Clinical pharmacology and prescribing: Prescribing in special groups

🩺 Prescribing in special groups. The same dose can be safe in one patient and dangerous in another. Kidney and liver disease, pregnancy, breastfeeding, childhood, older age, extremes of weight and surgery all change how drugs behave -and the BNF has a section on each. Detailed older-person prescribing is in the Medicine of the Older Person chapter; obstetric medicine is in the Obstetrics chapters.
Your four questions for every prescription: How well are the kidneys and liver working? Could the patient be pregnant or breastfeeding? Is the dose right for their age and weight? Are there any medicines to stop, start or adjust around surgery or acute illness?

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Prescribing in Kidney Disease

• Why it matters -renally cleared drugs accumulate; some drugs damage the kidneys; some drugs don't work when kidney function is low; patients with CKD are sensitive to fluid and electrolyte effects.
• Assess kidney function -eGFR for most drugs; creatinine clearance (Cockcroft–Gault) for DOACs, narrow therapeutic index drugs, older people and extremes of weight; consider trends.
• Approaches -reduce the dose, extend the interval, monitor levels, or choose another drug. Loading doses usually stay the same; maintenance doses are reduced.
• Drugs needing dose reduction or avoidance:

  Drug	Issue
  Metformin	Review dose if eGFR under 45; stop under 30 (lactic acidosis)
  Sulphonylureas, insulin	Hypoglycaemia (reduced clearance)
  DOACs	Dose by creatinine clearance; dabigatran most renally dependent
  LMWH (enoxaparin)	Reduce treatment dose if CrCl under 30; consider UFH
  Gentamicin, vancomycin	Level-guided dosing; nephrotoxic and ototoxic
  Morphine, codeine	Active metabolites accumulate -drowsiness, myoclonus, respiratory depression; use oxycodone carefully or alfentanil/fentanyl in severe CKD
  Gabapentin, pregabalin	Accumulate -sedation, falls
  Digoxin	Toxicity -reduce dose, monitor
  Lithium	Toxicity; also causes CKD
  Nitrofurantoin	Avoid if eGFR under 45 (may be used short-term down to 30 with caution) -ineffective and toxic
  Trimethoprim	Hyperkalaemia; raises creatinine (reduced secretion -not true GFR fall)
  Aciclovir, valaciclovir	Neurotoxicity and crystal nephropathy -reduce dose
  Allopurinol	Start low; hypersensitivity risk
  Methotrexate	Toxicity -reduce or avoid
  Bisphosphonates	Avoid alendronate if eGFR under 35; zoledronate if CrCl under 35
  SGLT2 inhibitors	Glucose-lowering effect falls with eGFR, but still used for kidney and heart protection (check current thresholds)
  Penicillins, cephalosporins, carbapenems	High doses -seizures in severe CKD; dose adjust

• Nephrotoxic drugs to avoid -NSAIDs, aminoglycosides, IV contrast (risk in AKI and CKD -hydrate), lithium, ciclosporin and tacrolimus, amphotericin.
• Hyperkalaemia risk -ACE inhibitors, ARBs, spironolactone, amiloride, trimethoprim, potassium supplements -monitor potassium.
• Dialysis -some drugs are removed (give after dialysis); seek renal pharmacy advice.

Medicines in Acute Kidney Injury

• Review all medicines in AKI (NICE NG148):
  • Stop or withhold drugs that worsen kidney function -NSAIDs, ACE inhibitors and ARBs, diuretics (if hypovolaemic), aminoglycosides, contrast (where possible).
  • Stop or reduce drugs that accumulate and cause harm -metformin (lactic acidosis), sulphonylureas (hypoglycaemia), DOACs and LMWH (bleeding), digoxin, lithium, opioids (morphine), gabapentinoids, methotrexate, SGLT2 inhibitors.
  • Adjust antibiotic and antiviral doses.
• eGFR is unreliable in AKI (creatinine isn't at steady state) -assume kidney function is worse than the number suggests.
• Restart withheld medicines (with a clear plan) when kidney function recovers and the patient is eating and drinking -don't forget ACE inhibitors in heart failure.
• "Sick day rules" -during dehydrating illness (vomiting, diarrhoea, fever), temporarily stop "SADMANS" -Sulfonylureas, ACE inhibitors, Diuretics, Metformin, ARBs, NSAIDs, SGLT2 inhibitors; restart after 24–48 hours of normal eating and drinking.
• Iodinated contrast -assess risk (eGFR under 30, AKI); IV hydration for high-risk patients; review metformin per local policy.

