Part A: Drugs Acting on the Nervous System

1. Introduction & Overview

The nervous system pharmacology is huge; for clarity we break it into:

• The autonomic nervous system (ANS) part – which covers the sympathetic (adrenergic) and parasympathetic (cholinergic) divisions; drugs that mimic or block each side.

• The central nervous system (CNS) part – which covers stimulants, sedatives/hypnotics/tranquillisers, antiepileptics, antidepressants/anxiolytics, analgesics/antipyretics/anti-inflammatories, rheumatology/gout, rigidity & tremor controllers (e.g., Parkinson’s), plus anaesthetics & muscle relaxants.

Understanding the ANS is foundational because many drugs either mimic or block the normal “fight-or-flight / rest-and-digest” balance. 

2. Autonomic Nervous System Drugs

2.1. Basic Physiologic Review

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• The ANS regulates involuntary body functions (heart rate, digestion, bronchi, pupils, glands). 

• Divided into:

  • Sympathetic (adrenergic): “fight or flight” – ↑ heart rate, dilate bronchi, dilate pupils, divert blood to muscles.

  • Parasympathetic (cholinergic): “rest and digest” – ↓ heart rate, ↑ GI motility, constrict pupils, stimulate secretions.

• Drugs can modify these by: stimulating (agonists) or blocking (antagonists) either branch. 

2.2. Classification of Autonomic Drugs

Major classification groups:

• Cholinomimetics (parasympathomimetics) – mimic acetylcholine at muscarinic/nicotinic receptors or inhibit acetylcholinesterase. 

• Anticholinergics (parasympatholytics) – block cholinergic receptors.

• Sympathomimetics (adrenergic agonists) – stimulate alpha/beta adrenergic receptors. 

• Sympatholytics (adrenergic antagonists) – block the adrenergic receptors (alpha-blockers, beta-blockers, etc.) 

2.3. Sympathomimetic Agents (Adrenergic Agonists)

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Mechanism: Activate adrenergic receptors (α, β) in target organs → mimic sympathetic stimulation. 
Main classes & examples

• Non-selective: e.g., adrenaline (epinephrine) – acts on α & β.

• α1 agonists: e.g., phenylephrine (vasoconstrictor).

• β1 agonists: e.g., dobutamine (cardiac stimulant).

• β2 agonists: e.g., salbutamol (bronchodilator) for asthma.
  Indications: Anaphylaxis (adrenaline), asthma/bronchospasm, cardiogenic shock, nasal congestion.
  Key side-effects: Tachycardia, hypertension, arrhythmias, tremor, anxiety.
  Key point for diploma students: Recognise that these drugs increase sympathetic output and expect “fight or flight” effects.

2.4. Sympatholytic Agents (Adrenergic Antagonists)

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Mechanism: Block adrenergic receptors → reduce sympathetic effects. pharmaguideline.com+1
Main classes & examples:

• α-blockers: e.g., prazosin (reduce peripheral resistance).

• β-blockers: e.g., propranolol (non-selective), metoprolol (β1 selective) – reduce heart rate, blood pressure.
  Indications: Hypertension, angina, arrhythmias, benign prostatic hyperplasia (for α-blockers).
  Side-effects: Bradycardia, hypotension, bronchospasm (with β2 block), impotence, fatigue.
  Key point: They reduce “fight or flight” output – useful when sympathetic overactivity is harmful.

2.5. Parasympathomimetic Agents (Cholinergic Agonists)

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Mechanism: Stimulate muscarinic/nicotinic receptors or inhibit acetylcholinesterase → increase parasympathetic tone. 
Examples:

• Direct-acting muscarinic agonists: bethanechol (bladder/urinary retention), pilocarpine (glaucoma).

• Indirect acting (acetylcholinesterase inhibitors): neostigmine (myasthenia gravis), physostigmine.
  Indications: Urinary retention, glaucoma, myasthenia gravis.
  Side-effects: Diarrhoea, bradycardia, bronchospasm, sweating, salivation.
  Key point: They promote rest-and-digest responses.

