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Overview

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This medicine contains an important and useful components, as it consists of
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Name

Hydrochlorothiazide

Precaution

Hydrochlorothiazide (HCTZ) is a thiazide diuretic commonly used for managing hypertension and fluid retention associated with conditions such as heart failure, kidney disease, and cirrhosis. Patients should be monitored for potential electrolyte imbalances, particularly low potassium (hypokalemia), sodium (hyponatremia), and magnesium levels. Regular blood tests are advised to monitor serum electrolytes and kidney function during treatment. Caution is required in patients with a history of gout, as hydrochlorothiazide can increase uric acid levels, potentially triggering gout attacks. It should also be used with care in patients with a history of diabetes, as it may elevate blood glucose levels. In patients with renal impairment, the dosage of hydrochlorothiazide may need to be adjusted, and renal function should be regularly monitored. Additionally, it should be used cautiously in patients who are pregnant or breastfeeding. HCTZ crosses the placenta and can have potential effects on the fetus, so its use during pregnancy should be limited to cases of clear need. For breastfeeding mothers, HCTZ is excreted in breast milk, and alternative treatments may be considered for those with known risks. Patients with an allergy to sulfonamides may also experience cross-reactivity with hydrochlorothiazide and should avoid its use.

Indication

Hydrochlorothiazide is primarily indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents, such as ACE inhibitors or angiotensin receptor blockers (ARBs). By reducing blood volume and dilating blood vessels, it helps lower blood pressure. It is also widely used for managing edema associated with heart failure, liver cirrhosis, kidney disease (including nephrotic syndrome), and corticosteroid therapy. In heart failure, it helps reduce fluid retention, alleviating symptoms like swelling and shortness of breath. Hydrochlorothiazide can also be used to prevent kidney stone formation in patients with hypercalciuria, a condition where excess calcium is excreted in the urine. Off-label uses include treating nephrogenic diabetes insipidus, as it may help reduce urine output. It can also be prescribed for patients with certain metabolic conditions, such as obesity or polycystic ovarian syndrome (PCOS), to help manage water retention.

Contra indication

Hydrochlorothiazide is contraindicated in patients with a known hypersensitivity to sulfonamide-derived drugs, as there is a potential for allergic reactions, including severe skin reactions, and cross-reactivity with sulfonylureas or other sulfonamide drugs. It is also contraindicated in patients with anuria (inability to produce urine) due to impaired renal function. The use of hydrochlorothiazide in these individuals can further impair kidney function. Additionally, it should not be used in patients with severe renal impairment (creatinine clearance below 30 mL/min), as it may exacerbate renal dysfunction. Hydrochlorothiazide is contraindicated in pregnancy during the second and third trimesters unless absolutely necessary, as it can lead to electrolyte imbalances and affect fetal development. During breastfeeding, caution is required, as the drug is excreted in breast milk, potentially causing harm to the infant.

Side Effect

The side effects of hydrochlorothiazide are primarily due to its diuretic activity and electrolyte disturbances. The most common adverse effects include: - **Electrolyte imbalances**: Hypokalemia, hyponatremia, and hypomagnesemia are common and may lead to symptoms such as weakness, fatigue, muscle cramps, and dizziness. - **Dehydration**: Excessive diuresis can result in dehydration, which may present with dry mouth, thirst, and reduced urine output. - **Hyperglycemia**: HCTZ can cause a slight increase in blood glucose levels, which may be concerning in diabetic patients. - **Hypercalcemia**: It may increase calcium levels, potentially leading to kidney stones or other complications. - **Rashes and allergic reactions**: Skin rashes, photosensitivity, or more severe allergic reactions, such as Stevens-Johnson syndrome, may occur. - **Gout**: By increasing serum uric acid levels, hydrochlorothiazide can precipitate gout attacks in susceptible individuals. - **Dizziness and hypotension**: Due to its blood pressure-lowering effects, dizziness or lightheadedness may occur, especially when standing up quickly (orthostatic hypotension). Patients should be monitored for these side effects, and the dose adjusted as needed. Severe reactions, such as angioedema or signs of severe electrolyte imbalance (e.g., confusion, arrhythmias), require immediate medical attention.

