MEDISART 300H TABLETS

Indications

• Hypertension
• Edema associated with congestive heart failure
• Edema due to renal dysfunction

Dosage

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

Adults: 2.5 mg daily, taken in the morning for hypertension; higher doses may be used for other indications.

Mechanism of action

Hydrochlorothiazide is transported into epithelial cells of the distal convoluted tubule via organic anion transporters OAT1, OAT3, and OAT4. It inhibits the sodium-chloride symporter (SLC12A3), preventing sodium reabsorption. This action reduces the concentration gradient that promotes water reabsorption, leading to increased urine production.

Pharmacodynamics

Hydrochlorothiazide increases the excretion of sodium and water, thereby promoting diuresis. It is effective in lowering blood pressure and has a wide therapeutic range, with doses typically ranging from 25 to 100 mg. The drug exhibits a greater antihypertensive effect at lower doses due to enhanced vasodilation, while higher doses primarily exert their effects through diuresis. Caution is advised in patients with renal or hepatic impairment.

Pharmacokinetics

Hydrochlorothiazide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours post-administration. It has a half-life of about 6-15 hours, depending on individual patient factors. The drug is primarily excreted unchanged in the urine. Dosage adjustments may be necessary in patients with renal impairment due to the risk of accumulation.

Contra-indications

• History of hypersensitivity to sulfonamides
• Acute porphyrias
• Severe renal impairment

Adverse effects

• Angina pectoris
• Arrhythmias
• Arthralgia
• Asthenia
• Chest pain
• Confusion
• Dry mouth
• Haemolytic anaemia
• Hepatic disorders
• Hyperkalaemia
• Hypokalemia
• Nausea
• Rhabdomyolysis
• Syncope
• Vertigo

Interactions

• Potassium-sparing diuretics
• Other antihypertensives
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids

Precautions

• Diabetes mellitus
• Elderly patients
• Basal cell carcinoma
• Cutaneous lupus erythematosus
• Patients with hepatic impairment
• Monitoring of electrolytes

Pregnancy

Hydrochlorothiazide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is advisable to avoid use, especially during the first trimester.

Breast-feeding

Hydrochlorothiazide is present in breast milk; however, the amount is probably too small to be harmful. Caution is advised as large doses may suppress lactation.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets: 12.5 mg, 25 mg
• Oral solution
• Combination products with amiloride

Indications

• Hypertension
• Heart failure
• Chronic kidney disease
• Diabetic nephropathy

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Irbisartan selectively antagonizes the angiotensin II receptors (specifically the AT1 subtype), blocking the effects of angiotensin II including vasoconstriction and aldosterone secretion. This ultimately results in decreased peripheral vascular resistance and reduced blood pressure.

Pharmacodynamics

Irbisartan's pharmacodynamic profile includes the reduction of blood pressure through vasodilation, decreased secretion of aldosterone, and reduced sympathetic nervous system activity. The onset of antihypertensive effect generally occurs within 1 to 2 hours after administration, with peak effects observed around 6 to 8 hours post-dose. The duration of action allows for once-daily dosing in most patients.

Pharmacokinetics

Irbisartan is well-absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a bioavailability of approximately 60%, and its absorption is not significantly affected by food. The drug is extensively bound to plasma proteins (approximately 96%). Irbisartan is primarily metabolized in the liver via glucuronidation and is excreted mostly in the feces (about 80%). The elimination half-life is about 11 hours, allowing for once-daily dosing.

Contra-indications

• Hypersensitivity to irbesartan or any of its excipients
• Severe hepatic impairment
• Pregnancy
• Severe renal impairment
• Concurrent use with aliskiren in patients with diabetes

Adverse effects

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

Interactions

• Other antihypertensive agents may have additive effects
• Potassium-sparing diuretics, potassium supplements, or salt substitutes may increase the risk of hyperkalemia
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect of irbesartan
• Lithium levels may increase when used with irbesartan

Precautions

• Monitor renal function and electrolytes periodically during treatment
• Use with caution in patients with a history of angioedema
• Caution in patients with renal artery stenosis
• Assess blood pressure regularly

Pregnancy

Irbesartan is contraindicated during pregnancy as it may cause fetal harm.

Breast-feeding

Use with caution. Limited data suggests that irbesartan may be excreted in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets: 75 mg, 150 mg, 300 mg

Mechanism of action

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4). Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water. Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Pharmacodynamics

Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.