for organophosphate poisoning/serine gas - reactivation of alkylphosphorylated AChE with Pralidoxime Chloride (2-PAM) ]
Echothiophate:
Half-life
Very long
Echothiophate:
Mechanism of Action
Irreversible AchE inhibitor
Echothiophate:
Rx
Used to produce long-term miosis in the treatment of open angle glaucoma
Atropine:
Mechanism of Action
Muscarinic ANTagonist
Atropine:
Rx (6)
- Reduces Excess secretions during surgery,
- Treats ↑ freq and urgency micturition associated
with cystitis/UTI - Relieves hypermobility of colon and hypertonicity of small intestines
- organophosphate poisoning/cholinesterase inhibitor induced poisoning
- Reverses bradycardia of vagal origin,
- Reduces mydriasis and cycloplegia (ie- paralysis of the ciliary muscle)
Scopolamine:
Mechanism of Action
Muscarinic antagonist
Scopolamine:
Rx (2)
- Motion Sickness and Chemotherapy N/V
2. Pre-OP anti-salilagogue (minimizes secretions for surgical anesthesia)
Glycopyrrolate:
Mechanism of Action
GI Muscarinic ANTagonist
Glycopyrrolate:
Rx (2)
- Prevents excessive [GUT muscarinic activation] during reversal of neuromuscular blockade
- antisalilagogue
Pilocarpine:
Half-life
1 hr
Pilocarpine:
MOA
How well does it move through BBB?
Neuronal Muscarinic agonist (crosses BBB very well)
Pilocarpine:
Rx (Indications) (2)
- Dry mouth from head and neck radiation
2. Narrow angle glaucoma
Pilocarpine:
Contraindications
Administer with care to pts taking B-blockers due to exacerbation of conduction slowing.
Neostigmine:
MOA (2)
How well does it move through BBB?
(1) AchE inhibitor (poor penetration of BBB)
(2) Direct stimulatory effect on nicotinic receptors of skeletal muscle endplate
Neostigmine:
Rx (Indications) (2)
- Myasthemia gravis
2. Reverse neuromuscular block
Neostigmine:
Side effects
Side effects related to excessive Ach action at peripheral muscarinic and nicotinic receptors.
Edrophonium:
Half-life
10 min
Edrophonium:
MOA (2)
- AchE inhibitor
2. Stimulates nicotinic receptors
Edrophonium:
Rx (Indications) (2)
- Diagnosis of myasthenia gravis (as oppose to a cholinergic crisis)
- Reversal of neuromuscular block
Edrophonium has a very ______ (rapid/slow) onset of action.
Edrophonium has a very RAPID(rapid/slow) onset of action.
Edrophonium:
Side effects (2)
- Excessive use can result in muscle weakness which can mimic and be mistaken for myasthenia gravis progression
- Bradycardia
Physostigmine:
MOA
How well does it move through the BBB?
Reversible AchE inhibitor
Readily cross the BBB
Physostigmine:
Rx (Indications) (2)
- Delirium from anticholinergic drugs
2. Glaucoma
How is Physostigmine inactivated?
Inactivated by plasma cholinesterases, but it takes a long time
Physostigmine:
Side effects
Side effects related to increased Ach at muscarinic or nicotinic receptors
Physostigmine:
Contraindications (3)
- Asthma
- Cardiac insufficiency
- Gut obstruction
Donepezil:
Rx (Indications)
Treatment of Alzheimer’s
Donepezil:
MOA
How well does it move through the BBB?
Reversible inhibitor of AchE in the CNS (so moves through BBB well)