Prescribing in Liver Disease

• Liver disease affects drugs in several ways:
  • Reduced metabolism -drugs and metabolites accumulate (especially in cirrhosis); LFTs don't predict this well -albumin, INR and bilirubin (Child–Pugh score) are better guides.
  • Low albumin -more free drug (phenytoin, warfarin).
  • Clotting problems -higher bleeding risk with anticoagulants and antiplatelets.
  • Fluid retention -worsened by NSAIDs, steroids and sodium-containing preparations (IV antibiotics, effervescent tablets).
  • Hepatic encephalopathy -precipitated by sedatives, opioids, constipation, diuretics (electrolyte changes), infection, GI bleeding.
  • Kidney function -hepatorenal syndrome; creatinine overestimates kidney function (low muscle mass).
  • Hepatotoxic drugs can worsen liver damage.
• Drugs to avoid or use with great care in cirrhosis:
  • NSAIDs -GI bleeding, kidney failure, fluid retention -avoid.
  • Opioids and sedatives (benzodiazepines, Z-drugs) -encephalopathy; if needed, low doses (e.g. short-acting, lorazepam over diazepam; oxycodone or fentanyl with care).
  • Paracetamol -safe at reduced dose (e.g. maximum 2–3 g/day in cirrhosis, low weight, malnutrition or alcohol excess).
  • Anticoagulants -bleeding (DOACs contraindicated in some Child–Pugh classes).
  • ACE inhibitors and ARBs -avoid in decompensated cirrhosis with ascites (hypotension, kidney failure).
  • Metformin -avoid in severe liver disease (lactic acidosis).
  • Statins -usually safe in compensated liver disease and fatty liver; avoid in decompensated disease.
  • Hepatotoxic drugs -methotrexate, high-dose amiodarone, valproate, some antibiotics (co-amoxiclav) -consider alternatives.
• Drugs used in liver disease -lactulose and rifaximin (encephalopathy), spironolactone (ascites), non-selective beta-blockers (carvedilol, propranolol -varices), terlipressin (variceal bleeding, hepatorenal syndrome), antibiotics (SBP prophylaxis).

Heart Failure and Other Conditions

• Heart failure -avoid drugs that cause fluid retention or depress the heart:
  • NSAIDs, pioglitazone, non-dihydropyridine calcium channel blockers (verapamil, diltiazem -in reduced EF), class I antiarrhythmics (flecainide), dronedarone (severe HF), tricyclics, itraconazole, high-sodium preparations, some chemotherapy (anthracyclines, trastuzumab).
• Asthma -avoid non-selective beta-blockers (propranolol, including eye drops -timolol); use cardioselective beta-blockers cautiously when strongly indicated; NSAID and aspirin sensitivity in some (especially with nasal polyps).
• Myasthenia gravis -many drugs worsen weakness: aminoglycosides, macrolides, quinolones, magnesium, beta-blockers, neuromuscular blockers, quinine, botulinum toxin.
• Epilepsy -drugs lowering seizure threshold: tramadol, bupropion, quinolones, carbapenems (with valproate -also lowers valproate levels), high-dose penicillins, tricyclics, antipsychotics, theophylline, withdrawal of benzodiazepines or alcohol.
• Parkinson's disease -avoid dopamine antagonists -metoclopramide, prochlorperazine, typical antipsychotics (haloperidol); use domperidone (antiemetic), quetiapine or clozapine (psychosis).
• G6PD deficiency -avoid oxidant drugs (primaquine, dapsone, nitrofurantoin, quinolones, sulfonamides, rasburicase).
• Porphyria -many drugs can trigger attacks -check the porphyria drug database.
• Glaucoma (angle-closure) -anticholinergics and some antidepressants can trigger acute attacks.
• Prostatic enlargement -anticholinergics, antihistamines, decongestants can cause retention.

