Cholinergics And Cholinergic Blockers

Cholinergics and Cholinergic Blockers I.

Cholinergics / Parasympathomimetics • mimics effects of acetylcholine, stimulating PSNS A. Effects of Cholinergics at receptor sites:

Muscarinic receptor

Nicotinic receptor

• • • • •

• muscle contraction

pupil constriction 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.