2.6. Parasympatholytic Agents (Cholinergic Antagonists)

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Mechanism: Block muscarinic receptors → reduce parasympathetic tone.
Examples: Atropine (↑ heart rate, reduce GI motility, mydriasis), ipratropium (bronchodilator).
Indications: Bradycardia, pre-anaesthetic (to reduce secretions), overactive bladder, COPD/asthma (anticholinergic inhalers).
Side-effects: Dry mouth, blurred vision, constipation, urinary retention, tachycardia.
Key point: They dampen rest-and-digest responses, so expect opposite effects to parasympathomimetic agents.

2.7. Summary Table – ANS Drug Classes

2.8. Clinical Notes & “Practical” Tips

• Always consider which receptor is involved (α vs β, muscarinic vs nicotinic) for mechanism and side-effects.

• Remember the balance between sympathetic and parasympathetic systems – many diseases or drug effects disturb this balance. 

• Think of what the body would do in fight/flight (symp) vs rest/digest (parasymp) – then predict what the drug will mimic or block.

• For practical use: know the key examples (bethanechol, atropine, salbutamol, propranolol) and their indications and side-effects.

• In your “practical” sessions you will often be asked: “which drug would you use for X condition?” (e.g., urinary retention → bethanechol; bradycardia induced by overdose → atropine).

• Also important: drug interactions and contraindications (e.g., β-blockers in asthma risk bronchospasm; anticholinergics in glaucoma worsen it).

3. CNS Drugs (Broader Nervous System Agents)

Because of vastness, I’ll summarise the major categories with key points and examples. For each category: classification, mechanism (brief), major drugs, indications, key side-effects.

3.1. CNS Stimulants

Mechanism: Increase CNS activity (e.g., through catecholamine release, blocking reuptake).
Examples: Amphetamines, methylphenidate (for ADHD), caffeine.
Indications: ADHD, narcolepsy, sometimes obesity (less common now).
Side-effects: Insomnia, tachycardia, hypertension, dependence.
Key student point: Recognise that stimulants increase alertness, treat sleepiness and inattentiveness.

3.2. Hypnotics, Sedatives & Tranquillisers

Mechanism: Depress CNS activity – varying depth from mild sedation to sleep induction to full anaesthesia.
Classification & examples:

• Benzodiazepines (e.g., diazepam, lorazepam) – sedative/tranquiliser/hypnotic.

• Non-benzodiazepine hypnotics (e.g., zolpidem).

• Barbiturates (less used now).
  Indications: Anxiety, insomnia, pre-operative sedation, seizures (some).
  Side-effects: Drowsiness, dependence, respiratory depression (especially with alcohol or opioids), cognitive impairment.
  Key student point: Distinguish sedative/tranquilliser (reduce anxiety) vs hypnotic (induce sleep) vs anaesthetic (loss of consciousness).

3.3. Antiepileptic / Anticonvulsant Drugs

Mechanism: Various (block sodium channels, enhance GABA, inhibit calcium channels).
Examples: Phenytoin, carbamazepine, valproate, lamotrigine.
Indications: Epilepsy (various types), sometimes mood stabilisation.
Side-effects: Ataxia, sedation, hepatotoxicity (valproate), blood dyscrasias (carbamazepine), teratogenicity.
Key student point: Know which drug for generalised vs focal seizures; monitor hepatic/haematologic side-effects.

3.4. Antidepressants & Anxiolytics

Mechanism: Increase availability of serotonin, norepinephrine, dopamine; anxiolytics usually enhance GABA or block anxiety circuits.
Examples: SSRIs (fluoxetine), SNRIs (venlafaxine), TCAs (amitriptyline), benzodiazepines (for anxiety).
Indications: Depression, anxiety disorders, sometimes chronic pain.
Side-effects: Sexual dysfunction (SSRIs), weight gain, sedation (TCAs), withdrawal (benzodiazepines), serotonin syndrome (when combined).
Key student point: SSRIs are first-line for depression; anxiolytics for short-term use; avoid long-term benzodiazepine dependence.