Principles of Prescribing in Pregnancy

• Most drugs cross the placenta; effects depend on the drug, dose and timing:
  • First 2 weeks after conception -"all or nothing" (miscarriage or no effect).
  • Weeks 3–8 (organogenesis) -highest risk of structural malformations.
  • Second and third trimesters -effects on growth and function (e.g. kidneys, ductus arteriosus), and on the neonate around delivery (withdrawal, respiratory depression, hypoglycaemia).
• Think about pregnancy in every woman of childbearing potential -ask about the last period, contraception and plans; test if in doubt before teratogenic drugs.
• Principles:
  • Avoid drugs in the first trimester unless the benefit clearly outweighs the risk.
  • Use drugs with the longest safety record, at the lowest effective dose, for the shortest time.
  • Don't stop essential treatment without advice -untreated disease (epilepsy, asthma, depression, hypertension, thyroid disease, diabetes, inflammatory disease) often harms mother and baby more than the drug.
  • Check the BNF and the UK Teratology Information Service (UKTIS) and its patient resource (bumps).
  • Pre-pregnancy counselling for women with chronic diseases -switch to safer drugs before conception; high-dose folic acid 5 mg where indicated (epilepsy drugs, diabetes, obesity, previous neural tube defect, sickle cell disease, coeliac disease).
• Physiological changes -larger blood volume, higher GFR (lower levels of renally cleared drugs -e.g. lamotrigine and levetiracetam levels fall, needing dose increases), altered protein binding.

Drugs to Avoid in Pregnancy

Drug	Main risk
Sodium valproate	Neural tube defects and other malformations (about 10%), neurodevelopmental disorders (up to 30–40%) -Pregnancy Prevention Programme
Carbamazepine, phenytoin, topiramate	Malformations (cleft lip and palate, heart defects); topiramate -low birth weight, possible neurodevelopmental effects (MHRA pregnancy prevention programme)
Isotretinoin, acitretin (retinoids)	Severe malformations -pregnancy prevention programmes
Warfarin	Embryopathy (weeks 6–12 -nasal hypoplasia, bone stippling), fetal bleeding -switch to LMWH
ACE inhibitors and ARBs	Fetal kidney failure, oligohydramnios, skull defects (second and third trimesters) -switch before or as soon as pregnancy is confirmed
Methotrexate, mycophenolate, leflunomide, cyclophosphamide	Miscarriage and malformations
Statins	Avoid (cholesterol needed for fetal development) -stop before conception
Tetracyclines (doxycycline)	Teeth discolouration and bone effects (after about 15 weeks)
Aminoglycosides	Fetal deafness (8th nerve damage)
Trimethoprim	Folate antagonist -avoid in first trimester
Nitrofurantoin	Avoid at term (neonatal haemolysis)
NSAIDs	Avoid from 20 weeks (fetal kidney problems, oligohydramnios) and especially from 28 weeks (premature closure of the ductus arteriosus)
Lithium	Cardiac malformations (Ebstein's anomaly -small risk); neonatal toxicity; levels change -specialist
Misoprostol, mifepristone	Miscarriage
Danazol, testosterone, finasteride	Virilisation of female fetus
Thalidomide, lenalidomide	Limb defects (phocomelia)
Radioactive iodine, carbimazole (first trimester)	Fetal thyroid damage; carbimazole embryopathy -use propylthiouracil in first trimester
Live vaccines (MMR, varicella, BCG, yellow fever)	Theoretical risk -avoid

