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Anxiolytics: Pharmacology, Rational Use and Dependence-Safe Prescribing Anxiolytics reduce distressing anxiety symptoms, but they are not all interchangeable. Some provide rapid relief of acute autonomic arousal; others treat the underlying anxiety disorder gradually; some are mainly short-term adjuncts. The safest plan combines diagnostic assessment, psychological care and carefully selected medicine rather than indefinite sedation. Learning outcomes Classify major anxiolytic drug groups. Explain benzodiazepine GABA-A pharmacology and its risks. Choose treatment for acute anxiety, panic, GAD and medically ill patients safely. Recognise withdrawal, overdose and dangerous sedative combinations. 1. Assess before medicating Anxiety may be a symptom of panic disorder, generalised anxiety disorder, depression, PTSD, psychosis, substance intoxication/withdrawal, hyperthyroidism, arrhythmia, asthma, hypoglycaemia, pain or a social crisis. Assess onset, triggers, sleep, mood, suicide risk, alcohol and other drug use, medications, pregnancy and red flags. Chest pain, severe dyspnoea, syncope, delirium, severe agitation or suspected withdrawal needs medical assessment; do not label a physiological emergency as “anxiety.” 2. Main drug groups Group Examples Place in care Benzodiazepines Diazepam, lorazepam, alprazolam, clonazepam, midazolam Rapid symptom control, acute seizures, alcohol withdrawal and procedural/acute agitation contexts. Shortest effective course for anxiety. SSRIs/SNRIs Sertraline, fluoxetine, escitalopram, venlafaxine, duloxetine Longer-term treatment for several anxiety disorders; delayed onset and possible early activation. Buspirone 5-HT1A partial agonist Selected GAD; not useful as immediate rescue and does not produce benzodiazepine-like dependence. Antihistamine/other sedating agents Hydroxyzine and context-specific agents Selected short-term use; sedation and anticholinergic burden matter. Beta blockers Propranolol May reduce peripheral symptoms in selected performance anxiety; not a primary treatment for GAD/panic and is unsafe in some airway/cardiac disease. 3. Benzodiazepines in depth Benzodiazepines bind an allosteric site on the GABA-A receptor and increase the frequency of chloride-channel opening in the presence of GABA, enhancing inhibitory neurotransmission. They cause anxiolysis, sedation, muscle relaxation, anticonvulsant effect and anterograde amnesia. They differ in onset, half-life and active metabolites; these differences matter in older adults, liver disease, withdrawal and next-day impairment. Dependence and respiratory depression Tolerance and physical dependence can develop, especially with daily use. Abrupt cessation after prolonged exposure can cause rebound anxiety, insomnia, tremor, perceptual disturbance, seizures and delirium. Benzodiazepines combined with opioids, alcohol or other sedatives can cause fatal respiratory depression. Avoid routine co-prescribing, use the lowest effective dose for the shortest time, check other sedatives and provide a clear stop/taper plan. 4. Overdose and withdrawal Isolated benzodiazepine overdose often causes drowsiness, ataxia and slurred speech, but co-ingestion changes risk dramatically. Assess airway, breathing, consciousness, glucose, trauma and co-ingestants; provide supportive care and urgent escalation when respiratory depression is present. Flumazenil can precipitate seizures/withdrawal and is not a routine antidote for undifferentiated overdose or chronic users; use only under expert protocol. For withdrawal, avoid abrupt stopping; individualise a supervised gradual taper and treat alcohol/substance-use disorder when present. 5. SSRIs/SNRIs and psychological care For persistent anxiety disorders, CBT and other evidence-based psychological interventions are central. SSRIs/SNRIs often need several weeks for benefit and may transiently increase jitteriness or sleep disruption. Start and review carefully; screen for bipolar disorder, suicide risk, interactions and serotonin syndrome. A short benzodiazepine bridge is occasionally used under close review, but it should never silently become a long-term prescription. 