pharm: cholinergic drugs

Muscarinic agonist: function + which drug

mimics ACh at muscarinic receptors.

Bethanechol

muscarinic antagonist: function + which drug

blocks ACh at muscarinic receptors

atropine

ganglionic stimulating agents: function + which drug

mimic ACh at nicotinic receptors

nicotine

ganglionic blocking agents: function + which drug

block ACh at nicotinic receptors

mecamylamine

neuromuscular blocking agents: function + which drug

blocks muscle receptors

d-tubocuraraine

cholinesterase inhibitor: function + which drugs (2)

blocks AChE (the enzyme that breaks down ACh, resulting in more ACh)

neostigmine and phsyostigmine

bethanechol is a

• “parasympathomimetic agent“ - mimics effects of the parasympathetic NS

• and a muscarinic agonist

effects of bethanecol

• bradychardia

• hypotension

• bronchioconstriction

• increased GI tone and motility

• contraction of depressor muscle (makes you pee)

• increased sweating, salivation, bronchial secretions and Gastric acid

• miosis and ciliary contraction

bethanechol ionization

it is a charged substance, so it doesn’t cross cell membranes

• meaning: only a small portion of the dose is actually absorbed and It is not long acting

the only approved use of bethanechol is

relieving urinary retention

adverse effects of bethanechol

• hypotension

• increased tone and motility of GI tract

• risk of bladder rupture if there is a blockage

• exacerbation of asthma

• dysrhythmias in patients with hyperthyroidism

how can someone overdose on muscarininc agents like bethanecol

certain mushrooms, overdose of the drug and cholinesterase inhibitors

how do you treat muscarininc agent overdoses

atropine - muscarinic antagonist. it stops the parasympathetic effects

pilocarpine

• muscarinic agonist

• used for topical therapy of glaucoma

• also used for dry mouth from sjögren syndrome or salivary gland damage

acetylcholine as a muscarinic agonist

• only clinical use is rapid miosis after lens delivery in cataract surgery

• too unselective to be used for other purposes bc it activates muscarininc and nicotinic receptors

• it also has a very short half life due to AChE

atropine

• competitive antagonist of ACh at muscarinic receptors

• parasympatholytic - blocks parasympathetic NS effects

effects of muscarinic antagonists like atropine

• dry mouth, dry eyes

• mydriases + cyclopegia (inability to focus near and far)

• tachycardia

• decreased GI tone and motility (constipation)

• deceased pressure on detrusor muscle (less urge incontinence)

• confusions + hallucinations

what other drugs can mimic muscarinic antagonist and what should they be avoided with

• antihistamines

• TCAs

• phenothiazine antipsychotics

• should be avoided with atropine

therapeutic uses of muscarinic antagonist (8)

• pre-anesthetic

• bradycardia

• GI hyper mobility

• eye disrders

• asthma

• peptic ulcer disease - slows GI acid

• biliary colic (gallstones in bile duct)

• muscarinic agonist poisoning

adverse effects of muscarinic antagonists

• tachy

• blurred vision

• photophobia (light sensitivity)

• urinary retention

• xerostomia (dry mouth)

• glaucomaa

• anhidrosis - dry, hot skin

• hallucinations

how do we treat muscarinic antagonist toxicity

• physostigmine - AChE inhibitor

scopolamine

• muscarinic antagonist

• causes sedation unlike atropine which causes CNS excitation

• used for motion sickness, eye procedures, pre-anesthesic sedation and obstetric anemia

ipratropium bromide

• anticholinergic drug

• used to treat asthma, COPD and rhinitis

• nasal spray or inhaler, not associated with systemic antimuscarinic effects (dry mouth, blurred vision, urinary retention etc.)

dicyclomine

• muscarinic antagonist

• indicated for irritable bowel syndrome

darifenacin

• anticholinergic drug indicated for overactive bowel syndrome

• greatest degree of Muscarinic 3 selectivity

• no effect on M1 receptors (brain) or M2 receptors (heart)

cholinesterase inhibitors are

drugs that prevent the degradation of ACh by acting on acetylcholinesterase (AChE)

• viewed as indirect acting cholinergic agonists

• lacks selectivity - can work on muscarinic, ganglionic, and neuromuscular

neostigmine

• reversible cholinesterase inhibitors

• used to treat myasthenia graves

• cannot cross cell membranes or BBB bc of positive charge

physostigmine

• reversible cholinesterase inhibitors

• main AChE inhibitor used to treat myasthenia graves

• not charged - can readily cross cell membrane and BBB

Donazepil

• reversible cholinesterase inhibitor used to treat Alzheimers

irreversible cholinesterase inhibitors

• only clinical use is glaucoma

• high toxic

• used in insecticides

• highly lipid soluble - can cross membranes and BBB

Myasthenia Gravis

• autoimmune disease where antibodies attack Nicotinic M receptors on skeletal muscle

• the receptors are constantly blocked

• characterized by fluctuating muscle weakness and predisposition to rapid fatigue

treatment of Myasthenia Gravis

• cholinesterase inhibitors provide symptomatic relief by increasing ACh to bind to those Nicotninc M receptors

cholinergic crisis + treatment

• caused by overdose of AChE inhibitor

• muscle weakness/ paralysis paired with muscarinic response (parasympathetic effects)

• treat with respiratory support and atropine

myasthenic crisis

• caused by lack of AChE inhibitor

• extreme muscle weakness

how can we distinguish between the 2 crisis?

• doctors give edrophonium (short acting AChE inhibitor)

• gets better = myasthenic crisis

• gets worse = cholinergic crisis