A Comparison with the Adrenaline/Epinephrine-Induced Fight, Flight and Fright Response

Understanding the action of drugs on the autonomic nervous system (ANS) can be simplified by drawing a comparison with the adrenaline/epinephrine-induced fight, flight, and fright response. This response, also known as the acute stress response, is the body’s physiological reaction to perceived harmful events, attacks, or threats to survival. To better comprehend the role of various drugs acting on the ANS, we’ll break down the two main divisions of the system and compare their functions to adrenaline’s effects.

The Sympathetic Nervous System (SNS) – Fight or Flight

The sympathetic nervous system is responsible for the fight or flight response, which prepares the body to react to potentially dangerous situations. When the SNS is activated, it triggers the release of adrenaline (epinephrine) and norepinephrine (noradrenaline), which act on various target organs to produce a series of physiological changes, including:

  • Increased heart rate and blood pressure
  • Dilated pupils
  • Increased blood flow to muscles
  • Enhanced mental alertness
  • Increased metabolism
effects of adrenaline

Drugs that mimic or amplify the effects of adrenaline/epinephrine in the SNS are known as sympathomimetics or adrenergic agonists. These drugs can be used to treat various conditions, such as asthma, nasal congestion, etc. Examples include epinephrine, norepinephrine, and pseudoephedrine.

Classification of SympathomimeticsMechanism of ActionExamples
Direct-acting adrenergic agonistsThese drugs bind directly to adrenergic receptors and activate the sympathetic nervous system.Adrenaline/Epinephrine, Norepinephrine, Dopamine, Phenylephrine, Albuterol
Indirect-acting adrenergic agonistsThese drugs enhance the release and/or inhibit the reuptake of norepinephrine and dopamine, leading to increased activation of the sympathetic nervous system.Amphetamines, Cocaine
Mixed-acting adrenergic agonistsThese drugs have both direct and indirect effects on adrenergic receptors, leading to increased activation of the sympathetic nervous system.Ephedrine, Pseudoephedrine, Methamphetamine
Alpha-adrenergic agonistsThese drugs selectively activate alpha-adrenergic receptors, leading to vasoconstriction and increased blood pressure.Phenylephrine, Clonidine
Beta-adrenergic agonistsThese drugs selectively activate beta-adrenergic receptors, leading to bronchodilation, increased heart rate, and increased contractility.Albuterol, Dobutamine

Conversely, drugs that inhibit or block the effects of adrenaline are known as sympatholytics or adrenergic antagonists. These drugs are used to treat conditions like hypertension, arrhythmias, anxiety, migraine headaches, etc. Examples include propranolol, metoprolol, and atenolol.

Classification of SympatholyticsMechanism of ActionExamples
Alpha-adrenergic blockersThese drugs block alpha-adrenergic receptors, leading to vasodilation and decreased blood pressure.Prazosin, Doxazosin, Terazosin
Beta-adrenergic blockersThese drugs block beta-adrenergic receptors, leading to decreased heart rate, decreased contractility, and decreased blood pressure.Propranolol, Atenolol, Metoprolol
Alpha-beta-adrenergic blockersThese drugs block both alpha- and beta-adrenergic receptors, leading to vasodilation, decreased heart rate, decreased contractility, and decreased blood pressure.Carvedilol, Labetalol
Centrally-acting alpha-adrenergic agonistsThese drugs stimulate alpha2-adrenergic receptors in the brain, leading to decreased sympathetic outflow and decreased blood pressure.Clonidine, Methyldopa
Ganglionic blockersThese drugs block the transmission of signals between sympathetic and parasympathetic ganglia, leading to decreased sympathetic activity and decreased blood pressure.Hexamethonium, Mecamylamine

The Parasympathetic Nervous System (PNS) – Rest and Digest

The parasympathetic nervous system works to counter the effects of the SNS and is responsible for the body’s “rest and digest”. This division of the ANS helps to conserve energy, slow down heart rate, and promote digestion and relaxation. When the PNS is activated, it releases neurotransmitters like acetylcholine (ACh) to elicit the following effects:

  • Decreased heart rate and blood pressure
  • Constricted pupils
  • Increased salivation and digestion
  • Stimulation of the urinary and digestive systems

Drugs that mimic or enhance the effects of acetylcholine in the PNS are called parasympathomimetics or cholinergic agonists. These drugs are used to treat conditions such as glaucoma, myasthenia gravis, curare poisoning, etc. Examples include pilocarpine, physostigmine, neostigmine, bethanechol, and donepezil.

Classification of ParasympathomimeticsMechanism of ActionExamples
Direct-acting cholinomimeticsThese drugs bind directly to muscarinic and/or nicotinic receptors and activate the parasympathetic nervous system.Pilocarpine, Bethanechol, Methacholine, Nicotine
Indirect-acting cholinomimeticsThese drugs inhibit the activity of acetylcholinesterase (AChE), which is the enzyme responsible for breaking down acetylcholine in the synapse. This leads to an increase in acetylcholine levels and activation of the parasympathetic nervous system.Physostigmine, Neostigmine, Donepezil, Galantamine, Rivastigmine
Cholinesterase reactivatorsThese drugs reactivate cholinesterase enzymes that have been inhibited by toxins, such as organophosphate poisoning. By reactivating the enzymes, excess acetylcholine can be broken down and the toxic effects can be reversed.Pralidoxime, Obidoxime, HI-6

On the other hand, drugs that inhibit or block the effects of acetylcholine are known as parasympatholytics or cholinergic antagonists. These drugs are used to treat various conditions like irritable bowel syndrome, organophosphate poisoning, overactive bladder, motion sickness, etc. Examples include atropine, scopolamine, and oxybutynin.

Classification of ParasympatholyticsMechanism of ActionExamples
Antimuscarinic agentsThese drugs block muscarinic receptors and inhibit the parasympathetic nervous system.Atropine, Scopolamine, Ipratropium, Tiotropium
Ganglionic blockersThese drugs block the transmission of signals between sympathetic and parasympathetic ganglia, leading to decreased parasympathetic activity.Trimethaphan, Mecamylamine
Neuromuscular blocking agentsThese drugs block the transmission of signals between nerves and muscles, leading to muscle paralysis.Rocuronium, Vecuronium, Pancuronium


Parasympathetic/cholinergic agonists Versus Sympathetic/sympathomimetic agonists

adrenaline vs cholinergic agonists

Parasympathetic blockers/cholinergic antagonists Versus Sympathetic blockers/sympatholytics/adrenergic antagonists

adrenergic antagonists vs cholinergic antagonists

Parasympathetic/cholinergic agonists Versus Sympathetic blockers/sympatholytics/adrenergic antagonists

cholinergic vs adrenergic blockers

Sympathetic agonists/sympathomimetics/adrenergic agonists Versus Parasympatholytics/Cholinergic antagonists

adrenergic drugs vs cholinergic antagonists
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.

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