Cholinergics and Cholinergic Blockers

I. Cholinergics / Parasympathomimetics
• mimics effects of acetylcholine, stimulating PSNS

A. Effects of Cholinergics at receptor sites:

Muscarinic receptor Nicotinic receptor

• pupil constriction • muscle contraction

• bronchoconstriction
• decrease HR, BP, & conduction
• increase GI peristalsis & secretions
• increase urinary bladder contraction, relax
urinary sphincters
• uterine contraction
• increase glandular secretions (sweat, tears,
saliva)
• erection

B. Inactivation of Acetylcholine
• Acetylcholinesterase

C. Classification of Cholinergics/ Parasympathomimetics

I. Direct acting cholinergics

 Muscarinic agonists
• bethanechol*
• carbachol
• pilocarpine
• metoclopramide (Reglan)

Indications: Tx of urinary retention, glaucoma, & gastroesophageal reflux

MOA: acts on muscarinic receptors to increase urination, constrict pupils & reduce
Intraocular pressure, increase GI peristalsis

CI : intestinal or urinary tract obstruction

  Nicotinic agonists
• Nicotine

MOA: stimulates nicotinic receptors at autonomic ganglia , neuromuscular junction

& CNS

Overdose: respiratory paralysis & cardiovascular collapse

 SE & adverse reactions of direct acting cholinergics:

• hypotension & bradycardia
• bronchoconstriction
• increase salivation & secretion of gastric acid
• Increase lacrimation
• Increase urination
• Increase defecation & abdominal cramps

II. Indirect Acting (Cholinesterase Inhibitors)

A. Reversible cholinesterase inhibitors

 Alzheimer’s disease drugs
• donezepil
• tacrine
• rivastigmine
• memantine
• Galantamine

MOA: blocks AChE and cross blood brain barrier thus improving memory by
increasing Ach in the brain

 Myasthenia Gravis Drugs

• ambenonium
• edrophonium (Tensilon)
• neostigmine
• physostigmine
• pyridostigmine *

MOA: blocks AChE, thus increasing Ach at synaptic cleft and cause increase in
muscle strength & tone.

 S/E of indirect acting :

• Same as direct acting

Caution in : bradycardia, asthma, peptic ulcer dse(PUD), hyperthyroidism

 CI: intestinal & urinary obstruction

B. Irreversible cholinesterase inhibitors

• organophosphate (malathion & parathion)
• nerve gas

uses : insecticide , chemical weapon

MOA: irreversibly bind with AChE causing excessive accumulation of Ach at

receptor sites parasympathetic crisis & muscle paralysis

 Cholinergic / Parasympathetic Crisis (DUMBBELSS)

 Diarrhea
 Urination
 Miosis
 Bronchospasm
 Bradycardia
 Excitation of skeletal muscles & CNS
 Lacrimation
 Sweating
 Salivation

II. Cholinergic Blockers/ Anticholinergics/ Parasympatholytics

• block stimulating effects of Ach, blocking PSNS

A. Cholinergic blockers (Antimuscarinics) for GIT

• Atropine*
• hyoscine bromide (Buscopan)
• dicylcomine (Bentyl)
• propantheline
• glycopyrrolate

Indications: antispasmodic in the Tx of peptic ulcer disease (PUD) & irritable bowel
Syndrome (IBS)

Atropine
Indications:
1. preop med to decrease salivary & respiratory secretions
2. tx PUD by decreasing GI spasms & peristalsis
3. tx sinus bradycardia by increasing HR
4. antidote for cholinergic drug overdose
5. mydriatic agent
 MOA: blocks Ach by occupying muscarinic receptors causing:
• increase HR by blocking vagus stimulation
• pupil dilation by paralyzing iris sphincter
• decrease secretions & GI motility

dosage: A : 0.4 – 0.6mg/ dose q 4- 6h PRN

C: 0.01 mg/ kg/dose ; max of 0.4 mg/ dose, q 4-6h PRN

 Common S/E & adverse Reactions of atropine & atropine-like drugs:

 Blurred vision
 Flushed skin
 Restlessness, headache, impotence, hallucination, delirium & coma
 Dry mouth & skin
 Decreased perspiration
 Constipation & urinary retention
 Muscle weakness

Blind as a bat.
Red as a beet
Mad as a hatter.
Hot as a hare.
Dry as a bone.

B. Cholinergic blockers for Parkinson’s Disease

• benztropine (Cogentin)
• biperiden (Akineton)
• procyclidine (Kemadrin)
• trihexyphenidyl (Artane)

Indications: control tremors & rigidity in parkinsonism & pseudoparkinsonism

MOA: block effects of Ach thus reducing tremors & rigidity, & decreasing
salivation in parkinson’s & pseudoparkinsonism

C. Cholinergic blockers for motion sickness

• Scopolamine

SE: same as atropine

Other antishistamines for motion sickness:

• dimenhydrinate (Dramamine)
• meclizine (Bonamine)
Whatsoever you sow, that you shall reap.