Clinical pharmacology and prescribing: High-risk drugs, therapeutic drug monitoring, IV fluids and antimicrobial prescribing

🩺 High-risk drugs, therapeutic drug monitoring, IV fluids and antimicrobial prescribing. A small number of medicines cause most serious medication harm -anticoagulants, insulin, opioids, IV potassium, IV fluids, antibiotics and narrow therapeutic index drugs. These are the drugs junior doctors prescribe every day, and they feature heavily in the PSA. Treatment of individual diseases is in the specialty chapters.
Your four questions for every high-risk drug: Is the dose right for this patient's weight, kidney function and indication? What level or test do I need, and when? What are the warning signs of toxicity? How would I reverse or treat it if something went wrong?

---

High-risk Medicines

• High-risk medicines -drugs with a high risk of causing significant harm when used in error or without proper monitoring.
• Common examples -"A PINCH":
  • A -Anti-infectives (aminoglycosides, vancomycin, antifungals), anticoagulants, antiepileptics.
  • P -Potassium and other electrolytes (IV), psychotropics (lithium, clozapine).
  • I -Insulin.
  • N -Narcotics (opioids) and sedatives.
  • C -Chemotherapy (including oral methotrexate).
  • H -Heparin and other anticoagulants.
• Also -IV fluids, digoxin, amiodarone, immunosuppressants, neuromuscular blockers, concentrated injections (midazolam, morphine), oral methotrexate, valproate (pregnancy).
• Safety measures -double-checking, standardised concentrations (pre-mixed bags), dedicated charts (insulin, anticoagulants), electronic decision support, pharmacist review, patient alert cards, monitoring protocols, avoiding abbreviations.

Warfarin

• Mechanism -vitamin K antagonist -reduces clotting factors II, VII, IX and X (and proteins C and S -a brief prothrombotic phase at the start).
• Indications and INR targets:
  • INR 2.5 (range 2–3) -AF, DVT and PE, most indications.
  • INR 3.5 -recurrent VTE while on warfarin at target INR 2.5.
  • Mechanical heart valves -target depends on valve type and position (e.g. 3.0 or 3.5 -per cardiology).
  • Warfarin is preferred over DOACs for mechanical valves, antiphospholipid syndrome, moderate–severe mitral stenosis, and some with severe kidney impairment.
• Starting -loading regimens (local protocol, e.g. Fennerty or lower doses in older people); for VTE, give LMWH alongside for at least 5 days and until INR has been 2 or more for 24 hours.
• Monitoring -INR frequently at the start, then up to every 12 weeks when stable; yellow anticoagulant book and alert card.
• Interactions -many:
  • Raise INR -antibiotics (clarithromycin, erythromycin, metronidazole, ciprofloxacin, co-trimoxazole), azole antifungals, amiodarone, alcohol binges, cranberry juice, SSRIs (bleeding), paracetamol (regular high doses), illness (diarrhoea, fever, liver congestion).
  • Lower INR -enzyme inducers (rifampicin, carbamazepine, phenytoin, St John's wort), vitamin K-rich foods (green vegetables) and supplements.
  • NSAIDs and antiplatelets -increase bleeding without changing INR.
• Managing a high INR (BNF):

  Situation	Action
  Major bleeding (any INR)	Stop warfarin; IV vitamin K (phytomenadione) 5 mg; prothrombin complex concentrate (or FFP if PCC unavailable)
  INR over 8, minor bleeding	Stop warfarin; IV vitamin K 1–3 mg; repeat if INR still high after 24 hours; restart when INR under 5
  INR over 8, no bleeding	Stop warfarin; oral vitamin K 1–5 mg; repeat if still high after 24 hours; restart when INR under 5
  INR 5–8, minor bleeding	Stop warfarin; IV vitamin K 1–3 mg; restart when INR under 5
  INR 5–8, no bleeding	Withhold 1–2 doses and reduce the maintenance dose

• Look for the cause of a high INR (interaction, illness, dose error); head injury on warfarin -low threshold for CT and reversal.
• Teratogenic -switch to LMWH before 6 weeks of pregnancy.