6. Special populations Older adults: increased falls, delirium, cognitive impairment and prolonged sedation; avoid or minimise benzodiazepines. Pregnancy/breastfeeding: risk-benefit assessment and specialist/obstetric guidance are needed; do not stop effective psychiatric treatment abruptly without review. Liver/respiratory disease: prolonged sedation and hypoventilation risk; select and monitor carefully. Substance-use disorder: assess dependence, diversion and withdrawal; coordinate addiction/mental-health care. OSCE points Rule out medical causes and suicidality before offering medicine. Explain that benzodiazepines are short-term and impair driving/alcohol safety. State the opioid–alcohol–benzodiazepine respiratory-depression warning explicitly. For long-term GAD/panic, combine psychological treatment with an appropriate maintenance plan and follow-up. Knowledge check How do benzodiazepines enhance GABA-A signalling? Why is alcohol plus diazepam dangerous? Why is flumazenil not routinely used in overdose? Which treatment is suitable for immediate relief versus longer-term GAD treatment? List four benzodiazepine withdrawal features. Further study Anxiolytics — supplied SlideShare resource

DCM 2101 · CNS Pharmacology Comprehensive Pharmacology of Major Drugs of Abuse Psychoactive substances are frequently encountered in clinical practice—whether prescribed for severe pain, used recreationally, or presenting as an acute toxicological emergency. A safe clinician does not begin by asking, “What sort of person is this?” Begin with: “What is happening physiologically, what is immediately life-threatening, and what care will reduce harm?” This comprehensive guide connects the deep pharmacology (MOA, pharmacokinetics, interactions) of common psychoactive substances to the bedside. It covers opioids, alcohol, sedatives, stimulants, entactogens, cannabinoids, hallucinogens, inhalants, anticholinergics, anabolic steroids, and nicotine. It clearly separates acute intoxication, medical withdrawal, and long-term rehabilitation. Core Learning Objectives Classify psychoactive substances by receptor pharmacology and physiological effects. Detail the MOA, pharmacokinetics, clinical indications, and contraindications of major drug classes. Recognise predictable adverse effects, toxic toxidromes, and dangerous drug interactions. Prioritise emergency assessment using a logical primary survey (ABCDE + glucose/temp). Outline evidence-based overdose care, withdrawal management, and formal rehabilitation modalities. Part 1: The Emergency Clinical Workflow The name of the substance matters, but physiology comes first. A patient with reduced consciousness can deteriorate while staff are still trying to identify what was taken. Approach the patient systematically. Phase 1: Primary Survey (ABCDE + Glucose + Temperature) Airway: Look for vomit, snoring/obstruction, or absent gag reflex. Position in the recovery position; suction and secure with basic/advanced adjuncts as necessary. Breathing: Count respiratory rate and depth. Slow, shallow breathing (Opioids/Sedatives) requires immediate bag-valve-mask (BVM) ventilation and high-flow oxygen before antidotes. Circulation: Check pulse, BP, capillary refill, and a 12-lead ECG. Establish large-bore IV access. Treat shock and life-threatening arrhythmias (e.g., QTc prolongation) promptly. Disability: Assess AVPU/GCS and pupil size (pinpoint vs. dilated). Always check bedside capillary glucose. Hypoglycaemia (common in alcohol toxicity) perfectly mimics intoxication, stroke, or coma. Exposure/Environment: Measure core temperature. Hyperthermia is highly lethal (Stimulants, MDMA, Anticholinergics). Fully expose the patient to find hidden injection sites, transdermal patches, or trauma. Part 2: Detailed Pharmacology by Drug Class 1. Opioid Analgesics Opioids are essential medicines for surgery, severe trauma, and palliative care, but their identical pharmacology causes sedation, tolerance, and fatal respiratory depression. Mechanism of Action (MOA) Receptor binding: Act primarily as agonists at G-protein-coupled opioid receptors (µ [mu], κ [kappa], and δ [delta]). µ (mu) receptor: Main clinical receptor for analgesia, euphoria, sedation, respiratory depression, miosis, constipation, and physical dependence. κ (kappa) receptor: Contributes to spinal analgesia, sedation, and dysphoria. δ (delta) receptor: Contributes