Drugs acting at the ANS

===Lecture Details===
Liz Davis; Week 8 MED1022; Pharmacology
===Lecture Content===
ACh synthesis is from hemicholinium which decreases the uptake of choline; choline is the precursor for ACh which uses acetyl-CoA and acetyl transferase. This occurs in the vesicle. This is then stored usually in vesicles, vesamicol blocks this. These vesicles are then released into the junction, blocked by presynaptic toxins eg botulinum. Botulism causes difficulty swallowing and speaking, progressive weakness with paralysis, nausea/vomiting, abdominal cramps, dry mouth and double vision as well as breathing difficulty and temporary lack of breathing. Botox can be used in eyelid spasms, hyperhydrosis (abnormal and excessive sweating), cerebral palsy.
ACh then crosses the junction. Acetylcholinesterase metabolises ACh in the junction to acetate and choline. Anticholinesterases eg neostigmine inhibit this. Non-specific cholinesterases also metabolise ACh eg suxamethonium which is present in plasma and the liver. Anticholinesterases are used in myasthenia gravis (neostigmine, pyridostigmine), Alzheimer's (donepezil, galantamine, rivastigmine). Causes increased salivation, nausea, diarrhoea, vomiting, abdominal cramps. Overtreatment may cause a cholinergic crisis such as with nerve gases (sarin) and insecticides. There are symptoms of parasympathetic overactivity (sweating, increased salivation, bradycardia) and fasciculations, neuromuscular blockade and resp failure. Treated with ventilation, atropine (blocks ACh). Pralidoxine can be used to treat.
Drugs acting at the autonomic ganglia are ganglion stimulants (nicotine, epibatidine) which have complex effects due to stimulation of sympathetics and parasympathetics. Ganglion stimulation may be followed by block and have no clinical use. Ganglion blocking drugs can be agonists, block the receptor (trimethaphan) or the channel (hexamethonium) and have complex effects. Ganglion blockade increases heart rate (M2), dilates vascular smooth muscle, decreases tone and motility of GIT (M3), has slight dilation of bronchial smooth muscle, urinary retention, blocked erection and ejaculation, blocked secretion of sweat glands, and pupil dilation/loss of accomodation (M3).
Muscarinic agonists are parasympathomimetics, muscarinic antagonists are parasympatholytics. Agonists can be ACh and synthetic choline esters (methacholine, carbachol, bethanechol) or naturally occuring cholinomimetics (pilocarpine, muscarine). Differ in selectivity, duration of action. Choline esters act on both M and N receptors, cholinomimetics just M. Agonists can be used to constrict pupil to decrease intraocular pressure (pilocarpine; glaucoma), stimulate GIT activity/bladder emptying (bethanechol, M3 selective).
Mushroom poisoning commonly contains toxins including muscarine. Antagonists can be atropine, hyoscine. They dilate pupil, inhibit secretions, increase HR, inhbit motility + gastric acid secretion, decrease bladder emptying. Red as a beet, dry as a bone, blind as a bat, hot as a hare, mad as a hatter (hallucinations, agitation). Can be to dilate pupil, used in asthma (ipratropium), antispasmodic (hyoscine) or prevent motion sickness.
===Readings===
Rang (6) 10 and 11