Autonomic Nervous System Pharmacology! – PharmaFactz

The autonomic nervous system is a part of our nervous system that provides fine, discrete control over the functions of many organs and tissues including heart muscle, smooth muscle and exocrine glands. Here, we review autonomic nervous system pharmacology that details the major drugs that impact this vital part of our nervous system.

The ANS is classified into the sympathetic and parasympathetic nervous systems. The primary neurotransmitters involved in the signaling of the autonomic nervous system are acetylcholine, epinephrine and norepinephrine.

CHOLINERGIC DRUGS

Drugs that bind to receptors activated by acetylcholine are called cholinergic drugs.

Acetylcholine is a neurotransmitter present at preganglionic and postganglionic terminals of the parasympathetic nervous system and only in preganglionic terminal of sympathetic nervous system. It is rapidly hydrolyzed by the action of enzyme acetylcholine esterase. 

The actions of acetylcholine include:

There are two types of receptors on which the acetylcholine acts: nicotinic receptors and muscarinic receptors.

MUSCARINIC RECEPTORS

These receptors bind to muscarine in addition to acetylcholine, which is an alkaloid present in poisonous mushrooms. Muscarinic receptors are located in the heart, smooth muscles, brain and exocrine glands.

NICOTINIC RECEPTORS

These receptors bind to nicotine in addition to acetylcholine but show a weak affinity to muscarine. They are located in the central nervous system, adrenal medulla, autonomic ganglia and the neuromuscular junction.

These receptors bind to nicotine in addition to acetylcholine but show a weak affinity to muscarine. They are located in the central nervous system, adrenal medulla, autonomic ganglia and the neuromuscular junction.

CHOLINERGIC AGONISTS

The cholinergic agonists produce effects like that of acetylcholine and broadly classified as direct-acting cholinergic agonist and indirect-acting cholinergic agonist based on their mode of action.

DIRECT ACTING CHOLINERGIC AGONISTS

They are also known as parasympathomimetics. They mimic the effects of acetylcholine and bind directly to its receptors. These drugs have a longer duration of action than acetylcholine but show little specificity in their actions, which limits their therapeutic use.

Drug	Therapeutic use	Receptor affinity
Bethanechol	In atonic bladder as in postpartum and postoperative urinary retention.In megacolon.	Strong muscarinic and no nicotinic activity.
Carbachol	In glaucoma as miotic agent.	Nicotinic and muscarinic activity.
Pilocarpine	Drug of choice in glaucoma.Sjogren’s syndrome as secretagogue.	Mainly muscarinic activity.

INDIRECT ACTING CHOLINERGIC AGONISTS

Drug	Therapeutic use
Physostigmine	In atony of bladder and GIT. In glaucoma. In overdose of anticholinergic drugs i.e atropine, phenothiazine, tricyclic antidepressants.
Neostigmine	Antidote for tubocurarine Symptomatic treatment for myasthenia gravis. Prevent postoperative abdominal distention and urinary retention.
Pyridostigmine	Chronic management of myasthenia gravis.
Edrophonium	Diagnosis of myasthenia gravis. Antidote for tubocurarine.
Echothiophate	Antidote for atropine. Open-angle glaucoma.

 They are also known as anticholinesterases and work by inhibiting the enzyme acetylcholinesterase hence preventing the destruction of acetylcholine at the synapse. 

Since they work indirectly by inhibiting the acetylcholine esterase and do not bind directly to the cholinoceptors, they have an equal effect on both the muscarinic and nicotinic receptors.

ADVERSE EFFECTS OF CHOLINERGIC AGONISTS

CHOLINERGIC ANTAGONISTS

They are also known as parasympatholytics, they bind directly to the cholinoceptors. They are subdivided on the basis of their spectrum of action into antinicotinic and antimuscarinic drugs. 

Antinicotinic drugs are further divided into ganglionic blockers and neuromuscular blocking drugs.

ANTIMUSCARINIC DRUGS These drugs exert antagonistic effects at the muscarinic receptors specifically.

DRUGS	THERAPEUTIC USE
Atropine	Cause mydriasis and cycloplegia. Antispasmodic in GIT and bladder  Antidote for cholinergic agonists Antisecretory.
Scopolamine	In motion sickness. Postoperative nausea and vomiting.
Ipratropium	Asthma.  COPD.
Tropicamide  Cyclopentolate	Cause mydriasis and cycloplegia.

ANTINICOTINIC DRUGS GANGLIONIC BLOCKERS These drugs specifically act on the nicotinic receptors of the autonomic nervous system.

Nicotine	No therapeutic benefit. Harmful for health.
Mecamylamine	Emergency drug to lower blood pressure.

NEUROMUSCULAR BLOCKING DRUGS These drugs specifically inhibit the actions of acetylcholine at the motor endplate.

Mivacurium	Short surgical procedures.
Cisatracurium	Mechanical ventilation.
Tubocurarine	May induce histamine release, therefore rarely used.
Rocuronium	Tracheal intubation.
Pancuronium	Vagolytic (increases heart rate).
Succinylcholine	Rapid endotracheal intubation during anaesthesia.