to analgesia and affective modulation. Cellular signalling (Gi/o coupled): Presynaptic: Decreases cAMP, closes voltage-gated calcium channels → decreases release of excitatory neurotransmitters (Substance P, glutamate). Postsynaptic: Opens potassium channels → K+ efflux causes hyperpolarisation, decreasing neuronal firing. Sites of action: Peripheral tissues, dorsal horn of the spinal cord, brainstem descending pathways, and the thalamus/limbic system (alters emotional response to pain). Pharmacokinetics (PK) & Classification Classification Examples Key PK & Clinical Points Full µ Agonists Morphine, Fentanyl, Methadone, Oxycodone No ceiling effect for analgesia or respiratory depression. Fentanyl is highly lipophilic (rapid onset). Methadone has a very long, variable half-life. Partial µ Agonists Buprenorphine High receptor affinity but partial activation. Has a ceiling effect for respiratory depression. Can precipitate withdrawal if given to full-agonist dependent patients. Mixed Agonist-Antagonists Nalbuphine, Pentazocine κ agonist / µ antagonist. Can precipitate withdrawal in dependent patients. Antagonists Naloxone, Naltrexone Naloxone: Short-acting IV/IM/IN for acute overdose. Naltrexone: Long-acting oral/IM for relapse prevention. Atypical / Weak Codeine, Tramadol Codeine is a prodrug requiring CYP2D6 to become morphine. Tramadol also inhibits serotonin/noradrenaline reuptake. Clinical Indications Severe acute pain (trauma, burns, post-operative). Cancer and palliative pain (including dyspnoea relief in end-of-life care). Anesthesia (adjunct to induction/maintenance). Opioid Use Disorder (OUD) maintenance (Methadone, Buprenorphine). Contraindications & Precautions Absolute: Acute respiratory depression, severe asthma/COPD without mechanical ventilation, paralytic ileus. Relative precautions: Renal impairment (morphine metabolites accumulate, causing neurotoxicity), hepatic failure, raised intracranial pressure (ICP), and sleep-disordered breathing. Side & Adverse Effects Respiratory: Dose-dependent respiratory depression (reduced brainstem sensitivity to CO2). GI: Constipation (does not develop tolerance), nausea/vomiting (CTZ stimulation), biliary colic (sphincter of Oddi spasm). Neuro: Sedation, miosis (pinpoint pupils), delirium in the elderly. Cardiovascular: Hypotension, bradycardia (often due to histamine release with morphine). Other: Pruritus (itch), urinary retention, endocrine suppression (hypogonadism), opioid-induced hyperalgesia (paradoxical increased pain). Drug Interactions Fatal Synergy: Opioids + Benzodiazepines + Alcohol = Massive additive respiratory depression. Serotonin Syndrome: Tramadol/Pethidine + SSRIs/MAOIs. QTc Prolongation: Methadone + Macrolides/Antipsychotics. Intoxication & Overdose Management Classic Toxidrome: Coma + Respiratory Depression (

DCM 2101 · CNS Pharmacology Local Anaesthetic Agents: Pharmacology, Techniques and Toxicity Local anaesthetic agents are medicines that produce a reversible loss of sensation in a limited area without loss of consciousness. They are central to safe minor surgery, dental work, wound care, obstetrics, regional anaesthesia, and acute pain control. A clinician must understand much more than the name of the drug: the quality and safety of a block depend fundamentally on nerve physiology, drug chemistry, accurate dosing, injection site vascularity, and specific patient factors. This chapter explores the profound neuropharmacology of local anaesthetics, heavily expands the profiles of individual agents (amides and esters), details modern regional techniques, and provides rigorous, step-by-step management protocols for life-threatening complications such as Local Anaesthetic Systemic Toxicity (LAST) and Methaemoglobinaemia. Learning objectives Explain the molecular mechanism by which local anaesthetics interrupt nerve conduction (state-dependent blockade). Relate physicochemical properties (pH, pKa, lipid solubility, and protein binding) to clinical onset, potency, and duration of action. Evaluate comprehensively the individual profiles of major esters and amides, including their mechanisms of action, indications, contraindications, side effects, and drug interactions. Choose a sensible technique based on the surgical requirement and use adjuncts (vasoconstrictors and alkalinising agents) safely. Calculate maximum safe dosages accurately based on patient weight and specific agent. Recognise, prevent, and begin immediate emergency management of LAST using current lipid-emulsion protocols. 