Autonomic Nervous System Effects Quiz

Cholinergic Agents

• Decrease in heart rate and cardiac output, similar to vagal stimulation, by releasing acetylcholine at the sinus node (SA node)
• Decrease in blood pressure via vasodilation, despite no parasympathetic innervation, but cholinergic receptors are found; increase intracellular Ca++ (atropine blocks these receptors)

Muscarinic Agents

• Bethanechol: structurally related to acetylcholine, but acetate is replaced by carbamate, and choline is methylated; not hydrolyzed by acetylcholinesterase, but by other esterases; strong muscarinic effect, little or no nicotinic action; 1-hour duration of action; acts on smooth muscle of GIT and bladder
• Increases GIT motility and tone, stimulates detrusor muscle of bladder, and relaxes trigone and sphincter → urine expulsion; used to treat atonic bladder (postpartum and postoperative non-obstructive retention)

Side Effects of Muscarinic Agents

• Sweating, salivation, flushing, decreased blood pressure, nausea, abdominal pain, diarrhea, bronchospasm

Carbachol (Carbamylcholine)

• Both muscarinic and nicotinic action; ester of carbamic acid; poor substrate for acetylcholinesterase; 1-hour duration of action; effects on both GIT and CVS due to ganglion-stimulating activity (stimulates then depresses these systems); on local eye application, causes miosis like acetylcholine; releases epinephrine from adrenal medulla by its nicotinic action; rarely used (long duration and high potency), so used in the eye only to cause constriction of pupils and decrease intraocular pressure (IOP)

Pilocarpine

• Tertiary amine, stable to hydrolyze by acetylcholinesterase; less potent than acetylcholine; used for eye application only (muscarinic action); causes rapid miosis, but not able to focus (spasm of accommodation); potent stimulant of secretion of sweat, tears, and saliva, but not used for this purpose (non-selective agents); used to treat:
  • Emergency lowering of IOP in both open and closed-angle glaucoma (effect lasts for 1 day)
  • Promoting salivation in xerostomia (resulting from head-neck irradiation) and Sjogren's syndrome (treated by oral tablet of pilocarpine)

Side Effects of Pilocarpine

• Enters CNS, causing disturbance; causes severe sweating and salivation

Cevimeline

• Other non-specific cholinergic agent like pilocarpine

Anticholinesterase (Reversible)

• Acetylcholinesterase enzyme that cleaves acetylcholine to acetate and choline; located in pre- and post-synaptic nerve terminals; inhibition of acetylcholinesterase → prolongs lifetime of acetylcholine and accumulates in synaptic space, introducing a response at muscarinic and nicotinic receptors (NMJ and Autonomic NS)

Neuro-Muscular Blocker Agents

• Block transmission of cholinergic between motor nerve ending and the nicotinic receptor on the neuromuscular end plate of skeletal muscle; structurally analogs of acetylcholine; divided into depolarizing (acetylcholine agonist) and non-depolarizing (acetylcholine antagonists) agents; useful for:
  • During surgery to produce complete muscle relaxation
  • Facilitating intubation

Depolarizing Agents

• Succinylcholine: used as IV, but of short duration of action, so used as continuous infusion; unlike acetylcholine, it persists for a long time in the synaptic cleft (time dependent on diffusion from motor end plate and hydrolysis by plasma cholinesterase) within synaptic cleft, not metabolized by cholinesterase until diffused to circulation; mode of action:
  • Attach to nicotinic receptor and depolarize the junction
  • 1st open Na channel → depolarize of the receptor (phase I) → transient muscle fasciculation
  • Then, within a few minutes, on continuous attachment to receptor, make receptor incapable of transmitting further impulses; continuous depolarizing gives way to gradual repolarization as Na channel closed or blocked, causing resistance to depolarization (phase II) and flaccid paralysis

Uses of Succinylcholine

• Endotracheal intubation (anesthesia induction)
• Electroconvulsive shock treatment

Action of Succinylcholine

• On eye: persistent mydriasis (dilate pupil), unresponsiveness to light, and cycloplegia (unable to focus for near vision); dangerous elevation of IOP, so short-acting agents like tropicamide or alpha adrenergic like phenylphrine are used for ophthalmic examination
• GIT: as antispasmolytic to reduce GIT activity, not affecting HCl production
• GUT: reduce hypermotility of urinary bladder (rare use in enuresis instead)
• CVS: at low dose, causes bradycardia (central activation of vagal efferent outflow block M1), at high dose, causes tachycardia (block M2 in SA node)
• Secretion: decrease salivation, sweat, and lacrimal glands
• Uses: for eye to measure refractive errors (induce mydriasis and cycloplegia), relax both GIT and bladder, antidote for cholinergic agonist poisoning, and as an antisecretary to reduce block secretion from upper and lower RS prior to surgery

Side Effects of Succinylcholine

• Dry mouth, blurred vision, tachycardia, constipation, on CNS: delirium, hallucination, and depression, collapse of respiratory system, and death; increase body temperature, especially in children; overdose treated by physostigmine

Scopolamine

• Tertiary amine, belladonna-derived, peripheral effects like atropine, high action on CNS than atropine; most effective anti-motion sickness agent, sedation, but at high dose, excitement, and induce euphoria (subject to abuse); used for motion sickness and amnesic action, so used in anesthesia; used for chronic treatment of open-angle glaucoma as a solution (effect lasts for 1 week after single use); side effects and causing cataracts limit its use

Reactivation of Acetylcholinesterase (Pralidoxime)

• Able to reactivate the enzyme if used at a time before aging of acetylcholinesterase (before losing its alkyl group); does not cross into CNS; acts by displacing the phosphate group from organophosphate and regenerating the enzyme; side effects like acetylcholinesterase inhibitors at high doses