Treating Common Problems in Pregnancy

Problem	Generally preferred options (check BNF/UKTIS)
Pain and fever	Paracetamol; avoid NSAIDs after 20 weeks; short-term opioids if needed (neonatal withdrawal risk with long-term use)
Nausea and vomiting	Antihistamines (cyclizine, promethazine), prochlorperazine; metoclopramide or ondansetron as second-line (small cleft risk with first-trimester ondansetron -discuss)
Hypertension	Labetalol first; nifedipine (MR); methyldopa
Pre-eclampsia prevention	Aspirin 75–150 mg from 12 weeks for high-risk women
VTE	LMWH (doesn't cross the placenta)
UTI	Nitrofurantoin (avoid at term), amoxicillin (if sensitive), cefalexin; avoid trimethoprim in first trimester
Epilepsy	Lamotrigine or levetiracetam; folic acid 5 mg; avoid valproate
Asthma	Continue inhalers (salbutamol, inhaled steroids) and oral steroids if needed
Depression	Sertraline often used; balance risks (small risk of persistent pulmonary hypertension of the newborn, neonatal adaptation)
Diabetes	Insulin, metformin; stop other agents
Hypothyroidism	Increase levothyroxine (often 25–50 micrograms) as soon as pregnancy is confirmed
Hyperthyroidism	Propylthiouracil (first trimester), then carbimazole
Reflux and constipation	Antacids, alginates; ranitidine alternatives (famotidine) or omeprazole; lactulose, ispaghula
Allergies	Loratadine, cetirizine; chlorphenamine

• Vaccines recommended in pregnancy -influenza (any stage), pertussis (from 16 weeks), COVID-19, RSV (from 28 weeks -UK programme).

Prescribing in Breastfeeding

• Most drugs pass into breast milk in small amounts -most are compatible with breastfeeding; encourage breastfeeding where possible.
• Factors increasing infant exposure -high maternal doses, long half-life, lipid-soluble, low protein binding, active metabolites; premature or very young babies (immature metabolism).
• Generally compatible -paracetamol, ibuprofen, most penicillins and cephalosporins, LMWH, warfarin, insulin, metformin, levothyroxine, labetalol, nifedipine, enalapril, prednisolone (low dose), sertraline, inhalers, most vaccines.
• Avoid or use with caution:
  • Codeine -contraindicated (ultra-rapid metabolisers → infant opioid toxicity and death) (MHRA); tramadol -caution.
  • Aspirin (analgesic doses) -Reye's syndrome risk.
  • Lithium -infant toxicity (specialist only).
  • Amiodarone, radioactive iodine, cytotoxics (methotrexate, cyclophosphamide), mycophenolate, leflunomide, retinoids.
  • Benzodiazepines (long-acting -infant sedation), sedating antihistamines.
  • Combined oral contraceptives -reduce milk supply (use progestogen-only methods in the first 6 weeks).
  • Ciprofloxacin, tetracyclines (short courses often acceptable), chloramphenicol, carbimazole (high doses).
• Resources -BNF, UK Drugs in Lactation Advisory Service (UKDILAS) (Specialist Pharmacy Service), LactMed.
• Advice -take doses just after a feed; watch the baby for drowsiness, poor feeding, rashes or diarrhoea.

Teratogens, Contraception and Pregnancy Prevention

• Pregnancy Prevention Programmes (MHRA) -required for:
  • Valproate -not to be started in patients under 55 (male or female) unless two specialists agree there's no alternative; women of childbearing potential need highly effective contraception and an annual risk acknowledgement form.
  • Isotretinoin (and other oral retinoids) -pregnancy tests and highly effective contraception.
  • Topiramate (2024) -pregnancy prevention programme for women of childbearing potential.
  • Thalidomide, lenalidomide, pomalidomide; mycophenolate (contraception and pregnancy testing).
• Highly effective contraception -the LARC methods (copper IUD, levonorgestrel IUS, implant) -failure under 1% a year; user-dependent methods (pill) are less reliable.
• Enzyme-inducing drugs (rifampicin, carbamazepine, phenytoin, topiramate at higher doses, St John's wort, some antiretrovirals) reduce the effectiveness of combined pills, progestogen-only pills, implants and oral emergency contraception -use a copper IUD, LNG-IUS or progestogen injection; continue for 28 days after stopping the inducer.
• Emergency contraception with enzyme inducers -copper IUD preferred; or double-dose levonorgestrel (3 mg); ulipristal is not recommended.
• Lamotrigine and combined pills -oestrogen lowers lamotrigine levels (seizure risk; toxicity in the pill-free week).
• Men -some drugs affect sperm or fertility (e.g. methotrexate -men can usually continue; mycophenolate -condoms advised; cyclophosphamide -sperm banking; finasteride -avoid exposure of pregnant partners to crushed tablets).

