Cholinergic antagonists

Sites of action of cholinergic antagonists

ganglia

skeletal muscle (NMJ blockers)

end organs of the PSNS

Cholinergic antagonist effects

anti-SLUDGE

dry mouth

dry eyes

tachycardia

urinary retention

decreased gastric secretion and decreased GI motility

blurred near vision (at high doses)

Anticholinergic effects: eyes

mydriasis (pupil dilation)

cycloplegia (prevent ciliary contraction, eye is fixed for far vision

reduction in lacrimal secretions

no major effect on IOP (except in patients predisposed to narrow angle glaucoma)

Anticholinergic uses: eyes

examination of the retina

product used penetrate well after topical administration

minimal systemic effects when locally administered

DOA 30-90 minutes

anticholinergic side effects: eye

photophobia

blurred vision

anticholinergic agents: topical agents for the eye

Homatropine

Tropicamide

Cyclopentolate

anticholinergic effects: cardiovascular system

Heart: increased chronotropy and inotropy (M2 receptors)

Blood vessels: no major change in vascular tone because blood vessels are predominantly controlled by the SNS

no significant change in BP

anticholinergic uses: cardiovascular system

Atropine: used in coronary care units or surgical settings, used when excess vagal tone causes bradycardia or AV block

anticholinergic side effects: cardiovascular system

atropine flush: in some patients, atropine dilates cutaneous blood vessels of the face which may be an indirect effect secondary to the rise in body temperature caused by the inhibition of sweating (SNS but muscarinic)

anticholinergic effects: GI system

relaxation of detrusor and smooth muscle of the ureters

increases tone of trigone sphincter

promotes urinary retention

anticholinergic uses: GI system

OAB

uninhibited bladder syndrome

bladder spasms

incontinence

enuresis (bed wetting)

anticholinergic side effects: GI system

peripheral (M3): xerostoma and constipation, blurred vision

central (M1): drowsiness, dizziness, confusion (mostle in elderly patients)

anticholinergic agents: GI system

Oxybutynin: high incidence of antimuscarinic side effects, transdermal/topical better tolerated

tolterodine: seems to have selectivity for bladder tissue and better tolerated

Trospium: quaternary nitrogen limits CNS penetration

Solifenacin and Darifenacin: both suggested to be more selective for M3 receptor over M1 receptors thereby reducing CNS side effects

Anticholinergic overdose

Blind as a bat

Hot as hades

Dry as a bone

mad as a hatter

bowel and bladder lose their tone

Heart races on alone

note: treatment is usually supportive

nicotine

ganglionic drug

readily absorbed through the small intestine, oral mucosa and skin

liquid, colorless, volatile base

ganglionic drugs: low doses

stimulatory at nicotinic receptors

ganglionic drugs: high doses

produces an initial stimulation followed by rapid desensitization of the receptor

nicotine: selectivity

relatively selective for neuronal nicotinic receptors over NMJ nicotinic receptors because it tends to distribute to CNS sites more readily

nicotine: routes of admin

inhalation: delivered rapidly to the brain. peripheral concentration is low in comparison

buccal and transdermal: slower absorption, low plasma levels and eventual CNS penetration

IV: rapid systemic circulation allows the drug to interact at the ganglia. typical response is to activate the ANS with the SNS predominating. as time goes on, the ANS shuts down because the nicotinic receptors are desensitized

nicotine: clinical uses

limited for smoking cessation replacement therapy at very low doses. no other clinical utility

ganglionic blockers

not clinically used

hexamethonium, trimethaphan, mecamylamine

these drugs block neurotransmission through the ganglia of the ANS

very good at lowering BP but have a huge number of side effects - stopping all ANS function