1. Neurophysiology: What normally happens in a peripheral nerve? To understand local anaesthetics, one must first understand normal nerve conduction: Resting Potential: The nerve cell maintains a negative resting membrane potential (approx. -70mV) via the Na+/K+ ATPase pump. Depolarisation: A sensory stimulus causes the membrane to reach a threshold potential. Voltage-gated sodium (Na+) channels open rapidly, and a massive influx of Na+ enters the axon. Propagation: This depolarisation travels along the nerve axon as an action potential, transmitting the pain signal to the dorsal horn of the spinal cord and up to the brain. Repolarisation: Potassium (K+) efflux then repolarises the membrane, resetting it for the next signal. Core Pharmacological Mechanism (The “Use-Dependent” Block) Local anaesthetic agents reversibly block voltage-gated sodium channels from the inside of the nerve membrane. They specifically target channels that are actively opening or in an inactivated state during rapid firing. If Na+ channel opening is prevented, the action potential cannot be generated or propagated: the brain perceives no pain. Because they bind more eagerly to rapidly firing channels, they exhibit use-dependent (or state-dependent) blockade. 2. Pharmacokinetics: How a local anaesthetic reaches the channel Most LA agents are formulated as weak bases (hydrochlorides) and exist in equilibrium between two forms: an uncharged, lipid-soluble base (B) and a charged, water-soluble cation (BH+). Crossing the sheath: Only the uncharged, lipid-soluble base (B) can physically penetrate the lipid bilayer of the nerve epineurium and axon membrane. Blocking the channel: Once inside the slightly more acidic intracellular environment of the axon, the drug re-equilibrates. The newly formed charged cation (BH+) physically plugs the Na+ channel from the inside. Physicochemical Property Determines Clinical Consequence pKa (Dissociation Constant) Onset of action Lower pKa (closer to body pH of 7.4) means more drug exists in the uncharged base form. This results in a faster onset (e.g., Lignocaine pKa 7.9 is faster than Bupivacaine pKa 8.1). Lipid Solubility Potency High lipid solubility allows easier penetration of nerve membranes, resulting in greater potency and tissue penetration, but also raises the risk of severe cardiovascular toxicity. Protein Binding (Alpha-1 acid glycoprotein) Duration of action High protein binding means the drug firmly attaches to the Na+ channel and local tissues, resulting in a longer duration of action (e.g., Bupivacaine > Lignocaine). Why blocks fail in infected or inflamed tissue Inflamed or infected tissue is highly acidic (pH 5.0 – 6.0). In this low-pH environment, the Henderson-Hasselbalch equation dictates that the vast majority of the local anaesthetic remains in the ionised (charged) state outside the nerve. Because charged molecules cannot cross the lipid membrane, less drug reaches the inside of the axon. A painful abscess will respond poorly to direct infiltration. Solution: Use systemic analgesia, perform a regional nerve block proximally through healthy (normal pH) tissue, or carefully alkalinise the LA agent with sodium bicarbonate. 3. Differential block: Why pain goes before motor power Not all nerve fibres are blocked at the same time. Local anaesthetics block smaller, myelinated, and rapidly firing fibres before larger, unmyelinated ones. The exact order of blockade is clinically crucial to assess before surgery: Fibre Type Anatomy / Myelination Function Lost Clinical Order of Blockade Type B Small, myelinated Autonomic / Sympathetic 1st (Earliest): Vasodilation and warmth occur first. Type C & A-delta Small, unmyelinated (C) / myelinated (A-delta) Pain and Temperature 2nd: Loss of sharp pain and cold sensation. Type A-gamma & A-beta Medium, myelinated Touch and Pressure 3rd: Patient may still feel pulling/pressure despite pain relief. Type A-alpha Large, heavily myelinated Motor function & Proprioception 4th (Last): Muscle paralysis occurs last and wears off first. Clinical Pearl: This explains why a patient may feel pressure or movement despite excellent analgesia, and why a block must always be tested with cold (ice) or a sharp point before incision, rather than simply assuming the block is complete. 