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CNS stimulants: why they matter Central nervous system (CNS) stimulants increase alertness, attention or wakefulness. They include prescribed medicines for attention-deficit/hyperactivity disorder (ADHD) and narcolepsy, as well as substances with major misuse potential. Their benefit depends on selecting the right diagnosis, using one formulation correctly, and monitoring cardiovascular, sleep, growth, psychiatric and misuse risks. Learning outcomes: classify stimulants; explain their mechanisms; use indicative dose/titration tables safely; recognise toxicity; and counsel patients about diversion and sleep hygiene. Use the dose table safely Doses below are common adult teaching ranges, not a substitute for the product label or local protocol. Confirm the exact formulation (immediate versus modified release), indication, age, comorbidity, interacting medicines and controlled-drug requirements before prescribing. Start low, titrate one product at a time, and document response and adverse effects. 1. Classification and mechanisms Group Examples Core pharmacology Amphetamine-type stimulants Dexamfetamine, lisdexamfetamine, amphetamine Increase synaptic dopamine and noradrenaline largely by promoting release and reversing transporters. Methylphenidate-type Methylphenidate Inhibits dopamine and noradrenaline reuptake transporters, increasing synaptic availability. Wakefulness-promoting agents Modafinil, armodafinil Mechanism is not fully defined; promotes wakefulness through several neurotransmitter systems and has interaction potential. Methylxanthines Caffeine, theophylline Adenosine-receptor antagonism; at higher exposures also affects phosphodiesterase activity and calcium handling. Historical/limited-use stimulants Cocaine, ephedrine and others Important for toxicology and misuse teaching; not routine long-term treatment choices. In ADHD, improving signalling in prefrontal networks can improve attention and impulse control. This is not the same as giving a stimulant to a healthy person for “study power”: higher exposure can worsen anxiety, insomnia, hypertension, psychosis and dependence without improving learning. 2. Clinical uses ADHD: part of a structured plan that includes diagnostic assessment, functional goals, education and behavioural support. Narcolepsy/excessive daytime sleepiness: selected wakefulness-promoting medicines or stimulants after sleep-disorder evaluation. Apnoea of prematurity: caffeine citrate is used in neonatal protocols—this is specialist neonatal prescribing, not an adult caffeine dose extrapolation. Other uses: some indications are country- and product-specific; do not assume that a drug approved for one indication is suitable for another. 3. Dose and formulation table Medicine Typical adult starting and titration approach Usual ceiling / practical checks Methylphenidate immediate release Product-dependent. A common adult regimen is divided oral doses 2–3 times daily, with individual titration. Give earlier in the day to reduce insomnia. Many immediate-release labels describe 20–30 mg/day as an average adult total and a maximum of 60 mg/day; modified-release products have different limits. Never interchange mg-for-mg without checking the formulation. Lisdexamfetamine Common ADHD labels start once-daily morning treatment at 30 mg and titrate at weekly intervals if needed. Typical labelled maximum 70 mg/day. Review pulse, blood pressure, appetite, sleep and psychiatric symptoms at each increase. Dexamfetamine Use a low morning dose and titrate cautiously in divided doses according to local ADHD/narcolepsy guidance. Exact maximum varies by indication and product. Avoid late dosing and avoid co-prescribing duplicate stimulant products unless specialist-directed. Modafinil For adult narcolepsy, many labels use 200 mg orally in the morning; some divide morning/noon dosing. Higher doses are not automatically more effective. Review hormonal-contraception interactions, rash, psychiatric history and hepatic impairment. Caffeine Dietary caffeine is not prescribed like ADHD medicine. Assess total daily intake from coffee, energy drinks, tablets and combination analgesics. High intake can produce tremor, anxiety, insomnia, tachycardia and arrhythmia. Do not use adult “energy” doses for neonates or children. Formulation pearl: immediate-release methylphenidate has a shorter duration and more dosing opportunities; modified-release preparations alter the release profile. Record the brand/formulation, dose time and total daily milligrams before changing anything. 4. Baseline assessment before prescribing Check Reason Diagnosis, functional impairment and treatment goal Prevents symptom-only prescribing and provides a measurable review target. Pulse, blood pressure, weight; cardiovascular history and family history of sudden death/arrhythmia Stimulants may increase pulse/BP and can be unsafe in serious structural heart disease or important arrhythmia. Sleep, anxiety, depression, mania, psychosis and tics Stimulants can worsen insomnia, anxiety and psychotic/manic symptoms. Substance use, diversion risk and safeguarding Misuse, snorting/injecting, sharing tablets and coercion can cause harm and legal consequences. Pregnancy potential, lactation, renal/hepatic disease and full medicine list Changes drug choice, dose, interaction risk and counselling. 