3.5. Analgesics, Antipyretics & Anti-Inflammatory Agents

a) Non-Opioid Analgesics & Antipyretics

Mechanism: Inhibit prostaglandin synthesis (e.g., COX inhibitors) → reduce pain/inflammation/fever.
Examples: Paracetamol (acetaminophen), ibuprofen, aspirin.
Indications: Mild/moderate pain, fever, inflammation (mild).
Side-effects: Gastric irritation/ulcer (NSAIDs), liver damage (paracetamol overdose), bleeding (aspirin).

b) Opioid Analgesics

Mechanism: Bind µ-opioid receptors in CNS → inhibit pain pathways.
Examples: Morphine, codeine, tramadol.
Indications: Moderate to severe pain.
Side-effects: Respiratory depression, constipation, dependence, sedation, nausea.

c) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Mechanism: Block COX1/COX2 → reduce prostaglandins.
Examples: Ibuprofen, naproxen, diclofenac.
Indications: Pain, inflammation (arthritis, gout), fever.
Side-effects: GI bleeding, renal impairment, cardiovascular risk (some).

d) Steroids as Anti-Inflammatory Agents

Mechanism: Glucocorticoids → suppress multiple inflammatory pathways (cytokines, prostaglandins, leukotrienes).
Examples: Prednisone, dexamethasone.
Indications: Severe inflammation (autoimmune disease, asthma exacerbation), immunosuppression.
Side-effects: Hyperglycaemia, immunosuppression, osteoporosis, adrenal suppression, weight gain.

Key student point: Distinguish analgesic vs anti-inflammatory; know when opioids vs non-opioids; NSAIDs carry GI/renal/cardiac risks; steroids carry many systemic side-effects.

3.6. Drugs for Rheumatic Diseases & Gout; Rigidity & Tremor Controllers

Rheumatology/gout:

• Drugs for gout: e.g., allopurinol (xanthine oxidase inhibitor), colchicine.

• Drugs for rheumatoid arthritis and other rheumatic diseases: NSAIDs, steroids, disease-modifying antirheumatic drugs (DMARDs – methotrexate), biologics (beyond diploma scope maybe).
  Rigidity & Tremor Controllers (e.g., Parkinson’s disease):

• Dopaminergic agents (levodopa), dopamine agonists (pramipexole), anticholinergics (trihexyphenidyl) for tremor, rigidity.
  Key student point: Know gout drug mechanism; tremor/rigidity controllers often adjust dopaminergic/anticholinergic balance in CNS.

3.7. Anaesthetics & Muscle Relaxants

Local Anaesthetics: e.g., lidocaine – block sodium channels locally to stop nerve conduction.
General Anaesthetics: e.g., propofol, inhalational agents (sevoflurane) – various mechanisms producing loss of consciousness, analgesia, muscle relaxation.
Skeletal Muscle Relaxants:

• Depolarising (succinylcholine) – neuromuscular block at NMJ.

• Non-depolarising (rocuronium) – block ACh at NMJ.
  Opioid Analgesics in Anaesthesia: Provide analgesia, sedation; e.g., fentanyl.
  Key student point: Understand which agents are used for local vs general anaesthesia; muscle relaxants allow surgery; opioids augment anaesthesia.

3.8. Practical Notes – Drugs Acting on Nervous System

• For your practical sessions: you may be asked to choose a drug for a scenario (e.g., anaesthesia for surgery: general anaesthetic + muscle relaxant; gout acute attack: colchicine + NSAID; tremor in Parkinson’s: trihexyphenidyl).

• Also expect dose, side-effects, monitoring parameters (e.g., opioids → monitor respiratory rate; NSAIDs → monitor kidney function & GI bleed; antidepressants → monitor mood changes, suicidal ideation).

• Clinical correlations: always link mechanism → clinical effect → side-effect (and contraindications).

• Use flowcharts and tables to summarise: e.g., analgesic ladder, classification of antiepileptics by mechanism, classification of antidepressants by generation.