Major Medication adverse reactions and toxicities

Syndrome / Adverse Event	Associated Drugs
Hyponatraemia	SSRIs, thiazides, carbamazepine, NSAIDs, oxcarbazepine
Serotonin Syndrome	SSRIs + MAOIs, tramadol, St John’s Wort, linezolid, fentanyl, triptans
Neuroleptic Malignant Syndrome (NMS)	Typical antipsychotics (e.g. haloperidol), atypicals, metoclopramide
QT Prolongation	Antipsychotics, macrolides, fluoroquinolones, TCAs, SSRIs, ondansetron, methadone
Ototoxicity	Aminoglycosides, loop diuretics (furosemide), cisplatin, vancomycin
Nephrotoxicity	NSAIDs, aminoglycosides, amphotericin, cisplatin, ACEi/ARB (esp. with diuretics)
Hepatotoxicity	Paracetamol, valproate, methotrexate, isoniazid, statins, nitrofurantoin
Hyperkalaemia	ACEi, ARBs, spironolactone, trimethoprim, NSAIDs, potassium supplements

Neuroleptic Malignant Syndrome (NMS)

• NMS is a rare but life-threatening reaction to antipsychotic medications characterized by a combination of hyperthermia, muscle rigidity, autonomic dysfunction, and altered mental status.
• Medications:
  • Typical antipsychotics (e.g., Haloperidol, Chlorpromazine)
  • Atypical antipsychotics (e.g., Olanzapine, Risperidone)
  • Anti-emetics (e.g., Metoclopramide)
  • Withdrawal from Parkinson’s disease medications (e.g., Levodopa)
• Risk Factors: High doses, rapid dose escalation, dehydration, agitation, and prior episodes of NMS.
• Signs and Symptoms:
  • Hyperthermia: Body temperature >38°C, often >40°C.
  • Muscle Rigidity: “Lead-pipe” rigidity, generalized muscle stiffness.
  • Autonomic Instability:
    • Tachycardia, labile blood pressure, diaphoresis
    • Dysrhythmias, elevated CK
  • Altered Mental Status:
    • Agitation, delirium, coma
• Diagnosis:
  • Primarily clinical, supported by:
    • Elevated creatine kinase (CK) (often >1000 IU/L)
    • Leukocytosis
    • Myoglobinuria (risk of rhabdomyolysis)
    • Elevated liver enzymes
• Treatment:
  • Discontinuation: Stop the offending antipsychotic medication.
  • Supportive Care:
    • IV fluids, cooling measures for hyperthermia
    • Monitoring and management of cardiovascular and respiratory status
  • Pharmacologic Treatment:
    • Benzodiazepines for agitation and muscle relaxation
    • Dopamine agonists (e.g., Bromocriptine) or dantrolene (muscle relaxant) in severe cases
  • ICU care: For intensive monitoring and treatment.
• Prevention:
  • Gradual titration of antipsychotics.
  • Monitoring for early signs of NMS in high-risk patients.
  • Avoiding re-challenge with antipsychotics if the patient has a history of NMS.

Serotonin Syndrome

• Serotonin Syndrome is a potentially life-threatening condition caused by an excess of serotonin in the central nervous system.
• Causes:
  • Medications:
    • SSRIs (e.g., Fluoxetine, Sertraline)
    • SNRIs (e.g., Venlafaxine, Duloxetine)
    • MAOIs (e.g., Phenelzine, Selegiline)
    • Tricyclic Antidepressants (e.g., Amitriptyline, Clomipramine)
    • Other serotonergic drugs (e.g., Tramadol, Linezolid, MDMA)
    • Over-the-counter supplements like St. John’s Wort
• Signs and Symptoms:
  • Cognitive:
    • Agitation, confusion, hypomania
    • Hallucinations, coma (in severe cases)
  • Autonomic:
    • Hyperthermia, diaphoresis
    • Tachycardia, hypertension
    • Shivering, mydriasis
  • Neuromuscular:
    • Tremor, hyperreflexia, clonus (inducible and spontaneous)
    • Myoclonus, muscle rigidity, ataxia
• Diagnosis:
  • Primarily clinical based on history and physical examination.
  • Hunter Criteria: A patient must have taken a serotonergic agent and meet one of the following:
    • Spontaneous clonus
    • Inducible clonus and agitation or diaphoresis
    • Ocular clonus and agitation or diaphoresis
    • Tremor and hyperreflexia
    • Hypertonia, temperature >38°C, and ocular or inducible clonus
• Treatment:
  • Discontinuation: Stop all serotonergic agents.
  • Supportive care: IV fluids, oxygen, sedation with benzodiazepines.
  • Antidote: Cyproheptadine (a serotonin antagonist) can be used in moderate to severe cases.
  • Cooling measures: For hyperthermia.
  • ICU care: For severe cases requiring more intensive monitoring and support.
• Prevention:
  • Avoiding combinations of serotonergic drugs.
  • Educating patients about the risks of over-the-counter supplements and drug interactions.

