Valsartan Tablets (Diovan) is a widely used angiotensin II receptor antagonist (ARB) in clinical practice, indicated mainly for the treatment of hypertension, heart failure, and reduction of cardiovascular risk post-myocardial infarction.
I. Mechanism of Action of Valsartan Tablets (Diovan)
Valsartan exerts its cardiovascular protective effects through a unique mechanism, acting primarily on the renin-angiotensin system.
1. Selective Blockade of Angiotensin II Receptors
(1) Valsartan is a specific, orally active non-peptide angiotensin II receptor antagonist.
(2) It binds selectively to the AT₁ receptor subtype of angiotensin II, thereby blocking the binding of angiotensin II to its receptor.
(3) This action directly inhibits multiple effects of angiotensin II, including vasoconstriction and aldosterone secretion.
2. Independence of Action
(1) Unlike angiotensin-converting enzyme inhibitors, valsartan does not inhibit ACE or affect bradykinin degradation.
(2) Consequently, the incidence of dry cough as an adverse reaction is significantly lower than that of ACE inhibitors.
(3) Its antihypertensive and organ-protective effects are achieved mainly by blocking the action of angiotensin II on the AT₁ receptor.
3. Pharmacodynamic Effects
(1) Following a single oral dose, the antihypertensive effect begins within approximately 2 hours, peaks at 6 hours, and persists for 24 hours.
(2) During long-term treatment, a significant reduction in blood pressure usually occurs within 2 weeks, with the maximal effect achieved after 4 weeks.
II. Drug Interactions
1. Concomitant Use with Drugs Affecting Serum Potassium
(1) Co-administration with other drugs affecting the renin-angiotensin system (e.g., ACEIs, aliskiren), potassium-sparing diuretics (e.g., spironolactone), potassium supplements, or potassium-containing salt substitutes may significantly increase the risk of hyperkalemia. In patients with heart failure, it may also elevate serum creatinine levels.
(2) Close monitoring of serum potassium levels is required during combined use.
2. Concomitant Use with Non-Steroidal Anti-Inflammatory Drugs
(1) Non-steroidal anti-inflammatory drugs (including selective COX-2 inhibitors) may attenuate the antihypertensive effect of valsartan. In elderly patients, volume-depleted patients, or those with renal impairment, they may increase the risk of worsening renal function and even acute renal failure.
(2) Renal function should be monitored regularly during long-term co-administration.
3. Dual Blockade of the Renin-Angiotensin System
(1) Dual blockade using valsartan combined with an ACE inhibitor or aliskiren increases the risk of hypotension, hyperkalemia, and renal impairment compared with monotherapy, and generally provides no additional benefit.
(2) Therefore, such combinations should generally be avoided. Co-administration of valsartan and aliskiren is contraindicated in diabetic patients.
4. Concomitant Use with Lithium
(1) Valsartan may increase serum lithium concentrations and raise the risk of lithium toxicity.
(2) Serum lithium levels must be monitored regularly during combined use.
III. Precautions
1. Contraindications in Pregnancy and Lactation
(1) Valsartan has fetal toxic effects. Use in the second and third trimesters of pregnancy may cause fetal injury or even death.
(2) The drug should be discontinued immediately if pregnancy is detected.
(3) Valsartan is excreted in rat milk; the risk to human infants is unknown. Use is therefore not recommended during breastfeeding.
2. Risk of Hypotension
(1) Symptomatic hypotension may occur during the initial phase of treatment, especially in volume-depleted patients (e.g., those receiving high-dose diuretics, vomiting, diarrhea, or a low-salt diet) or patients with heart failure.
(2) Volume status should be corrected before initiating treatment, and therapy should start at a low dose. If dizziness or syncope occurs, the patient should lie down and consult a physician.
3. Monitoring of Renal Function and Serum Potassium
In patients whose renal function depends on the renin-angiotensin system (e.g., renal artery stenosis, heart failure, dehydration), treatment may lead to an acute decline in renal function, requiring regular monitoring.
