Hydrochlorothiazide

The dosage of hydrochlorothiazide is highly individualized based on the condition being treated and the patient's response to therapy.

• For Hypertension: The typical starting dose for adults is 12.5 mg to 25 mg taken once daily. If the blood pressure response is insufficient, a healthcare provider may increase the dose to 50 mg daily. While doses up to 100 mg were used historically, modern clinical guidelines (such as JNC 8 and AHA/ACC) suggest that doses above 50 mg rarely provide additional blood pressure lowering benefits but significantly increase the risk of electrolyte imbalances.
• For Edema: The initial dose for fluid retention usually ranges from 25 mg to 100 mg daily. In some cases, a provider may recommend 'intermittent' dosing (taking the medication every other day or 3-5 days per week) to maintain fluid balance while minimizing side effects.

Hydrochlorothiazide may be used in children, but the dosage must be strictly calculated based on the child's body weight.

• Infants and Children: The usual dosage is approximately 1 mg to 2 mg per kilogram of body weight per day, administered in one or two divided doses.
• Infants under 6 months: May require up to 3 mg per kg per day in some clinical scenarios.
• Maximum Dose: Pediatric doses typically should not exceed 37.5 mg daily for younger children or 100 mg daily for older children, depending on the specific condition.

Renal Impairment

Hydrochlorothiazide loses its effectiveness as kidney function declines. It is generally not recommended for patients with severe renal impairment (Creatinine Clearance less than 30 mL/min). In such cases, 'loop diuretics' like furosemide are often preferred. Your doctor will monitor your GFR (Glomerular Filtration Rate) to ensure the medication is still appropriate.

Hepatic Impairment

Patients with significant liver disease (cirrhosis) must use this medication with extreme caution. Minor alterations in fluid and electrolyte balance can precipitate hepatic coma (loss of brain function due to liver failure).

Elderly Patients

Older adults are more sensitive to the effects of diuretics. Healthcare providers usually start with the lowest possible dose (12.5 mg) to prevent excessive dehydration, dizziness, or falls resulting from a sudden drop in blood pressure (orthostatic hypotension).

• Consistency is Key: Take this medication at the same time every day.
• Time of Day: Because hydrochlorothiazide increases urination, it is strongly recommended to take it in the morning. Taking it late in the evening (usually after 6:00 PM) can lead to 'nocturia' (waking up multiple times during the night to urinate), which disrupts sleep.
• With or Without Food: It can be taken with or without food. If it causes stomach upset, taking it with a meal or a glass of milk may help.
• Storage: Store at room temperature (68°F to 77°F or 20°C to 25°C), away from moisture and direct light. Keep the bottle tightly closed.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Never take two doses at once to make up for a missed one, as this significantly increases the risk of dehydration and electrolyte depletion.

An overdose of hydrochlorothiazide can lead to severe dehydration and dangerous electrolyte imbalances.

• Signs of Overdose: Extreme thirst, confusion, muscle weakness, heart palpitations (arrhythmia), nausea, and fainting.
• Emergency Measures: If an overdose is suspected, contact a Poison Control Center or seek emergency medical attention immediately. Treatment usually involves fluid replacement and correction of electrolyte levels in a hospital setting.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, even if you feel well, as hypertension often has no symptoms.

Most patients tolerate hydrochlorothiazide well, but because it alters the way the body handles fluids and minerals, certain side effects are common:

• Frequent Urination: This is the intended effect of the drug but can be bothersome during the first few weeks of therapy.
• Dizziness or Lightheadedness: Especially when rising quickly from a sitting or lying position (orthostatic hypotension). This happens as the body adjusts to lower fluid volumes.
• Headache: Often mild and transient as the body adapts to the medication.
• Increased Thirst: A natural response to the diuretic effect.

• