DRUGS ACTING ON THE PERIPHERAL NERVOUS SYSTEM: NEUROHUMORAL TRANSMISSION, CHOLINERGIC, ANTICHOLINERGIC, ADRENERGIC, ANTI-ADRENERGIC DRUGS, NEUROMUSCULAR BLOCKING AGENTS, LOCAL ANAESTHETICS AND NSAIDs: A TEACHER’S COMPREHENSIVE GUIDE
Welcome, future pharmacologists and healthcare professionals!
The Peripheral Nervous System (PNS) is a fascinating and complex network that connects the central nervous system to the rest of the body. Drugs acting on the PNS are among the most important and widely used medications in clinical practice—from local anaesthetics that make dental procedures painless to neuromuscular blockers that enable delicate surgeries. As a pharmacology educator with years of experience teaching this subject, I have observed that students often find this topic challenging due to the many drugs and their mechanisms. Let me tell you: Understanding drugs acting on the peripheral nervous system is essential for every healthcare professional.
In this comprehensive guide, I will walk you through neurohumoral transmission, cholinergic drugs, anticholinergic drugs, adrenergic drugs, anti-adrenergic drugs, neuromuscular blocking agents, drugs used in myasthenia gravis, local anaesthetics, and NSAIDs. By the end of this article, you will have a thorough understanding of these essential pharmacological agents. Let us begin!
Dpharmguru’s exam insights:
Drugs acting on the PNS are frequently tested in pharmacology exams. Remember: Neurohumoral transmission involves the release of neurotransmitters (ACh, NA) at synapses. Cholinergic drugs mimic ACh; Anticholinergic drugs block ACh. Adrenergic drugs stimulate the sympathetic system; Anti-adrenergic drugs block it. Neuromuscular blockers are used as muscle relaxants during surgery. Local anaesthetics block sodium channels. NSAIDs inhibit COX enzymes. These are classic exam questions!
NEUROHUMORAL TRANSMISSION
Neurohumoral transmission is the transmission of a nervous impulse either from one neuron to another or from a neuron to the effector organ by a neurohumoral substance.
Neurotransmitters
Neurotransmitters are chemical compounds present in the brain. They transmit information from one neuron to another. Major body functions like movement, emotional response, and the ability to experience pleasure and pain are controlled by neurotransmitters.
Steps Involved in Neurohumoral Transmission
STEP 1: Initiation of an Action Potential and Axonal Conduction
- Resting membrane potential is -70 mV
- High concentration of K⁺ and low levels of Na⁺ and Cl⁻ inside the cell
- Energy-dependent sodium pump maintains ionic gradients
- Depolarisation occurs when membrane becomes more permeable to Na⁺
- Opening of K⁺ channels causes outflux of K⁺ and re-polarisation
- Action Potential (AP) is propagated
STEP 2: Arrival of AP at Nerve Terminal
- Neurotransmitters synthesised and stored in synaptic vesicles
- Influx of Ca²⁺ promotes fusion of vesicles with membrane
- Vesicular contents discharged (exocytosis) into synaptic cleft
STEP 3: Events at Synaptic Cleft and Post-Junctional Sites
- Diffusion of neurotransmitter across synaptic cleft
- Interaction with post-junctional receptors
- Excitatory Postsynaptic Potential (EPSP) with influx of Ca²⁺
- Inhibitory Postsynaptic Potential (IPSP) with influx of Cl⁻ or outflux of K⁺
STEP 4: Termination of Effect
- Cholinergic sites: Acetylcholinesterase (AChE) inactivates ACh
- Adrenoceptor sites: Monoamine Oxidase (MAO) or Catechol-O-methyl Transferase (COMT)
- Reuptake of neurotransmitter into nerve terminals
CHOLINERGIC DRUGS
Cholinergic drugs (or parasympathomimetic drugs) act upon the neurotransmitter acetylcholine (ACh). They exert their actions by directly binding to cholinergic receptors (cholinergic agonists) or by increasing the availability of acetylcholine (indirect acting agents).
Classification of Cholinergic Drugs
- Direct Acting Agents (Cholinergic Agonists):
- Choline Esters: Acetylcholine, Methacholine, Carbachol, Bethanechol
- Cholinergic Alkaloids: Muscarine, Pilocarpine, Arecoline, Oxotremorine
- Indirect Acting Agents (Anticholinesterase):
- Reversible Enzyme Inhibitors:
- Carbamates: Physostigmine, Distigmine, Neostigmine, Pyridostigmine
- Acridine: Tacrine
- Irreversible Enzyme Inhibitors:
- Organophosphorus Compounds: DFP, Sarin, Parathion, Tabun, Soman, Echothiophate, TEPP
- Carbamates: Carbaryl, Propoxur
- Reversible Enzyme Inhibitors:
Pharmacological Actions of Acetylcholine
Muscarinic Actions
- CVS: Negative chronotropic (bradycardia), negative inotropic, decreased conductivity
- Respiratory: Bronchoconstriction, increased mucous secretions
- Smooth Muscles: Bronchoconstriction, increased peristalsis, urinary bladder contraction
- Exocrine Glands: Increased secretions (salivary, gastric, pancreatic)
- Eye: Miosis (pupillary constriction), accommodation for near vision, increased aqueous humour drainage
Nicotinic Actions
- Autonomic Ganglia: Activation of both sympathetic and parasympathetic ganglia
- Skeletal Muscles: Contraction of muscle fibres, twitching, fasciculation
Pilocarpine
Indications: Glaucoma, Sjögren syndrome, xerostomia
Adverse Effects: Headache, cataract, retinal detachment, bradycardia, bronchospasm, sweating
Anticholinesterase Drugs
Indications: Myasthenia gravis, Alzheimer’s disease, Lewy body dementia, antidote for anticholinergic poisoning, glaucoma
Adverse Effects: Increased sweating, salivation, abdominal cramps, nausea, vomiting, diarrhoea, bradycardia, tremors, hypotension
Individual Drugs:
- Physostigmine (Eserine): Tertiary amine from Calabar bean. Used in wide-angle glaucoma, atropine poisoning. Contraindicated in GI obstruction, asthma, diabetes, cardiovascular diseases.
- Neostigmine (Prostigmine): Synthetic quaternary ammonium compound. Used in myasthenia gravis, curare poisoning. Poor oral absorption, does not enter CNS.
ANTI-CHOLINERGIC DRUGS
Anticholinergic drugs (or parasympatholytic drugs) occupy the ACh receptors and prevent ACh from binding, thus blocking the actions of ACh.
Classification
- Anti-Muscarinic Agents: Atropine, Scopolamine, Ipratropium, Homatropine, Propantheline, Tiotropium bromide, Pirenzepine, Dicyclomine, Trihexyphenidyl, Tropicamide
- Anti-Nicotinic Agents:
- Ganglionic Blockers (Nₙ Blockers): Mecamylamine, Trimethaphan, Nicotine
- Neuromuscular Blockers (Nₘ Blockers): Atracurium, Doxacurium, Vecuronium, Tubocurarine, Succinylcholine
Atropine
Pharmacological Actions:
- CNS: Mild stimulation; high doses cause restlessness, hallucination, delirium
- Eye: Mydriasis (pupil dilation), cycloplegia (loss of accommodation)
- CVS: Initial bradycardia followed by tachycardia
- Respiratory: Bronchodilatation, decreased glandular secretion
- Skin: Drastically reduces sweating
- Secretions: Dryness of mouth; large doses inhibit gastric secretion
- Motility: Decreased GI motility—antispasmodic and anti-diarrhoeal
Indications: Mydriatic and cycloplegic, pre-anaesthetic medication, sialorrhoea, COPD and bronchial asthma, GI colic and diarrhoea, urinary disorders, organophosphorus poisoning, sinus bradycardia, Parkinsonism
Contraindications: Hypersensitivity to belladonna alkaloids, open-angle or angle-closure glaucoma, increased intraocular pressure, Down’s syndrome in infants
Adverse Effects: Dryness of mouth, nausea, flushing, vomiting, impotency, constipation, confusion, loss of libido, urinary hesitancy, blurred vision
ADRENERGIC DRUGS
Adrenergic drugs (or sympathomimetic agents) cause stimulation of the adrenergic receptors in the sympathetic nervous system.
Classification
- Direct-acting: Epinephrine, Norepinephrine
- Indirect-acting: Amphetamine
- Mixed-acting: Ephedrine
Epinephrine (Adrenaline)
Pharmacological Actions:
- Cardiovascular: Positive chronotropic, increased contractility, increased cardiac output
- Respiratory: Powerful bronchodilator (β₂ receptors)
- Hyperglycaemic: Decreases insulin release, increases glucagon release, glycogenolysis
Indications: Anaphylactic shock (drug of choice), asthma, cardiac arrest, local anaesthetic adjunct, superficial bleeding
Contraindications: Hypersensitivity, angle-closure glaucoma, non-anaphylactic shock
Adverse Effects: Hypertensive crisis, dysrhythmias, angina pectoris, necrosis, hyperglycaemia
Amphetamine (Indirect-acting)
Indications: ADHD, narcolepsy, hyperkinetic syndrome, obesity (anorexiant)
Adverse Effects: Palpitation, restlessness, headache, tremors, agitation, anxiety, confusion, paranoid psychosis, visual hallucinations
Ephedrine (Mixed-acting)
Indications: Bronchial asthma, bronchial spasms, asthmatic bronchitis, nasal decongestant, mydriatic
Contraindications: Coronary artery disease, hypertension, hyperthyroidism, angina
Adverse Effects: Anxiety, tremors, headache, insomnia, tachycardia, severe hypertension
ANTI-ADRENERGIC DRUGS
Alpha-Adrenoceptor Blocking Drugs
Examples: Phenoxybenzamine, Prazosin, Terazosin, Doxazosin, Tamsulosin
Indications: Essential hypertension, congestive heart failure, haemorrhagic and endotoxic shock, peripheral vascular diseases, hypertensive emergencies, migraine, benign prostatic hyperplasia (BPH)
Adverse Effects: Sudden fall in blood pressure, syncope, orthostatic hypotension, dizziness, headache, constipation
Beta-Adrenoceptor Blocking Drugs
Pharmacological Actions:
- Cardiac: Reduced myocardial contractility, decreased cardiac output, decreased myocardial oxygen requirement
- Blood Pressure: Decreased cardiac output, decreased Plasma Renin Activity (PRA)
- Bronchi: Bronchoconstriction (β₂ blockade) – harmful for asthmatics
- Intraocular Pressure: Decreased secretion of aqueous humour
Indications: Angina, cardioprotective, dysrhythmias, hypertension, migraine, glaucoma
Adverse Effects: Atrioventricular block, bradycardia, heart failure, dizziness, fatigue, depression, nausea, vomiting, constipation, diarrhoea, bronchospasm, impotence
Propranolol
Prototype of first-generation beta blockers. Produces non-selective beta blockade (blocks both β₁ and β₂ receptors).
Indications: Hypertension, angina pectoris, cardiac arrhythmias, myocardial infarction, pheochromocytoma, migraine, hyperthyroidism, Parkinson’s disease, anxiety, gastrointestinal bleeding
α + β Blockers
Examples: Labetalol, Carvedilol, Celiprolol
Indications: Hypertensive emergencies (rapid effect due to concurrent α₁ blockade)
NEUROMUSCULAR BLOCKING AGENTS
Classification
- Non-depolarising Blockers:
- Long Acting (60-120 min): Doxacurium, Pancuronium, Pipecuronium, Vecuronium
- Intermediate Acting (20-50 min): Atracurium, Rocuronium
- Short Acting (10-20 min): Mivacurium
- Depolarising Blockers: Succinylcholine
- Centrally Acting: Diazepam, Baclofen, Mephenesin
- Directly Acting on Muscle: Dantrolene
Indications
- Adjuvants to general anaesthesia
- Ventilatory support in ICUs
- Electroconvulsive and trauma
- Severe tetanus and status epilepticus
Centrally Acting Muscle Relaxants
Examples: Baclofen, Carisoprodol, Chlorzoxazone, Cyclobenzaprine, Diazepam, Methocarbamol
Indications: Acute muscle spasms, anxiety and tension, spastic neurological diseases, tetanus, orthopaedic manipulations
Directly Acting Drugs
Dantrolene:
- Indications: Reduces spasticity, treatment of malignant hyperthermia, pre-operative prophylaxis
- Adverse Effects: Muscular weakness, sedation, nausea, vomiting, diarrhoea, dose-dependent liver toxicity
DRUGS USED IN MYASTHENIA GRAVIS
- Modulation of Neuromuscular Transmission: Anticholinesterases (Pyridostigmine, Neostigmine)
- Immunomodulation: Plasma exchange, IVIG, Immunoabsorption
- Immunosuppression: Corticosteroids (Prednisone), Azathioprine, Cyclosporin
LOCAL ANAESTHETICS
Definition: Local anaesthetic agents act locally to abolish sensory perception over a specific area. They bind to cell membrane sodium channels and inhibit sodium ion passage, preventing depolarisation.
Classification
- Injectable Anaesthetics:
- Low potency, short duration: Procaine, Chloroprocaine
- Intermediate potency, duration: Lignocaine, Prilocaine
- High potency, long duration: Tetracaine, Bupivacaine, Ropivacaine, Dibucaine
- Surface Anaesthetics:
- Soluble: Cocaine, Lignocaine, Tetracaine, Benoxinate
- Insoluble: Benzocaine, Butylaminobenzoate, Oxethazine
Indications: Surface anaesthesia, infiltration anaesthesia, nerve block anaesthesia, intravenous regional anaesthesia, epidural anaesthesia
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
Classification
- Non-selective COX inhibitors: Aspirin, Ibuprofen, Diclofenac, Indomethacin, Piroxicam, Mefenamic acid
- Preferential COX-2 inhibitors: Nimesulide, Meloxicam, Nabumetone
- Selective COX-2 inhibitors: Celecoxib, Rofecoxib, Valdecoxib
- Analgesic-antipyretics: Paracetamol (Acetaminophen)
Aspirin (Acetylsalicylic Acid)
Pharmacological Actions:
- Analgesic: Alleviation of peripheral pain receptors
- Antipyretic: Promotes heat loss, resets hypothalamic thermostat
- Anti-inflammatory: At high doses
- Antiplatelet: Prevents thrombus formation
Indications: Inflammation, analgesia, antipyresis, prevention of thrombus formation (transient ischemia, unstable angina, post-CABG)
Contraindications: Peptic ulcer, bleeding tendencies, children with chickenpox or influenza, chronic liver disease, pregnancy, breastfeeding
Adverse Effects: GI toxicity (epigastric distress, heartburn, bleeding), salicylism (tinnitus, hearing defects, dizziness), hypersensitivity (rhinitis, bronchospasm, urticaria)
Ibuprofen
Indications: Headache, menstrual cramps, muscle aches, fever, minor aches
Adverse Effects: Nausea, dyspepsia, GI ulceration/bleeding, raised liver enzymes, diarrhoea, headache, dizziness, salt and fluid retention, hypertension
Paracetamol (Acetaminophen)
Indications: Mild to moderate pain, fever, headache, migraine, toothache, dysmenorrhoea, rheumatic pain, cold and influenza symptoms
Adverse Effects: Allergic reactions, bloody or black stools, fever, sore throat, ulcers or white spots in mouth, decreased urine output
Dpharmguru’s exam insights:
Drugs acting on the PNS are frequently tested. Remember: Cholinergic drugs mimic ACh and cause parasympathetic effects. Anticholinergic drugs block ACh and cause sympathetic-like effects. Adrenergic drugs stimulate sympathetic system. Anti-adrenergic drugs block sympathetic effects. Neuromuscular blockers are used as muscle relaxants during surgery. Local anaesthetics block sodium channels. NSAIDs inhibit COX enzymes and reduce prostaglandin synthesis. These are classic exam questions!