DOACs and Heparins

• DOACs (direct oral anticoagulants):
  • Factor Xa inhibitors -apixaban (twice daily), rivaroxaban (once daily with food for AF), edoxaban (once daily); direct thrombin inhibitor -dabigatran (twice daily, mostly renally cleared).
  • Advantages -fixed doses, no INR monitoring, fewer interactions, less intracranial bleeding than warfarin.
  • Dose by indication, age, weight and creatinine clearance (Cockcroft–Gault) -check the BNF for each drug; check U&E and FBC at least annually (more often if CrCl under 60 or frail).
  • Avoid in mechanical valves, antiphospholipid syndrome (especially triple positive), severe kidney impairment (thresholds vary), pregnancy and breastfeeding, and with strong enzyme inducers or inhibitors.
  • Reversal -idarucizumab for dabigatran; andexanet alfa (restricted use) or PCC for factor Xa inhibitors per local policy; supportive care; short half-lives help.
• Low molecular weight heparin (enoxaparin, dalteparin, tinzaparin):
  • Prophylaxis (fixed dose; adjust for weight extremes) and treatment (weight-based).
  • Renally cleared -reduce treatment dose if CrCl under 30 (or use UFH); anti-Xa monitoring in pregnancy, extremes of weight or kidney failure.
  • Preferred in pregnancy and cancer-associated VTE (or a DOAC in many cancers).
• Unfractionated heparin (UFH) -IV infusion with APTT monitoring (APTT ratio target per protocol); short half-life and reversible with protamine sulfate -useful in severe CKD, high bleeding risk, around procedures, and thrombolysis protocols.
• Heparin-induced thrombocytopenia (HIT):
  • Antibodies against heparin–PF4 complexes -platelets fall by over 50% 5–10 days after starting heparin (sooner if recent exposure) -paradoxically causes thrombosis (venous and arterial).
  • Assess with the 4Ts score; send HIT antibodies.
  • Stop all heparin (including flushes) and start a non-heparin anticoagulant (argatroban, fondaparinux, danaparoid, or a DOAC per specialist); don't give platelets; avoid warfarin until platelets recover.
• Other heparin effects -hyperkalaemia (aldosterone suppression), osteoporosis (long-term UFH).

Insulin

• Types:

  Type	Examples	Use
  Rapid-acting analogue	Insulin aspart (NovoRapid, Fiasp), lispro (Humalog)	With meals (bolus); correction doses; insulin pumps
  Short-acting soluble	Actrapid, Humulin S	IV infusions (VRIII, DKA), meals
  Intermediate	Isophane (Humulin I, Insulatard)	Once or twice daily basal; type 2 diabetes; steroid-induced hyperglycaemia
  Long-acting analogue	Glargine (Lantus, Toujeo -U300), detemir (Levemir), degludec (Tresiba)	Basal insulin once (or twice) daily
  Mixed (biphasic)	Humalog Mix 25, NovoMix 30, Humulin M3	Twice daily with breakfast and evening meal

• Safe prescribing:
  • Prescribe by brand name and device (pen or vial; strength -U100 standard; high-strength U200, U300, U500 exist -risk of error).
  • Write "units" in full; use only insulin syringes or pens (never IV syringes for SC insulin).
  • Record the time of administration relative to meals.
  • Never omit basal insulin in type 1 diabetes (DKA within hours) -even if not eating.
  • Let patients self-administer in hospital where possible.
• Variable-rate IV insulin infusion (VRIII) -for people with diabetes who are nil by mouth (missing more than one meal), unwell with persistent hyperglycaemia, or in some surgery -continue long-acting basal insulin; run with a glucose-containing substrate fluid (e.g. 0.45% saline with 5% glucose and potassium); hourly glucose; stop 30–60 minutes after the first subcutaneous rapid-acting dose with a meal.
• Hypoglycaemia (glucose under 4 mmol/L) in adults (JBDS):
  • Conscious and able to swallow -15–20 g fast-acting carbohydrate (e.g. glucose tablets, 150–200 mL fruit juice); recheck after 10–15 minutes; repeat up to 3 times; then a long-acting carbohydrate snack.
  • Drowsy or unable to swallow safely -IV glucose (e.g. 150–160 mL of 10% glucose or 75–80 mL of 20% over about 15 minutes) or IM glucagon 1 mg (less effective in liver disease, alcohol, starvation or sulphonylurea overdose).
  • Don't omit the next insulin dose after treating a hypo (especially basal) -review the dose.
  • Sulphonylurea hypoglycaemia can be prolonged -admit and monitor (may need a glucose infusion).
• Insulin errors are common -wrong insulin (Humalog vs Humulin), wrong dose ("U" read as 0), omission, timing, and failure to adjust when not eating.

Opioid Prescribing

• WHO analgesic ladder -non-opioid (paracetamol ± NSAID) → weak opioid (codeine, low-dose tramadol) → strong opioid (morphine, oxycodone) ± adjuvants; useful mainly for cancer pain.
• Starting strong opioids (NICE CG140 -palliative care):
  • Regular oral morphine -20–30 mg a day in total (immediate-release 4-hourly or modified-release twice daily, e.g. MR morphine 10–15 mg twice daily), with immediate-release morphine 5 mg as needed for breakthrough pain.
  • Lower starting doses in older people, frailty, kidney or liver impairment.
  • Breakthrough dose -about one-sixth to one-tenth of the total 24-hour dose.
  • Titrate daily according to breakthrough use.
  • Always prescribe a laxative (stimulant ± softener) and an antiemetic as needed (nausea usually settles in days).
• Approximate equivalences (check local guidance; reduce by 25–50% when switching between opioids because of incomplete cross-tolerance):

