Dihydrotachysterol
**Dihydrotachysterol (DHT)** is a synthetic, fat-soluble **vitamin D analog** primarily utilized in veterinary medicine to manage hypocalcemia secondary to hypoparathyroidism or severe renal disease. While historically significant, its clinical use has largely been supplanted by **calcitriol** due to commercial availability issues and calcitriol's more favorable pharmacokinetic profile (faster onset and shorter duration of action, which makes managing accidental hypercalcemia easier). Key clinical points: * **Faster onset** than ergocalciferol (Vitamin D2), but slower than calcitriol. * **Bypasses renal activation**: Unlike cholecalciferol, DHT does not require the enzyme 1-alpha-hydroxylase in the kidneys to become active, making it effective in patients with severe renal failure. * **Toxicity risk**: Because its effects can take 1 to 3 weeks to dissipate, iatrogenic hypercalcemia is a significant risk and requires diligent monitoring.
Mecanismo: **Dihydrotachysterol** acts as a synthetic analog of 1,25-dihydroxyvitamin D. Its mechanism of action involves several key steps: * **Hepatic Activation**: DHT is absorbed from the GI tract and transported to the liver, where it undergoes hydroxylation by **hepatic 25-hydroxylase** → **25-hydroxydihydrotachysterol** (the active metabolite). * **Receptor Binding**: The active metabolite binds to **Vitamin D Receptors (VDR)** in target tissues (primarily intestine, bone, and kidneys). * **Calcium Homeostasis**: * **Intestine**: Stimulates the synthesis of calcium-binding proteins (e.g., calbindin) → significantly enhances dietary calcium and phosphorus absorption. * **Bone**: Works synergistically with parathyroid hormone (PTH) to promote the accretion and resorption of minerals, mobilizing calcium into the extracellular fluid. * **Kidneys**: Promotes the reabsorption of calcium by the renal tubules. > **Clinical Pearl**: Because the active form of DHT is structurally similar to 1,25-dihydroxyvitamin D, it effectively bypasses the need for **renal 1-alpha-hydroxylase**, an enzyme often deficient in chronic kidney disease.
Dosificación por especie
- Hypocalcemia secondary to hypoparathyroidism · Initially give 0.03 mg/kg PO for several days or until effect is demonstrated, then give 0.02 mg/kg for 2 days, then 0.01 mg/kg per day. · PO · q24h · Pet should remain hospitalized until serum calcium concentration remains stable between 8-9.5 mg/dL. Recheck serum calcium on a weekly basis during early stages of treatment; recheck every 2-3 months long-term. Some dogs and cats that appear to be resistant to treatment on tablets or capsules may respond to the liquid form.
- Chronic hypocalcemia with oral calcium tx · Initially: 0.02-0.03 mg/kg/day PO. Maintenance: 0.01-0.02 mg/kg PO q24-48h. · PO · q24-48h
- Hypocalcemia secondary to hypoparathyroidism · Initially give 0.03 mg/kg PO for several days or until effect is demonstrated, then give 0.02 mg/kg for 2 days, then 0.01 mg/kg per day. · PO · q24h · Pet should remain hospitalized until serum calcium concentration remains stable between 8-9.5 mg/dL. Recheck serum calcium on a weekly basis during early stages of treatment; recheck every 2-3 months long-term. Some dogs and cats that appear to be resistant to treatment on tablets or capsules may respond to the liquid form.
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Vías de administración
Contraindicaciones
- Pre-existing hypercalcemia
- Vitamin D toxicity
- Malabsorption syndromes
- Abnormal sensitivity to the effects of vitamin D
Efectos adversos
- Hypercalcemia (manifesting as polydipsia, polyuria, anorexia, vomiting, lethargy)
- Nephrocalcinosis (soft tissue mineralization)
- Hyperphosphatemia
Interacciones farmacológicas
- Calcium-containing phosphorus binding agents (e.g., calcium carbonate) · Use with vitamin D analogs may induce severe hypercalcemia.
- Corticosteroids · Can nullify the calcium-elevating effects of vitamin D analogs.
- Digoxin · Patients are highly sensitive to the arrhythmogenic effects of hypercalcemia; intensified monitoring is required.
- Verapamil · Patients are sensitive to the effects of hypercalcemia; intensified monitoring is required.
- Mineral oil · May reduce the amount of DHT absorbed from the GI tract.
- Sucralfate · May reduce the amount of DHT absorbed from the GI tract.
- Cholestyramine · May reduce the amount of DHT absorbed from the GI tract.
- Phenytoin · May induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs, thus decreasing their activity.
- Barbiturates · May induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs, thus decreasing their activity.
- Primidone · May induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs, thus decreasing their activity.
- Thiazide diuretics · May cause hypercalcemia when given in conjunction with Vitamin D analogs.
Monitoreo
- Serum calcium levels (closely/twice daily during initial treatment; at least 2-4 times yearly during maintenance)
- Serum phosphorus levels (particularly in renal failure patients)
- Calcium-phosphorus product (Ca x P)
Sobredosis
### Acute Toxicity Acute ingestions should be managed using established protocols for GI decontamination. **Orally administered mineral oil** may reduce absorption and enhance fecal elimination. ### Chronic Toxicity (Hypercalcemia) Hypercalcemia secondary to chronic dosing is a serious complication. 1. **Discontinue Therapy**: Immediately stop DHT and any exogenous calcium supplementation. 2. **Severe Hypercalcemia Management**: Administer **furosemide**, **calcium-free IV fluids** (e.g., 0.9% normal saline) to promote diuresis, urine acidification, and **corticosteroids** (which decrease intestinal calcium absorption and increase renal excretion). 3. **Monitoring**: Because of the long duration of action of DHT (usually one week and potentially up to 3 weeks), hypercalcemia may persist for an extended period. 4. **Re-initiation**: Restart DHT/calcium therapy at a reduced dosage with diligent monitoring only when serum calcium levels return to the normal range.
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