PH3.1-9 | Central Nervous System Pharmacology — Glossary

A syndrome associated with heavy chronic cannabis use, characterised by apathy, social withdrawal, reduced ambition, and decreased ability to concentrate; linked to CB₁ receptor downregulation in the prefrontal cortex and hippocampus.

The three pharmacological goals of general anaesthesia: unconsciousness/amnesia, analgesia, and muscle relaxation — each typically achieved by a different drug class.

A class of sedative-hypnotic/anticonvulsant drugs that potentiate GABA-A by increasing the duration of Cl⁻ channel opening, and at high doses can open the channel directly without GABA — producing a narrow therapeutic index and dose-dependent respiratory depression without a ceiling.

A class of sedative-hypnotic drugs that allosterically potentiate GABA-A receptors by increasing the frequency of Cl⁻ channel opening; require GABA to be present; reversible with flumazenil.

Progressive reduction in the anxiolytic effect of benzodiazepines with repeated use, due to down-regulation of GABA-A receptors; the basis for dose escalation and the clinical unsuitability of BZDs for long-term anxiety management.

The ratio of anaesthetic concentration in blood to that in alveolar gas at equilibrium; a low coefficient indicates low solubility and faster onset and recovery.

A partial μ-opioid agonist and κ-opioid antagonist; exhibits a ceiling effect on respiratory depression due to partial agonism; very high receptor affinity displaces full agonists; used for moderate pain and opioid use disorder treatment.

A sublingual combination for opioid use disorder maintenance: buprenorphine (partial μ-agonist — prevents withdrawal, reduces craving, ceiling on respiratory depression) combined with naloxone (opioid antagonist — abuse deterrent, precipitates withdrawal if injected).

A 5-HT₁A partial agonist anxiolytic; effective for GAD with delayed onset of 2-4 weeks; no sedation, no dependence, no cross-tolerance with benzodiazepines; not effective for panic disorder or acute anxiety.

Physical dependence on benzodiazepines that develops with regular use beyond 4 weeks; characterised by tolerance and a withdrawal syndrome (anxiety, insomnia, tremor, seizures) on abrupt discontinuation — managed by gradual tapering.

Rebound anxiety (often more severe than the pre-treatment baseline) occurring when benzodiazepines are abruptly discontinued after chronic use; due to GABA-A receptor down-regulation and re-emergence of suppressed excitatory tone; managed by gradual tapering with a long-acting BZD.

A peripheral DOPA-decarboxylase (DDC) inhibitor that does not cross the BBB; combined with levodopa to block peripheral conversion to dopamine, reducing nausea/vomiting and increasing CNS bioavailability of levodopa.

A ~1-2% risk of severe WBC reduction (agranulocytosis) with clozapine use; requires mandatory WBC monitoring (weekly ×18 weeks, then fortnightly); clozapine must be stopped immediately if WBC <3,000 or ANC <1,500; rechallenge is contraindicated.

Cocaine blocks DAT, NET, and SERT simultaneously (reuptake inhibitor, not releaser); causes sympathomimetic effects including coronary vasospasm; beta-blockers are contraindicated in cocaine toxicity (unopposed alpha stimulation worsens vasospasm and hypertension).

A property of barbiturates (especially phenobarbitone) by which they induce hepatic CYP450 enzymes, accelerating the metabolism of co-administered drugs (warfarin, oral contraceptives, corticosteroids) and reducing their efficacy.

A ryanodine receptor blocker that halts uncontrolled Ca²⁺ release from skeletal muscle sarcoplasmic reticulum; the definitive pharmacological treatment for malignant hyperthermia.

The most severe form of alcohol withdrawal, occurring 48-96 hours after last drink; characterised by severe autonomic instability (tachycardia, hypertension, fever), hallucinations, agitation, and confusion; life-threatening without treatment; managed with IV benzodiazepines in a high-dependency unit.

The pharmacologically active metabolite of diazepam (and several other BZDs); has a half-life of up to 200 hours; responsible for prolonged sedation with diazepam use, especially in elderly and those with liver disease.

Hypoxia occurring at termination of N₂O anaesthesia as large volumes of N₂O rapidly exit the blood into alveoli, diluting alveolar O₂; prevented by administering 100% O₂ for 5 minutes at recovery.

An irreversible inhibitor of aldehyde dehydrogenase (ALDH) used as a pharmacological deterrent in alcohol use disorder; blocks ethanol metabolism at the acetaldehyde step, causing aversive symptoms (flushing, tachycardia, hypotension) on alcohol ingestion; even small amounts of alcohol in food/medicines can trigger the reaction.