Pregnancy Category ID

2

Mode of Action

Hydrochlorothiazide works by inhibiting the sodium-chloride symporter in the distal convoluted tubule of the nephron in the kidney. This inhibition reduces sodium reabsorption, leading to an increase in sodium and water excretion. As a result, the overall blood volume decreases, contributing to a reduction in blood pressure. Additionally, the increased sodium excretion leads to a loss of water, which helps alleviate edema. The diuretic effect is more pronounced in individuals with conditions such as heart failure, hypertension, and kidney disease. Hydrochlorothiazide also promotes potassium excretion, which can sometimes lead to hypokalemia, a key consideration during its use. By decreasing the reabsorption of sodium, HCTZ also reduces the reabsorption of chloride and bicarbonate, contributing to its diuretic and antihypertensive effects. Its effectiveness in controlling blood pressure and fluid retention is attributed to its action in the kidneys, which helps to normalize the body's fluid balance and lower systemic vascular resistance.

Interaction

Hydrochlorothiazide may interact with several classes of drugs, affecting both its efficacy and the risk of adverse effects. The most notable interactions include the following: - **Antihypertensive agents**: When used in combination with other blood pressure-lowering medications (such as ACE inhibitors, ARBs, beta-blockers, or calcium channel blockers), the antihypertensive effects may be potentiated, leading to a further reduction in blood pressure. - **Lithium**: HCTZ can increase lithium levels by decreasing renal clearance, leading to the risk of lithium toxicity. Careful monitoring of lithium levels is required when these medications are used together. - **Non-steroidal anti-inflammatory drugs (NSAIDs)**: NSAIDs can reduce the diuretic and antihypertensive effects of HCTZ by promoting sodium and water retention. Combining these drugs may reduce HCTZ’s efficacy. - **Digoxin**: Since HCTZ can cause hypokalemia (low potassium), combining it with digoxin increases the risk of digoxin toxicity, which can cause arrhythmias. Potassium levels should be monitored closely when these drugs are used together. - **Corticosteroids**: Corticosteroids can exacerbate potassium loss, increasing the risk of hypokalemia when combined with HCTZ. Monitoring of electrolytes is recommended in these cases. - **Antidiabetic medications**: HCTZ may impair glucose tolerance, potentially requiring adjustments in the doses of antidiabetic medications for patients with diabetes mellitus.

Pregnancy Category Note

Information not available

Adult Dose

The standard starting dose of hydrochlorothiazide for hypertension is 12.5 to 25 mg orally once daily. The dose can be increased based on the patient's response, with the typical maintenance dose ranging from 25 to 50 mg per day. For edema, the usual starting dose is 25 to 100 mg per day, depending on the severity of fluid retention. If the desired therapeutic effect is not achieved, the dose may be increased gradually, typically in 25 mg increments. For patients with hypertension, it is often used as a single-agent therapy or in combination with other antihypertensive medications. The maximum dose for adults is generally 100 mg per day, although this dose is rarely necessary due to the drug's efficacy at lower doses. When starting therapy, it is important to monitor electrolytes and kidney function regularly. For patients with renal impairment, dosing should be adjusted accordingly to avoid excess fluid loss and electrolyte imbalance.

Child Dose

Hydrochlorothiazide may be used in pediatric patients for the treatment of hypertension and edema, though the dosing in children is typically lower than in adults. For hypertension, the usual dose in children aged 6 years and older is 1 to 2 mg/kg/day, with a maximum dose of 25 mg per day. For edema, the dose in children is generally 1 to 3 mg/kg/day, with a maximum of 37.5 mg per day. The drug should be used with caution in children with renal or electrolyte imbalances, and regular monitoring of electrolytes, hydration status, and kidney function is necessary. Hydrochlorothiazide is generally not recommended in infants under 6 months of age unless the benefits outweigh the risks, and alternative therapies should be considered.

Renal Dose

In patients with renal impairment, particularly those with creatinine clearance less than 30 mL/min, the use of hydrochlorothiazide is typically avoided, as its effectiveness is diminished and the risk of side effects increases. In patients with mild to moderate renal dysfunction (creatinine clearance between 30 and 60 mL/min), the dose may need to be adjusted to avoid excessive diuresis and electrolyte disturbances. Monitoring of renal function and electrolytes is essential in these patients. For severe renal impairment, an alternative diuretic, such as a loop diuretic (e.g., furosemide), is often preferred. Hydrochlorothiazide should be used with caution in patients with a history of renal disease, and close monitoring of renal function is required throughout treatment.

Administration

Information not available