Usage
Hydrochlorothiazide is primarily prescribed for:
- Hypertension (High Blood Pressure): It is used as monotherapy or in combination with other antihypertensives to lower blood pressure.
- Edema (Fluid Retention): It helps reduce swelling caused by conditions like heart failure, kidney disease, and liver cirrhosis.
It’s pharmacological classification is a thiazide diuretic. It works by inhibiting the reabsorption of sodium and chloride in the distal convoluted tubule of the nephron, leading to increased excretion of water, sodium, and chloride. This reduces blood volume and, consequently, blood pressure.
Alternate Names
Hydrochlorothiazide is also known as HCTZ or HTC. Popular brand names include Microzide, Aquazide H, and Esidrix.
How It Works
Pharmacodynamics: Hydrochlorothiazide lowers blood pressure by decreasing blood volume and peripheral vascular resistance. Its effects involve inhibiting sodium and chloride reabsorption in the distal convoluted tubule, impacting electrolyte balance.
Pharmacokinetics:
- Absorption: Hydrochlorothiazide is well-absorbed orally.
- Metabolism: Minimally metabolized.
- Elimination: Primarily excreted unchanged in the urine via renal tubular secretion.
Mode of Action: It inhibits the sodium-chloride symporter in the distal convoluted tubule, reducing sodium reabsorption. This diuresis decreases blood volume, thereby lowering blood pressure.
Elimination Pathways: Hydrochlorothiazide is primarily eliminated renally.
Dosage
Standard Dosage
Adults:
- Hypertension: Initially 12.5–25 mg orally once daily. The dose may be increased to 50 mg daily if needed. Doses exceeding 50 mg are not typically recommended and are associated with electrolyte imbalances.
- Edema: 25-100 mg orally once daily or in divided doses. The dose may be administered on alternate days or for 3–5 days per week to minimize the risk of electrolyte imbalance.
Children:
- Less than 6 months: 1–2 mg/kg/day orally divided into two doses. Maximum dose: 37.5 mg/day.
- 6 months to 2 years: 1–2 mg/kg/day orally as a single or two divided doses. Maximum dose: 37.5 mg/day.
- 2–12 years: 1–2 mg/kg/day orally as a single or two divided doses. Maximum dose: 100 mg/day.
Special Cases:
- Elderly Patients: Start with a lower dose (12.5 mg) and titrate upwards based on response and tolerance. Closely monitor for hypotension and electrolyte imbalances.
- Patients with Renal Impairment: Patients with creatinine clearance less than 30 ml/minute may require dosage adjustment or combination with a loop diuretic for optimal efficacy. For those with severe renal impairment (creatinine clearance less than 10 ml/minute), use is often avoided.
- Patients with Hepatic Dysfunction: Use with caution in patients with severe hepatic impairment, as fluid and electrolyte imbalances are more likely. Closely monitor electrolyte levels.
- Patients with Comorbid Conditions (Diabetes, Cardiovascular Disease): Monitor blood glucose levels in diabetic patients. Adjust doses of other antihypertensives as needed to prevent excessive blood pressure lowering.
Clinical Use Cases
Hydrochlorothiazide’s clinical use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency scenarios is not a standard practice. Other diuretics, such as loop diuretics like furosemide, are more commonly used in these settings.
Dosage Adjustments
Adjustments based on renal or hepatic function, electrolyte imbalances, and other medications are crucial.
Side Effects
Common Side Effects:
Dizziness, lightheadedness, headache, weakness, erectile dysfunction, tingling in extremities, photosensitivity, muscle spasms, and gastrointestinal upset (diarrhea, nausea).
Rare but Serious Side Effects:
Severe hypotension, electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia), hyperglycemia, hyperuricemia, gout, and allergic reactions. Pancreatitis and jaundice have also been reported.
Long-Term Effects:
Electrolyte disturbances, gout, impaired glucose tolerance. Increased risk of non-melanoma skin cancer has also been associated with long-term use.
Adverse Drug Reactions (ADR):
Severe hypotension, anaphylaxis, Stevens-Johnson syndrome (rare).
Contraindications
Anuria, hypersensitivity to sulfonamide-derived drugs, severe renal or hepatic impairment, Addison’s disease, and some electrolyte disturbances (hypercalcemia).
