Autonomic Pharmacology Overview

Study Notes

Drugs target the entire autonomic nervous system, affecting both sympathetic and parasympathetic systems
Nicotinic ACh receptors are found at synapses between pre- and postganglionic neurons in both systems, as well as skeletal muscles
Skeletal muscle AChRs are pentameric, using α subunits, while autonomic AChRs use 2-7 subunits
Hexamethonium is a non-competitive antagonist of autonomic nicotinic ACh receptors, blocking both sympathetic and parasympathetic effects without affecting skeletal muscles
It's no longer used due to numerous side effects
Postganglionic parasympathetic neurons use muscarinic ACh receptors to target effectors

Muscarinic ACh receptors are G-protein coupled receptors with 7 transmembrane domains
Five types exist, with M1, M2, and M3 being significant
M1 receptors are in the stomach and salivary glands, activating phospholipase C (PLC)
M2 receptors are in cardiac muscle, inhibiting adenylyl cyclase to reduce cAMP levels
M3 receptors are in smooth muscle, bronchi, and exocrine glands, activating PLC

These drugs activate muscarinic ACh receptors, mimicking parasympathetic stimulation
Effects include decreased heart rate, vasodilation, smooth muscle contraction (gut, respiratory tract), salivation, and lacrimation

Used to treat asthma, bradycardia, constricted pupils, urinary incontinence, and motion sickness
Ipratropium/tiotropium relax bronchial smooth muscle, atropine increases heart rate, tropicamide relaxes iris sphincter muscle, oxybutynin/tolterodine relaxes bladder smooth muscle, and hyoscine treats motion sickness
Muscarinic agonists can counteract effects of ACh esterase inhibitors
ACh esterase inhibitors are used post-surgery to prevent paralysis, but can cause unwanted ACh effects, so atropine counteracts these side-effects. AChE inhibitors are also administered in myasthenia gravis.

Sympathetic postganglionic neurons use noradrenaline (NA) as a neurotransmitter
Adrenoceptors are G-protein coupled receptors, with 5 types (α1, α2, β1, β2, β3)
α1 receptors cause smooth muscle contraction (vasoconstriction), often coupled with local anaesthetics to prevent spread
α2 receptors are involved in CNS control of hypertension and facial erythema
β1 receptors increase heart rate and contractility
β2 receptors cause smooth muscle relaxation (bronchi, blood vessels, bladder) and stimulate lipolysis
β3 receptors cause smooth muscle relaxation and stimulate lipolysis

Drugs can be agonists (mimicking) or antagonists (blocking) for these receptors
Agonists and antagonists have various clinical uses, including hypertension treatment, nasal decongestion, and shock treatment

Noradrenaline (NA) is synthesized from tyrosine, stored in vesicles, and released into synapses
NA's action is ended by reuptake via the Noradrenaline Transporter (NAT)
Enzymes like Monoamine oxidase (MAO) break down NA within neurons
Drugs can inhibit NAT or MAO to regulate NA levels
Examples of NAT inhibitors include desipramine and cocaine, including side effects like tachycardia and dysrhythmia

Amphetamine-like drugs are structurally similar to NA, transported into neurons by NAT, and into vesicles by VMAT
These lead to NA leakage, causing effects like bronchodilation, vasoconstriction, and increased blood pressure, being common drugs in substance abuse.
Examples of sympathetic amines include amphetamine, ephedrine, and tyramine.