The aversive pharmacodynamic reaction that occurs when a patient on disulfiram ingests any alcohol — acetaldehyde accumulates due to ALDH inhibition, causing flushing, headache, nausea, vomiting, tachycardia, and hypotension; the physiological basis of disulfiram's deterrent action.

A reversible acetylcholinesterase inhibitor (AChEI) used for symptomatic treatment of mild-moderate Alzheimer's dementia; increases synaptic acetylcholine in the hippocampus and cortex; ADRs include GI disturbance and vagally-mediated bradycardia.

Tremor, rigidity, and bradykinesia caused by antipsychotic D2 blockade in the nigrostriatal pathway; treated with anticholinergic drugs (benztropine, trihexyphenidyl) — NOT with levodopa (which is ineffective for this indication and can worsen psychosis).

Parkinsonism caused by D2 receptor blockade in the nigrostriatal pathway by antipsychotics (haloperidol) or antiemetics (metoclopramide); clinically identical to idiopathic PD but potentially reversible; treated with anticholinergics (trihexyphenidyl), not levodopa.

A T-type calcium channel blocker used exclusively for absence seizures; suppresses the thalamo-cortical oscillation responsible for the 3 Hz spike-and-wave discharge of absence epilepsy.

An imidazole IV anaesthetic that is haemodynamically neutral, making it the preferred induction agent in cardiovascular instability; single doses suppress cortisol production for 6-8 hours.

Motor side-effects from antipsychotic D2 blockade in the nigrostriatal pathway: acute dystonia (hours), akathisia (days), drug-induced parkinsonism (weeks), and tardive dyskinesia (months-years of exposure).

A competitive GABA-A antagonist at the benzodiazepine binding site; used to reverse benzodiazepine-induced sedation/respiratory depression.

A competitive inhibitor of alcohol dehydrogenase (ADH); first-line antidote for methanol and ethylene glycol poisoning; blocks the enzymatic conversion of these alcohols to their toxic metabolites (formate and oxalate respectively).

The toxic metabolite of methanol metabolism (methanol → formaldehyde → formic acid, both steps by ADH and ALDH); causes high anion-gap metabolic acidosis and selective optic nerve mitochondrial toxicity (blindness); the primary target of antidotal therapy in methanol poisoning.

A water-soluble prodrug of phenytoin that can be given IV faster and with fewer cardiovascular adverse effects than phenytoin; used for acute IV loading in seizures and status epilepticus.

A reversible, drug-induced state of unconsciousness, analgesia, amnesia, and muscle relaxation sufficient for surgery, produced by pharmacological agents acting primarily on GABA-A and NMDA receptors.

A chronic anxiety disorder characterised by persistent, excessive worry about multiple daily concerns, muscle tension, sleep disturbance, and concentration difficulties; pharmacologically managed long-term with SSRI/SNRI or buspirone (first-line); short-term BZD adjunct only at initiation.

A GABA-B receptor agonist (and GHB receptor agonist) used as a drug-facilitated sexual assault agent; colourless, nearly tasteless; causes sedation, anterograde amnesia, and rapid incapacitation; detection window in urine is only 4-8 hours — immediate specimen collection is essential.

A quaternary ammonium anticholinergic drug that does not cross the blood-brain barrier; used as an antisialagogue pre-med without central anticholinergic side-effects.

A class adverse effect of dopamine agonists (pramipexole, ropinirole) — compulsive gambling, hypersexuality, binge eating, and compulsive shopping; driven by D3 receptor stimulation in the mesolimbic reward circuit; requires proactive patient and family counselling.

An NMDA-receptor antagonist that produces dissociative anaesthesia — unconsciousness with preserved airway reflexes and sympathomimetic effects; contraindicated in raised ICP and hypertension.

A broad-spectrum Na⁺ channel-blocking antiseizure drug; preferred in women of childbearing potential as an alternative to valproate; risk of Stevens-Johnson syndrome (especially with rapid dose titration or concurrent valproate).

A broad-spectrum antiseizure drug that binds synaptic vesicle protein 2A (SV2A), inhibiting neurotransmitter exocytosis; unique mechanism, minimal drug interactions (no CYP induction), renally excreted.

The amino acid precursor of dopamine that crosses the blood-brain barrier; the most effective symptomatic treatment for Parkinson's disease; always combined with carbidopa (peripheral DDC inhibitor) to reduce peripheral conversion and ADRs.

The alveolar concentration of an inhalational anaesthetic at 1 atmosphere that prevents 50% of patients from moving in response to a standard surgical stimulus; the benchmark measure of inhalational GA potency.

A life-threatening hypermetabolic syndrome triggered by volatile anaesthetics or succinylcholine in genetically susceptible patients (RYR1 mutation), presenting with hyperthermia, muscle rigidity, acidosis; treated definitively with dantrolene.