Prescribing for Children

• Children are not small adults -absorption, body water, liver enzymes and kidney function change rapidly with age, especially in neonates (immature liver and kidneys -longer half-lives).
• Use the BNF for Children (BNFC) and local paediatric guidance.
• Dosing:
  • Usually by weight (mg/kg) or age band; sometimes by body surface area (chemotherapy).
  • Always weigh the child (estimated weights cause errors) and record the weight on the chart.
  • Never exceed the adult dose -overweight children may need doses based on ideal weight.
  • Double-check calculations -tenfold errors are a major risk (decimal points, mg vs micrograms).
• Formulations -liquids (check strength -mg per 5 mL; sugar-free if long-term), dispersible tablets, suppositories; use oral syringes for oral liquids.
• Off-label use is common and accepted (GMC) -use the BNFC.
• Involving children -explain at the right level; consent (Gillick competence for under 16s); adherence (taste, school-time doses -choose once- or twice-daily regimens).
• Paracetamol and ibuprofen -weight- or age-based dosing; avoid giving both "just in case" for fever alone (NICE -consider swapping if distress persists).

Drugs to Avoid or Use Carefully in Children

Drug	Problem
Aspirin	Reye's syndrome (liver failure and encephalopathy) -avoid under 16 (except specific indications -e.g. Kawasaki disease)
Codeine	Contraindicated under 12, and under 18 after tonsillectomy or adenoidectomy for sleep apnoea (CYP2D6 ultra-rapid metabolism -deaths)
Tetracyclines	Tooth discolouration and enamel damage -avoid under 12
Fluoroquinolones	Joint and tendon damage -use only when benefit outweighs risk
Chloramphenicol (systemic)	"Grey baby syndrome" in neonates (immature glucuronidation)
Ceftriaxone in neonates	Displaces bilirubin (kernicterus); precipitates with IV calcium
Sulfonamides in neonates	Kernicterus (bilirubin displacement)
Metoclopramide	Extrapyramidal reactions (oculogyric crises) -restricted use
Antidepressants	Increased suicidal thinking in young people -fluoxetine is first choice with monitoring
Valproate	Liver toxicity (especially under 3 years and with metabolic disorders); teratogenicity in girls
Lidocaine and benzocaine (teething gels)	Toxicity, methaemoglobinaemia in infants
Honey (as a remedy)	Infant botulism under 1 year
Over-the-counter cough and cold medicines	Not for children under 6 (sedation, arrhythmias, little benefit)

• Accidental poisoning -common in toddlers (iron, paracetamol, button batteries, laundry capsules, family members' medicines) -child-resistant containers, safe storage.

Prescribing for Older People

• Older people are the largest users of medicines and suffer the most ADRs -see the Medicine of the Older Person chapter page on Prescribing and Deprescribing.
• Key points:
  • Kidney function is often lower than creatinine suggests -use creatinine clearance for dosing.
  • Increased sensitivity to sedatives, opioids, anticholinergics and antihypertensives -start low, go slow.
  • Polypharmacy -review regularly using STOPP/START; deprescribe.
  • Falls-risk drugs, anticholinergic burden, hyponatraemia (thiazides, SSRIs), hypoglycaemia.
  • Practical issues -swallowing, dexterity, vision, cognition, packaging.