5. Adverse effects, interactions and toxicity Common adverse effects are reduced appetite, weight loss, headache, dry mouth, nausea, tremor, sweating, anxiety, insomnia, tachycardia and raised blood pressure. Important but less common harms include chest pain, arrhythmia, severe hypertension, peripheral vasculopathy, hallucinations, mania or psychosis. Assess new suicidal thinking or marked behavioural change promptly. Dangerous interactions include monoamine oxidase inhibitors (MAOIs), other sympathomimetics, some decongestants and medicines that independently raise heart rate or blood pressure. Modafinil can reduce the reliability of hormonal contraception through enzyme induction; check the current product information and discuss an effective alternative during treatment and for the recommended period after stopping. Stimulant overdose: initial management Suspect overdose with severe agitation, panic, hyperthermia, hypertension, tachyarrhythmia, chest pain, seizures, delirium or rhabdomyolysis. Use ABCDE assessment, check glucose/temperature/ECG, manage agitation and seizures according to emergency protocol, cool hyperthermia, treat complications and contact toxicology/critical-care support. Do not leave an agitated, hyperthermic patient unmonitored. 6. Dependence, diversion and patient counselling Explain that tablets must never be shared, sold, crushed, snorted or injected. Use the lowest effective dose and review regularly; treatment is not “set and forget.” Take morning/early-day doses as directed; avoid extra caffeine and ask before using cold remedies or supplements. Seek urgent care for chest pain, fainting, severe headache, hallucinations, suicidal thoughts or suspected overdose. Store controlled medicines securely and count remaining tablets when diversion is a concern. 7. OSCE and exam points OSCE structure: confirm the indication and formulation; measure BP, pulse and weight; ask about sleep, appetite, mood, psychosis and substance use; screen for interacting medicines; agree a functional target; explain timing, storage and red flags; schedule review after each titration. In an exam, distinguish methylphenidate reuptake blockade from amphetamine-promoted catecholamine release. Further study CNS stimulants and cognitive enhancers — supplied slides Methylphenidate prescribing information

Adrenergic Agonists (Sympathomimetics): Comprehensive Pharmacological Guide, Dosing, and Safe Clinical Use What this comprehensive chapter covers This guide provides an extensive, medicine-by-medicine deep dive into adrenergic pharmacology. Synthesizing standard physiological foundations with clinical applications, it ensures students and practitioners understand the biosynthesis, mechanism of action (MOA), pharmacokinetics, receptor profiles, and precise indications for each major adrenergic agonist. Detailed sections are provided for every drug, segregating common side effects from severe adverse events, outlining strict contraindications, and cataloging vital drug-drug interactions. Critical Pre-Prescription Safety Review Identify the exact clinical problem: Anaphylaxis, acute asthma exacerbation, cardiogenic shock, septic shock, symptomatic bradycardia, and orthostatic hypotension possess entirely different pathological mechanisms requiring highly specific receptor targeting. Baseline & Continuous Assessment: Check BP, pulse rate, cardiac rhythm, continuous ECG (for IV infusions), oxygenation (SpO2), serum K+, blood glucose, renal function, hydration/volume status, and pregnancy status. Verify Formulations & Concentrations: A classic lethal error is confusing adrenaline concentrations. Adrenaline 1 mg/mL (1:1000) is for IM use only. Adrenaline 0.1 mg/mL (1:10,000) is for IV resuscitation. They are never interchangeable [1]. IV Vasoactive Protocol: Always use a central line when possible, an infusion pump, a traceable protocol, and frequent reassessment with documented targets (e.g., MAP > 65 mmHg, improved capillary refill, urine output > 0.5 mL/kg/hr). Introduction to Adrenergic Pharmacology The sympathetic nervous system (SNS) regulates the body’s “fight or flight” response through the release of endogenous catecholamines (dopamine, noradrenaline, and adrenaline). Understanding how to manipulate this system pharmacologically requires a firm grasp of catecholamine life cycles and receptor mechanics. Biosynthesis: Synthesized in adrenergic neurons and the adrenal medulla. The pathway begins with the amino acid Tyrosine → DOPA (via Tyrosine Hydroxylase, the rate-limiting step) → Dopamine → Noradrenaline (Norepinephrine) → Adrenaline (Epinephrine) [1]. Storage & Release: Catecholamines are stored in presynaptic vesicles (protected from degradation) and released into the synaptic cleft upon calcium influx triggered by an action potential. Termination of Action: Reuptake into the presynaptic neuron (via NET/DAT) is the primary termination method. Enzymatic degradation is handled by Monoamine Oxidase (MAO) in the mitochondria and Catechol-O-Methyltransferase (COMT) in the synaptic space and liver. The final urinary metabolite for epinephrine and norepinephrine is Vanillylmandelic Acid (VMA) [1]. 1. Receptor Foundation & Second Messengers Receptor G-Protein / 2nd Messenger Major Physiologic Effect Clinical Consequence & Application α1 Gq → PLC → IP3/DAG → ↑ Intracellular Ca2+ Smooth muscle contraction (arterial/venous vasoconstriction), mydriasis (pupil dilation), contraction of bladder sphincter. Raises Systemic Vascular Resistance (SVR) and BP; relieves nasal mucosal edema; causes urinary retention and potential tissue ischemia. α2 Gi → inhibits Adenylyl Cyclase → ↓ cAMP Presynaptic inhibition of noradrenaline release; decreases central sympathetic outflow. Lowers BP and heart rate centrally; abrupt withdrawal causes severe rebound hypertension. β1 Gs → stimulates Adenylyl Cyclase → ↑ cAMP Increased chronotropy (heart rate), inotropy (contractility), dromotropy (AV conduction), and renin release (kidneys). Raises cardiac output; increases myocardial oxygen demand; may provoke angina or tachyarrhythmias. β2 Gs → stimulates Adenylyl Cyclase → ↑ cAMP Smooth muscle relaxation (bronchodilation, uterine relaxation, vasodilation of skeletal muscle beds), glycogenolysis, cellular K+ uptake. Relieves bronchospasm; suppresses premature labor; triggers fine