4. Classification: Esters and Amides Local anaesthetics are divided into two distinct chemical classes based on the intermediate chain linking their lipophilic aromatic ring to their hydrophilic amine group. A simple memory aid: Amides have two “i”s in their generic name, Esters have only one “i”. Esters (e.g., Cocaine, Procaine, Tetracaine, Benzocaine) Metabolism: Rapidly hydrolysed in the blood by plasma pseudocholinesterase. Allergy Risk: High. Metabolism produces Para-Aminobenzoic Acid (PABA), a known highly allergenic compound. Cautions: Patients with atypical pseudocholinesterase will have severely prolonged half-lives of these drugs. Amides (e.g., Lignocaine, Bupivacaine, Ropivacaine, Prilocaine) Metabolism: Biotransformed in the liver by Cytochrome P450 enzymes (dealkylation and hydrolysis). Allergy Risk: Extremely rare. A reported “allergy” is usually a reaction to the preservative (methylparaben), an intravascular adrenaline rush, or a vasovagal syncopal episode. Cautions: Clearance is significantly reduced in severe liver disease (cirrhosis), low cardiac output

Cholinergic Antagonists: Muscarinic and Nicotinic Blocking Drugs Cholinergic antagonists reduce acetylcholine action. Most clinically familiar medicines are antimuscarinics, used for bradycardia, poisoning, bronchodilation, eye examination, bladder disease, motion sickness and drug-induced movement disorders. Nicotinic antagonists include neuromuscular blockers used during anaesthesia and airway management. They can be lifesaving, but their predictable toxicity—delirium, hyperthermia, urinary retention, bronchospasm, paralysis or apnoea—must be anticipated. This chapter gives common adult teaching doses only: verify indication, formulation, patient factors and current local protocol before prescribing. Learning outcomes Link muscarinic receptor blockade to organ effects and toxidrome findings. Use separate drug knowledge—mechanism, common dose, indication, adverse effects, contraindications, interactions and counselling—for each major agent. Recognise anticholinergic toxicity and when expert-supervised physostigmine may be appropriate. Explain that neuromuscular blockers cause paralysis only: they do not provide analgesia, amnesia or unconsciousness. 1. What muscarinic blockade does Site/receptor Normal ACh effect Effect of antagonism Clinical consequence M2, heart Vagal slowing of SA node and AV conduction. Increased rate and AV conduction. Atropine may treat vagal bradycardia; tachyarrhythmia risk. M3, glands/airway Saliva, tears, sweat and bronchial secretion; bronchoconstriction. Drying and bronchodilation. Useful before anaesthesia/COPD; dry mouth, thick sputum and heat intolerance. M3, eye Miosis and accommodation for near vision. Mydriasis and cycloplegia. Useful for examination; blurred vision and possible acute angle closure. M3, gut/bladder Peristalsis and detrusor contraction. Reduced gut and bladder contraction. Useful in overactive bladder; constipation, ileus and urinary retention. CNS Cholinergic attention/memory pathways. Variable, greatest with tertiary amines crossing BBB. Sedation, impaired memory, agitation or delirium. Anticholinergic toxidrome: act on the physiology Dry: dry mouth, absent sweating, dry warm skin, reduced bowel sounds and urinary retention. Blind: dilated pupils, blurred near vision, photophobia; acute angle closure may present with eye pain/red eye. Hot/red/fast: hyperthermia, flushing, tachycardia and hypertension may occur. Confused: agitation, hallucinations, delirium, seizures or coma, especially with CNS-penetrant agents. Initial management: stop culprit medicines; ABC, ECG, temperature and glucose; treat agitation/seizures and hyperthermia; obtain toxicology help. Physostigmine is reserved for selected severe confirmed central toxicity with continuous monitoring. 