Lithium Toxicity

• Lithium is commonly used for mood stabilization in bipolar disorder but has a narrow therapeutic index, making toxicity a significant concern.
• Causes:
  • Overdose: Intentional or accidental.
  • Drug interactions: NSAIDs, ACE inhibitors, diuretics (especially thiazides) increase lithium levels.
  • Dehydration: Increased lithium reabsorption in the kidneys.
  • Renal impairment: Reduced clearance of lithium.
• Signs and Symptoms:
  • Early (mild to moderate toxicity):
    • Nausea, vomiting, diarrhea
    • Tremor, mild ataxia
    • Lethargy, weakness
  • Late (severe toxicity):
    • Severe ataxia, muscle rigidity
    • Confusion, stupor, seizures, coma
    • Renal failure
• Diagnosis:
  • Serum lithium levels: Therapeutic range is 0.6-1.2 mEq/L. Levels >1.5 mEq/L indicate toxicity.
  • Electrolytes and renal function: Assess for dehydration and renal impairment.
  • ECG: Look for QT prolongation and other cardiac effects.
• Treatment:
  • Discontinuation: Stop lithium immediately.
  • Hydration: IV fluids to enhance renal excretion.
  • Gastrointestinal decontamination: Gastric lavage and activated charcoal if the patient presents shortly after ingestion.
  • Hemodialysis: Indicated for severe toxicity (levels >4.0 mEq/L or severe symptoms) or renal failure.
• Prevention:
  • Regular monitoring of serum lithium levels.
  • Educating patients on maintaining hydration and avoiding drugs that interact with lithium.
  • Adjusting doses in cases of renal impairment.

QT Prolongation

• Signs and Symptoms:
  • Syncope
  • Palpitations
  • Torsades de pointes (a specific type of polymorphic ventricular tachycardia)
  • Sudden cardiac death
• Common Drugs:
  • Antipsychotics (e.g., Haloperidol, Ziprasidone)
  • Antidepressants (e.g., Citalopram, Escitalopram)
  • Antiarrhythmics (e.g., Amiodarone, Sotalol)
  • Antibiotics (e.g., Macrolides, Fluoroquinolones)

Hepatotoxicity

• Signs and Symptoms:
  • Jaundice
  • Elevated liver enzymes (AST, ALT, ALP)
  • Fatigue, nausea, vomiting
  • Abdominal pain
• Common Drugs:
  • Acetaminophen (overdose)
  • Statins (e.g., Atorvastatin, Simvastatin)
  • Antiepileptics (e.g., Valproate, Phenytoin)
  • Antibiotics (e.g., Isoniazid, Amoxicillin-clavulanate)

Rhabdomyolysis

• Signs and Symptoms:
  • Muscle pain and weakness
  • Dark, cola-colored urine
  • Elevated creatine kinase (CK)
  • Myoglobinuria, acute kidney injury (AKI)
• Common Drugs:
  • Statins (e.g., Atorvastatin, Simvastatin)
  • Antipsychotics (e.g., Olanzapine)
  • Illicit drugs (e.g., Cocaine, Heroin)
  • Severe exercise or trauma can also contribute

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

• Signs and Symptoms:
  • Flu-like symptoms (fever, malaise)
  • Painful red or purplish rash that spreads and blisters
  • Mucosal involvement (oral, ocular, genital)
  • Skin peeling and necrosis
• Common Drugs:
  • Antiepileptics (e.g., Lamotrigine, Carbamazepine)
  • Antibiotics (e.g., Sulfonamides, Penicillins)
  • NSAIDs (e.g., Ibuprofen)
  • Allopurinol