muscle tremor, reflex tachycardia, hyperglycemia, and hypokalemia. D1 Gs → stimulates Adenylyl Cyclase → ↑ cAMP Vasodilation in renal, mesenteric, and coronary beds. Improves renal and splanchnic blood flow at low dopamine doses (though “renal-dose dopamine” to prevent AKI is no longer supported by evidence). Detailed Drug Profiles 2. Adrenaline (Epinephrine) Class & Receptor Profile: Endogenous catecholamine; potent direct non-selective agonist at α1, α2, β1, and β2 receptors. Pharmacokinetics: Poorly absorbed orally (rapidly destroyed by gut MAO/COMT). Given IM, SC, IV, or via inhalation. Does not readily cross the blood-brain barrier. Extremely short half-life (~2 minutes). Mechanism of Action (MOA): Dose-dependent effects. Low doses primarily stimulate β receptors (causing vasodilation and increased heart rate). High doses heavily stimulate α1 receptors (causing profound vasoconstriction that overrides β2 vasodilation). β2 agonism provides strong bronchodilation and inhibits mast cell degranulation. Clinical Indications: Acute anaphylaxis (first-line), cardiac arrest (VF, pulseless VT, asystole, PEA), severe acute asthma (when inhaled agents fail), combined with local anesthetics (to induce local vasoconstriction, reducing systemic absorption and prolonging anesthesia). Dosage & Administration: Anaphylaxis: 0.3–0.5 mg IM of 1 mg/mL (1:1000) into the anterolateral mid-thigh. Repeat every 5–15 minutes PRN. Cardiac Arrest: 1 mg IV/IO of 0.1 mg/mL (1:10,000) every 3–5 minutes during CPR. Contraindications: No absolute contraindications in life-threatening anaphylaxis. Relative contraindications in non-emergencies: narrow-angle glaucoma, severe cardiac disease, non-anaphylactic shock, and known sulfite allergy (present in some formulations) [2]. Common Side Effects: Tremor, restlessness, anxiety, tension, palpitations, headache, sweating, pallor, and nausea. Severe Adverse Effects: Ventricular arrhythmias (VF/VT), fatal myocardial ischemia (due to massive increase in O2 demand), severe hypertension, cerebrovascular accident (hemorrhage), and pulmonary edema. Extravasation can cause severe tissue necrosis. Drug Interactions: Non-selective Beta-Blockers (e.g., Propranolol): Blocks β2 vasodilation, leaving α1 vasoconstriction unopposed → life-threatening hypertensive crisis with reflex bradycardia. MAOIs & TCAs: Prevent catecholamine breakdown/reuptake → exaggerated pressor effects. Halogenated Anesthetics (e.g., Halothane): Sensitize the myocardium to epinephrine, greatly increasing the risk of arrhythmias. Monitoring: Continuous ECG, BP, heart rate, SpO2, blood glucose (can cause hyperglycemia), and serum potassium (can cause transient hypokalemia). 3. Noradrenaline (Norepinephrine) Class & Receptor Profile: Endogenous catecholamine; potent α1 and α2 agonist, moderate β1 agonist, minimal to no β2 activity. Pharmacokinetics: Administered exclusively via IV infusion. Rapid onset (1-2 mins), very short duration (metabolized by COMT/MAO). Mechanism of Action (MOA): Massive α1 stimulation leads to intense peripheral vasoconstriction, significantly increasing systemic vascular resistance (SVR) and both systolic and diastolic blood pressures. While it has β1 chronotropic effects, the sudden surge in blood pressure often triggers a vagal baroreceptor reflex that causes reflex bradycardia, masking the direct heart rate increase. Clinical Indications: First-line vasopressor for distributive/septic shock, neurogenic shock, and profound hypotension unresolved by adequate fluid resuscitation. Dosage & Administration: Titrated IV infusion via a central venous catheter (to avoid extravasation). Typically starts at 8–12 mcg/min and titrated to achieve a Mean Arterial Pressure (MAP) > 65 mmHg. Contraindications: Uncorrected hypovolemia (must replace fluids first), mesenteric

Adrenergic Antagonists (Sympatholytics): Comprehensive Drug-by-Drug Pharmacology, Dosing, and Safe Clinical Use What this comprehensive chapter covers Adrenergic antagonists (sympatholytics) are pharmacological agents that bind to adrenoceptors (alpha and beta) but do not trigger the usual intracellular response, thereby blocking the actions of endogenous catecholamines (noradrenaline and adrenaline). This extensively detailed, advanced-level guide dissects every major alpha and beta antagonist. For each individual drug, you will find an expanded exploration of its receptor profile, mechanism of action (MOA), pharmacokinetics, specific formulations, precise clinical indications, common side effects, severe adverse events, strict contraindications, and major drug-drug interactions. Critical Pre-Prescription Safety Review & The “Alpha Before Beta” Rule Identify the exact clinical problem: Beta-blockers are life-saving for chronic Heart Failure with reduced Ejection Fraction (HFrEF), but they can be fatal if initiated during acute decompensated heart failure (cardiogenic shock/pulmonary edema). The Pheochromocytoma Rule (Alpha First, Beta Second): In states of massive catecholamine excess (e.g., pheochromocytoma, cocaine toxicity, MAOI crisis), you MUST establish adequate alpha-blockade first. Administering a beta-blocker first blocks β2-mediated vasodilation, leaving α1-mediated vasoconstriction completely unopposed. This results in a catastrophic, life-threatening hypertensive crisis and acute pulmonary edema. Assess Baseline Hemodynamics: Always check baseline BP, heart rate, continuous ECG (for pre-existing AV block), respiratory history (asthma/COPD), renal/hepatic function, and peripheral vascular status before initiating sympatholytics. 1. Introduction to Adrenergic Antagonism & Pharmacological Concepts Adrenergic antagonists exert their effects by inhibiting the sympathetic nervous system. To master this class, you must understand three advanced pharmacological properties that differentiate these drugs: Selectivity vs. Non-Selectivity: Selective agents (e.g., β1 blockers) target specific receptors, minimizing unwanted side effects (like β2 bronchoconstriction). However, selectivity is dose-dependent; at high doses, selective agents lose their specificity. Intrinsic Sympathomimetic Activity (ISA): Some beta-blockers (like Pindolol and Acebutolol) are actually partial agonists. They block potent endogenous catecholamines but provide a weak baseline stimulation, preventing severe resting bradycardia. Membrane Stabilizing Activity (MSA): Also known as local anesthetic action. Drugs like Propranolol block fast neuronal sodium channels at high doses, which is useful for treating arrhythmias but dangerous in overdose (causing widened QRS and seizures). Receptor Blocked Mechanism of Blockade Useful Clinical Effect Predictable Hazard / Adverse Effect α1 Blocks Gq pathway (↓ IP3/DAG & Ca2+) Vasodilation (↓ BP); relaxation of prostate capsule and bladder neck smooth muscle. Postural (orthostatic) hypotension, first-dose syncope, reflex tachycardia, nasal congestion, miosis. α2 Blocks Gi pathway (removes negative feedback) Historically not targeted alone; blocking it increases presynaptic noradrenaline release. Significant reflex tachycardia (seen with non-selective alpha-blockers like phentolamine). β1 Blocks Gs pathway (↓ cAMP in heart/kidneys) Decreases heart rate (chronotropy), contractility (inotropy), AV conduction (dromotropy), and renin release. Severe bradycardia, complete heart block, acute worsening of heart failure, fatigue. β2 Blocks Gs pathway (↓ cAMP in smooth muscle/liver) Historically used to reduce skeletal muscle tremor. Life-threatening bronchospasm in asthma; prevents glycogenolysis (prolonging and masking hypoglycemia). 2. Non-Selective Alpha Blockers Phenoxybenzamine Class & Receptor Profile: Non-selective, irreversible (covalent) α1 and α2 blocker. (Haloalkylamine derivative). Mechanism of Action (MOA): Binds covalently (alkylates) to alpha receptors, causing an irreversible blockade. The body must synthesize entirely new adrenoceptors to overcome the drug’s effect, which takes several days. α1 block: Causes massive peripheral vasodilation, lowering BP. α2 block: Removes presynaptic negative feedback, causing excess noradrenaline to flood the synapse, which strongly stimulates β1 receptors (causing profound reflex tachycardia). Pharmacokinetics: Oral absorption is variable. Slow onset (takes hours to fully act as the active intermediate forms) but highly prolonged duration of action (3-4 days). Formulations & Dosing: Oral capsules (10 mg). Pre-operative pheochromocytoma preparation usually begins at 10 mg twice daily, slowly titrated over weeks to 20–40 mg two or three times daily depending on BP response. Indications: Pre-operative preparation and chronic medical management of Pheochromocytoma to prevent fatal hypertensive crises during surgical tumor manipulation. Never used for essential hypertension. Common Side Effects: Severe postural dizziness, intense reflex tachycardia, palpitations, profound nasal congestion, miosis, fatigue, and failure of ejaculation. Serious Adverse Effects: Severe syncope, profound hypotension (patients require aggressive IV fluid loading pre-operatively), and angina/myocardial infarction driven by extreme reflex tachycardia. Contraindications: Severe hypotension, cardiogenic shock. Extreme caution in patients with severe coronary artery disease (CAD) or cerebrovascular disease. Interactions: Nitrates, PDE-5 inhibitors (e.g., sildenafil), and alcohol cause catastrophic additive hypotension. Monitoring: Lying and standing BP, heart rate, and strict volume status. Phentolamine Class & Receptor Profile: Non-selective, reversible competitive α1 and α2 blocker. (Imidazoline derivative). Mechanism of Action (MOA): Competitively antagonizes alpha receptors causing rapid, short-acting vasodilation. Because it is competitive, its effects can be overcome by massive surges of circulating catecholamines. It also possesses mild histamine-releasing and cholinergic properties. Pharmacokinetics: Administered IV or locally. Very rapid onset and short duration of action (half-life ~19 minutes). Formulations & Dosing: IV injection or local tissue infiltration. Emergency Crisis: 5 mg IV slowly, repeated PRN. Extravasation: 5-10 mg diluted in 10 mL saline injected subcutaneously around the ischemic site. Indications: Intra-operative management of hypertensive crises during pheochromocytoma resection. MAOI-tyramine crisis (the “cheese reaction”), severe cocaine toxicity, or clonidine withdrawal crisis. Extravasation Antidote: Saves tissue from necrosis when a severe vasoconstrictor (like noradrenaline or dopamine) leaks into subcutaneous tissue. Common Side Effects: Flushing, headache, nasal congestion, reflex tachycardia, GI hypermotility (diarrhea). Serious Adverse Effects: Severe hypotension, fatal arrhythmias, angina, or acute MI (due to reflex tachycardia). Contraindications: Recent MI, history of coronary artery disease. Interactions: Potentiates all other antihypertensive medications; epinephrine reversal (giving epinephrine after phentolamine causes paradoxical hypotension because only β2 vasodilation is left intact). 3. Selective Alpha-1 Blockers Prazosin, Doxazosin, and Terazosin Class & Receptor Profile: Highly selective α1 receptor competitive blockers. (Quinazoline derivatives). Mechanism of Action (MOA): Selectively block α1 receptors on arterioles and venules, reducing systemic vascular resistance, preload, and afterload. They also relax smooth muscle in the prostate and bladder neck. Crucially, they leave α2 intact, which maintains negative feedback on noradrenaline release—resulting in significantly less reflex tachycardia compared to non-selective agents. They also modestly improve lipid profiles (↓ LDL, ↑ HDL). Pharmacokinetics: Prazosin is short-acting (dosed BID/TID). Doxazosin and Terazosin have longer half-lives (up to 22 hours), allowing