2. Classification Systemic antimuscarinics Atropine: bradycardia and cholinergic poisoning. Glycopyrrolate: secretion control and peri-operative co-medication. Hyoscine (scopolamine): motion sickness/secretions. Organ-selective use Ipratropium, tiotropium: inhaled bronchodilation. Oxybutynin, solifenacin: overactive bladder. Tropicamide, cyclopentolate: ophthalmic mydriasis/cycloplegia. Benztropine/procyclidine: selected extrapyramidal reactions. Nicotinic blockade Rocuronium, vecuronium, cisatracurium: non-depolarising NM blockers. Succinylcholine: depolarising NM blocker. Ganglion blockers are largely historical due to widespread autonomic adverse effects. 3. Individual antimuscarinic drug cards Atropine Mechanism and receptor profile Competitive, reversible muscarinic antagonist with central and peripheral activity. Blocks vagal M2 effects in the heart and M3-mediated secretions, bronchial tone, pupil constriction and smooth-muscle contraction. Formulations and common adult teaching doses IV/IM/SC injection and ophthalmic preparations exist; doses differ substantially by indication. For symptomatic adult bradycardia, a common resuscitation teaching regimen is 1 mg IV, repeated every 3–5 minutes to a maximum 3 mg according to current ALS/local protocol. For organophosphate poisoning, give repeated escalating doses titrated to drying of bronchial secretions and adequate ventilation, not to pupil size or heart rate; follow toxicology protocol. Indications Selected symptomatic bradycardia due to vagal excess or AV nodal block when the algorithm indicates it. Life-threatening muscarinic manifestations of organophosphate/carbamate or muscarinic-mushroom poisoning. Reduction of secretions/peri-operative vagal bradycardia and selected ophthalmic uses. Common side effects Dry mouth and thirst: salivary secretion is reduced. Blurred near vision/photophobia: mydriasis and cycloplegia impair accommodation. Tachycardia/palpitations: vagal restraint on the SA node is blocked. Constipation and urinary hesitancy: gut and detrusor contraction are reduced. Serious adverse effects Acute angle-closure glaucoma: pupil dilation can obstruct aqueous drainage in a susceptible eye. Delirium, hallucinations or hyperthermia: particularly with high systemic exposure and in older adults. Myocardial ischaemia/tachyarrhythmia: excessive heart-rate increase raises oxygen demand in coronary disease. Contraindications and cautions In a true life-threatening poisoning or bradycardic emergency, there may be no absolute contraindication; weigh risk against immediate benefit. Use caution in narrow-angle glaucoma, prostatic obstruction/urinary retention, pyloric obstruction/ileus, severe ulcerative colitis, fever and coronary disease. Atropine may not be effective in transplanted-heart bradycardia; prepare alternative pacing/vasoactive strategies. Interactions Antihistamines, TCAs, antipsychotics, antiparkinsonian drugs and many bladder medicines add anticholinergic burden. Anticholinesterases/cholinomimetics oppose the effect; this is used deliberately in selected anaesthetic/toxicology situations. Monitoring and counselling Monitor ECG, BP, perfusion, secretions, ventilation, temperature, pupils, urine output and mental state. In poisoning, airway suction and oxygenation are not optional: atropine does not reverse nicotinic weakness or replace ventilation. Glycopyrrolate (glycopyrronium) Mechanism and receptor profile Quaternary antimuscarinic that acts predominantly peripherally and has limited BBB penetration. Reduces airway/salivary secretions, blocks vagal bradycardia and counteracts muscarinic effects of neostigmine. Formulations and common adult teaching doses Injection, oral and inhaled products exist; dosing depends greatly on indication. With neostigmine reversal, a commonly taught IV dose is 0.2 mg glycopyrrolate per 1 mg neostigmine, administered together or beforehand under anaesthesia protocol. For peri-operative secretion control, typical adult doses are 0.1–0.2 mg IV/IM, titrated by the clinician. Indications Reduction of secretions and prevention/treatment of peri-operative vagal bradycardia. Co-administration with neostigmine for reversal of non-depolarising neuromuscular blockade. Inhaled long-acting products may be used in COPD according to local availability. Common side effects Dry mouth and thick secretions: glandular M3 blockade. Constipation and urinary retention: reduced gut/detrusor smooth-muscle activity. Tachycardia: vagal blockade at the heart. Serious adverse effects Heat intolerance/hyperthermia: impaired sweating, especially in a febrile or hot environment. Glaucoma or urinary retention: potentially serious consequences in susceptible patients. Contraindications and cautions Caution in angle-closure glaucoma, obstructive uropathy, paralytic ileus, severe ulcerative colitis and tachyarrhythmia. Limited CNS entry may reduce delirium risk but does not eliminate peripheral toxicity. Interactions Additive toxicity occurs with other antimuscarinics. It deliberately antagonises neostigmine’s muscarinic effects but not its NMJ reversal effect. Monitoring and counselling Monitor pulse, secretions, airway patency, bladder function and bowel activity. During reversal, verify objective recovery of neuromuscular function and adequate ventilation—not just a dry mouth or faster pulse. Hyoscine (scopolamine) Mechanism and receptor profile Tertiary antimuscarinic that crosses the BBB; blocks vestibular and vomiting-pathway cholinergic signalling. CNS penetration explains motion-sickness benefit and the risk of sedation, confusion and delirium. Formulations and common adult

Mood Stabilisers: the clinical idea Mood stabilisers are medicines used to treat bipolar disorder by reducing acute mood episodes and preventing relapse. They are not simply “calming drugs”: each has a different role in acute mania, bipolar depression and long-term maintenance. Good prescribing combines a clear diagnosis, safety monitoring, psychosocial care, and a relapse plan. Learning outcomes: classify the principal agents; select treatment according to the phase of illness; recognise dangerous toxicity and interactions; and counsel a patient safely. 1. Start with the phase of bipolar disorder Clinical phase Typical features Drug principle Acute mania or hypomania Elevated/irritable mood, reduced sleep, grandiosity, risky behaviour, psychosis or severe agitation Rapid control commonly needs an antipsychotic; lithium or valproate may be used where appropriate. Bipolar depression Low mood, anhedonia, biological symptoms, impaired function and possible suicidal thinking Use a bipolar-depression strategy; avoid casually starting antidepressant monotherapy because it can precipitate mood elevation in susceptible people. Maintenance Recovery between episodes; relapse risk remains Choose the agent with best evidence for the patient’s previous episode pattern and tolerability, then support adherence and early detection of relapse. Before prescribing, confirm that symptoms are not due to alcohol, stimulants, corticosteroids, thyroid disease, delirium or another medical condition. Ask about pregnancy potential, renal and liver disease, epilepsy, current medicines, substance use, self-harm risk and the availability of family support. 2. The main medicines at a glance Lithium A classic maintenance medicine with anti-manic and relapse-prevention benefit. It has a narrow therapeutic index, so monitoring is essential. Valproate An anticonvulsant used particularly for acute mania and maintenance in selected patients. It has major fetal risk and requires liver and blood-count monitoring. Lamotrigine Useful especially in prevention of depressive episodes. It must be titrated slowly because a serious rash can occur. Carbamazepine An alternative anticonvulsant in selected cases. It causes important interactions and can affect blood counts and sodium. Atypical antipsychotics Several agents are used for mania, bipolar depression or maintenance. Match the agent to the episode and monitor metabolic effects. 3. Lithium: high-yield pharmacology and safe use Lithium is a small ion that influences intracellular second-messenger signalling and neuronal plasticity. In practice, its key lesson is not a single receptor: lithium effectiveness depends on keeping the blood concentration in a safe therapeutic range. It is used in acute mania in some settings and is an important maintenance option, particularly when relapse prevention and suicide-risk reduction are priorities. Before and during treatment Why it matters Check renal function, electrolytes, thyroid function and calcium; assess pregnancy potential. Lithium is cleared by the kidney and can impair renal and thyroid function over time. Measure lithium concentrations at the local protocol interval, including after dose changes. There is a small