Agranulocytosis

• Signs and Symptoms:
  • Severe neutropenia (absolute neutrophil count <500 cells/mm³)
  • Fever, sore throat, infections
  • Weakness, fatigue
• Common Drugs:
  • Clozapine (antipsychotic)
  • Carbimazole (antithyroid drug)
  • Sulfonamides (antibiotic)
  • Antiepileptics (e.g., Carbamazepine)

Neutropenia

• Signs and Symptoms:
  • Low neutrophil count
  • Increased susceptibility to infections
  • Fever, sore throat, mouth ulcers
• Common Drugs:
  • Chemotherapy agents (e.g., Cyclophosphamide)
  • Immunosuppressants (e.g., Methotrexate)
  • Antithyroid drugs (e.g., Methimazole)
  • Clozapine

Drug/Class	Examples	Mechanism / Immunosuppressive Action	Key Adverse Effects / Considerations
Corticosteroids	Prednisone, dexamethasone	↓ T-cell and macrophage function, anti-inflammatory	Immunosuppression, osteoporosis, hyperglycaemia, weight gain, insomnia, psychiatric effects, risk of TB reactivation
Methotrexate	Methotrexate	Anti-metabolite, inhibits DHFR → ↓ DNA synthesis	Bone marrow suppression, hepatotoxicity, pulmonary fibrosis, stomatitis, teratogenicity
Azathioprine	Azathioprine	Converted to 6-MP → inhibits purine synthesis	Myelosuppression, ↑ infection risk, pancreatitis, hepatotoxicity
Mycophenolate	Mycophenolate mofetil	Inhibits guanosine nucleotide synthesis in lymphocytes	GI upset, leukopenia, teratogenicity, ↑ infection risk
Calcineurin inhibitors	Cyclosporine, tacrolimus	Inhibit IL-2 transcription → ↓ T-cell activation	Nephrotoxicity, hypertension, neurotoxicity, hyperkalaemia, gum hypertrophy (cyclosporine)
Biologics (TNF inhibitors)	Adalimumab, etanercept, infliximab	Block TNF-α (key cytokine)	Reactivation of TB/latent infections, demyelination, malignancy risk, injection reactions
JAK inhibitors	Tofacitinib, baricitinib	Block intracellular cytokine signaling	Herpes zoster, ↑ lipids, ↑ thrombosis, serious infections

Thrombocytopenia

• Signs and Symptoms:
  • Low platelet count
  • Easy bruising, petechiae
  • Bleeding gums, nosebleeds
  • Prolonged bleeding from cuts
• Common Drugs:
  • Heparin (Heparin-induced thrombocytopenia)
  • Chemotherapy agents
  • Quinine
  • Valproate

Acute Kidney Injury (AKI)

• Signs and Symptoms:
  • Reduced urine output (oliguria)
  • Elevated serum creatinine and BUN
  • Fluid retention (swelling in legs, ankles)
  • Fatigue, confusion
• Risk Factors:
  • Elderly patients
  • Patients with pre-existing kidney disease
  • Patients with heart failure or other conditions causing reduced renal perfusion
  • Patients on high doses or prolonged courses of these medications
• Prevention:
  • Avoiding the concurrent use of these medications if possible
  • Regular monitoring of renal function (serum creatinine, blood urea nitrogen (BUN), and electrolytes)
  • Educating patients about the risks of combining these medications
  • Ensuring adequate hydration, especially in patients requiring these medications for chronic conditions
• Common Drugs:
  • Triple Whammy : When these three classes of drugs are used together, they can have a compounded negative effect on kidney function:
    • NSAIDs reduce renal blood flow by constricting the afferent arterioles.
    • ACE inhibitors/ARBs reduce the pressure within the glomerulus by dilating the efferent arterioles.
    • Diuretics decrease blood volume, further reducing renal perfusion.
  • Contrast agents (for imaging studies)
  • Aminoglycosides (e.g., Gentamicin)

Ototoxicity

• Signs and Symptoms:
  • Hearing loss
  • Tinnitus (ringing in ears)
  • Balance disturbances (vertigo)
• Common Drugs:
  • Aminoglycosides (e.g., Gentamicin)
  • Loop diuretics (e.g., Furosemide)
  • Chemotherapy agents (e.g., Cisplatin)
  • High-dose Aspirin

