Clinical Pharmacology and Prescribing in Special Situations

Renal Impairment

•    Avoid nephrotoxic drugs:

o    NSAIDs: ↓ renal perfusion

o    Aminoglycosides: ATN risk

o    Lithium: narrow therapeutic index

o    Metformin: risk of lactic acidosis if eGFR <30 mL/min

•    Dose adjustment required for renally-excreted drugs:

o    Low molecular weight heparin (LMWH)

o    Digoxin

o    Antibiotics: aminoglycosides, vancomycin, penicillins

Hepatic Impairment

•    Avoid or reduce dose of hepatotoxic drugs:

o    Paracetamol: increased risk of hepatotoxicity

o    Statins, methotrexate, valproate

•    Altered metabolism:

o    ↓ cytochrome P450 function → drug accumulation

o    ↑ risk with benzodiazepines, opioids, warfarin

•    Monitor INR, albumin, bilirubin, and signs of encephalopathy

Pregnancy

•    Avoid known teratogens:

o    ACE inhibitors: renal agenesis

o    Warfarin: fetal warfarin syndrome

o    Valproate: neural tube defects

•    Safe alternatives:

o    Hypertension: labetalol, nifedipine, methyldopa

o    Diabetes: insulin preferred over oral hypoglycaemics

o    Thyroid disease: propylthiouracil (1st trimester), carbimazole (2nd–3rd)

•    Use Pregnancy Risk Categories and local guidelines

Breastfeeding

•    Generally safe:

o    Paracetamol, penicillins, cephalosporins, heparins

o    Most vaccines (except yellow fever)

•    Avoid:

o    Amiodarone: thyroid dysfunction

o    Lithium: toxicity

o    Tetracyclines: teeth discolouration

o    Chloramphenicol: “grey baby” syndrome

Elderly Patients

•    Polypharmacy → ↑ risk of adverse drug reactions (ADRs), falls, hospitalisation

•    Pharmacokinetic changes:

o    ↓ renal function (check eGFR)

o    ↓ hepatic metabolism

o    ↓ albumin → ↑ free drug concentration (e.g. phenytoin, warfarin)

•    Start low, go slow: careful dose titration

QT Prolongation

•    Common culprits:

o    Antibiotics: macrolides (e.g. erythromycin), quinolones

o    Antipsychotics: haloperidol, risperidone

o    Antidepressants: TCAs, SSRIs (e.g. citalopram)

o    Antiarrhythmics: amiodarone, sotalol

•    Risk: torsades de pointes → syncope, sudden death

•    Check QTc on ECG if high-risk meds are prescribed

•    Avoid combinations of QT-prolonging drugs

Principles of Safe Prescribing

•    Always check:

o    Allergies

o    Renal and hepatic function

o    Drug interactions

o    BNF/local guidelines

o    Dose, route, and timing

•    Use electronic prescribing systems and decision support tools

•    Monitor therapeutic drug levels: e.g. lithium, digoxin, phenytoin

Principles of drug metabolism and interactions

Clinical pharmacology and prescribing in special situations

System-based theraputics and core drug classes

Drug side effects and adverse reactions

Troxicology and drug overdose