ANS Pharmacology

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:

  • Decrease in heart rate
  • Decrease in cardiac output
  • Decrease in blood pressure
  • Increased intestinal secretions and motility
  • Increased bronchiolar and salivary secretions 
  • Increased tone of detrusor muscle
  • Constriction of the pupillae sphincter muscle (miosis)

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.

DrugTherapeutic useReceptor 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.
PyridostigmineChronic 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

  • Diarrhea 
  • Diaphoresis 
  • Miosis
  • Nausea
  • Urinary urgency

CHOLINERGIC ANTAGONISTS

In autonomic nervous system pharmacology, 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.
DRUGSTHERAPEUTIC 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.
MivacuriumShort surgical procedures.
Cisatracurium Mechanical ventilation.
Tubocurarine May induce histamine release, therefore rarely used.
Rocuronium Tracheal intubation.
Pancuronium Vagolytic (increases heart rate).
SuccinylcholineRapid endotracheal intubation during anaesthesia.

ADVERSE EFFECTS OF CHOLINERGIC ANTAGONISTS

  • Blurred vision
  • Confusion
  • Constipation
  • Urinary urgency

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:

  • Positive ionotropic and chronotropic on heart
  • Bronchodilation
  • Increased glycogenolysis
  • Increased release of glucagon
  • Decreased release of insulin
  • Lipolysis

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:

α1α2β1β2
Vasoconstriction Inhibition of norepinephrine release.TachycardiaVasodilation 
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.
DrugsTherapeutic useReceptor specificity
EpinephrineCardiac 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.
EphedrineChronic asthma.
Nasal decongestion.
α1, β
Pseudoephedrine Nasal congestion.
Congestion of eustachian tubes.

ADVERSE EFFECTS OF ADRENERGIC AGONISTS

  • Arrhythmias.
  • Headache.
  • Hyperactivity.
  • Insomnia. 
  • Nausea.
  • Tremors.

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 usesReceptor specificity
ALPHA ADRENERGIC BLOCKERS
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

ADVERSE EFFECTS OF ADRENERGIC ANTAGONISTS

α BLOCKERS

  • Orthostatic hypotension
  • Tachycardia
  • Vertigo
  • Sexual dysfunction (males)

β BLOCKERS

  • Bronchoconstriction
  • Arrhythmias
  • Fatigue
  • Dizziness
  • Dry mouth

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.