Cholinergic Agonists: Muscarinic, Nicotinic and Anticholinesterase Drugs Cholinomimetics reproduce acetylcholine (ACh) effects either by directly stimulating muscarinic/nicotinic receptors or by inhibiting acetylcholinesterase (AChE). They are powerful but unforgiving medicines: the same mechanism that restores bladder tone or neuromuscular transmission can cause bronchospasm, bradycardia, diarrhoea, seizures or cholinergic crisis. Doses below are common adult teaching ranges; prescribe only after checking the current product, indication, patient factors and local protocol. Learning outcomes Differentiate direct muscarinic agonists, nicotine-receptor agonists and indirect AChE inhibitors. Predict organ effects using M1, M2, M3, NN and NM receptors. Give drug-by-drug indications, doses, adverse effects, contraindications and interactions. Recognise cholinergic crisis and organophosphate poisoning as emergencies. 1. Receptor map Receptor Where it matters Stimulation effect Clinical consequence M2 SA/AV node Slows rate and conduction. Bradycardia and AV block in toxicity. M3 Glands, bronchi, gut, bladder, eye Secretions, bronchoconstriction, gut/bladder contraction, miosis. Useful for dry mouth/glaucoma/bladder atony; dangerous in asthma/obstruction. NM Neuromuscular junction Skeletal muscle depolarisation. Improves MG with AChE inhibitors; excess causes fasciculation then weakness. NN Autonomic ganglia/CNS Autonomic stimulation and CNS reward pathways. Nicotine dependence, variable BP/HR effects. Cholinergic toxidrome: recognise it early Muscarinic: salivation, lacrimation, urination, diarrhoea, GI cramp, emesis, miosis, sweating, bronchorrhoea, bronchospasm and bradycardia. Nicotinic: fasciculation, weakness, hypertension/tachycardia early, then paralysis. CNS: anxiety, confusion, seizures and coma may occur with agents that enter the brain or organophosphates. Emergency action: PPE/decontamination where needed, ABC support, suction/oxygen/ventilation and protocol-directed atropine plus oxime therapy for organophosphate poisoning. 2. Classification Direct muscarinic agonists Choline esters: bethanechol, carbachol. Alkaloids/analogues: pilocarpine, cevimeline. Nicotinic agonists Nicotine replacement products. Varenicline: partial α4β2 nicotinic agonist. Indirect agonists: AChE inhibitors Neostigmine, pyridostigmine (peripheral). Physostigmine (crosses CNS). Irreversible organophosphates: toxicology, not routine treatment. 3. Individual drug cards Bethanechol Mechanism and receptor profile Synthetic choline ester that directly stimulates muscarinic receptors; it has negligible nicotinic action. Increases detrusor contraction and GI smooth-muscle tone; it is resistant to AChE relative to acetylcholine. Formulation and common adult teaching dose Oral tablets; common teaching dose 10–50 mg orally three or four times daily, using the lowest effective dose. Give on an empty stomach if possible: nausea/vomiting may be more troublesome near meals. Check local product guidance. Indications Acute postoperative/postpartum non-obstructive urinary retention. Selected neurogenic bladder atony with retention after mechanical obstruction has been excluded. Common side effects Abdominal cramps and diarrhoea: M3 stimulation increases gut tone/motility. Salivation, sweating and flushing: glandular and autonomic stimulation. Urinary urgency: detrusor stimulation may be excessive. Headache/dizziness: can accompany BP or autonomic changes. Serious adverse effects Bronchospasm/bronchorrhoea: potentially severe in asthma or COPD. Bradycardia/hypotension: muscarinic cardiac and vascular effects can compromise perfusion. Bladder rupture risk: do not stimulate a bladder against an unrecognised obstruction. Contraindications and cautions Contraindicated/cautioned in mechanical urinary or GI obstruction, peptic ulcer disease, asthma, marked bradycardia/hypotension, coronary disease, epilepsy and Parkinsonism. Confirm that retention is functional, not due to enlarged prostate, stone, clot, stricture or pelvic pathology. Interactions Other cholinergic drugs and AChE inhibitors increase muscarinic toxicity. Antimuscarinics oppose the desired effect; beta blockers can worsen clinically important bradycardia. Monitoring and counselling Assess voiding, post-void residual where available, abdominal pain, BP, pulse, wheeze and diarrhoea. Seek urgent review for severe colic, inability to pass urine, fainting, wheeze or profuse secretions. Pilocarpine Mechanism and receptor profile Direct muscarinic agonist that stimulates exocrine secretion and contracts the iris sphincter/ciliary muscle. In the eye it causes miosis and ciliary muscle contraction, increasing trabecular outflow; orally it increases salivation. Formulations and common adult teaching doses Oral: commonly 5 mg three times daily for radiation-related xerostomia; Sjögren syndrome regimens may use 5 mg four times daily, subject to product guidance. Ophthalmic: concentration and frequency depend on glaucoma indication and ophthalmology protocol; do not copy an oral dose into eye-drop prescribing. Indications Dry mouth from salivary-gland hypofunction after head/neck radiotherapy or in Sjögren syndrome. Selected glaucoma/ocular uses under ophthalmology care. Common side effects Sweating: a dose-limiting consequence of glandular M3 stimulation. Salivation, nausea, diarrhoea and urinary frequency: general muscarinic effects. Blurred vision/headache: miosis and accommodation spasm alter visual function, particularly in dim light. Serious adverse effects Bronchospasm or increased bronchial secretions: dangerous in uncontrolled airway disease. Bradyarrhythmia/hypotension: risk is greater in important cardiovascular disease. Retinal detachment risk: rare ocular concern