A hypertensive crisis caused by eating tyramine-rich foods (aged cheese, wine, fermented meats) while on an irreversible MAOI (phenelzine, tranylcypromine); dietary tyramine bypasses first-pass MAO-A degradation and triggers massive noradrenaline release from sympathetic nerve terminals.

An NMDA receptor antagonist that reduces glutamate excitotoxicity; used for moderate-severe Alzheimer's dementia, often combined with donepezil; well tolerated with minimal ADRs.

The reward circuit running from the ventral tegmental area (VTA) to the nucleus accumbens; all dependence-producing drugs increase dopamine release in this pathway — the common neurobiological substrate of drug reward and addiction.

The primary target for opioid analgesia; Gi-coupled GPCR mediating analgesia, euphoria, respiratory depression, miosis, constipation, and physical dependence; all major clinical opioids exert their principal effects via μ receptor activation.

A pure competitive opioid receptor antagonist (μ, κ, δ) used for reversal of opioid overdose; administered IV/IM/intranasal; short half-life (~1h) — re-narcotisation occurs if the opioid has a longer duration; does not reverse barbiturate overdose.

A μ-opioid receptor antagonist used in alcohol use disorder; reduces the rewarding effects of alcohol by blocking opioid receptor-mediated mesolimbic dopamine activation; reduces craving and relapse rate; given orally daily or as a monthly depot injection.

A rare, life-threatening reaction to antipsychotics (dopamine receptor blockade), presenting with hyperthermia, 'lead-pipe' muscle rigidity, autonomic instability, and altered consciousness; treated by stopping the antipsychotic, administering dantrolene (muscle relaxant), and bromocriptine (D2 agonist).

The active and toxic metabolite of pethidine; has a half-life of 14-21 hours and accumulates in renal failure; acts as a CNS excitant causing tremors, myoclonus, and seizures — the basis for pethidine's contraindication in renal impairment.

A long-term complication of levodopa therapy in Parkinson's disease — unpredictable switches between 'on' (mobile) and 'off' (akinetic) states correlating with plasma levodopa fluctuations; managed with COMT inhibitors, MAO-B inhibitors, or continuous dopamine agonist delivery.

A three-step framework for cancer and non-cancer pain: Step 1 = non-opioid (paracetamol/NSAID); Step 2 = weak opioid (codeine, tramadol) ± non-opioid; Step 3 = strong opioid (morphine, fentanyl) ± non-opioid ± adjuvants — titrate upward when the current step fails.

The classic clinical presentation of opioid toxicity: coma (unresponsive), pinpoint pupils (miosis — due to μ-receptor activation of the Edinger-Westphal nucleus), and respiratory depression (bradypnoea or apnoea).

Acute anticipatory anxiety triggered by specific performance demands (public speaking, exams, concerts); characterised by somatic symptoms (tremor, palpitations, sweating); managed with propranolol PRN (peripheral sympathetic blockade) without sedation or cognitive impairment.

A Na⁺ channel blocker antiseizure drug with zero-order kinetics at therapeutic concentrations (therapeutic range 10-20 µg/mL); causes gingival hyperplasia, hirsutism, folate deficiency, and teratogenicity; IV formulation is cardiotoxic if given too rapidly.

A pharmacological state in which the body requires a drug to function normally; withdrawal symptoms appear on cessation; most pronounced with opioids, alcohol, and benzodiazepines.

Drugs given before anaesthesia to reduce anxiety, secretions, and aspiration risk, and to potentiate anaesthetic effects — typically include anticholinergics, benzodiazepines, opioids, and antiemetics.

Acute severe withdrawal syndrome triggered by administering an opioid antagonist (naloxone, naltrexone) or a partial agonist (buprenorphine given too early) to a physically opioid-dependent patient with active opioid receptor occupancy.

A phenol-derivative IV anaesthetic that potentiates GABA-A receptors; used for induction and TIVA; has an anti-emetic property; causes hypotension and pain on injection.

Compulsive drug-seeking and drug-taking driven by craving and conditioned learning, persisting despite adverse consequences; present in all substance use disorders.

A selective melatonin MT₁/MT₂ receptor agonist used as a hypnotic; no GABA-A activity; no dependence liability; suitable for sleep-onset insomnia, especially in elderly.

Re-emergence of opioid-induced sedation and respiratory depression after naloxone wears off (half-life ~1h), in a patient who ingested a longer-acting opioid; requires monitoring and possible repeat naloxone dosing or infusion.

A reversible, selective MAO-A inhibitor (e.g., moclobemide); safer than irreversible MAOIs because dietary tyramine can compete with and displace moclobemide from MAO-A, dramatically reducing the hypertensive tyramine interaction risk.