Prescribing in Obesity and Low Body Weight

• Obesity changes drug distribution (more fat, larger blood volume, higher clearance for some drugs).
• Which weight?:
  • Actual body weight -LMWH (treatment doses, up to a cap -check local guidance; monitor anti-Xa in extremes), some antibiotics.
  • Ideal body weight -drugs that distribute mainly into lean tissue (e.g. some anaesthetic drugs, digoxin).
  • Adjusted body weight -aminoglycosides (gentamicin) in obesity: IBW + 0.4 × (actual − IBW).
• Thromboprophylaxis -higher doses of LMWH in obesity (e.g. BMI over 40 or weight over 100–150 kg per local protocol).
• Fixed doses may be too low (e.g. some antibiotics, emergency contraception -levonorgestrel less effective over BMI 26 or weight 70 kg -copper IUD preferred or double-dose levonorgestrel).
• Creatinine clearance -Cockcroft–Gault overestimates in obesity if actual weight is used -use adjusted weight per local guidance.
• Low body weight (under 50 kg) -reduce paracetamol (e.g. 15 mg/kg per dose; maximum per local guidance), DOAC dose criteria (apixaban -weight 60 kg or less is one criterion; edoxaban 60 kg or less), care with nephrotoxic and sedating drugs.
• After bariatric surgery -reduced absorption of some drugs (modified-release preparations, oral contraceptives -use non-oral), avoid NSAIDs (ulcers), lifelong vitamin and mineral supplements.

Medicines Around Surgery

Drug	Usual plan (follow local guidance and the surgeon/anaesthetist)
Warfarin	Stop about 5 days before; check INR (under 1.5 for most surgery); bridging LMWH only for high thrombotic risk (mechanical mitral valve, recent VTE)
DOACs	Stop 1–3 days before (longer with low CrCl, dabigatran, high bleeding risk surgery); no bridging
Antiplatelets	Aspirin often continued; clopidogrel and ticagrelor stopped 5–7 days before (prasugrel 7) -never stop after recent coronary stents without cardiology advice
Insulin and diabetes drugs	Per CPOC guidance -reduce basal insulin (e.g. 80% of usual dose the night before or morning of); omit most oral agents on the day; SGLT2 inhibitors stopped the day before and day of surgery (longer for some -euglycaemic DKA risk); variable-rate insulin if prolonged fasting
Steroids	Continue; give extra hydrocortisone cover (e.g. 100 mg IV at induction for major surgery, then 200 mg/24 hours) for people on long-term steroids
ACE inhibitors and ARBs	Often omitted on the morning of surgery (hypotension) -local policy
Beta-blockers	Continue (don't start new ones just before surgery)
Combined pill and HRT	Combined pill -stop 4 weeks before major surgery or immobilisation (VTE); HRT -individual assessment, thromboprophylaxis
Lithium	Often stopped 24 hours before major surgery; restart when eating, drinking and kidney function normal
Methotrexate	Usually continued for elective orthopaedic surgery (BSR); biologics timed around the dosing interval
Antiepileptics, Parkinson's drugs	Continue -give with sips of water; NG or patch alternatives if nil by mouth
MAOIs	Specialist anaesthetic advice (interactions with pethidine, vasopressors)
Herbal remedies (ginkgo, garlic, St John's wort)	Stop about 2 weeks before (bleeding, interactions)