ADVERSE EFFECTS OF CHOLINERGIC ANTAGONISTS

ADRENERGIC DRUGS

Adrenergic drugs are some of the most widely known drugs in autonomic nervous system pharmacology. They are drugs that act on receptors activated by the catecholamines, epinephrine and norepinephrine.

Epinephrine and norepinephrine are neurotransmitters involved in the signaling between preganglionic neurons of both, sympathetic and parasympathetic nervous system and the postganglionic nerve endings of the sympathetic nervous system only. 

Epinephrine and norepinephrine are very similar to each other, but epinephrine has more effects on the heart while norepinephrine has more effects on blood vessels. Epinephrine and norepinephrine are also known as adrenaline and noradrenaline respectively. 

They are metabolized by enzymes monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). The effects produced by epinephrine and norepinephrine are:

The receptors on which these neurotransmitters act (adrenoceptors) can be classified as:

α1, α2, β1, β2. 

The effects produced by stimulation of different adrenoceptors are as follows:

α1	α2	β1	β2
Vasoconstriction	Inhibition of norepinephrine release.	Tachycardia	Vasodilation
Mydriasis	Inhibition of acetylcholine release.	Increased myocardial contractility.	Bronchodilation
	Inhibition of insulin release.		Increased glycogenolysis.
			Increased release of glucagon.
			Relaxed uterine smooth muscle.

ADRENERGIC AGONISTS

These drugs are also called sympathomimetic drugs and act directly on receptors that are stimulated by norepinephrine or epinephrine. They are further classified on the basis of their action as direct, indirect and mixed action acting agonists.

DIRECT ACTING ADRENERGIC AGONISTS. These drugs bind to adrenoceptors without interacting with the presynaptic neuron.

Drugs	Therapeutic use	Receptor specificity
Epinephrine	Cardiac arrest. Glaucoma. Bronchospasm. Anaphylactic shock. With local anesthetics as a vasoconstrictor.	α1, α2, β1, β2
Norepinephrine	Shock.	α1, α2, β1
Isoproterenol	AV block or cardiac arrest. Asthma.	β1, β2
Dopamine	Drug of choice for shock.	α1, β1
Dobutamine	Congestive heart failure.	β1
Oxymetazoline	Nasal decongestant.	α1
Phenylephrine	Nasal decongestion. Cause mydriasis. Raises blood pressure. Supraventricular tachycardia.	α1
Methoxamine	Paroxysmal supraventricular tachycardia. Hypotension during surgery.	α1
Clonidine	Hypertension.	α2
Metaproterenol	Asthma.	β2 > β1
Albuterol  Pirbuterol  Terbutaline	Asthma.	β2
Salmeterol  Formoterol	Asthma.	β2

INDIRECT ACTING ADRENERGIC AGONISTS These drugs cause norepinephrine release from the presynaptic terminals or inhibit its uptake.

Amphetamine

Hyperactivity in children. Narcolepsy.  Appetite control.

α

MIXED ACTION ADRENERGIC AGONISTS These drugs induce the release of norepinephrine from presynaptic terminals and also activate adrenoceptors on the postsynaptic membrane.

Ephedrine	Chronic asthma. Nasal decongestion.	α1, β
Pseudoephedrine	Nasal congestion. Congestion of eustachian tubes.

ADVERSE EFFECTS OF ADRENERGIC AGONISTS

ADRENERGIC ANTAGONISTS

These drugs are also known as sympatholytic agents. They bind directly to the adrenoceptors, preventing their activation by endogenous catecholamines. They are classified as alpha and beta-blockers, on the basis of receptors they act on.

Drug

Therapeutic uses

Receptor specificity

Phenoxybenzamine	Pheochromocytoma.	α1 postsynaptic,
	Raynaud’s disease.	α2 presynaptic.
Phentolamine	Short term management of  pheochromocytoma.	α1, α2
Prazosin  Terazosin Doxazosin	Hypertension.	α1
Tamsulosin  Alfuzosin	Benign prostatic hyperplasia.	α1

BETA ADRENERGIC BLOCKERS

Propranolol	Hypertension. Cardiac arrhythmia. Angina pectoris. Myocardial infarction. Congestive heart failure. Migraine(prophylaxis). Hyperthyroidism. Glaucoma.	β1, β2
Timolol  Nadolol	Hypertension. Glaucoma.	β1, β2
Acebutolol  Atenolol  Esmolol  Metoprolol	Hypertension.	β1
Pindolol	Hypertension.	β1, β2
Carvedilol  Labetalol	Congestive heart failure. Hypertension.	α1, β1, β2

α BLOCKERS

β BLOCKERS

That concludes our study of autonomic nervous system pharmacology; a wide and diverse range of medicines that operate on some of the most fundamental neural architecture of the body. For even more on ANS pharmacology, take a few moments to become a registered member of PharmaFactz.