Another name for Cholinergic Drugs:
Parasympathomimetic drugs or Muscarinic Agonists
*Bind to muscarinic receptors activating receptors in all effectors organs of the parasympathetic nervous system
Cholinergic Drug Actions:
*Decrease intraoccular pressure by constricting pupil and contracting ciliary bodies of the eyes
*Heart brake: lower heart rate, decrease output, lowers BP
*Dilates blood vessels Skin, Viscera, Mucus Membranes (GI)
*Increase tone and motility of GI smooth
Common Cholinergic Drug Uses:
*Eye for glaucoma
*Bladder for stimulating urination
*Bowels encourage peristalsis
*Treatment of Myasthenia gravis
*Antagonist to Atropine: reverse effects
Points to remember with Cholinergic Drugs:
*Not very selective, therefore....
Side Effects:
*Salivation
*Bradycardia
*Dilation of the blood vessels
*Cause abd cramping, NVD
*Diaphoresis, flushing
*Urgency
*To reduce systemic side effects when administering cholinergic eye drops, hold the inner can
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Mechanism of Action:
*Bethanechol is a direct acting muscarinic agonist.
*Binds directly to muscarinic cholinergic receptors and causes activation
*At therapeutic doses acts selectively at muscarinic receptors having little or no effects on nicotinic receptors in ganglia or s
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Pharmacologic Effects: Eyes
Eye
*Miosis (pupillary constriction)
*Contraction of the ciliary muscle resulting in accomodation for near vision
*The ciliary muscle, which is attached to the lens, focuses the eye for near vision by altering lens curvature.
*Decrease intraoccular pressu
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Pharmacologic Effects: Heart
Heart
*Bradycardia
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Pharmacologic Effects: Exocrine glands
Exocrine glands
*Increase sweating
*Increase salivation
*Increase Bronchial secretions
*Increase secretion of gastric acid
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Pharmacologic Effects: Smooth muscles
*Constriction of the bronchi
*Increased tone and motility of the GI tract
*Contraction of the detrusor muscle & relaxation of the trigone and sphincter results in the emptying of the bladder
*Dilation of vascular smooth muscle resulting in lowered BP & po
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Pharmacokinetics:
*Bethanechol is available for oral administration only!
*Effects begin in 30 to 60 minutes and persist about 1 hour
*Quaternary ammonium compound that crosses membranes poorly; as a result only a small portion of each dose is absorbed.
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Therapeutic Uses:
Urinary Retention (primary use)
*Bethanechol is used to treat urinary retention in postoperative and postpartum patients.
*Relieves retention by activating muscarinic receptors of the urinary tract resulting in....
*Increased bladder pressure by contracti
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Should not be used to treat urinary retention caused by physical obstruction of the urinary tract!
Why?
Because increased pressure in the tract in the presence of blockage could cause injury.
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Therapeutic Use: Gastrointestinal
Gastroesophageal Reflux
*On an investigational basis
*Benefits may result from increased esophageal motility & increased pressure in the lower esophageal sphincter.
Can help treat disorders associated with GI paralysis. *Benefits derive from increased ton
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Adverse Effects: Heart
Relatively Rare with oral dosing!
*Hypotension and bradycardia: contraindicated for patients with low blood pressure or low cardiac output
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Adverse Effects: GI tract
At usual therapeutic doses, Bethanechol can cause:
*Excessive salivation
*Increased secretion of gastric acid
*Abdominal cramps
*Diarrhea
At higher doses can cause:
*Involuntary defecation
Contraindicated:
*Patients with gastric ulcers
*Intestinal obstruc
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Adverse Effects: Urinary Tract
Contraindicated:
*Patients with urinary tract obstruction
*Weakness in bladder wall
Reason:
Because of its ability to contract the bladder detrusor, and thereby increase pressure within the urinary tract it could lead to rupture of the bladder
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Adverse Effects: Exacerbation of Asthma
*By activating muscarinic receptors in the lungs, bethanechol can cause bronchoconstriction.
*Contraindicated in patients with latent or active asthma
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Adverse Effects: Dysrhythmias in Hyperthyroid Patients
*May increase heart rate to the point of initiating a dysrhythmia: opposite to the effect that muscarinic agonists have in most patients
*Initial cardiovascular response is normal: bradycardia and hypotension.