Special Groups at a Glance

Group	Key rules
CKD	Reduce maintenance doses of renally cleared drugs; avoid NSAIDs; Cockcroft–Gault for DOACs
AKI	Stop NSAIDs, ACE inhibitors, ARBs, diuretics, metformin; reduce DOACs, opioids, gabapentinoids
Liver disease	Avoid NSAIDs and sedatives; reduce paracetamol; watch for encephalopathy
Pregnancy	Avoid valproate, warfarin, ACE inhibitors, methotrexate, statins, retinoids, tetracyclines; NSAIDs from 20 weeks
Pregnancy choices	Paracetamol, labetalol, nifedipine, LMWH, insulin, metformin, lamotrigine, levetiracetam
Breastfeeding	Avoid codeine, aspirin, lithium, amiodarone, cytotoxics; combined pill reduces milk
Children	BNFC; weigh; mg/kg; never exceed adult dose; no aspirin under 16; no codeine under 12
Older people	Start low, go slow; CrCl; avoid anticholinergics and sedatives; deprescribe
Obesity	Actual vs ideal vs adjusted body weight; higher LMWH prophylaxis
Surgery	Stop warfarin 5 days, clopidogrel 7 days, SGLT2 inhibitor before surgery, COC 4 weeks; steroid cover

Spot the Diagnosis

Clue	Answer
Drowsiness and myoclonus on morphine with eGFR 15	Morphine metabolite accumulation -switch opioid
Lactic acidosis in a man on metformin with eGFR 22	Metformin should have been stopped
Creatinine rises slightly on trimethoprim without true kidney injury	Reduced tubular creatinine secretion
Confusion after lorazepam in a man with cirrhosis and ascites	Hepatic encephalopathy precipitated by a sedative
AKI after ibuprofen in a man with decompensated cirrhosis	NSAID -avoid in cirrhosis
Spina bifida in a baby whose mother took an epilepsy drug	Valproate
Oligohydramnios in a woman who continued ramipril into the second trimester	ACE inhibitor fetotoxicity
Nasal hypoplasia and stippled bones in a newborn	Warfarin embryopathy
Raised TSH at 8 weeks of pregnancy in a woman on levothyroxine	Needs dose increase
Rising seizures in pregnancy on lamotrigine	Falling lamotrigine levels -increase dose
Sleepy, poorly feeding baby whose mother takes co-codamol	Codeine in breastfeeding
Vomiting, encephalopathy and liver failure after aspirin for chickenpox	Reye's syndrome
Oculogyric crisis after metoclopramide in a teenager	Acute dystonic reaction
Unplanned pregnancy on the implant and carbamazepine	Enzyme induction
DKA with glucose 9 mmol/L after bowel surgery	SGLT2 inhibitor not stopped -euglycaemic DKA
Hypotension and vomiting after surgery in a patient on long-term prednisolone	Adrenal crisis -no steroid cover
Weakness and respiratory failure after gentamicin in myasthenia gravis	Aminoglycoside worsening myasthenia
Severe rigidity after haloperidol in Parkinson's disease	Dopamine antagonist -avoid

Exam-style Scenarios

1. A 76-year-old woman (55 kg) is admitted with AKI (creatinine 210, baseline 90) after diarrhoea. Her medicines are ramipril, furosemide, metformin, gliclazide, apixaban 5 mg twice daily and naproxen.
Answer: Medicines review in AKI.

• Stop naproxen; withhold ramipril, furosemide, metformin and gliclazide (monitor glucose; insulin if needed).
• Reassess apixaban -calculate creatinine clearance; she meets two dose-reduction criteria (weight 60 kg or less and creatinine 133 µmol/L or more) -2.5 mg twice daily, or withhold temporarily if CrCl is very low.
• IV fluids; monitor U&E; plan to restart ACE inhibitor and diabetes drugs when kidney function recovers; never restart naproxen; teach sick day rules.

2. A 29-year-old woman with epilepsy on sodium valproate tells you she wants to try for a baby.
Answer: Pre-conception planning -switch from valproate.

• Urgent neurology referral to switch to a safer drug (e.g. lamotrigine or levetiracetam) before conception; continue contraception until switched and stable.
• Don't stop valproate suddenly (seizure risk -SUDEP).
• Start folic acid 5 mg daily before conception; refer to joint obstetric–neurology care; drug levels in pregnancy.

3. A 33-year-old woman at 30 weeks of pregnancy has lower back pain and asks for ibuprofen. She is also taking labetalol for hypertension.
Answer: Avoid NSAIDs in late pregnancy.