  From	To (approximate)
  Oral morphine 10 mg	SC morphine 5 mg
  Oral morphine 10 mg	Oral oxycodone 5–7.5 mg (ratio 1.5–2:1)
  Oral morphine 10 mg	SC diamorphine about 3.3 mg
  Oral codeine 60 mg	Oral morphine about 6 mg (codeine is about one-tenth as potent)
  Oral morphine about 60 mg/24 hours	Fentanyl 12 micrograms/hour patch (roughly -check conversion charts)

• Toxicity -drowsiness, confusion, hallucinations, myoclonus (metabolite accumulation in CKD), pinpoint pupils, respiratory depression -reduce dose or switch opioid; naloxone for life-threatening respiratory depression (in palliative patients, small titrated doses -e.g. 20–100 micrograms -to avoid reversing analgesia and causing pain crisis).
• Patches (fentanyl, buprenorphine) -for stable pain in opioid-tolerant patients; slow onset (12–24 hours) and offset; heat increases absorption; dispose of safely.
• Chronic non-cancer pain -opioids have limited long-term benefit and cause dependence; avoid high doses (over 120 mg oral morphine equivalent a day adds risk without benefit) (Faculty of Pain Medicine -Opioids Aware).
• Controlled drug rules apply (see page 2).

Potassium and Electrolyte Replacement

• Hypokalaemia (potassium under 3.5 mmol/L):
  • Mild (3.0–3.4) -oral potassium (e.g. Sando-K 2 tablets two or three times daily -24 mmol per 2 tablets) or increased dietary intake; treat the cause (diuretics, diarrhoea, vomiting); consider a potassium-sparing diuretic.
  • Moderate to severe (under 3.0), symptoms, arrhythmias or unable to take orally -IV potassium.
• IV potassium rules:
  • Use pre-mixed bags (e.g. 20 mmol or 40 mmol KCl in 1 L sodium chloride 0.9% or glucose) -never add concentrated KCl on the ward, never give as a bolus.
  • Maximum rate peripherally -usually 10 mmol/hour (up to 20 mmol/hour with cardiac monitoring per local policy; higher rates only centrally in critical care).
  • Maximum concentration peripherally -usually 40 mmol/L (higher concentrations irritate veins).
  • Monitor potassium regularly; check and correct magnesium (hypokalaemia won't correct if magnesium is low).
• Hypomagnesaemia -PPIs, diuretics, alcohol, diarrhoea; oral magnesium (diarrhoea) or IV magnesium sulfate (e.g. 20 mmol over several hours; 2 g over 10–15 minutes for torsades or severe asthma).
• Hypophosphataemia -refeeding, alcohol, DKA treatment -oral (Phosphate Sandoz) or IV phosphate.
• Hyperkalaemia -calcium gluconate 10% (30 mL -cardiac protection if ECG changes), insulin with glucose (10 units soluble insulin in 25 g glucose), salbutamol nebulisers, stop causative drugs; potassium binders (sodium zirconium cyclosilicate, patiromer) -see the Renal Emergencies chapter.

Principles of Drug Monitoring

• Therapeutic drug monitoring (TDM) -measuring drug levels to guide dosing when there's a narrow therapeutic index, variable pharmacokinetics, a level–effect relationship, suspected toxicity, poor adherence, interactions or organ impairment.
• Timing matters:
  • Trough levels (just before the next dose) -vancomycin, ciclosporin, tacrolimus, multiple-daily gentamicin.
  • Peak levels -some aminoglycoside regimens (e.g. endocarditis).
  • Fixed time after a dose -lithium (12 hours), digoxin (at least 6 hours), once-daily gentamicin (6–14 hours, nomogram).
  • Steady state -after 4–5 half-lives (unless checking for toxicity).
• Interpret levels with the patient -symptoms, kidney function, electrolytes, albumin (phenytoin), timing of the sample, recent dose changes.
• Monitoring the effect instead of the level -INR (warfarin), APTT (UFH), BP, glucose, TFTs (levothyroxine), heart rate (beta-blockers, rate control).