SUMMARY TABLE: DRUGS ACTING ON PNS
| Drug Class | Mechanism | Examples | Key Uses |
|---|---|---|---|
| Cholinergic Agonists | Activate ACh receptors | Pilocarpine, Bethanechol | Glaucoma, urinary retention |
| Anticholinesterases | Inhibit AChE | Neostigmine, Physostigmine | Myasthenia gravis, glaucoma |
| Anticholinergics | Block ACh receptors | Atropine, Scopolamine | Pre-anaesthetic, bradycardia, poisoning |
| Adrenergic Agonists | Stimulate adrenergic receptors | Epinephrine, Ephedrine | Anaphylaxis, asthma, nasal congestion |
| Alpha Blockers | Block α receptors | Prazosin, Tamsulosin | Hypertension, BPH |
| Beta Blockers | Block β receptors | Propranolol, Atenolol | Hypertension, angina, arrhythmias |
| Neuromuscular Blockers | Block NMJ transmission | Succinylcholine, Atracurium | Surgical muscle relaxation |
| Local Anaesthetics | Block Na⁺ channels | Lignocaine, Procaine | Local anaesthesia |
| NSAIDs | Inhibit COX enzymes | Aspirin, Ibuprofen, Paracetamol | Pain, inflammation, fever |
FREQUENTLY ASKED QUESTIONS (FAQs)
1. What is the difference between cholinergic and anticholinergic drugs?
Cholinergic drugs mimic the action of acetylcholine (ACh) and stimulate the parasympathetic nervous system. Anticholinergic drugs block the action of ACh at muscarinic receptors, inhibiting parasympathetic effects.
2. What is the mechanism of action of local anaesthetics?
Local anaesthetics bind to cell membrane sodium channels and inhibit sodium ion passage, thus preventing depolarisation of nerve cell membranes and blocking nerve impulse conduction.
3. What is the difference between non-depolarising and depolarising neuromuscular blockers?
Non-depolarising blockers compete with ACh at the neuromuscular junction and cause flaccid paralysis (e.g., Tubocurarine, Atracurium). Depolarising blockers act as ACh agonists, causing initial depolarisation followed by paralysis (e.g., Succinylcholine).
4. What are the adverse effects of beta-blockers?
Adverse effects include bradycardia, heart failure, bronchospasm (in asthmatics), dizziness, fatigue, depression, nausea, vomiting, impotence, and masked symptoms of hypoglycaemia.
5. What is the mechanism of action of NSAIDs?
NSAIDs inhibit the enzyme cyclooxygenase (COX), which reduces the synthesis of prostaglandins—mediators of pain, inflammation, and fever.
6. What is the first-pass metabolism?
First-pass metabolism is the phenomenon where a drug is metabolized at a particular location (usually the liver) before reaching the systemic circulation, significantly reducing its bioavailability.
SUMMARY
This comprehensive guide covered the essential drugs acting on the peripheral nervous system:
- Neurohumoral Transmission: Involves neurotransmitters (ACh, NA) released at synapses; steps include AP initiation, release, binding, and termination
- Cholinergic Drugs: Mimic ACh (direct agonists) or increase ACh availability (anticholinesterases); used in glaucoma, myasthenia gravis, Alzheimer’s
- Anticholinergic Drugs: Block ACh at muscarinic or nicotinic receptors; used as pre-anaesthetic, in bradycardia, Parkinsonism, organophosphorus poisoning
- Adrenergic Drugs: Stimulate sympathetic system (α and β receptors); used in anaphylaxis, asthma, cardiac arrest
- Anti-adrenergic Drugs: Block α or β receptors; used in hypertension, angina, arrhythmias, BPH
- Neuromuscular Blocking Agents: Non-depolarising and depolarising; used as muscle relaxants during surgery
- Local Anaesthetics: Block Na⁺ channels; used for local anaesthesia
- NSAIDs: Inhibit COX enzymes; used for pain, inflammation, fever
As I always tell my students: “Understanding the pharmacology of the peripheral nervous system is the foundation of rational drug therapy in anaesthesia, cardiology, neurology, and pain management.”
REFERENCES AND FURTHER READING
- Pharmacy Council of India (PCI). (2022). Pharmacology Syllabus. New Delhi: PCI.
- Rang, H. P., & Dale, M. M. (2021). Rang & Dale’s Pharmacology (9th ed.). Elsevier.
- Goodman, L. S., & Gilman, A. (2018). Goodman & Gilman’s The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill.
- Katzung, B. G. (2021). Basic and Clinical Pharmacology (15th ed.). McGraw-Hill.
- World Health Organization (WHO). (2022). Essential Medicines and Pharmacology. Retrieved from https://www.who.int.
Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare professionals for medical concerns. Pharmaceutical regulations and guidelines may vary by region—always refer to your local regulatory authorities for specific requirements.
written by:
Dr. N. Sujith Kumar
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