in susceptible patients; new flashes/floaters require urgent eye review. Contraindications and cautions Avoid where miosis is undesirable, such as narrow-angle glaucoma unless specialist-directed; use caution in asthma, peptic ulcer and cardiovascular disease. Patients with night-driving duties need counselling about impaired dark adaptation/blurred vision. Interactions Antimuscarinics reduce efficacy; other cholinergic medicines increase toxicity. BP/rate-lowering medicines may magnify symptomatic hypotension or bradycardia. Monitoring and counselling Assess salivary response, hydration, sweating, wheeze, GI tolerance and ocular symptoms. For drops, teach exact instillation and punctal occlusion; avoid driving in poor light until vision effects are understood. Cevimeline Mechanism and receptor profile Direct muscarinic agonist with relative M1/M3 activity; promotes salivary secretion. It is a practical alternative to pilocarpine where available, but shares cholinergic systemic hazards. Formulation and common adult teaching dose Oral capsules; a common adult regimen for Sjögren-related xerostomia is 30 mg three times daily. Use the product-specific hepatic/renal advice and do not treat dose as interchangeable with pilocarpine. Indications Symptomatic dry mouth in Sjögren syndrome where licensed/available. Common side effects Excess sweating: often the most limiting adverse effect. Nausea, diarrhoea and abdominal discomfort: increased GI smooth-muscle activity/secretions. Rhinitis and urinary frequency: mucosal/bladder muscarinic stimulation. Serious adverse effects Bronchospasm: can worsen asthma or chronic obstructive disease. Cardiac rhythm/BP effects: susceptible patients may not tolerate autonomic haemodynamic changes. Visual disturbance: may impair driving or machine operation. Contraindications and cautions Contraindicated in uncontrolled asthma and where miosis is undesirable, including narrow-angle glaucoma without specialist direction. Use caution with cardiovascular disease, active peptic ulcer and airway disease. Interactions Antimuscarinics oppose benefit; other cholinomimetics/AChE inhibitors add toxicity. Review medicines that lower pulse/BP before starting. Monitoring and counselling Monitor symptom relief, fluid loss from sweating, GI effects, wheeze and visual symptoms. Maintain hydration and report breathlessness, severe diarrhoea or troublesome blurred vision. Carbachol Mechanism and receptor profile Direct cholinergic agonist with muscarinic and

Antipsychotic Drugs: Individual Medicines, Doses, Adverse Effects and Safe Monitoring Antipsychotics are used mainly for schizophrenia-spectrum psychosis, acute mania and selected severe behavioural disturbance after medical causes have been assessed. Their therapeutic effect comes chiefly from dopamine D2 antagonism or partial agonism; their harms arise because dopamine, histamine, muscarinic and alpha1 receptors also regulate movement, prolactin, alertness, metabolism and autonomic function. The doses below are common adult teaching ranges—not personal prescriptions. Always verify the diagnosis, product, local mental-health protocol, pregnancy status, organ function, ECG risk and drug interactions. Learning outcomes Use receptor pharmacology to predict benefit and adverse effects. Choose between typical and atypical agents using individual drug risks, not only class labels. Recognise acute dystonia, akathisia, parkinsonism, tardive dyskinesia, NMS, hyperprolactinaemia and metabolic toxicity. Plan baseline and ongoing physical monitoring, including the special requirements for clozapine. 1. Dopamine pathways: why D2 blockade helps and harms Pathway Effect of D2 blockade Clinical meaning Mesolimbic Reduces dopamine signalling. Reduces hallucinations, delusions and thought disorganisation. Nigrostriatal Interferes with movement pathways. Acute dystonia, akathisia, parkinsonism and tardive dyskinesia. Tuberoinfundibular Removes dopamine’s restraint on prolactin. Galactorrhoea, sexual dysfunction, menstrual disturbance, infertility and bone-risk effects. Mesocortical Strong blockade may be unhelpful for cognition/negative symptoms. Drug choice should consider function, not positive symptoms alone. 2. Class pattern—then individualise First-generation / typical High potency: haloperidol, fluphenazine—more D2 blockade and EPS/prolactin risk. Low potency: chlorpromazine—more sedation, antimuscarinic effects and postural hypotension. Second-generation / atypical Serotonin–dopamine pharmacology often means less EPS at usual doses, but not zero EPS. Metabolic, prolactin, cardiac, anticholinergic and haematological risks differ markedly by agent. Before starting any agent Exclude delirium, hypoglycaemia, hypoxia, infection, intoxication/withdrawal, pain and neurological disease. Record target symptoms, capacity/consent, suicide/violence risk, medicines and physical baseline. 3. Individual antipsychotic drug cards Chlorpromazine Mechanism and receptor profile Low-potency first-generation antipsychotic: D2 antagonism with substantial H1, M1 and alpha1 blockade. Less EPS than high-potency typicals at comparable clinical effect, but more sedation, hypotension and anticholinergic toxicity. Formulations and common adult teaching doses Oral tablets/liquid and IM injection; product availability varies. For psychosis, a common oral start is 25–50 mg two or three times daily, then gradual titration; total daily ranges vary widely by setting and local protocol. Indications Schizophrenia-spectrum psychosis and acute mania where appropriate. Selected severe agitation, nausea/vomiting or intractable hiccups only under indication-specific guidance. Common side effects Sedation: H1 blockade impairs alertness and increases falls risk. Dry mouth, constipation and blurred vision: antimuscarinic action. Postural dizziness: alpha1 blockade