💊 Drug Dosing in Special Populations

 By Dr. Sk Sabir Rahaman, MBBS, MD (Pharmacology), DFM(Family Medicine), FCFM, CCEBDM, CCLSD

🧾 Core Definitions

• Dose
  👉 The quantity of a drug taken at one time.

  • Example: Aspirin

    • Analgesic/antipyretic: 300–600 mg every 4–6 h (max ~1 g per dose)

    • Anti-inflammatory (RA): 3–5 g/day in divided doses

    • Antiplatelet: 75–150 mg once daily

• Dosage
  👉 The complete regimen = drug + form + route + dose + interval + duration.

  • Example: Ciprofloxacin

    • 500 mg tablet, oral, every 12 h after food × 10 days

    • Each dose = 500 mg

    • Total daily = 1000 mg

    • Course = 10 days

📌 Key Point: Dose = “how much at once,” dosage = “the entire schedule.”

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👶 Pediatric Prescribing

(Children are not “small adults”)

Step 1 — Pharmacokinetics in Children

• Absorption:

  • Slow gastric emptying → delayed oral absorption.

  • ↑ Skin permeability → risk of toxicity from topicals.

  • Rectal absorption variable → unpredictable.

• Distribution:

  • ↑ Total body water → hydrophilic drugs (aminoglycosides) → larger Vd → need higher mg/kg.

  • ↓ Plasma proteins → ↑ free fraction of highly protein-bound drugs (phenytoin, sulfonamides).

• Blood–Brain Barrier: More permeable → ↑ risk of CNS toxicity.

  • Eg: Sulfonamides → displace bilirubin → kernicterus.

• Metabolism:

  • Immature at birth → poor drug clearance (chloramphenicol → gray baby).

  • 1–9 years → hyperactive enzymes → some drugs cleared faster (e.g., theophylline, phenytoin).

• Excretion:

  • GFR low at birth → slower clearance of renally excreted drugs (aminoglycosides, digoxin).

  • Matures by 6–12 months.

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Step 2 — Child-Friendly Dosage Forms

• Use liquids, dispersible tablets, inhalers with spacers.

• For seizures → rectal diazepam if IV not available.

• Avoid painful IM injections; be cautious with topical formulations.

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Step 3 — Dose Adjustments

• Use mg/kg or mg/m² (esp. in oncology, narrow TI drugs).

• Some drugs need higher mg/kg in children due to rapid clearance:

  • Digoxin: Adults 3–5 μg/kg/day vs. children 8–12 μg/kg/day.

  • Phenytoin, theophylline → higher clearance in kids.

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Step 4 — Avoid High-Risk Drugs

• Aspirin → Reye’s syndrome.

• Tetracyclines (<8 yrs) → teeth staining, bone growth defects.

• Fluoroquinolones → arthropathy.

• Aminoglycosides → ototoxicity/nephrotoxicity.

• Chloramphenicol → gray baby syndrome.

• Valproate (<3 yrs) → hepatotoxicity.

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👵 Geriatric Prescribing

Step 1 — General Rule

“Start low, go slow – but go.”

Step 2 — Pharmacokinetics in Elderly

• Absorption: Slightly delayed; ↓ first-pass metabolism (↑ bioavailability of propranolol, nitrates).

• Distribution:

  • ↑ Fat → lipophilic drugs (diazepam, amiodarone) last longer.

  • ↓ Water & albumin → ↑ free fraction of drugs like digoxin, warfarin.

• Metabolism:

  • ↓ Hepatic clearance (esp. Phase I CYP450 metabolism).

  • Phase II (conjugation) relatively preserved.

• Excretion:

  • CrCl falls ~1%/year after 40.

  • Use Cockcroft–Gault formula (serum creatinine alone is misleading).

Step 3 — Class-Specific Changes

• ↓ β-receptor sensitivity → weaker response to β-agonists/β-blockers.

• ↑ Sensitivity to:

  • Anticoagulants (warfarin).

  • Digoxin.

  • CNS depressants (benzodiazepines, opioids).

Step 4 — Safer Choices

• Avoid barbiturates; if BZD needed, use LOT drugs: Lorazepam, Oxazepam, Temazepam (no Phase I metabolism).

• Avoid strong anticholinergics:

  • First-gen antihistamines, TCAs, atropine.

• Prefer simplified regimens, pill boxes, blister packs.

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🤰 Pregnancy

Step 1 — PK Changes in Pregnancy

• ↑ Vd (↑ plasma volume).

• ↓ Albumin → ↑ free drug fraction.

• ↑ GFR → faster elimination of renally cleared drugs.

• Altered hepatic enzymes → faster metabolism of some drugs.

Step 2 — Organogenesis (Day 18–55 / Weeks 3–8)

Highest teratogenic risk.

• Thalidomide → limb defects.

• Phenytoin, valproate → cleft lip, neural tube defects.

• Warfarin → bone/cartilage defects.

• Tetracyclines → teeth/bone defects.

• Methotrexate → abortion.

Step 3 — After 8 Weeks (Growth/Functional Defects)

• ACE inhibitors/ARBs → fetal renal failure.

• Androgens/progestins → virilization of female fetus.

• NSAIDs (late pregnancy) → premature ductus arteriosus closure.

• Lithium/antithyroid drugs → fetal goiter.

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🧪 Renal Dysfunction

Step 1 — Assess Function

• Estimate CrCl (Cockcroft–Gault) → adjust dose or interval.

Step 2 — Avoid/Adjust

• Avoid nephrotoxic & renally excreted drugs:

  • Aminoglycosides, digoxin, meperidine, nitrofurantoin.

Step 3 — Antimicrobials Requiring Adjustment

• Carbenicillin, cephalexin, cefotaxime, ethambutol, fluoroquinolones, acyclovir, metronidazole.

Step 4 — Diuretics

• Loop diuretics (furosemide) effective even at low GFR.

• Thiazides ineffective <30 mL/min.

• K⁺-sparing → risk of hyperkalemia.

Step 5 — Other Considerations

• Use calcitriol instead of vitamin D.

• Treat anemia with erythropoietin.

• Avoid urinary antiseptics at low GFR.

• Use TDM (therapeutic drug monitoring) for narrow TI drugs (digoxin, aminoglycosides, vancomycin).

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✅ Quick Checklist

✔ Dose vs Dosage distinction
✔ Pediatric dosing: mg/kg, avoid unsafe drugs
✔ Elderly: “Start low, go slow,” use CrCl-based dosing
✔ Pregnancy: Avoid teratogens (especially 3–8 weeks)
✔ Renal impairment: Adjust by CrCl, avoid nephrotoxins, use TDM 

📌 Key Takeaway:
Drug dosing in special populations must consider altered pharmacokinetics, pharmacodynamics, and unique risks (developmental, functional, organ impairment). A personalized, cautious, and evidence-based approach ensures both safety and efficacy. 

📘 Prepared by Dr. Sk Sabir Rahaman

📍 Specialist Family Physician | Consultant Pharmacologist | Lifestyle & Diabetes Expert

📧 dr.sabir.rahaman@gmail.com 

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