Hyponatremia

Drug Class	Examples	Mechanism	Clinical Notes
SSRIs / SNRIs	Sertraline, fluoxetine, venlafaxine	↑ ADH secretion (SIADH)	Common in elderly, female sex; may cause falls, confusion
Thiazide diuretics	Hydrochlorothiazide, indapamide	↑ Na⁺ loss in urine	Often causes hypovolaemic hyponatraemia
Carbamazepine / Oxcarbazepine	Antiepileptics	↑ ADH-like action	Commonly implicated, especially in elderly
TCAs	Amitriptyline, nortriptyline	SIADH-like mechanism	Especially when used for pain or insomnia in older adults
Antipsychotics	Haloperidol, risperidone	Stimulate ADH release or ↑ sensitivity	All typicals and some atypicals carry risk
MDMA / Ecstasy	Recreational drug	Massive ADH release	Risk of acute cerebral oedema, seizures
NSAIDs	Ibuprofen	Potentiate ADH effect at the nephron	Usually in combination with other risk factors
Cyclophosphamide	Chemotherapy agent	Direct ADH secretion	Acute, dose-dependent

Hyperglycemia

• Signs and Symptoms:
  • Increased thirst, frequent urination
  • Fatigue, blurred vision
  • Headaches
  • Unintentional weight loss

Drug Class	Examples	Mechanism	Notes
ACE inhibitors	Perindopril, ramipril	↓ aldosterone → ↓ K⁺ excretion	Monitor K⁺ after initiation or dose increase
ARBs	Irbesartan, candesartan	Same as above
Potassium-sparing diuretics	Spironolactone, eplerenone, amiloride	Block aldosterone or Na⁺ channels → ↓ K⁺ excretion	Additive hyperkalaemia risk with ACEi/ARB
NSAIDs	Ibuprofen, diclofenac	↓ renal perfusion → ↓ K⁺ excretion	Especially risky in elderly and those with CKD
Trimethoprim	Trimethoprim (incl. in TMP-SMX)	Acts like K⁺-sparing diuretic at DCT	Especially in elderly, renal impairment
Heparin	Unfractionated or LMWH	↓ aldosterone synthesis	Rare but documented effect
Beta-blockers	Metoprolol, propranolol	↓ cellular K⁺ uptake (minor contributor)	Not typically a sole cause, but additive effect
Cyclosporine, tacrolimus	Immunosuppressants	Impaired renal function, ↓ K⁺ excretion	Monitor K⁺ closely in transplant or nephrology patients
Succinylcholine	Neuromuscular blocker	K⁺ release from muscle cells	Avoid in burns, neuromuscular disease, crush injury

Hyperkalemia

• Signs and Symptoms:
  • Muscle weakness, paralysis
  • Cardiac arrhythmias (e.g., peaked T waves on ECG)
  • Fatigue, nausea
  • Palpitations
• Common Drugs:
  • ACE inhibitors (e.g., Lisinopril)
  • ARBs (e.g., Losartan)
  • Potassium-sparing diuretics (e.g., Spironolactone)
  • NSAIDs

Angioedema

• Signs and Symptoms:
  • Swelling of the face, lips, tongue, and throat
  • Difficulty breathing, swallowing
  • Abdominal pain (if intestines involved)
• Common Drugs:
  • ACE inhibitors (e.g., Lisinopril)
  • ARBs (e.g., Valsartan)
  • NSAIDs
  • Penicillins

Anaphylaxis

• Signs and Symptoms:
  • Rapid onset of difficulty breathing, wheezing
  • Swelling of the face and throat
  • Rash, hives
  • Hypotension, shock
• Common Drugs:
  • Penicillins
  • Cephalosporins
  • NSAIDs
  • Contrast media

Teratogenic – Category C, D & X medicines in pregnancy ± breastfeeding safety

Drug / class (common examples)	Pregnancy category	Key fetal risks (trimester-specific where relevant)	Breastfeeding (AMH / eTG)
NSAIDs – ibuprofen, diclofenac (≤30 w)	C – may cause reversible harmful effects but no malformations	Constriction of ductus, ↓-renal perfusion if used late; avoid ≥30 w (then behaves as D)	Short-term doses compatible; avoid high-dose / >3 d in neonates
Short-acting β₂-agonists – salbutamol	C	Transient fetal tachycardia; overall benefit > risk in asthma	Compatible
SSRIs – sertraline, fluoxetine	C	Poor neonatal adaptation PPHN rare	Compatible (monitor for irritability/poor feeding)
Benzodiazepines – diazepam	C	Hypotonia withdrawal if high dose near term	Occasional dose compatible; chronic use avoid (sedation)
ACE inhibitors / ARBs	D – may cause malformations / irreversible damage	Fetal renal dysgenesis, oligohydramnios (2ⁿᵈ/3ʳᵈ tri), skull ossification defects	Compatible (milk conc. low); monitor neonatal BP / Cr
Anticonvulsants – valproate, carbamazepine, phenytoin, topiramate	D	Major malformations, neuro-developmental delay (valproate highest)	Compatible except valproate: monitor LFTs/platelets; lamotrigine safe but watch rash
Lithium	D	Ebstein anomaly (1ˢᵗ tri), neonatal toxicity	Transfer high → avoid if possible; if essential, monitor infant level, TFT, Cr
Warfarin	D	Fetal warfarin syndrome (6-12 w), CNS bleeding later	Minimal milk transfer → compatible (monitor INR if preterm)
Tetracyclines – doxycycline	D	Tooth/bone discoloration (after 16 w)	Short course (≤3 d) acceptable; prolonged use avoid
Methotrexate (low-dose RA, high-dose oncology)	D	Skeletal & cranial defects, miscarriage	Contra-indicated; wait ≥1 wk (low-dose) or ≥3 mo (high-dose) before breastfeeding
Isotretinoin (oral), acitretin	X – high risk of permanent fetal damage; contra-indicated	Severe multiple malformations	Contra-indicated (fat-soluble, accumulates); must stop ≥4 w before BF
Thalidomide & analogues	X	Phocomelia, ear/eye anomalies	No data – contra-indicated
Finasteride / Dutasteride	X	Abnormal external genitalia in male fetus	Limited data; avoid handling crushed tabs in lactation
Mifepristone ± misoprostol	X (used for medical termination)	Pregnancy loss	Compatible once pregnancy terminated; avoid breastfeeding during 7 days course for misoprostol
Live-virus vaccines – rubella, varicella	X (contra-indicated)	Theoretical teratogenicity	Generally safe in lactation (live vaccine not transmitted)

How to interpret the categories

Category	Regulatory meaning (✔ = licensed use possible)
C	Drugs that, owing to their pharmacological effects, have caused (or may cause) reversible harmful effects on the fetus without malformations. Most are still used if maternal benefit outweighs risk.
D	Drugs that have caused, are suspected to have caused, or may be expected to cause an increased incidence of human fetal malformations or permanent damage. Not absolutely contra-indicated when life-saving – specialist input required.
X	Drugs with such high teratogenic risk that they must not be used in pregnancy or when pregnancy is possible.

by DRUG CLASSES

Diuretics

Sub-class	Key precipitated / worsened conditions	Rationale / mechanism
Thiazides (hydrochlorothiazide, indapamide)	• Gout  • Hyponatraemia  • Hypokalaemia-induced arrhythmia  • Hyperglycaemia  • Dyslipidaemia	↓ Renal urate excretion; renal Na/K loss; altered carbohydrate & lipid metabolism
Loop (frusemide, bumetanide)	• Hypokalaemia & hypomagnesaemia → torsades  • Ototoxicity (esp. IV high dose)  • Pre-renal AKI	Potent Na/K/2Cl blockade; volume depletion
K-sparing (spironolactone, amiloride)	• Hyperkalaemia (risk ↑ with ACEI/ARB, NSAID)  • Gynecomastia (spironolactone)	Aldosterone antagonism / ENaC blockade
Carbonic anhydrase inhibitor (acetazolamide)	• Metabolic acidosis  • Calcium-phosphate renal stones	Bicarbonaturia with alkaline urine

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Renin–Angiotensin Agents

Class	Conditions precipitated	Mechanism / note
ACE inhibitors & ARBs	• Hyperkalaemia  • Acute decline in eGFR in bilateral renal-artery stenosis  • Symptomatic hypotension in volume depletion  • Angio-oedema (ACEI)	↓ Aldosterone; efferent arteriole dilation; bradykinin accumulation (ACEI)
ARNI (sacubitril / valsartan)	• Angio-oedema > ACEI alone	Neprilysin + RAAS blockade

