Cholinergic Pharmacology I Flashcards
Types of cholinoceptor stimulants (2)
Direct-acting cholinomimetics
Indirect-acting cholinomimetics
Types of direct-acting cholinomimetic agonists (2)
Muscarinic and nicotinic
Types of muscarinic cholinoceptor agonists (2)
Choline esters and alkaloids
Types of nicotinic cholinoceptor agonists (1)
Alkaloids
Choline esters (4)
Acetylcholine
Methacholine
Carbachol
Bethanechol
Acetylcholine muscarinic effects: Cardiovascular Respiratory Excretion Urination Eye
Cardio- low doses causes hypotension and reflex tachycardia
Respiratory- bronchial secretion and constriction
Excretion- salivation, lacrimation, sweating
Urination- bladder contraction
Eyes- short-lasting miosis
Acetylcholine nicotinic effects
Not commonly seen
Clinical use of acetylcholine (2)
Eye surgery- miosis
Provocation test in coronary angiography (Dx of coronary vasospasm)
Methacholine (provocholine) clinical use
Diagnosis of bronchiolar hypersensitivity/asthma through excessive bronchoconstriction via M3 receptors
Carbachol clinical use
Glaucoma: contracts ciliary muscle
Enlarges canal of schlemm, increases drainage, and decreases intraocular pressure
Bethanechol (urecholine) clinical use:
GI and GU
Genitourinary: increase detrusor tone, decrease outlet resistance of internal sphincter
Gastrointestinal: increase motility & secretion
Bethanechol acts primarily on which receptor
Acts on M3, weak M2 response
Bethanechol indications (3)
- Gastric atony after vagotomy to reduce reflux (increases lower esophageal sphincter tone);
- Gastric emptying abnormalities
- Urinary retention (in the absence of obstruction)
Type of muscarinic alkaloids (2)
Muscarine
Pilocarpine
Muscarine acts on which receptors? Why does it have longer duration of action than ACh?
Muscarine causes excessive activation of all muscarinic receptors (M1, M2, and M3)
Longer duration because it is not a choline ester so it is not broken down by AChE
Symptoms of muscarine poisoning Excretion GI Respiratory Vision
Excretion: salivation, sweating, lacrimation
GI: Abdominal pain, nausea, diarrhea
Respiratory: Dyspnea (due to constriction and secretion)
Vision: blurred vision due to M3 activation
Pilocarpine (isoptocarpine, salagen) has predominant effects where?
Opthalmic M3 effects
Clinical Uses for pilocarpine (2)
Glaucoma: Rx of choice because it works on wide and narrow-angle glaucoma
Test on autonomic state (e.g., pilocarpine hypersensitivity –> PANS dysfunction)
Contraindications for direct-acting cholinoceptor agonists (3)
Peptic ulcers
GI tract disorders
Asthma
What two types of drugs should not be used with muscarinic agonists?
- Antiarrhythmics
2. Tricyclic antidepressants
What are the two nicotinic direct-acting agonists?
- Nicotine
2. Succinylcholine
Nicotine Action on NM subtype receptors (3)
skeletal muscle contraction
fasciculations, spasm
depolarizing blockade
Nicotine Action on NN subtype nicotinic receptors Cardiac Vascular GI Carotid bodies Medullary emetic chemoreceptors
- Stimulate sympathetic & parasympathetic post-ganglionic neurons:
Cardiac: increased heart rate (sympathetic > parasympathetic)
Vascular: mostly sympathetic innervation -> peripheral vasoconstriction
GI: increased gut motility & secretion
Carotid bodies: increased respiratory rate
Medullary emetic chemoreceptors: nausea & vomiting
Indirect-acting cholinoceptor agonists- reversible (6)
- Edrophonium
- Neostigmine
- Pyridostigmine
- Physostigmine
- Donepezil
- Tacrine
Edrophnium clinical use
Dx – myasthenia; used to differentiate myasthenia from cholinergic crisis
Neostigmine and pyridostigmine
Rx – ileus, urinary retention, myasthenia, reversal of non-depolarizing NM blockers
Physostigmine
Rx- antidote in atropine overdose; glaucoma
Donepezil and tacrine
Rx- Alzheimers
Treatment options for cholinesterase inhibitors (2)
Atropine and palidoxime (2-pam)
DUMBBELS
D-Diarrhea U- Urination M- Miosis B- Bronchiolar constriction B- Bradycardia E- Excitement/Emesis L- Lacrimation S- Sweating S- Salivation