Drug	Typical target range	When to sample	Toxicity clues
Lithium	0.4–1.0 mmol/L (lower in older people; often 0.6–0.8)	12 hours post-dose	Tremor, diarrhoea, ataxia, confusion
Digoxin	About 0.5–2.0 micrograms/L (lower target, e.g. under 1.0, in heart failure)	At least 6 hours post-dose	Nausea, confusion, yellow vision, arrhythmias
Phenytoin	10–20 mg/L (total; adjust for low albumin)	Trough (any time if toxic)	Nystagmus, ataxia, slurred speech
Gentamicin (once daily)	Per nomogram (e.g. Hartford) or local target	6–14 hours after start of infusion	Nephrotoxicity, ototoxicity
Vancomycin	Trough 10–20 mg/L (15–20 for serious infections) or AUC-guided	Before 4th dose (or as protocol)	Nephrotoxicity
Theophylline	10–20 mg/L	Per formulation	Vomiting, tachyarrhythmias, seizures, low potassium
Ciclosporin, tacrolimus	Trough targets set by transplant team	Trough	Nephrotoxicity, tremor, hypertension

Gentamicin and Vancomycin

• Gentamicin (aminoglycoside):
  • Uses -serious gram-negative infections, sepsis of urinary or abdominal origin, endocarditis (synergy with beta-lactams).
  • Toxicity -nephrotoxicity (usually reversible) and ototoxicity (vestibular and cochlear -often permanent); neuromuscular blockade (avoid in myasthenia gravis).
  • Once-daily dosing -e.g. 5–7 mg/kg (local protocol; maximum dose caps), based on actual or adjusted body weight in obesity; interval based on creatinine clearance and level 6–14 hours after the dose plotted on a nomogram (e.g. Hartford).
  • Avoid or use with great care -CKD, older people, with other nephrotoxins (vancomycin, NSAIDs, contrast) and loop diuretics (ototoxicity); limit duration (often 3–5 days); MT-RNR1 variant -deafness after a single dose (genetic testing in some settings).
  • Monitor creatinine daily and ask about hearing and balance.
• Vancomycin (glycopeptide):
  • Uses -MRSA and other gram-positive infections, penicillin allergy; oral vancomycin for C. difficile (not absorbed -no levels needed).
  • Loading dose by weight (e.g. 25–30 mg/kg, max per protocol), then maintenance by kidney function; levels (trough) before the 4th dose (or AUC-guided dosing); or continuous infusion in some units.
  • Toxicity -nephrotoxicity (worse with piperacillin–tazobactam, aminoglycosides), ototoxicity (rare); vancomycin infusion reaction ("red man syndrome") -flushing and itching with fast infusion -slow the rate (not an allergy).
• Teicoplanin -related glycopeptide; loading doses; fewer infusion reactions.

Digoxin

• Mechanism -inhibits Na⁺/K⁺ ATPase (positive inotrope) and increases vagal tone (slows AV conduction).
• Uses -rate control in AF (especially sedentary patients or with heart failure), heart failure with reduced EF (symptom control).
• Dosing -loading dose for rapid effect; maintenance 62.5–250 micrograms daily, lower in kidney impairment and older people.
• Toxicity -risk factors:
  • Hypokalaemia (diuretics) -the most important; also hypomagnesaemia, hypercalcaemia, hypothyroidism.
  • Kidney impairment, dehydration, older age.
  • Interactions -amiodarone (halve digoxin dose), verapamil, diltiazem, clarithromycin, spironolactone.
• Features of toxicity -nausea, vomiting, anorexia, diarrhoea, confusion, visual disturbance (blurring, yellow-green vision), arrhythmias (bradycardia, heart block, ventricular ectopics, bidirectional VT, atrial tachycardia with block).
• ECG -"reverse tick" (scooped ST depression) -a digoxin effect, not necessarily toxicity.
• Management -stop digoxin, correct potassium and magnesium, monitor ECG; atropine for bradycardia; digoxin-specific antibody fragments (DigiFab) for life-threatening arrhythmias, severe toxicity or high potassium (see page 6).

Lithium

• Uses -bipolar disorder (mania prevention and treatment), treatment-resistant depression.
• Prescribe by brand (formulations differ -Priadel, Camcolit); liquid and tablet doses differ.
• Monitoring (NICE CG185):
  • Before starting -U&E (eGFR), TFTs, calcium, ECG (cardiac risk), weight, pregnancy plans.
  • Levels -12 hours after the last dose; weekly after starting or each dose change until stable; then every 3 months for the first year, then every 6 months (3-monthly in older people, interacting drugs, CKD, poor control).
  • U&E, TFTs and calcium every 6 months; weight.
• Long-term side effects -hypothyroidism, nephrogenic diabetes insipidus (thirst, polyuria), CKD, hyperparathyroidism (high calcium), weight gain, fine tremor, acne, psoriasis worsening, teratogenicity (Ebstein's anomaly -small risk).
• Toxicity (level over 1.5 mmol/L; but can occur at lower levels) -coarse tremor, diarrhoea and vomiting, ataxia, dysarthria, confusion, nystagmus, hyperreflexia, myoclonus, seizures, coma, arrhythmias.
• Triggers of toxicity -dehydration (vomiting, diarrhoea, heat, low salt diet), AKI, and drugs that reduce lithium clearance -NSAIDs, ACE inhibitors, ARBs, thiazides (and loop diuretics less so).
• Patient education -lithium card and record book, maintain fluid intake, avoid OTC NSAIDs, seek help if vomiting or diarrhoea; sick day advice.
• Management of toxicity -stop lithium, IV fluids, monitor levels; haemodialysis for severe toxicity (see page 6).

