Miscellaneous

Drugs that affect the autonomic nervous system or ANS: The autonomic nervous system is composed of the sympathetic and parasympathetic nervous systems with control centers in the medulla of the brain. It is responsible for various vital and involuntary functions like heart function, breathing, body temperature regulation, digestion and absorption of food, bowel and bladder functions, functioning of nerves, and movement of muscles. Many functions of the ANS are coordinated by neurotransmitters. Acetylcholine, or ACh, is the major neurotransmitter of the parasympathetic nervous system, while epinephrine (adrenaline) and norepinephrine (noradrenaline) belong to the sympathetic nervous system.

Cholinergic drugs: These drugs act on the parasympathetic nervous system or PNS. They consist of cholinergic agonists or parasympathomimetics, which enhance the action of acetylcholine, and anticholinergics or parasympatholytics, which antagonize the action of acetylcholine. Cholinergic agonists that directly mimic the action of ACh and bind to ACh receptors are called direct-acting agonists, while indirect-acting agonists prevent the breakdown of ACh by enzymes called acetylcholinesterases (AChE). ACh receptors are of two types - muscarinic and nicotinic.

Examples of direct-acting agonists include bethanechol (Urecholine), carbachol (Carbastat, Miostat), methacholine (Provocholine), varenicline (Chantix, Tyrvaya), cevimeline (Evoxac) and pilocarpine (Salagen, Pilocar, Qlosi, Ocu-Carpine). Pilocarpine is used topically in the eye to treat dry eyes or xerostomia. Varenicline is used for cigarette smoking cessation. In 2021, the popular varenicline brand Chantix was discontinued due to nitrosamine contamination, which may increase the risk of cancers. Other uses of direct agonists are to increase gastrointestinal motility and urine excretion, treatment of glaucoma, and treatment of dry mouth in Sjogren’s syndrome.

Neostigmine (Bloxiverz), physostigmine (Antilirium), and pyridostigmine (Mestinon, Regonol) are indirect-acting agonists of ACh. They are used in the treatment of myasthenia gravis and reversal of muscle paralysis and neuromuscular blockade caused by nondepolarizing muscle relaxants. Adverse effects include blurred vision, chest tightness, difficulty breathing, and weakness. Pyridostigmine may cause severe bradycardia and cardiac arrhythmias. It may exacerbate asthma. Indirect agonists enhance the effect of succinylcholine, which is another type of muscle relaxant. Overdose can precipitate a cholinergic crisis resulting from excess acetylcholine, which presents as increased salivation, lacrimation, diarrhea, blurred vision, urinary incontinence, muscle paralysis, and respiratory failure.

Anticholinergics or parasympatholytics block the effect of acetylcholine by blocking ACh muscarinic or nicotinic receptors. The prototype drug is atropine. Their effects include increased heart rate, urinary retention, dilate bronchi, decreased secretions in the respiratory and gastrointestinal tracts, dilated pupils, blurred vision, dry eyes, constipation, increase in skin temperature by reducing sweating, hallucinations, and coma.

Adrenergic drugs: Adrenergic drugs include adrenergic agonists that enhance the action of sympathetic neurotransmitters adrenaline and noradrenaline, and adrenergic antagonists that block the action of adrenaline and noradrenaline.

Adrenergic agonists may be direct-acting or indirect-acting agonists. Adverse effects include increased heart rate and blood pressure, cardiac arrhythmias, intracranial bleeding, anxiety, headache, and tremors.

Direct-acting adrenergics facilitate adrenergic receptors like beta and alpha adrenergic receptors. Albuterol (ProAir, Ventolin), levalbuterol (Xopenex), formoterol (Foradil, Perforomist), and salmeterol (Serevent) are used as bronchodilators to treat asthma and COPD. Phenylephrine (Sudafed) and ephedrine are used as nasal decongestants to treat colds and sinusitis. Clonidine (Catapres, Onyda) is used to treat hypertension. Dopamine (Intropin) and dobutamine (Dobutrex) are used to improve cardiac contractility and support cardiac function.

Indirect-acting adrenergics inhibit the uptake of neurotransmitters at the synaptic cleft, hence enhancing their effects. They are primarily used in the treatment of ADHD, Tourette syndrome and bipolar disorder. They include atomoxetine (Strattera) and viloxazine (Qelbree).

Adrenergic antagonists block receptors to stop the effect of neurotransmitters. Drugs like phentolamine (OraVerse) and phenoxybenzamine (Dibenzyline) block the alpha receptor. Beta-blockers block beta receptors. Labetalol (Trandate, Normodyne) blocks both alpha and beta receptors. They are mainly used in the treatment of hypertension.

Topical anesthetics: Topical anesthetics are applied locally over the skin, eye, or mucous membranes to cause superficial loss of pain. They block nerve conduction locally in the area of application. They are available in various forms, such as creams, sprays, patches, ointments, gel, eye and ear drops, etc. They are used for minor surgical procedures like skin biopsy, laser, dental procedures, etc., and for decreasing pain following insect bites, burns, etc. Examples include benzocaine (Americaine, BeeGentle, Benzo-Jel), dibucaine (Nupercainal), lidocaine (Xylocaine, RectiCare, Lidocan, Bruselix), pramoxine (Gold Bond Anti-Itch, Pramox), prilocaine (Citanest) and phenol (Assure Sore Throat, Castellani Paint). They are also available in combination with menthol, capsaicin, hydrocortisone, salicylic acid, and zinc. Adverse effects include local redness, swelling, stinging sensation, and rarely seizures and cardiac arrhythmias.