Pharmacology - Autonomics Chlorinergics


1. Drug identification type questions that involve mechanism of action. You need to know the following types of facts:
a. atropine, scopolamine, propantheline are competitive muscarinic receptor blockers which sometimes are used to control salivary secretions. An additional fact that often gets asked about atropine has to do with the fact that it blocks vagal reflexive control of heart rate, resulting in tachycardia.
b. physostigmine and neostigmine are reversible anticholinesterases that differ in that physostigmine acts both centrally and peripherally, neostigmine only peripherally, but neostigmine also has some direct ACh like activity at the neuromuscular junction, in addition to prolonging the activity of endogenous ACh. They sometimes see use in treating xerostomia.
c. pilocarpine, methacholine, etc. are direct acting cholinergic agonists. May be used for xerostomia.
d. organophosphates and insecticides irreversibly inhibit cholinesterase
e. pralidoxime is an enzyme regenerator used in organophosphate toxicity
f. succinylcholine is a depolarizing neuromuscular junction blocker, subject to rapid inactivation by plasma pseudocholinesterase: it is used to prevent laryngospasm g. d-tubocurarine is a non-depolarizing neuromuscular junction blocker
h. mecamylamine and hexamethonium are ganglionic blockers that produce orthostatic hypotension

2. The 2nd type of question has to do with physiological effects of cholinergic stimulation, blockade, or overdose toxicity situations (and what drug you would give to reverse the toxicity).
a. cholinergic crisis symptoms: bradycardia, lacrimation, salivation, voluntary muscle weakness, diarrhea, bronchoconstriction -treat by giving atropine
b. scopolamine overdose: disorientation, confusion, hallucinations, burning dry mouth, hyperthermia: treat with physostigmine
c. An additional fact that often gets asked about atropine has to do with the fact that it blocks vagal reflexive control of heart rate, resulting in tachycardia.

Questions regarding physiological actions of cholinergic drugs:
OK, here’s an outline of cholinergic stimulation effects:
Eye: miosis and reduction of intraocular pressure
CV: bradycardia; vasodilation (but only from injected cholinergic agents, since the muscarinic receptors on the vascular smooth muscle has no neural input)
GI tract: increased spasmodic activity, increased salivation and acid secretion (overdose: nausea, vomiting, diarrhea)
Urinary tract: increased urination
Respiratory: bronchoconstriction
Glandular: lacrimation, sweating
Skeletal muscle: tremor and ataxia (overdose: muscle weakness, cramps and fasciculations)

Anticholinergic (antimuscarinic) actions are the reverse of the above:
Eye: mydriasis and loss of accommodation and increase of intraocular pressure
CV: increased heart rate (overdose: tachycardia)
GI tract: decreased spasmodic activity, decreased salivation and acid secretion (overdose:)
Urinary tract: decreased urination
Respiratory: bronchodilation
Glandular: decreased lacrimation, decreased sweating (overdose: hot, dry skin, hyperthermia)
Skeletal muscle: no effects, since they don’t act on nicotinic receptors, only muscarinic
CNS: tertiary amines such as atropine get into the brain and cause restlessness, headache, excitement, hallucinations and delirium. Quaternary amines like methantheline and propantheline only have peripheral actions