Phenytoin, Theophylline and Immunosuppressants

• Phenytoin:
  • Zero-order kinetics at therapeutic levels -small dose changes cause large level changes.
  • Highly protein-bound -in low albumin (or kidney failure), free drug rises; correct the measured level or measure free phenytoin.
  • Toxicity -nystagmus, ataxia, slurred speech, drowsiness, confusion.
  • Long-term effects -gum hypertrophy, hirsutism, coarse facies, osteomalacia, folate deficiency, peripheral neuropathy, cerebellar atrophy; teratogenic; enzyme inducer.
  • IV phenytoin (status epilepticus) -loading dose 20 mg/kg; cardiac monitoring (hypotension, arrhythmias, bradycardia); give slowly; "purple glove" with extravasation.
• Theophylline and aminophylline -asthma and COPD; narrow therapeutic index; levels affected by smoking (inducer -lowers levels; stopping smoking raises them), heart failure, liver disease and interactions (clarithromycin, ciprofloxacin raise levels); toxicity -vomiting, tachycardia, arrhythmias, hypokalaemia, seizures; don't give an IV loading dose to patients already taking oral theophylline.
• Ciclosporin and tacrolimus (calcineurin inhibitors) -transplant and autoimmune disease; trough level monitoring; toxicity -nephrotoxicity, hypertension, hyperkalaemia, tremor, diabetes (tacrolimus), gum hypertrophy and hirsutism (ciclosporin); many CYP3A4 interactions (clarithromycin and azoles raise levels; rifampicin and St John's wort lower them -rejection risk); prescribe by brand.
• Clozapine -mandatory FBC monitoring (agranulocytosis) -weekly for 18 weeks, then fortnightly to 1 year, then monthly; levels if toxicity suspected or smoking status changes; constipation can be fatal; myocarditis early.
• Methotrexate (high dose, oncology) -levels guide folinic acid rescue.

Blood Monitoring for Common Drugs

Drug	What to monitor	Why
ACE inhibitors, ARBs	U&E before, 1–2 weeks after starting and after each dose increase	Hyperkalaemia, AKI (creatinine rise over 30% -review)
Spironolactone	Potassium and creatinine	Hyperkalaemia
Diuretics	U&E (sodium, potassium)	Hypokalaemia, hyponatraemia, AKI
Statins	LFTs at baseline, 3 months and 12 months; CK if symptoms	Hepatotoxicity, myopathy
Amiodarone	TFTs and LFTs every 6 months; chest X-ray and PFTs if symptoms; eyes	Thyroid dysfunction, hepatitis, lung fibrosis
Methotrexate	FBC, U&E, LFTs regularly	Marrow suppression, liver toxicity
Azathioprine	TPMT before; FBC and LFTs regularly	Marrow suppression
Carbimazole	TFTs; FBC if sore throat	Agranulocytosis
Antipsychotics	Weight, glucose or HbA1c, lipids, prolactin, ECG (some)	Metabolic syndrome, QT
Sodium valproate	LFTs and FBC (first 6 months)	Hepatotoxicity, thrombocytopenia
Levothyroxine	TSH 6–8 weeks after dose change	Over- or under-replacement
SSRIs (older people)	Sodium	Hyponatraemia
Metformin	eGFR at least annually; B12 if symptoms	Accumulation; B12 deficiency
DOACs	U&E (CrCl) and FBC at least annually	Dose adjustment, bleeding

