Vitamin D
Vitamin D
Generic Name
Vitamin D
Mechanism
Vitamin D metabolism culminates in the hormonally active 1,25‑dihydroxyvitamin D₃ (calcitriol), which:
• Binds the intracellular vitamin D receptor (VDR) forming a heterodimer with RXR.
• Regulates transcription of target genes through vitamin D response elements (VDREs).
• Enhances intestinal synthesis of calbindin → ↑ calcium and phosphate absorption.
• Suppresses parathyroid hormone (PTH) secretion (negative feedback).
• Modulates immune cells (T‑cell differentiation, dendritic cell maturation) and inhibits proliferation of malignant cells.
Pharmacokinetics
- Absorption: Intestinal uptake requires dietary fat; facilitated by micelles.
- Distribution: Lipid‑soluble; stored in adipose tissue and liver.
- Metabolism:
- *24‑hydroxycholesterol* → 25‑hydroxyvitamin D₃ (25(OH)D₃) in liver (primary circulating form).
- Kidney 1α‑hydroxylase → 1,25‑dihydroxyvitamin D₃ (calcitriol).
- Half‑life: 25(OH)D₃ ≈ 15–20 days; active 1,25(OH)₂D₃ ≈ 4–6 hours.
- Excretion: Renal → excretion in urine as calcitroic acid.
Indications
Vitamin D is indicated for:
• Deficiency (25(OH)D < 20 ng/mL).
• Rickets and osteomalacia in children/adults.
• Osteoporosis prevention (daily supplementation).
• Hypocalcemia secondary to hypoparathyroidism or vitamin D deficiency.
• Maintenance in chronic kidney disease (CKD) stages 2‑4, adjusting for impaired hydroxylation.
• Immune‑mediated disorders (MS, lupus) as adjunctive therapy.
Contraindications
- Hypervitaminosis D (serum Ca²⁺ > 10.5 mg/dL).
- Hypercalcemia or hypercalciuria.
- Granulomatous diseases (sarcoidosis, TB) → risk of excess calcitriol production.
- Severe CKD (stage 5) without dialysis: monitor closely; possible calcitriol therapy may be necessary.
- History of nephrolithiasis – evaluate risk before high‑dose therapy.
Dosing
| Form | Dose | Indication | Frequency | Notes |
| Ergocalciferol (D₂, oral) | 1,000–2,000 IU/day | Mild‑moderate deficiency | Daily | Less potent, shorter half‑life. |
| Cholecalciferol (D₃, oral) | 1,000–2,000 IU/day | Mild‑moderate deficiency | Daily | Preferred due to higher potency. |
| High‑dose therapy | 50,000 IU weekly or 10,000 IU daily | Severe deficiency | Once weekly or daily | Use for rapid repletion; monitor 25(OH)D levels. |
| Calcifediol (25‑OH‑D₃) | 0.25–0.5 µg/kg/day | CKD stages 2‑4 | Daily | Bypasses hepatic conversion. |
| Calcitriol (1,25‑OH₂‑D₃) | 0.25–2 µg/day | CKD stages 5, hypoparathyroidism | Daily | Potent; careful with calcium. |
| Intramuscular (D₂) | 10 000–50 000 IU | Poor oral absorption | Monthly | Rarely used. |
| Liquid (D₂/D₃) | 1,000 IU/day | Pediatric, malabsorption | Daily | No swallowing issues. |
Administration Tips:
• Take with a meal containing fat for optimal absorption.
• Measure 25(OH)D first; target > 30 ng/mL (≥ 75 nmol/L).
Adverse Effects
Common:
• Nausea, vomiting, constipation.
• Hypercalcemia → fatigue, muscle weakness.
Serious:
• Severe hypercalcemia → nephrolithiasis, arrhythmias (QT prolongation), encephalopathy.
• Renal dysfunction or failure in predisposed individuals.
• Vit-D‑induced hypercalcemia in granulomatous disease or with high calcitriol doses.
Monitoring
- Baseline & follow‑up 25(OH)D: measure every 3–6 months during repletion.
- Serum calcium & phosphate: monitor 2–4 weeks after dose escalation.
- Renal function (CrCl/ eGFR): baseline and every 3–6 months.
- PTH: useful in CKD / osteoporosis management.
- Urinary calcium excretion (24‑h) in patients with hypercalcemia risk.
Clinical Pearls
- Sun is the best source: 10–30 min of midday sun (30% skin) yields ~1,000–2,000 IU/day; adjust for pigmentation, age, and latitude.
- D₂ vs. D₃? D₃ is more potent and longer lasting; use when repleting severe deficiency.
- Half‑life matters: 25(OH)D can remain elevated for months; avoid overtreating.
- Vitamin D + calcium synergy: co‑administration enhances bone health; aim for 800–1,200 IU/day of vitamin D with 1,000–1,200 mg/day of elemental calcium.
- Pediatric note: 400 IU/day is sufficient for infants; higher doses for at‑risk populations (prematurity, malabsorption).
- Pregnancy: 600 IU/day recommended; monitor serum 25(OH)D to avoid deficiency‐related complications.
- Screening thresholds: Use ≥ 20 ng/mL as deficiency, 20–30 ng/mL as insufficiency, and > 30 ng/mL as adequate for most adults.
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• *This drug card is a quick reference for medical students and clinicians. Verify dosing and monitoring in the context of individual patient factors and current guidelines.*