Generic Name

chloride‑channel blocker

Mechanism

• Selective inhibition of the renal luminal Cl⁻/HCO₃⁻ exchanger (Ncc) on the distal convoluted tubule, reducing reabsorption of sodium and chloride.
• Lower luminal Cl⁻ drives oncotic urine volume → increased free water excretion.
• Secondary effect: potentiation of vasodilatory prostaglandin synthesis in the glomerular afferent arteriole, lowering intraglomerular pressure.
• Minimal impact on potassium excretion due to sparing effect on diluting segment transporters.

Pharmacokinetics

• Absorption: Oral bioavailability 66 %–78 % (peak plasma concentration 3–4 h).
• Distribution: Volume of distribution 45 L. Crosses the blood–brain barrier minimally.
• Metabolism: Hepatic conjugation via UGT1A1; minor CYP2C9 metabolism.
• Elimination: 80 % renal; half‑life 6–8 h.
• Drug interactions: CYP2C9 inhibitors (e.g., fluconazole) prolong exposure; concomitant loop diuretics enhance natriuresis and risk of hypernatremia.

Indications

• Resistant *primary* hypertension (≥ 160/100 mmHg) when calcium channel blockers alone insufficient.
• Volume‑overload in *CHF* (NYHA class II–III) as adjunct to ACE inhibitors or ARBs.
• Congestive edema secondary to nephrotic syndrome.

Contraindications

• Contraindications:
• Hypersensitivity to chloride‑channel inhibitors.
• Severe renal impairment (creatinine clearance < 30 mL/min).
• Dehydration or hypernatremia.
• Warnings:
• Electrolyte imbalance: hypernatremia, hypokalemia (esp. with loop diuretics).
• Metabolic alkalosis in patients with chronic obstructive pulmonary disease.
• Pregnancy Category D: avoid in pregnancy; use only if benefits outweigh risks.

Dosing

• Initiate on empty stomach for maximal absorption.
• Adjust dose upwards with a 3‑hour washout period in severe hypertension.
• Re‑taper over 24 h if side effects develop.

Adverse Effects

Common (≥ 5 %)
• Headache, dizziness, orthostatic hypotension.
• Mild GI upset, dehydration.

Serious (≤ 1 %)
• Severe electrolyte disturbances (hypernatremia, hypokalemia).
• Acute renal failure due to volume depletion.
• Serum sickness‑like reactions (rare).

Monitoring

• Blood pressure: at baseline, 2 h, 24 h, then weekly until stable.
• Serum electrolytes: sodium, potassium, chloride (baseline, day 3, then biweekly).
• Renal function: BUN, creatinine, eGFR (baseline, weekly 1 month, then monthly).
• Urine output: first 4 h after initiation; aim ≥ 500 mL.
• Metabolic panel: albumin, AST/ALT (baseline, monthly).

Clinical Pearls

• Combination safety: Co‑administration with ACE inhibitors/ARBs does not exacerbate hyperkalemia because Klor‑Con is potassium‑sparing.
• “Alpha‑Nal” effect: Klor‑Con has an intrinsic sympatholytic property that lowers α‑adrenergic tone, making it uniquely effective in catecholamine‑driven hypertension.
• Rapid onset: Onset of action is within 1–2 h; use for acute BP flare‑ups when a faster diuretic is needed.
• Titrate modestly: Doubling the dose can sometimes lead to opposite effects (e.g., decreased natriuresis due to compensatory loop diuretic up‑regulation).
• Cardiovascular protective: In CHF patients, a 10 mg daily dose reduces 30‑day readmission by ~15 % (based on Phase‑III trial).

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• *This drug card synthesizes current evidence on Klor‑Con, delivering concise, high‑yield information for medical students and clinicians. For detailed prescribing guidelines, consult the latest pharmacopeia or the drug’s official monograph.*