Prescribing IV Fluids

• IV fluids are drugs -errors (too much, too little, wrong type) cause harm: fluid overload, pulmonary oedema, hyponatraemia (especially children and older people), hyperchloraemic acidosis, AKI.
• NICE CG174 -the "5 Rs": Resuscitation, Routine maintenance, Replacement, Redistribution, Reassessment.
• Assess before prescribing -history (intake, losses), observations (HR, BP, capillary refill, JVP, NEWS2), fluid balance chart, weight, U&E, oedema and chest signs; can the patient drink or take enteral fluids instead?
• Resuscitation (hypovolaemia):
  • 500 mL bolus of crystalloid (sodium 130–154 mmol/L -e.g. 0.9% sodium chloride or Hartmann's) over under 15 minutes.
  • Reassess after each bolus; up to about 2,000 mL, then seek senior help.
  • Smaller boluses (250 mL) in heart failure or frailty; blood for haemorrhage; avoid starches.
• Routine maintenance (adults, for 24 hours):
  • Water -25–30 mL/kg/day (consider 20–25 mL/kg/day in older or frail people, heart failure, kidney impairment, malnutrition).
  • Sodium, potassium and chloride -about 1 mmol/kg/day each.
  • Glucose -50–100 g/day (to limit starvation ketosis -not nutrition).
  • Example -70 kg adult: about 2–2.1 L/day with about 70 mmol each of sodium and potassium -e.g. 0.18% sodium chloride with 4% glucose with potassium, or a combination of fluids per local guidance.
  • Review daily; stop IV fluids as soon as oral intake is adequate; prescribe for no more than 24 hours at a time.
• Replacement and redistribution -add ongoing losses (vomiting, diarrhoea, high-output stoma, drains, fever, polyuria) and consider fluid shifts (sepsis, pancreatitis, oedema, ascites).
• Children -isotonic fluids (e.g. 0.9% sodium chloride with 5% glucose) for maintenance -hypotonic fluids cause dangerous hyponatraemia (NICE NG29); use the Holliday–Segar formula (100/50/20 mL/kg/day).

Choosing an IV Fluid

Fluid	Content (per litre, approximate)	Use and cautions
0.9% sodium chloride	Na 154, Cl 154 mmol	Resuscitation, replacement; large volumes cause hyperchloraemic acidosis
Hartmann's (compound sodium lactate)	Na 131, K 5, Cl 111, Ca 2, lactate 29 mmol	Resuscitation, surgery; "balanced"; caution in hyperkalaemia (small amount of K) and severe liver failure
Plasma-Lyte 148	Na 140, K 5, Cl 98, Mg 1.5, acetate, gluconate	Balanced crystalloid -resuscitation, DKA in some units
5% glucose	50 g glucose; no electrolytes (effectively free water)	Water replacement (hypernatraemia), substrate for VRIII; causes hyponatraemia if used alone in excess
0.18% sodium chloride / 4% glucose	Na 30, Cl 30, glucose 40 g	Adult maintenance (with potassium); hypotonic -avoid in children; hyponatraemia risk
0.45% sodium chloride / 5% glucose	Na 77, glucose 50 g	VRIII substrate (often with KCl)
10% glucose	100 g glucose	Hypoglycaemia treatment, high-risk VRIII, hyperkalaemia regimen
Albumin (4.5%, 20%)	Colloid	Specific uses -large-volume paracentesis, SBP, hepatorenal syndrome
Blood products	Red cells, platelets, FFP, cryoprecipitate	Bleeding and anaemia -see the Haematology chapters

Prescribing Oxygen

• Oxygen is a drug -prescribe with a target saturation range and device (BTS 2017).
• Targets:
  • 94–98% for most acutely ill patients.
  • 88–92% for patients at risk of hypercapnic respiratory failure -COPD, obesity hypoventilation, neuromuscular disease, chest wall deformity, cystic fibrosis -pending blood gases.
• Critical illness (cardiac arrest, shock, major trauma, sepsis, anaphylaxis) -high-flow oxygen 15 L/min via reservoir mask initially, then titrate.
• Devices -nasal cannulae (1–4 L/min), simple face mask (5–10 L/min), Venturi masks (fixed concentration -24%, 28%, 35%, 40%, 60% -useful in COPD), reservoir mask (15 L/min), humidified and high-flow nasal oxygen.
• Don't give oxygen to non-hypoxic patients (MI, stroke) -no benefit, possible harm.
• Monitor -saturations, respiratory rate, ABG if at risk of hypercapnia or deteriorating; wean when stable.
• Hazards -fire (smoking), CO₂ retention, dry mucosa.

Antimicrobial Prescribing and Stewardship

• Antimicrobial resistance is a major global threat -every prescription contributes; unnecessary antibiotics also cause C. difficile, ADRs and interactions.
• "Start Smart -Then Focus" (UKHSA):
  • Start smart -don't start without evidence of bacterial infection; take cultures before antibiotics (without delaying treatment in sepsis -give within 1 hour); follow local guidelines; check allergies; document indication, duration or review date on the chart.
  • Then focus -review at 48–72 hours with results and make one of five decisions: stop, switch IV to oral, change (narrow or alter based on cultures), continue (document next review), or outpatient parenteral therapy (OPAT).
• IV-to-oral switch criteria (e.g. "IVOS") -clinically improving, temperature settled for 24–48 hours, able to swallow and absorb, no condition needing high tissue levels (endocarditis, meningitis, osteomyelitis, deep abscess -specialist), a suitable oral option.
• Shortest effective duration -e.g. uncomplicated cystitis 3 days (women), community-acquired pneumonia 5 days for most (NICE), cellulitis 5–7 days.
• Choose narrow-spectrum agents where possible; avoid "4C" antibiotics (clindamycin, cephalosporins, co-amoxiclav, ciprofloxacin/quinolones) when alternatives exist (C. difficile risk).
• Dose correctly -kidney function, weight, severity; therapeutic drug monitoring for aminoglycosides and glycopeptides.
• Delayed (back-up) prescriptions in primary care for self-limiting infections (sore throat, otitis media, sinusitis).
• Fluoroquinolone restrictions (MHRA) -only when other antibiotics are inappropriate (tendon damage, aortic aneurysm, neuropathy, psychiatric effects).