lowers BP on standing. Weight gain: appetite/metabolic receptor effects may be substantial. Serious adverse effects QT prolongation/arrhythmia: risk rises with high dose, electrolyte disturbance and other QT drugs. Cholestatic jaundice: new pruritus, dark urine or jaundice needs urgent review. NMS or seizures: rare but life-threatening dopamine-blockade complications. Contraindications and cautions Caution in dementia/frailty, cardiovascular disease, glaucoma, prostatic obstruction, constipation/ileus, seizure disorder and hepatic impairment. In Parkinson disease or Lewy-body dementia, antipsychotic sensitivity and motor worsening can be severe. Interactions Alcohol, opioids, benzodiazepines and sedatives add CNS/respiratory depression. Other anticholinergics add retention/ileus; QT-prolonging drugs increase arrhythmia risk. Monitoring and counselling Monitor BP sitting/standing, sedation/falls, bowel/bladder function, weight and ECG when risk factors exist. Advise slow standing, avoid alcohol/driving until response is known, and report fever/rigidity, jaundice, palpitations or severe constipation. Haloperidol Mechanism and receptor profile High-potency first-generation D2 antagonist with relatively little antimuscarinic or alpha1 activity. Strong D2 blockade gives reliable control of positive psychosis but high EPS and hyperprolactinaemia risk. Formulations and common adult teaching doses Oral tablets/liquid, short-acting IM and long-acting decanoate injections exist. Common oral adult starts for psychosis are 0.5–2 mg once or twice daily; acute IM regimens and depot conversion must follow specialist/local protocol with ECG risk review. Indications Schizophrenia-spectrum psychosis, acute agitation when appropriate, mania and selected delirium pathways with careful medical assessment. Choice in agitation must never replace de-escalation, diagnosis and treatment of cause. Common side effects Acute dystonia: painful neck/jaw/eye spasm can occur within hours–days, especially in young men. Akathisia: unbearable inner restlessness/pacing may be mistaken for worsening agitation. Parkinsonism: tremor, rigidity, bradykinesia and masked face reflect nigrostriatal D2 blockade. Hyperprolactinaemia: causes galactorrhoea, sexual dysfunction and menstrual disturbance. Serious adverse effects QT prolongation/torsades: ECG risk increases with high dose, IV use, low K/Mg or other QT-prolonging drugs. NMS: fever, lead-pipe rigidity, autonomic instability, altered mental state and raised CK are an emergency. Tardive dyskinesia: late, potentially persistent involuntary oro-facial/limb movements. Contraindications and cautions Caution/avoidance in Parkinson disease, Lewy-body dementia, known long-QT/arrhythmia, severe electrolyte disturbance and seizure disorder. Older adults with dementia have increased mortality/cerebrovascular risk with antipsychotics—use only when justified and reviewed. Interactions QT-prolonging antiarrhythmics, macrolides, fluoroquinolones, methadone and some antidepressants add torsades risk. Levodopa/dopamine agonists oppose efficacy and may worsen parkinsonism; CNS depressants increase sedation. Monitoring and counselling Document an EPS baseline, check pulse/BP, ECG/electrolytes when indicated, and ask about restlessness, rigidity, fever and involuntary movements every review. Urgent review is required for eye/neck spasm, severe restlessness, collapse/palpitations, fever with rigidity or swallowing/breathing difficulty. Risperidone Mechanism and receptor profile Second-generation antipsychotic with D2 and 5-HT2A antagonism; EPS becomes more likely as dose rises. Notable for comparatively high and persistent prolactin elevation among atypical antipsychotics. Formulations and common adult teaching doses Oral tablets, solution, orodispersible tablets and long-acting injectables exist. For adult schizophrenia, start commonly at 1–2 mg/day, titrating gradually; common range 2–6 mg/day. Long-acting preparations have different initiation/oral-overlap rules. Indications Schizophrenia-spectrum psychosis and acute mania; other licensed uses vary with age and local protocol. Long-acting injection may support adherence after an effective/tolerated oral trial. Common side effects Hyperprolactinaemia: D2 blockade may cause amenorrhoea, galactorrhoea, erectile dysfunction, reduced libido and infertility. EPS/akathisia: dose-related, especially at higher doses. Weight gain and sedation: usually less than olanzapine/clozapine but still clinically important. Postural dizziness: alpha1 blockade can lower BP. Serious adverse effects Persistent hyperprolactinaemia: hypogonadism can reduce bone density over time. Stroke/mortality warning in dementia-related psychosis: avoid casual use for non-psychotic behaviour. NMS, severe EPS or QT risk: uncommon but serious class events. Contraindications and cautions Use caution in Parkinson/Lewy-body disease, epilepsy, cardiovascular disease, diabetes, hyperprolactinaemia history and renal/hepatic