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β-Blockers

Sub-class	Conditions precipitated / worsened	Notes
Non-selective (propranolol) & cardio-selective (metoprolol, bisoprolol)	• Bronchospasm in asthma/COPD (esp. non-selective)  • Brady-arrhythmias / heart block  • Acute decompensation of severe peripheral vascular disease  • Masking of hypoglycaemia symptoms in insulin-treated diabetes  • Worsening depression / fatigue	β₂ blockade, negative chronotropy/inotropy

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Calcium-Channel Blockers

Class	Precipitated conditions	Mechanism
Non-dihydropyridines (verapamil, diltiazem)	• Bradycardia, AV block  • Decompensated heart failure (reduced inotropy)  • Severe constipation (verapamil)	AV-node depression
Dihydropyridines (amlodipine, nifedipine)	• Ankle oedema  • Reflex tachycardia (short-acting agents)	Preferential arteriolar dilation

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NSAIDs (including COX-2 inhibitors)

• Shared across the class*

• Acute kidney injury (afferent arteriolar constriction)
• Fluid retention / worsening heart failure & hypertension
• GI ulceration & bleeding (↓ prostaglandin) – even with COX-2 in high CV-risk or with aspirin
• Exacerbation of asthma / AERD bronchospasm
• ↑ Cardiovascular & cerebrovascular events (diclofenac, high-dose ibuprofen, COX-2)

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Glucocorticoids (systemic)

• Steroid-induced hyperglycaemia / diabetes
• Osteoporosis & vertebral fractures
• Peptic ulcer / GI bleeding (synergistic with NSAID)
• Psychosis / mood instability (esp. high dose)
• Hypertension & oedema
• Avascular necrosis (femoral head)
• Adrenal suppression → adrenal crisis if abruptly stopped

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Antidepressants

Class	Precipitated conditions	Key points
SSRIs / SNRIs	• Hyponatraemia (SIADH) – elderly, thiazide co-use  • ↑ GI bleeding (serotonin in platelets) esp. with NSAID/anticoagulant  • Serotonin syndrome (with MAOI, linezolid, tramadol)	Inhibits 5-HT re-uptake
TCAs (amitriptyline, nortriptyline)	• Anticholinergic delirium, urinary retention, narrow-angle glaucoma  • Arrhythmia in IHD (QT prolongation, QRS widening)  • Orthostatic hypotension	Na-channel blockade, antimuscarinic
MAOIs	• Hypertensive crisis with tyramine / sympathomimetics	Irreversible MAO-A/B inhibition

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Antipsychotics

• Metabolic syndrome (weight gain, dyslipidaemia, diabetes) – highest with olanzapine, clozapine
• QT prolongation → torsades (ziprasidone, haloperidol IV)
• Neuroleptic Malignant Syndrome
• Hyperprolactinaemia → amenorrhoea, infertility, osteoporosis (risperidone, paliperidone)
• VTE & sudden-cardiac-death risk (clozapine)

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Opioids

• Respiratory depression & CO₂ retention – triggers hypercapnic failure in COPD/OSA
• Severe constipation → bowel obstruction / perforation
• Urinary retention (especially in BPH)
• Opioid-induced hypogonadism

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Anticholinergics (oxybutynin, amitriptyline, antihistamines, phenothiazines)

• Acute angle-closure glaucoma
• Urinary retention in BPH
• Confusion/delirium in elderly (“anticholinergic burden”)
• Severe constipation / ileus

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Anticoagulants / Antiplatelets

Drug	Conditions precipitated	Pearls
Warfarin, DOACs	• Major GI / intracranial haemorrhage  • Skin necrosis (warfarin first days in protein-C deficiency)	Monitor INR; renal dosing for DOAC
Heparin / LMWH	• HIT → thrombosis  • Osteoporosis (prolonged use)	Platelet count 5–14 d
Aspirin, clopidogrel	• Peptic ulcer bleed, epistaxis  • Bronchospasm (aspirin-exacerbated)	Enteric-coating does not reduce ulcer risk

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Statins & Lipid-modifying Drugs

Agent	Precipitated condition	Note
Statins	• Myopathy / rhabdomyolysis (↑ with CYP3A4 inhibitors, fibrates)  • Transaminase elevation → hepatotoxicity	Check CK, LFTs
Fibrates (fenofibrate, gemfibrozil)	• Gallstones (cholesterol)  • Myopathy (with statin)	Avoid gemfibrozil–statin combo