*In reaction to hypotension the baroreceptor
Muscarinic Agonist Prototype:
Bethanechol (Urecholine, Duvoid)
Preparations, Dosage, and Administration
Available in tablets: 5, 10, 25, 50 mg for oral therapy
Adults: 10 to 50mg given 3 to 4 times a day
Administration with meals can cause nausea & vomiting and hence dosing should be done one hour before meals or 2 hours after meals
Muscarinic Agonist:
Pilocarpine (Isoptocarpine)
Trade name: Salagen
Therapeutic Use:
*Topical therapy of glaucoma
*Oral therapy of dry mouth resulting from Sjogren's syndrome, or from salivary gland damage caused by radiation therapy of head & neck cancer
Principle Adverse Effects:
*Sweating in 29% patients with recommend
Muscarinic Agonist:
Pilocarpine (Isoptocarpine)
Trade Name: Salagen
Effects on the Eye?
*Miosis via constriction of the pupil via contraction of the iris sphincter
*Contraction of the ciliary muscle: an action that focuses the lens for near vision
*IOP lo
Effects on the Eye:
*Pt's w/ open angle glaucoma, IOP reduced because the tension generated by contracting ciliary muscle promotes widening of the spaces w/in the trabecular meshwork, facilitating outflow of aqueous humor
*Angle-closure glaucoma, contract
Muscarinic Agonist:
Pilocarpine (Isoptocarpine)
Trade Name: Salagen
Therapeutic Uses?
Therapeutic Uses:
*2nd line drug for open-angle glaucoma
*Emergency treatment of acute angle-closure glaucoma
Muscarinic Agonist:
Pilocarpine (Isoptocarpine)
Trade Name: Salagen
Adverse Effects?
*Occasionally, sustained contraction of the ciliary muscle causes retinal detachment
*Focuses the lens for near vision: corrective lenses can provide partial compensation for this problem (blurry vision)
*Constriction of the pupil may decrease visual acui
Muscaranic Agonists
Generic Name: Bethanechol Chloride
Trade Names:
*Duvoid
*Urecholine
Muscarinic Agonists
Generic Name: Pilocarpine
Trade Names:
Salegen
Muscarinic Agonists
Generic Name: Physostigmine Salicylate
*AChE inhibitor
Trade Names:
*Eserine
*Antilirium
Uses:
*Reversal of anticholinergic excess
*Antidote to Atropine overdose
*Antidote to Curare
Muscarinic Agonists
Generic Name: Pyridostigmine
*AChE inhibitor
Trade Names:
*Mestinon
*Regonal
Uses:
*Increase muscle strength in the symptomatic treatment of myasthenia gravis
*Reversal of nondepolarizing neuromuscular blocking agents
*Prophylaxis of lethal effects of poisening with the nerve agent soman
Muscarinic Agonists
Generic Name: Neostigmine
*AChE inhibitor
Trade Name:
*Prostigmin
Uses:
*Improvement in muscle strength in symptomatic treatment of myasthenia gravis
*Prevention and treatment of postoperative bladder distention and urinary retention or ileus
*Reversal of nondepolarizing neuromuscular blockers
*Antidote to C
Muscarinic Agonists
Generic Name: Edrophonium
*AChE inhibitor
Trade Name:
*Tensilon
*Enlon
Uses:
*Diagnosis of myasthenia gravis
*Assessment of adequacy of anticholinesterase therapy in myasthenia gravis
*Differentiating myasthenic from cholinergic crisis
*Reversal of muscle paralysis from nondepolarizing neuromuscular blocking
Sources of Muscarinic Poisening
*Overdose of direct acting muscarinic agents such as bethanechol and pilocarpine
*Overdose cholinesterase inhibitors
Symptoms of Muscarinic Poisening
*Profuse salivation
*Lacrimation
*Visual disturbances
*Bronchospasms
*Diarrhea
*Bradycardia
*Hypotension
*Severe poisening can produce cardiovascular collapse
Treatment for Muscarinic Poisening
*Administration of Atropine: by blocking muscarinic receptors can reverse most signs of toxicity
*Provide supportive therapy