• NSAIDs after 20 weeks risk fetal kidney problems and oligohydramnios, and after 28 weeks premature closure of the ductus arteriosus.
• Use paracetamol, heat, physiotherapy and support belts; short-term opioid only if needed.
• Check BP and for pre-eclampsia features if new symptoms.

4. A 4-year-old boy weighing 16 kg needs oral amoxicillin for pneumonia. The suspension is 250 mg/5 mL. The BNFC dose for his age is 250 mg three times daily (or by weight per local guidance).
Answer: Paediatric liquid prescription and calculation.

• 250 mg from 250 mg/5 mL = 5 mL three times daily (check the BNFC and local guideline dose); usually 5 days.
• Record weight on the chart; prescribe in mg (not mL alone); use an oral syringe; check allergies.
• Advise on completing the course, fever management, and safety-netting (breathing difficulty, poor feeding).

5. A 58-year-old man with type 2 diabetes on dapagliflozin, metformin and gliclazide is listed for elective hip replacement. He also takes clopidogrel (stroke 2 years ago).
Answer: Perioperative medicines plan.

• Stop dapagliflozin the day before and the day of surgery (euglycaemic DKA risk); omit metformin and gliclazide on the day (local policy); monitor glucose; restart when eating and drinking.
• Clopidogrel -usually stopped 7 days before (discuss with surgeon; consider aspirin cover); restart after surgery when bleeding risk allows.
• VTE prophylaxis after surgery; check kidney function; follow CPOC diabetes guidance.

Key Points

• In CKD, reduce maintenance doses of renally cleared drugs; loading doses usually stay the same.
• Avoid NSAIDs in CKD, AKI, liver disease and heart failure.
• Sick day rules -SADMANS.
• Liver disease -LFTs don't predict drug handling; avoid sedatives and NSAIDs; reduce paracetamol.
• Avoid dopamine antagonists in Parkinson's; aminoglycosides and macrolides in myasthenia; non-selective beta-blockers in asthma.
• Pregnancy -avoid drugs in weeks 3–8 if possible; don't stop essential treatment without advice; use UKTIS.
• Key teratogens -valproate, retinoids, warfarin, ACE inhibitors and ARBs, methotrexate, mycophenolate, statins, tetracyclines, carbimazole (first trimester).
• Pregnancy choices -paracetamol, labetalol, nifedipine, LMWH, insulin, metformin, lamotrigine, levetiracetam.
• NSAIDs -avoid from 20 weeks of pregnancy.
• Breastfeeding -most drugs compatible; avoid codeine, aspirin, lithium, amiodarone, cytotoxics.
• Enzyme inducers reduce hormonal contraception -use a copper IUD, LNG-IUS or injection.
• Valproate and topiramate need pregnancy prevention programmes.
• Children -weigh, use the BNFC, mg/kg, never exceed adult doses, beware tenfold errors.
• No aspirin under 16 (Reye's); no codeine under 12; no tetracyclines under 12.
• Before surgery -stop warfarin 5 days, clopidogrel 7 days, SGLT2 inhibitors, COC 4 weeks; steroid cover; continue Parkinson's and epilepsy drugs.

Guidelines and Further Reading

• BNF and BNFC: Prescribing in renal impairment, hepatic impairment, pregnancy, breastfeeding and children
• NICE NG148: Acute kidney injury -prevention, detection and management
• Think Kidneys (UK Renal Registry): Medicines optimisation and sick day guidance
• UK Teratology Information Service (UKTIS) and "bumps" (best use of medicines in pregnancy)
• Specialist Pharmacy Service: UK Drugs in Lactation Advisory Service (UKDILAS)
• MHRA: Valproate, topiramate and isotretinoin pregnancy prevention programmes; codeine in children and breastfeeding
• FSRH: Drug interactions with hormonal contraception
• Centre for Perioperative Care (CPOC): Guideline for perioperative care for people with diabetes
• Association of Anaesthetists: Perioperative management of steroid-dependent patients
• BNF -for current doses