7.4 Special Populations & Complex Care

7.4 Special Populations & Complex Care

Optimal pharmacotherapy requires tailored dosing and safety checks in vulnerable patient groups: pregnant and lactating women, paediatrics, patients with renal impairment, and frail elderly individuals experiencing polypharmacy.

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Prescribing in Pregnancy & Lactation

Physiological changes during pregnancy (increased intravascular volume, altered plasma protein binding, accelerated renal clearance) alter pharmacokinetics, while drug transfer across the placenta poses teratogenic risks.

High-Risk Teratogenic Drugs (Strictly Contraindicated)

Safe Therapeutic Alternatives in Pregnancy

• Hypertension: Labetalol, Methyldopa, or Modified-Release Nifedipine. (Avoid ACEi, ARBs, and Thiazides).
• Diabetes: Human Insulins (Isophane, Soluble) or Insulin Aspart/Lispro. (Metformin may be used, but insulin is gold standard).
• Anticoagulation: Low-Molecular-Weight Heparins (LMWH, e.g., Enoxaparin). LMWH does not cross the placenta.
• Analgesia: Paracetamol (first-line). NSAIDs should be avoided, particularly in the 3rd trimester (causes premature closure of ductus arteriosus and oligohydramnios).

Lactation Principles

Drug transfer into breast milk is minimized when drugs have high plasma protein binding (>90%), high molecular weight (>800 Da), low lipid solubility, and low Relative Infant Dose (RID <10%). Safe drugs in breastfeeding include Paracetamol, Ibuprofen, Sertraline, Amoxicillin, and Enoxaparin.

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Paediatric Prescribing Principles

Paediatric drug dosing must never be approximated from adult doses. Calculations must use exact body weight (mg/kg) or Body Surface Area (BSA in m²).

$\text{BSA (m}^2\text{)} = \sqrt{\frac{\text{Height (cm)} \times \text{Weight (kg)}}{3600}}$

Formulation Safety & High-Risk Excipients

                  PAEDIATRIC EXCIPIENT SAFETY WARNINGS
                  ====================================

   Benzyl Alcohol   ──> Causes fatal 'Gasping Syndrome' in neonates
                        (metabolic acidosis, CNS depression, respiratory failure).
   Propylene Glycol ──> Accumulates in infants <4 years -> hyperosmolality & seizures.
   Ethanol          ──> Risk of CNS depression and hypoglycemia.

Age-Specific Drug Contraindications

• Aspirin (<16 years): Strictly contraindicated due to risk of Reye's Syndrome (rare but fatal encephalopathy and acute fatty liver degeneration following viral illness).
• Tetracyclines (e.g., Doxycycline) (<8 years): Causes permanent enamel staining, dental hypoplasia, and binding to growing bone tissue.
• Ceftriaxone in Neonates: Contraindicated in neonates with hyperbilirubinaemia (displaces bilirubin from albumin, worsening kernicterus) or those receiving IV Calcium (forms fatal pulmonary/renal calcium-ceftriaxone precipitates).

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Renal Impairment & Dose Adjustments

Renal insufficiency leads to drug accumulation, prolonged half-life, and elevated toxicity.

Estimating Renal Function: CrCl vs. eGFR

For drug dosing adjustments (BNF/SmPC guidance), Creatinine Clearance (CrCl) calculated via the Cockcroft-Gault equation MUST be used (especially in elderly, low body weight, or high-risk drugs):

$\text{CrCl (mL/min)} = \frac{(140 - \text{Age}) \times \text{Weight (kg)} \times \text{Constant}}{\text{Serum Creatinine (}\mu\text{mol/L)}}$ (Constant = 1.23 for Males; 1.04 for Females)

Note: eGFR (CKD-EPI equation) is used for staging Chronic Kidney Disease, but underestimates impairment in elderly patients with low muscle mass.

Critical Renal Dose Adjustments

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Geriatric Polypharmacy & STOPP/START Criteria

Polypharmacy is defined as the concurrent use of >=5 regular medications (Hyperpolypharmacy >=10). It drives adverse drug reactions (ADRs), non-adherence, and prescribing cascades (treating an unrecognized ADR with a new drug).

STOPP/START Criteria (2023 Version 3 Update)

The STOPP/START tool provides an evidence-based framework for medication reviews in older adults.

• STOPP (Screening Tool of Older Persons' Prescriptions): Identifies potentially inappropriate medications (PIMs).
  • PPIs at max dose >8 weeks: Discontinue/step down (fracture and C. diff risk).
  • Benzodiazepines / Z-drugs: Avoid due to ataxia, confusion, falls, and fractures.
  • Tricyclic Antidepressants (TCAs): Avoid in dementia/cardiac disease (anticholinergic burden).
  • NSAIDs + ACEi + Diuretic: Avoid combination ('The Triple Whammy' causes severe Acute Kidney Injury).
• START (Screening Tool to Alert doctors to Right Treatment): Identifies prescribing omissions.
  • SGLT2i / ACEi in HFrEF: Initiate if omitted.
  • Statins in Established CVD: Initiate for secondary prevention.
  • Bone Protection: Initiate bisphosphonate + Calcium/Vit D for patients on systemic corticosteroids >3 months.