Antidepressants: Drug-by-Drug Pharmacology, Doses and Safe Clinical Use Antidepressants are prescribed for depression and selected anxiety, obsessive-compulsive, panic and pain disorders. Benefit is gradual, whereas adverse effects, activation and drug interactions may occur early. The following are common adult teaching doses, not individual prescriptions: verify diagnosis, bipolar history, suicide risk, product, organ function, pregnancy and local protocol. Before treatment Screen for bipolar disorder: previous mania/hypomania, reduced need for sleep, episodic elevated/irritable mood or family history make antidepressant monotherapy hazardous. Assess suicide risk: document thoughts, plan, means and supports; review early after starting or changing dose. Check interactions: serotonergic drugs, MAOIs, OTC cold remedies, NSAIDs/anticoagulants, alcohol and herbal products can materially change safety. Individual drug cards Fluoxetine Mechanism and dose SSRI; start 20 mg once daily, commonly 20–60 mg/day. Long half-life reduces withdrawal but prolongs interactions. Indications Depression, OCD, panic disorder and selected eating-disorder pathways. Common side effects Nausea/diarrhoea: serotonergic GI stimulation. Insomnia/activation: consider morning dosing and review anxiety. Sexual dysfunction: ask specifically; it is often not volunteered. Serious effects, cautions and interactions Serotonin syndrome: clonus, hyperreflexia, fever, sweating and agitation require urgent assessment. Hyponatraemia/bleeding: increased risk in frail adults and with NSAIDs/anticoagulants. Do not combine with MAOIs; CYP2D6 inhibition affects several medicines. Long washout is needed when switching. Monitoring and counselling Review mood, suicidal thoughts, sleep, sexual function and interactions early; do not stop without a plan. Sertraline Mechanism and dose SSRI; start 25–50 mg once daily, usual range 50–200 mg/day. Indications Depression, anxiety disorders, OCD, panic disorder and PTSD where locally indicated. Common side effects Diarrhoea/nausea: commonly early and dose-related. Sexual dysfunction: libido, orgasm and erection effects need review. Sleep change/tremor: distinguish from anxiety or relapse. Serious effects, cautions and interactions Serotonin syndrome, hyponatraemia and bleeding: key class emergencies/risks. MAOIs/linezolid are unsafe combinations; NSAIDs, aspirin and anticoagulants increase bleeding risk. Monitoring and counselling Review benefit, activation, suicidality, sodium/bleeding risk and withdrawal before any taper. Venlafaxine and duloxetine Mechanism and dose SNRIs increase serotonin and noradrenaline. Venlafaxine: 37.5–75 mg/day to start, commonly 75–225 mg/day. Duloxetine: 30 mg daily then commonly 60 mg daily. Indications Depression/anxiety; duloxetine also has selected neuropathic and chronic-pain uses. Common side effects Nausea, sweating and sexual dysfunction: serotonergic effects. Insomnia/activation and raised BP: noradrenergic effects, particularly with higher venlafaxine doses. Serious effects, cautions and interactions Severe discontinuation syndrome: dizziness, electric-shock sensations, anxiety and flu-like symptoms after abrupt venlafaxine cessation. Hypertension/serotonin syndrome: monitor BP and combinations. Duloxetine needs caution in liver disease, heavy alcohol use and severe renal impairment. Monitoring and counselling Monitor BP/pulse, pain/function, mood and withdrawal; taper slowly. Amitriptyline and clomipramine Mechanism and dose TCAs block monoamine reuptake plus muscarinic, histamine, alpha and cardiac sodium channels. Amitriptyline pain starts at 10–25 mg at night; depression doses need gradual specialist titration. Clomipramine commonly begins 25 mg/day for OCD/depression pathways. Common side effects Dry mouth, constipation, blurred vision and retention: antimuscarinic block. Sleepiness/weight gain: histamine block. Postural hypotension: alpha-blockade causes falls. Serious effects, cautions and interactions Cardiotoxic overdose: seizures, QRS widening and ventricular arrhythmia can be fatal. Delirium, ileus and angle closure: anticholinergic emergencies. Avoid casual use with MAOIs/SSRIs, QT drugs or in high overdose risk, conduction disease, glaucoma, BPH or severe constipation. Monitoring and counselling Consider ECG when risk is present; dispense limited quantities where overdose risk matters. Suspected overdose needs urgent ECG/ABC care. Mirtazapine Mechanism and dose Alpha2 antagonist with serotonergic and H1 effects; start 15 mg at night, commonly 15–45 mg nightly. Indications Depression when insomnia, poor appetite or weight loss is prominent. Common side effects Sleepiness: histamine blockade can be useful or disabling. Increased appetite/weight gain: requires active monitoring. Dry mouth/constipation: may occur. Serious effects, cautions and interactions Neutropenia: fever/sore throat/infection needs urgent FBC evaluation. Do not combine with MAOIs; alcohol, opioids and benzodiazepines add sedation. Monitoring and counselling Monitor weight, daytime sedation, mood and infection symptoms; report mania or self-harm thoughts urgently. Bupropion, trazodone and MAOIs Mechanism and dose Bupropion: noradrenaline–dopamine reuptake inhibitor; XL often 150 mg each morning then 300 mg/day. Trazodone: serotonergic antidepressant with sedating H1/alpha effects; often 50–100 mg at night initially. MAOIs: irreversible monoamine-oxidase inhibitors for specialist treatment-resistant depression; doses and washouts must follow exact protocol. Critical safety Bupropion seizure: contraindicated in seizure disorder and anorexia/bulimia; avoid with abrupt alcohol/sedative withdrawal. Trazodone priapism: painful prolonged erection is an emergency; also causes orthostasis/falls. MAOI hypertensive crisis/serotonin syndrome: tyramine, sympathomimetics, SSRIs/SNRIs/TCAs, tramadol and linezolid can be dangerous. Monitoring and counselling For bupropion review sleep, anxiety, alcohol, seizures and eating disorder; for trazodone warn about sedation/slow standing; MAOI patients need written food and drug-interaction instructions. Serotonin syndrome, withdrawal and suicide safety Serotonin syndrome: stop serotonergic agents, assess ABCs, cool/support, treat agitation/seizures by protocol and obtain urgent toxicology/emergency help. Withdrawal: taper rather than stopping suddenly, especially venlafaxine/paroxetine; distinguish discontinuation symptoms from relapse. Suicide/mania: review early after initiation and dose changes; urgent escalation for imminent self-harm risk or new mania. Further study Antidepressants — supplied SlideShare resource DailyMed — verify current product-specific doses and switching requirements