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Hypoglycaemic Agents

Class	Precipitated conditions	Key
Sulfonylureas (gliclazide)	• Severe hypoglycaemia (esp. renal/liver impairment, geriatrics)	Insulin secretagogue
Metformin	• Lactic acidosis (rare; risk ↑ in eGFR < 30, sepsis, hypoxia)	Hold peri-contrast or acute illness
SGLT2 inhibitors (empagliflozin)	• Euglycaemic ketoacidosis (peri-op, low carb diet)  • Genital mycotic infections  • Volume depletion → dizziness	Ensure sick-day rules
Insulin	• Hypoglycaemia	Dose individualised; driving advice

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Antibiotics

Class	Key precipitated conditions	Mechanism / risk factor
Fluoroquinolones	• QT prolongation  • Tendon rupture (Achilles)  • Peripheral neuropathy, CNS toxicity  • Dysglycaemia	Avoid with macrolide/anti-arrhythmic
Macrolides (erythro-, clarithro-, azithro-)	• QT prolongation / torsades • Cholestatic hepatitis (erythro)	CYP3A4 inhibition interactions
Aminoglycosides	• Irreversible ototoxicity  • Nephrotoxicity (ATN)	Trough monitoring
Penicillins / Cephalosporins	• Immediate or delayed hypersensitivity: anaphylaxis, SJS/TEN	Allergy documentation critical

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Antiepileptics

Drug	Precipitated conditions	Salient issue
Valproate	• Neural-tube defects in pregnancy  • Weight gain, PCOS  • Hyperammonaemic encephalopathy	Folic acid 5 mg pre-conception
Carbamazepine / Oxcarbazepine	• Hyponatraemia (SIADH)  • SJS/TEN in HLA-B*1502 Asians	Monitor Na+, genotype where relevant
Phenytoin	• Osteomalacia via vit-D metabolism  • Gingival hyperplasia  • Cerebellar ataxia	Saturable kinetics

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Hormonal Agents

• Combined oral contraceptive pill → VTE, ischaemic stroke, hypertension; worsens migraine with aura.
• Tibolone / menopausal HRT → Recurrent hormone-sensitive breast cancer; VTE.
• Exogenous testosterone / anabolic-androgenic steroids → Polycythaemia, LV hypertrophy, infertility.

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Bisphosphonates (alendronate, zoledronic acid)

• Erosive oesophagitis / ulcer (oral formulations)
• Atypical femoral fractures & osteonecrosis of jaw (long-term)
• May precipitate hypocalcaemia in severe vitamin-D deficiency / hypoparathyroidism

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Chemotherapy / Biologic Agents (selected examples)

Agent	Condition precipitated	Comment
Anthracyclines (doxorubicin)	Dose-dependent cardiomyopathy	Baseline & serial echo
Cisplatin	Irreversible ototoxicity nephrotoxicity hypomagnesaemia	Aggressive hydration
Immune-checkpoint inhibitors (nivolumab, pembrolizumab)	Autoimmune colitis thyroiditis, pneumonitis hypophysitis	Treat with high-dose steroids

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Others of Practical Importance in General Practice

Drug / Class	Condition precipitated	Clinical reminder
Allopurinol (first weeks)	Acute gout flare	Use prophylactic colchicine/NSAID
Clopidogrel / ticagrelor	Severe epistaxis / bruising	Check dental/OT bleeding plan
Digoxin	Toxic arrhythmias in hypokalaemia / renal failure	Monitor K+, dig level
PDE-5 inhibitors (sildenafil)	Severe hypotension with nitrates	24–48 h wash-out
Lithium	Nephrogenic DI, hypothyroidism, chronic kidney disease	Regular TFTs, U&Es
Thyroxine excess	Atrial fibrillation, osteoporosis	TSH monitoring
Cholinesterase inhibitors (donepezil)	Bradycardia, syncope	ECG if baseline conduction disease

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Using this list in practice

1. Review comorbidities before prescribing new drugs; cross-check here or in ETG/AMH.
2. Monitor relevant labs (e.g., Na⁺ with SSRIs, K⁺ with ACEI + spironolactone).
3. Educate patients on symptom red-flags (e.g., melena on NSAIDs, myalgia on statins).
4. Apply “sick-day” rules for
   • metformin
   • SGLT2 inhibitors
   • ACEI/ARB
   • NSAIDs to reduce AKI / DKA risk.
5. Document and communicate any drug-disease cautions in the shared health summary.