cholinoreceptor stimulants

Question 1

Acetylcholine

Answer 1

Rapid destruction by AChE  limited clinical use (IV).

Prototype agent. Major tool in physiology & pharmacology.

Question 2

Acetylcholine Muscarinic effects

Answer 2

Cardiovascular effects:
Low doses: vasodilation  reflex tachycardia
Higher doses: bradycardia;  A-V conduction; (-) inotropy
Bronchial constriction, increased bronchial secretion
Salivary excretion, tears, sweat
Urinary bladder contraction
Eye: short-lasting miosis

Question 3

Acetylcholine nicotinic effects

Answer 3

not commonly seen, since Ach does not penetrate the fat surrounding skeletal muscle and autonomic ganglia

Question 4

Ache clinical use

Answer 4

eye surgery (short-lasting miosis) 
	provocation test in coronary angiography (Dx coronary vasospasm)

Question 5

Methacholine

Answer 5

Similar to ACh in action
Longer T1/2 (methyl group)

Clinical uses:

Diagnosis of bronchiolar hypersensitivity: “methacholine challenge”  excessive bronchoconstriction via M3 receptors in bronchial muscle in asthmatic patients

Question 6

Carbachol

Answer 6

Effects: 
- Therapeutic doses: activate both nicotinic and muscarinic cholinoceptors  	nicotinic effects: 
	autonomic ganglia 
	adrenal medulla
	skeletal muscle
- High doses: may induce cardiac arrest.  
Clinical Use: Glaucoma:
		contracts ciliary muscle 
 enlarges canal of Schlemm 
 increases drainage of aqueous humor
 decreases intraocular pressure

Question 7

Bethanachol

Answer 7

Quarternary choline ester
Acts predominantly on M3:
Genitourinary: increase detrusor tone, decrease outlet resistance of internal sphincter
Gastrointestinal: increase motility & secretion
Week effects on M2 receptors: minimal cardiac effects

Indications:
Gastric atony after vagotomy to reduce reflux (increases lower esophageal sphincter tone);
Gastric emptying abnormalities
Urinary retention (in the absence of obstruction)

Question 8

Muscarine

Answer 8

Properties:
quaternary ammonium compound,
no nicotinic activity,
100 times more potent than ACh
Longer duration of action than ACh (not a choline ester not broken down by AChE).
Muscarine poisoning:
Salivation, sweat, tear flow
Abdominal pain, nausea, diarrhea, blurred vision, dyspnea
Symptoms generally subside within 2 hrs.
Severe cases: cardiac & respiratory failure may lead to death

Question 9

Pilocarpine

Answer 9

Properties:
- Tertiary amine
Opthalmic (M3) effects predominate: topical application; poor systemic absorption
Contracts iris sphincter muscles  miosis
Frees entrance to canal of Schlemm (therapy for narrow-angle glaucoma)
Enhances tone of trabecular network (therapy for wide-angle glaucoma)
Contracts the ciliary muscle: accommodation and loss of far vision.

Clinical uses:
Glaucoma: Rx of choice
Xerostomia: given orally to stimulate saliva secretion
Test on autonomic state (e.g., pilocarpine hypersensitivity  PANS dysfunction)

Question 10

Contraindications and Drug interactions for Musarinic choloniergic agonists (Direct)

Answer 10

Contraindications:
Peptic ulcers
GI tract disorders
Asthma

Drug Interactions: Drugs having antimuscarinic properties can block the effects of the muscarinic agonists

Quinidine (antiarrhythmics)
Procainamide (antiarrhythmics)
Tricyclic antidepressants

Question 11

Nicotine

Answer 11

Prototypical agonist for nicotinic acetylcholine receptors
Action on NM subtype receptors (at neuromuscular endplate)
skeletal muscle contraction
fasciculations, spasm
depolarizing blockade
Action on NN subtype nicotinic receptors: stimulate both 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

clinical:aid in smoking cessation