Hydrochlorothiazide and triamterene
Hydrochlorothiazide
Generic Name
Hydrochlorothiazide
Mechanism
- Hydrochlorothiazide (HCTZ) is a thiazide diuretic that blocks the sodium–chloride co‑transporter (Na⁺/Cl⁻) in the distal convoluted tubule (DCT), reducing Na⁺, Cl⁻, and water reabsorption and increasing urinary output.
- Triamterene is a potassium‑sparing diuretic that competitively inhibits the Na⁺/K⁺/2Cl⁻ co‑transporter in the collecting duct, diminishing Na⁺ reabsorption while sparing K⁺.
- The combination delivers sustained diuresis with a lower risk of hypokalemia compared to HCTZ alone, making it ideal for managing hypertension and edema.
Pharmacokinetics
| Parameter | Hydrochlorothiazide | Triamterene | Combination (generic ratio 2:1) |
| Absorption | 77–87 % GI; peak 2–4 h | 56–77 % GI; peak 1–3 h | Similar to components |
| Distribution | Vd ≈ 0.8 L/kg | Vd ≈ 0.7 L/kg | Same |
| Metabolism | Minimal hepatic | Minimal hepatic | Same |
| Elimination | Renal (≈ 70 % unchanged) | Renal (≈ 70 % unchanged) | 70 % unchanged |
| Half‑life | 6–10 h | 4–8 h | 6–8 h |
| Food effect | ↓Absorption (≈ 30 %) | ↓Absorption (≈ 20 %) | Same |
• Renal function limits the clearance of both agents; dose adjustment is required with CrCl < 30 mL/min.
Indications
- Hypertension – first‑line combination diuretic therapy.
- Congestive heart failure (HF) – adjunct to ACEi/ARB and β‑blocker to control fluid overload.
- Edema related to liver cirrhosis, nephrotic syndrome, or renal disease.
- Low‑dose dual therapy may be used in patients who are intolerant to higher‑dose monotherapy.
Contraindications
- Severe renal or hepatic impairment (serum creatinine >2.5 mg/dL).
- Hyperkalemia or a history of serious electrolyte disturbances.
- Sulfonamide allergy (HCTZ carries a sulfa core).
- Gout – monitor uric acid; HCTZ can precipitate attacks.
- Female pregnancy – avoid in pregnancy; use with caution in lactation.
- Use of potassium‑sparing diuretics or potassium supplements – increases hyperkalemia risk.
Dosing
| Age/Weight | HCTZ (mg) | Triamterene (mg) | Frequency | Notes |
| Adult | 12.5–25 | 80–160 | Once daily (preferably morning) | Start low, titrate to target BP. |
| Pediatric (≥12 yrs) | 25–75 | 160–320 | Once daily | Weight‑based dosing. |
| Geriatric | 12.5–25 | 80–160 | Once daily | Lower starting dose due to decreased renal function. |
• Form: oral tablets; chewable formulations are unavailable.
• Take with food to reduce GI irritation.
Adverse Effects
| Category | Example Agents | Incidence | Comments |
| Electrolyte | Hypokalemia, hyponatremia | 4–8 % | Mitigated by triamterene; monitor K⁺. |
| Metabolic | Hyperuricemia, hyperlipidemia | 2–5 % | Baseline uric acid check; treat gout if needed. |
| Renal | Crystal nephropathy, renal impairment | <1 % | Avoid in CrCl <30 mL/min; consider alternative diuretics. |
| Skin | Rash, photosensitivity | 1–3 % | Counsel sun protection. |
| Ophthalmologic | Visual disturbances (blurry vision) | <1 % | Use caution in high doses or long‑term therapy. |
| Serious | Hyperkalemia, seizures, anaphylaxis | <0.05 % | Monitor K⁺, educate on signs of hyperkalemia. |
Monitoring
- Baseline: Serum electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻), BUN/Creatinine, fasting blood glucose, fasting lipids, uric acid, eye exam if prolonged therapy.
- Follow‑up (1–2 weeks): Repeat electrolytes and renal panel.
- Long‑term: Blood pressure, weight, electrolytes q 3–6 months, uric acid q 6 months, and visual acuity if >12 months of therapy.
- Special: In patients with diabetes, monitor glucose and adjust insulin if needed.
Clinical Pearls
- Hypokalemia Mitigation – The addition of Triamterene allows use of lower HCTZ doses, reducing the risk of hypokalemia seen with high‑dose thiazides.
- Gout‑Prone Patients – Baseline uric acid should be checked; if hyperuricemic, consider substituting HCTZ with a loop diuretic or adding allopurinol.
- Renal Consideration – In patients with CrCl 30–60 mL/min, use the *12.5/80 mg* dosage and re‑evaluate renal function at 4 weeks.
- Sulfa Allergy – Never prescribe Hydrochlorothiazide to patients with sulfonamide hypersensitivity; alternative thiazide‑like agents (e.g., chlortalidone) are safer.
- Pregnancy – The combination is Category B; however, the risk of dehydration and electrolyte disturbance make it best avoided.
- Combination with Spironolactone – Co‑administration can lead to significant hyperkalemia; monitor electrolytes frequently.
- Long‑Term Therapy >1 yr – Periodic eye exams are recommended due to the risk of transient visual changes.
- Drug Interactions – Non‑steroidal anti‑inflammatory drugs (NSAIDs) may blunt diuretic efficacy; consider dose adjustment.
- Patient Education – Emphasize oral hydration, monitor for signs of electrolyte imbalance (muscle cramps, palpitations), and adherence to dosing schedule.
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