The pharmacological guideline that SSRIs or SNRIs are the first-line pharmacotherapy for all chronic anxiety disorders (GAD, panic disorder, social anxiety, PTSD, OCD), replacing BZDs as long-term agents because of efficacy, safety, and absence of dependence.

A selective MAO-B inhibitor that reduces dopamine catabolism in the striatum; used in early Parkinson's disease and as a levodopa adjunct; at standard doses, no tyramine reaction (MAO-A in gut is preserved — unlike non-selective MAOIs).

A potentially life-threatening syndrome of excess serotonergic activity, presenting with the triad of neuromuscular hyperexcitability (clonus, tremor, hyperreflexia), autonomic instability (hyperthermia, tachycardia, diaphoresis), and altered mental status (agitation, confusion); caused by combinations of serotonergic drugs, most dangerously SSRI/SNRI/TCA + MAOI.

A potentially fatal adverse reaction caused by excess serotonergic activity, occurring when pethidine or tramadol (serotonin-reuptake inhibiting opioids) are combined with MAOIs, SSRIs, or SNRIs; presents with hyperthermia, agitation, clonus, tremor, and seizures.

A class of antidepressants that selectively block the serotonin transporter (SERT), increasing synaptic 5-HT; first-line for major depression, generalised anxiety, OCD, and PTSD; safer than TCAs in overdose.

A seizure lasting ≥5 minutes or two or more seizures without recovery of consciousness between them; a neurological emergency requiring immediate stepwise pharmacological management.

A dual orexin receptor antagonist (DORA) that blocks the wake-promoting orexin signal; approved for sleep-onset and sleep-maintenance insomnia; low dependence liability.

A synaptic vesicle membrane protein involved in neurotransmitter exocytosis; the primary binding target of levetiracetam, which modulates its function to reduce neuronal excitability.

Low-threshold voltage-gated calcium channels in thalamic relay neurons that generate rhythmic oscillatory activity; their abnormal activation drives the 3 Hz spike-and-wave discharge of absence seizures; blocked by ethosuximide and valproate.

Irreversible repetitive involuntary orofacial movements (lip-smacking, chewing, tongue protrusion) resulting from prolonged D2 receptor blockade by antipsychotics (upregulation and supersensitivity of D2 receptors in the striatum); risk higher with typical than atypical antipsychotics; treated with VMAT2 inhibitors.

The mechanism of tricyclic antidepressant lethality in overdose: Na⁺ channel blockade in the cardiac His-Purkinje system and ventricular myocardium causes QRS widening, ventricular arrhythmias, and cardiac arrest; treated with IV sodium bicarbonate (alkalinisation reverses Na⁺-channel block).

An ultra-short-acting barbiturate IV anaesthetic that potentiates GABA-A by prolonging Cl⁻ channel open-time; rapid induction by redistribution; no analgesic activity; contraindicated in porphyria.

A weak μ-opioid agonist with additional serotonin and noradrenaline reuptake inhibition; risks serotonin syndrome with SSRIs/SNRIs/MAOIs and lowers seizure threshold — avoid in epilepsy and patients on serotonergic drugs.

A centrally-acting anticholinergic drug (muscarinic antagonist) used for drug-induced parkinsonism and tremor-dominant Parkinson's disease; reduces the relative cholinergic excess in the striatum; ADRs include dry mouth, urinary retention, and cognitive impairment in elderly.

Sodium valproate is a major human teratogen associated with neural tube defects (~1-2% risk) and autism spectrum disorder in offspring; should be avoided in women of childbearing potential unless no safer alternative is effective.

A partial agonist at α₄β₂ nicotinic acetylcholine receptors; the most effective pharmacological aid for smoking cessation; reduces nicotine withdrawal while blocking the reward from cigarettes; ADRs include nausea and mood changes.

An acute neurological emergency caused by thiamine (vitamin B1) deficiency, common in chronic alcoholism; presents with ophthalmoplegia, ataxia, and confusion; treated with parenteral thiamine — must be given BEFORE glucose administration; untreated progresses to irreversible Korsakoff's psychosis.

Non-benzodiazepine sedative-hypnotics (zolpidem, zopiclone, zaleplon) that act at the BZD binding site of GABA-A with relative selectivity for α₁ subunits (sedation/hypnosis); carry dependence risk and risk of parasomnias.

A pattern of drug elimination where a constant amount (not constant fraction) of drug is eliminated per unit time because the metabolising enzyme is saturated; small dose increments cause disproportionately large rises in plasma drug level — characteristic of phenytoin at therapeutic concentrations.