Valsartan | Pharmacology Mentor

Generic Name

Valsartan

Competitive antagonist of AT₁ receptors in vascular smooth muscle, myocardium, kidney, and adrenal gland ➜ blocks vasoconstriction, aldosterone secretion, and sympathetic activation induced by angiotensin II.
Improved NO-mediated vasodilation and reduced oxidative stress through downstream signaling inhibition.
Results in sustained vasodilation, reduced afterload and preload, and decreased sympathetic tone.

Parameter	Detail
Absorption	Rapid, ~90 % oral bioavailability (single‑dose). Peak plasma concentration at 2‑4 h (pH‑dependent; less in acidic milieu).
Distribution	Highly protein‑bound (≈90 %) mainly to albumin. Large volume of distribution (~140 L).
Metabolism	Minimal CYP-mediated metabolism; ~30 % hepatic glucuronidation (UGT).
Excretion	Renal (≈64 %) and biliary; half‑life 6–9 h. Dose adjustment required in severe renal impairment.
Drug Interactions	Potentiates K⁺‑retaining diuretics, ACE inhibitors, and NSAIDs → ↑ hyperkalemia, renal dysfunction. Metabolized by UGTs (low CYP interaction).

Hypertension: monotherapy or in combination with diuretics/ACE inhibitors.
Heart Failure: chronic therapy (≥2 weeks) post–MI or de novo in NYHA II–IV.
Left Ventricular Dysfunction: improves survival in post‑MI patients with reduced ejection fraction.
Secondary Prevention: reduction in mortality & hospitalizations in high‑risk cardiovascular patients (phase II/III trials).

Contraindications: hypersensitivity to valsartan or any ARB component; use with ACE inhibitors (or in same patients) => severe hyperkalemia, hypotension. Avoid pregnancy (category D).
Warnings:
Hypotension: caution after initiation or dose increase, especially in volume‑depleted patients.
Renal impairment: monitor renal function and electrolytes (K⁺ >5.5 mmol/L).
Hyperkalemia: especially with K⁺‑retaining agents, NSAIDs, or cholestyramine.
Adrenal insufficiency: abrupt withdrawal may precipitate adrenal crisis in patients on long‑term steroids.

Adults: 80–320 mg once daily; start low (80 mg) then titrate to 160–320 mg based on BP response.
Hypertension (Monotherapy): 160 mg once daily; titrate to 320 mg.
Heart Failure: 80 mg twice daily (or 40 mg BID in renal impairment) → up to 320 mg BID.
Renal or hepatic impairment: start at the lowest dose; titrate slowly with caution.
Take with water, about 30 min after meals. Food may slightly reduce absorption.

Common: dizziness, headache, fatigue, cough (rare vs. ACE inhibitors), hyperkalemia, hypotension.
Serious: renal failure, severe hyperkalemia, angioedema (rare), visual disturbances (rare), hepatic dysfunction (monitor LFTs).

Blood pressure & heart rate at every visit.
Serum electrolytes (K⁺, Na⁺) after initiation and quarterly thereafter.
Renal function: serum creatinine, BUN, eGFR baseline then 1st week, 1st month, and every 3 months.
Liver enzymes: baseline, then yearly.
Pregnancy: periodic urine pregnancy test if women of childbearing potential.

ARB–ACE IDe for combination therapy: The Valsartan/Losartan combo offers superior BP control with reduced cough and angioedema because ARBs do not increase bradykinin.
Statin interaction: Use spatular monitoring; ARBs are safe with statins, but monitor liver enzymes when combined with hepatotoxic statins.
Bile salt sequestrants (cholestyramine) reduce valsartan absorption by ~50 %; administer at least 4 h apart.
Renin‑Angiotensin‑Neprilysin Inhibitor (ARNI) controversy: Valsartan combined with sacubitril shows better outcomes in HFrEF; consider if patient fails monotherapy.
Hyperkalemia Check: In patients on diuretics, restrict dietary potassium sources and periodically check K⁺ — threshold for hold: >5.5 mmol/L or symptomatic hyperkalemia.
Snoring/Apnea: Valsartan does not worsen obstructive sleep apnea; useful in hypertensive OSA patients.
Kidney‑protective effect: In diabetic nephropathy, valsartan slows GFR decline; merge with glipizide or other agents cautiously.

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