LOSAKIND-25

Indications

• Hypertension
• Diabetic nephropathy
• Reduction of stroke risk in hypertensive patients with left ventricular hypertrophy

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: The usual starting dose is 50 mg once daily, which may be adjusted based on blood pressure response.

Mechanism of action

Losartan reversibly and competitively prevents angiotensin II from binding to the AT1 receptor, predominantly found in vascular smooth muscle and the adrenal gland. By blocking this action, losartan induces relaxation of vascular smooth muscle, which decreases blood pressure. Its active metabolite is significantly more potent than the parent compound, enhancing the drug's efficacy in blocking the physiological effects of angiotensin II, including vasoconstriction and aldosterone secretion.

Pharmacodynamics

Losartan exhibits a long duration of action, allowing for once-daily dosing. It effectively lowers blood pressure and has protective effects on renal function in diabetic nephropathy. Regular monitoring of blood pressure, renal function, and potassium levels is recommended for patients on losartan due to the potential for hypotension and hyperkalemia.

Pharmacokinetics

Losartan is well-absorbed following oral administration, with peak plasma concentrations occurring approximately 1 hour post-dose. It undergoes extensive hepatic metabolism, primarily by cytochrome P450 2C9, to its active metabolite. The elimination half-life of losartan is about 2 hours, while the half-life of its active metabolite ranges from 6 to 9 hours. Losartan and its metabolites are primarily excreted in urine.

Contra-indications

• Hypersensitivity to losartan or any of its components
• Severe hepatic impairment
• Pregnancy

Adverse effects

• Dizziness
• Hypotension
• Hyperkalemia
• Renal impairment
• Fatigue
• Angioedema

Interactions

• Potassium-sparing diuretics may increase serum potassium levels
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of losartan
• Lithium levels may increase when used with losartan

Precautions

• Caution in patients with renal artery stenosis
• Monitor renal function and potassium levels periodically
• Use with caution in patients with a history of angioedema

Pregnancy

Losartan is contraindicated during pregnancy due to the risk of fetal harm.

Breast-feeding

It is not known whether losartan is excreted in human milk. Use with caution if breastfeeding.

Storage

Store at room temperature, in a dry place, away from light.

Formulations

• Tablets: 25 mg, 50 mg, 100 mg

Mechanism of action

Losartan reversibly and competitively prevents angiotensin II binding to the AT₁ receptor in tissues like vascular smooth muscle and the adrenal gland. Losartan and its active metabolite bind the AT₁ receptor with 1000 times more affinity than they bind to the AT₂ receptor. The active metabolite of losartan is 10-40 times more potent by weight than unmetabolized losartan as an inhibitor of AT₁ and is a non-competitive inhibitor. Losartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation, lowering blood pressure. Angiotensin II would otherwise bind to the AT₁ receptor and induce vasoconstriction, raising blood pressure. Angiotensin II (formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)), is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g., vascular smooth muscle, adrenal gland). There is also an AT2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Both losartan and its principal active metabolite do not exhibit any partial agonist activity at the AT1 receptor and have much greater affinity (about 1000-fold) for the AT1 receptor than for the AT2 receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT1 receptor. The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT1 receptor. Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n = 51) were allocated to placebo, 25 or 100 mg losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrations, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 and 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hours after dosing, compared with the run-in day, 100 mg losartan increased plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapril increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, plasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of losartan, plasma renin activity and Ang II changes were similar to placebo changes by 36 hours. These results indicate that long-term blockade of the feedback Ang II receptor in hypertensive patients produces modest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist. /Salt not specified/ IL-1beta is a potent proinflammatory, pro-fibrogenetic and pro-athrosclerosis cytokine which has been shown to play an important role in an expanding number of noninfectious, chronic inflammatory conditions including cardiovascular disease, renal fibrosis, rheumatoid arthritis and even type 2 diabetes. Losartan is an angiot

Pharmacodynamics

Losartan is an angiotensin II receptor blocker used to treat hypertension, diabetic nephropathy, and to reduce the risk of stroke. Losartan has a long duration of action as it is given once daily. Patients taking losartan should be regularly monitored for hypotension, renal function, and potassium levels.