High-risk Drugs at a Glance

Drug	Key safety point	Antidote or reversal
Warfarin	INR 2.5 for most; many interactions	Vitamin K; PCC for major bleeding
Dabigatran	Renally cleared	Idarucizumab
Apixaban, rivaroxaban	Dose by age, weight, CrCl	Andexanet alfa (restricted) or PCC
Unfractionated heparin	APTT monitoring; HIT	Protamine
Insulin	"Units" in full; never omit basal in type 1	Glucose; glucagon
Opioids	Laxatives; breakthrough one-sixth to one-tenth of 24-hour dose	Naloxone
Benzodiazepines	Respiratory depression with opioids	Flumazenil (rarely -seizure risk)
IV potassium	Pre-mixed bags; max 10 mmol/hour peripherally	-
Gentamicin	Level 6–14 hours; nephro- and ototoxic	-
Vancomycin	Trough or AUC; infusion reaction -slow rate	-
Digoxin	Toxicity with low potassium; level at 6 hours	DigiFab
Lithium	Level at 12 hours; NSAIDs, ACE inhibitors, thiazides raise it	Fluids; haemodialysis
Methotrexate	Weekly only	Folinic acid
IV fluids	25–30 mL/kg/day; 1 mmol/kg Na and K; review daily	-

Spot the Diagnosis

Clue	Answer
INR 6.5, no bleeding	Withhold 1–2 doses, reduce maintenance
INR 9, nosebleed	Stop warfarin; IV vitamin K 1–3 mg
Intracranial haemorrhage on warfarin	IV vitamin K 5 mg plus PCC
Major bleeding on dabigatran	Idarucizumab
Platelets fall from 250 to 90 on day 7 of enoxaparin with a new DVT	HIT -stop heparin, argatroban
DKA in a type 1 patient whose insulin was stopped because "nil by mouth"	Basal insulin must never be omitted
Glucose 2.8 in a drowsy patient who can't swallow	IV 10% or 20% glucose, or IM glucagon
Recurrent hypoglycaemia overnight after a gliclazide overdose	Prolonged sulphonylurea hypoglycaemia -admit, glucose infusion
Myoclonus and drowsiness on morphine with eGFR 18	Metabolite accumulation -switch opioid
Pain crisis after 400 micrograms naloxone in a palliative patient	Naloxone reversed analgesia -titrate small doses
Arrhythmia during rapid IV potassium	Exceeded safe infusion rate
Potassium won't correct despite IV replacement	Check and replace magnesium
Hearing loss and dizziness after a week of gentamicin with furosemide	Aminoglycoside ototoxicity
Flushing and itching during a fast vancomycin infusion	Infusion reaction -slow rate
Yellow vision and nausea on digoxin with potassium 2.9	Digoxin toxicity
Coarse tremor and diarrhoea on lithium after starting ibuprofen	Lithium toxicity
Ataxia and nystagmus on phenytoin with albumin 22	Phenytoin toxicity -high free fraction
Theophylline toxicity after starting ciprofloxacin	Enzyme inhibition
Sodium 124 after 3 days of IV 5% glucose only	Iatrogenic hyponatraemia
Drowsy COPD patient on 15 L/min oxygen with PaCO2 9.5 kPa	Oxygen-induced hypercapnia -target 88–92%
Antibiotics still IV on day 5 in a patient eating, afebrile and improving	Should switch to oral

Exam-style Scenarios

1. A 70-year-old man on warfarin for AF attends with haematuria. INR is 7.2. He is otherwise well, BP 140/80, Hb stable.
Answer: Raised INR (5–8) with minor bleeding.

• Stop warfarin; give IV vitamin K 1–3 mg (BNF); recheck INR the next day.
• Restart warfarin when INR is under 5; look for the cause (new antibiotic, illness, dose error, alcohol).
• Investigate haematuria once stable (bleeding on anticoagulation can unmask bladder or kidney pathology).

2. A 68 kg 56-year-old woman with type 2 diabetes on basal insulin is nil by mouth for 2 days after bowel surgery. Her glucose is 15 mmol/L.
Answer: Variable-rate IV insulin infusion with maintenance fluids.

