Generic Name

Hydrochlorothiazide

Mechanism

• Hydrochlorothiazide is a *thiazide‑type diuretic* that blocks the sodium‑chloride co‑transporter (Na⁺/Cl⁻ cotransporter) in the distal convoluted tubule, promoting natriuresis, kaliuresis, and diuresis.
• Lisinopril is an *angiotensin‑converting enzyme (ACE) inhibitor* that prevents conversion of angiotensin I to angiotensin II, resulting in vasodilation, decreased aldosterone secretion, and reduced systemic vascular resistance.
• When combined, the diuretic–ACE‑inhibitor regimen reduces preload and afterload, augments sodium loss, and enhances renal perfusion, yielding superior antihypertensive efficacy and improved cardiac output.

Pharmacokinetics

• Hydrochlorothiazide
• *Absorption*: >80 % oral, peak plasma 1–2 h.
• *Distribution*: Vd ≈ 0.3 L/kg; highly protein‑bound (~90 %).
• *Metabolism*: Minimal; excreted unchanged in urine.
• *Half‑life*: 6–10 h (extended to ~13 h in combination therapy).
• Lisinopril
• *Absorption*: ~25 % oral, peak 2–3 h.
• *Distribution*: Vd ≈ 0.3 L/kg; no significant protein binding.
• *Metabolism*: Non‑enzymatic; mostly unchanged.
• *Half‑life*: 12–13 h (renal clearance predominant).
• *Drug‑Drug Interaction*: No CYP450 induction/inhibition; primarily additive pharmacodynamic interaction.

Indications

• Hypertension (primary or secondary).
• Heart failure (NYHA Class II–III) – reduced cardiac remodeling.
• Angioedema prophylaxis (initially).
• Edema (tertiary indication in diuretic‑responsive patients).
• Early stage diabetic nephropathy (ACE‑inhibitor benefit).
• *Combination* enhances control in patients requiring dual pathway blockade.

Contraindications

• Contraindications
• Severe renal impairment or oliguria (elevated BUN/Cr > 30 mg/dL).
• Hyperkalemia > 5.5 mmol/L.
• Known hypersensitivity to thiazide diuretics or ACE‑inhibitors.
• Pregnancy (category D) – teratogenicity.
• Warnings
• *Hypotension* (especially postural).
• *Electrolyte imbalance* (hypokalemia, hyponatremia).
• *ACE‑inhibitor flare* (e.g., cough, angioedema).
• *Renal function decline* after initiation.
• Monitor for *hyperglycemia* in diabetics.

Dosing

• Hydrochlorothiazide
• Start 12.5–25 mg PO qd; titrate to 50–100 mg qd.
• Typically taken in the morning to avoid nocturia.
• Lisinopril
• Start 2.5–5 mg PO qd; titrate 5–10 mg qd to 20 mg qd.
• Optimal dosing: 10–20 mg qd for hypertension.
• Combined regimen
• Administer together in the morning; allow >30 min between doses if required.
• Adjust based on office BP, serum electrolytes, and renal function.

Adverse Effects

• Common
• Electrolyte disturbances: hypokalemia, hyponatremia (≤5 %)
• GI upset (nausea, diarrhea)
• Heat‑related symptoms (heat‑stroke, dehydration)
• ACE‑inhibitor cough (≈10–15 %)
• Serious
• Angioedema (±0.2 %)
• Renal failure (especially in volume‑depleted patients)
• Hyperkalemia (≥ 5.5 mmol/L) – rare but severe
• Hypotension (postural syncope)
• Nephrotic syndrome (rare)

Monitoring

Clinical Pearls

• Synergistic titration: The diuretic reduces volume, making ACE‑inhibitor more effective; titrate after 2–3 days to avoid precipitous hypotension.
• Post‑prandial administration: Giving hydrochlorothiazide after meals may reduce GI irritation.
• Potassium‑oriented patients: Pair with a potassium‑sparing agent (e.g., spironolactone) if hypokalemia persists.
• Renal risk in heart failure: Start low dose; monitor creatinine and potassium closely; consider adjunctive loop diuretic if ascites/pleural effusion.
• Pregnancy: Both drugs are contraindicated from conception to term; switch to hydralazine or labetalol in pregnancy‑induced hypertension.
• First‑time users: Inform patients that an ACE‑inhibitor cough may lessen over time; if persists, switch to ARB.
• Office BP check: Diuretics can attenuate the winter dip—measure BP in the morning, before water intake.

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• *This drug card presents a sharp, data‑driven snapshot for clinicians and students, integrating pharmacologic nuances, dosing precision, and key monitoring checkpoints to maximize therapeutic safety and efficacy.*