gap between therapeutic and toxic concentrations. Ask about fluid intake, vomiting, diarrhoea, fever and heavy sweating. Dehydration and sodium loss can increase lithium concentration. Review all medicines. NSAIDs, ACE inhibitors, ARBs and thiazide diuretics can raise lithium concentrations. Recognise lithium toxicity early New worsening tremor, nausea, vomiting, diarrhoea, slurred speech, ataxia, confusion, coarse tremor, seizures or reduced consciousness should be treated as possible toxicity. Withhold further doses, assess urgently, check level/renal function/electrolytes, correct dehydration and seek senior or specialist advice. Severe toxicity may need haemodialysis. Counselling: take it regularly; do not double a missed dose; keep salt and fluid intake reasonably consistent; avoid self-starting NSAIDs; and seek advice promptly during significant illness with fluid loss. 4. Anticonvulsant mood stabilisers Medicine Useful place in treatment Key safety points Valproate Acute mania and maintenance in selected patients. Check baseline/ongoing liver function and blood count. Warn about weight gain, tremor, gastrointestinal effects, thrombocytopenia, pancreatitis and hepatotoxicity. Avoid in pregnancy where possible: fetal harm risk is substantial; use a pregnancy-prevention and specialist pathway where relevant. Lamotrigine Maintenance, especially where depressive relapse predominates; not a rapid solution for severe acute mania. Titrate slowly. Stop and assess urgently if rash, mucosal lesions, fever or systemic illness occurs because Stevens–Johnson syndrome/toxic epidermal necrolysis is rare but serious. Carbamazepine Alternative for mania or maintenance when first-line approaches are unsuitable. Check full blood count, liver function and sodium. Watch for rash, dizziness, hyponatraemia and blood dyscrasias. It induces hepatic enzymes and can reduce the effectiveness of many medicines, including hormonal contraception. Exam pearl: “Anticonvulsant” does not mean interchangeable. Valproate, lamotrigine and carbamazepine have different strengths, onset patterns, reproductive risks, interaction profiles and monitoring requirements. 5. Antipsychotics in bipolar disorder Second-generation antipsychotics are frequently used as mood-stabilising agents, particularly when mania has psychotic symptoms, severe agitation or a need for rapid symptom control. Some also have evidence in bipolar depression or maintenance. Their use must include baseline and follow-up weight, waist circumference where possible, blood pressure, glucose and lipids. Ask actively about sedation, extrapyramidal symptoms, sexual adverse effects and adherence. For a severely agitated or psychotic manic patient, first ensure safety: assess risk to self/others, capacity, medical causes and substance intoxication. Urgent mental-health input and a safe environment are part of treatment; medication alone is not the whole management plan. 6. A practical prescribing and monitoring checklist Define the episode: mania, depression, mixed state, psychosis, emergency or maintenance? Assess immediate risk: suicide, neglect, violence, exploitation, inability to care for self, intoxication and pregnancy. Choose an agent deliberately: previous response, dominant episode pattern, medical disease, interactions, reproductive safety and monitoring capacity all matter. Record baseline tests: targeted to the medicine—renal/thyroid/calcium for lithium; FBC/LFT for valproate or carbamazepine; metabolic measures for antipsychotics. Give a clear safety-net: toxicity symptoms, rash warning, pregnancy advice, missed-dose advice and contact route. Make a relapse plan: regular review, adherence support, sleep routine, substance-use care and early warning signs agreed with the patient and family where appropriate. 7. OSCE station: counselling a patient starting lithium Open: explain the indication and that regular monitoring makes treatment safer. Check: renal/thyroid history, pregnancy possibility, diarrhoea/vomiting, current pain medicines and diuretics. Advise: consistent fluids and salt; no unsupervised NSAIDs; avoid dehydration; attend blood tests. Safety net: urgent review for worsening tremor, vomiting/diarrhoea, unsteadiness, confusion or seizures. Close: check understanding and provide a follow-up