Drug Interactions
Hydrochlorothiazide interacts with many medications, including:
- Other antihypertensives (additive effect).
- Lithium (increased lithium levels).
- NSAIDs (decreased hydrochlorothiazide effectiveness).
- Diabetes medications (altered blood glucose control).
- Cholesterol-lowering medications (may decrease hydrochlorothiazide effectiveness).
- Corticosteroids (increased potassium loss).
- Digoxin (hypokalemia can increase digoxin toxicity).
Pregnancy and Breastfeeding
Hydrochlorothiazide can pass into breast milk and may cause side effects in the nursing infant. While low doses (≤50 mg/day) are considered acceptable by some guidelines during lactation, a decision to continue or discontinue breastfeeding should consider the infant’s health and the mother’s need for the medication.
Data regarding pregnancy is limited. It is categorized historically as FDA Pregnancy Category B, but this system has been deprecated. Thiazides cross the placental barrier, so use during pregnancy should be reserved for situations where the benefits outweigh the potential risks to the fetus. Potential fetal risks include thrombocytopenia and jaundice.
Drug Profile Summary
- Mechanism of Action: Inhibits sodium-chloride reabsorption in the distal convoluted tubule, leading to diuresis and blood pressure reduction.
- Side Effects: Dizziness, lightheadedness, electrolyte imbalances, hyperglycemia, hyperuricemia.
- Contraindications: Anuria, sulfonamide hypersensitivity, severe renal/hepatic impairment.
- Drug Interactions: Other antihypertensives, lithium, NSAIDs, diabetes medications.
- Pregnancy & Breastfeeding: Use with caution. Low doses may be acceptable in breastfeeding; pregnancy use only if clearly needed.
- Dosage: Hypertension: 12.5–50 mg/day; Edema: 25-100 mg/day.
- Monitoring Parameters: Blood pressure, electrolytes (potassium, sodium, magnesium, calcium), blood glucose, uric acid.
Popular Combinations
Hydrochlorothiazide is frequently combined with other antihypertensives like lisinopril, valsartan, and amlodipine to achieve better blood pressure control. These combinations offer synergistic effects and address multiple mechanisms involved in hypertension.
Precautions
- General Precautions: Baseline renal and hepatic function tests, electrolyte levels monitoring.
- Specific Populations: Pregnancy (use with caution, if clearly needed), breastfeeding (low doses permissible but assess infant), elderly (initiate with low dose), children (dose by weight).
- Lifestyle: Alcohol can exacerbate hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydrochlorothiazide?
A: The recommended starting dosage for adults is 12.5–25 mg daily for hypertension and 25–100 mg daily for edema. Pediatric doses are weight-based, and geriatric patients usually require a lower starting dose.
Q2: What are the common side effects of Hydrochlorothiazide?
A: Common side effects include dizziness, lightheadedness, headache, electrolyte imbalances, and increased urination.
Q3: How does Hydrochlorothiazide work to lower blood pressure?
A: It inhibits sodium reabsorption in the kidneys, promoting increased water and sodium excretion (diuresis), leading to decreased blood volume and lower blood pressure.
Q4: Is Hydrochlorothiazide safe during pregnancy and breastfeeding?
A: While low doses during breastfeeding are generally considered acceptable, use during pregnancy should be reserved for essential cases where the potential benefits outweigh the risks.
Q5: What are the contraindications for Hydrochlorothiazide?
A: Anuria, sulfonamide allergy, severe renal or hepatic failure, and Addison’s disease.
Q6: What are the significant drug interactions with Hydrochlorothiazide?
A: Interactions include other antihypertensives, lithium, NSAIDs, and certain diabetes medications.
Q7: How should Hydrochlorothiazide be taken?
A: Administer orally once daily, preferably in the morning to avoid nocturia.
Q8: What should I monitor in patients taking Hydrochlorothiazide?
A: Monitor blood pressure, electrolyte levels, blood glucose, and uric acid levels.
Q9: Can Hydrochlorothiazide be used in children?
A: Yes, it can be used in children with hypertension or edema. Dosing is based on weight, with specific limits depending on the age range.