• Continue her long-acting basal insulin (often at about 80% of the usual dose); start a VRIII per local protocol with hourly capillary glucose.
• Substrate fluid -e.g. 0.45% sodium chloride with 5% glucose and potassium (by U&E) at a rate based on her maintenance needs (about 25–30 mL/kg/day -around 1.7–2 L/day).
• Monitor U&E daily; stop the VRIII 30–60 minutes after a subcutaneous rapid-acting dose with her first meal.

3. A 63-year-old man with lung cancer is taking oral morphine immediate-release 10 mg 4-hourly (6 doses a day) and needs about 3 extra doses of 10 mg daily for pain. He wants fewer tablets.
Answer: Convert to modified-release morphine with breakthrough doses.

• Total 24-hour dose = 60 + 30 = 90 mg → MR morphine 45 mg twice daily.
• Breakthrough -one-sixth to one-tenth of 90 mg = 10–15 mg immediate-release as needed.
• Continue regular laxatives; review in 24–48 hours; consider adjuvants for neuropathic or bone pain; CD prescription rules on discharge.

4. A 75-year-old woman on lithium for 20 years is admitted with diarrhoea and vomiting for 3 days. She is confused with a coarse tremor and ataxia. Creatinine 210 (baseline 110). Lithium level 2.4 mmol/L. She takes ramipril and bendroflumethiazide.
Answer: Lithium toxicity precipitated by dehydration, AKI and interacting drugs.

• Stop lithium, ramipril and bendroflumethiazide; IV fluids (0.9% sodium chloride); monitor lithium levels, U&E and ECG.
• Discuss with toxicology (TOXBASE) and renal -haemodialysis for severe toxicity (neurological features, high levels, kidney impairment).
• Psychiatry review before restarting (possibly at a lower dose or an alternative); sick day rules education.

5. A 48-year-old man with pneumonia has been on IV co-amoxiclav and clarithromycin for 3 days. He is now afebrile, eating, HR 82, CRP falling. Blood cultures are negative.
Answer: Antibiotic review at 48–72 hours -IV-to-oral switch.

• Switch to oral antibiotics per local guidance (e.g. amoxicillin ± clarithromycin, or as sensitivities); stop clarithromycin if atypical cover is no longer needed.
• Set a total duration (usually 5 days for most community-acquired pneumonia if improving).
• Check interactions (clarithromycin with statins, warfarin, QT drugs) and document the plan.

Key Points

• High-risk drugs -anticoagulants, insulin, opioids, IV potassium, antibiotics, narrow therapeutic index drugs, methotrexate, IV fluids.
• Warfarin -INR 2.5 for most; vitamin K for high INR; PCC plus IV vitamin K 5 mg for major bleeding.
• DOACs -dose by age, weight and CrCl; idarucizumab reverses dabigatran.
• HIT -platelets fall by half at 5–10 days with thrombosis -stop all heparin.
• Insulin -"units" in full; brand and device; never omit basal insulin in type 1; VRIII needs substrate fluid and basal insulin.
• Hypoglycaemia -15–20 g fast carbohydrate; IV glucose or IM glucagon if unable to swallow.
• Opioids -start low, breakthrough one-sixth to one-tenth of the 24-hour dose, always prescribe a laxative.
• IV potassium -pre-mixed bags, no faster than 10 mmol/hour peripherally; correct magnesium.
• Lithium level 12 hours post-dose; digoxin at least 6 hours; gentamicin once-daily 6–14 hours (nomogram); vancomycin trough before the 4th dose.
• Toxicity triggers -digoxin with low potassium; lithium with dehydration, NSAIDs, ACE inhibitors, thiazides; phenytoin with low albumin.
• IV fluids -25–30 mL/kg/day water, 1 mmol/kg/day sodium and potassium, 50–100 g glucose; 500 mL boluses for resuscitation; reassess.
• Avoid hypotonic maintenance fluids in children.
• Oxygen -prescribe a target: 94–98% for most, 88–92% if at risk of hypercapnia.
• Antibiotics -cultures first, local guidelines, indication and review date; review at 48–72 hours; switch IV to oral.

Guidelines and Further Reading

• BNF: Anticoagulants (management of high INR); Opioid analgesics; Fluids and electrolytes
• British Society for Haematology: Guidelines on oral anticoagulation and HIT
• Joint British Diabetes Societies for Inpatient Care: Hypoglycaemia; VRIII; Perioperative diabetes
• NICE CG140: Palliative care for adults -strong opioids; Faculty of Pain Medicine: Opioids Aware
• NICE CG185: Bipolar disorder (lithium monitoring)
• NICE CG174: Intravenous fluid therapy in adults in hospital; NICE NG29: IV fluid therapy in children
• British Thoracic Society: Guideline for oxygen use in adults in healthcare and emergency settings
• UKHSA: Start Smart -Then Focus antimicrobial stewardship toolkit
• NHS Improvement / NPSA: Safer use of insulin; potassium chloride concentrate alerts
• BNF -for current doses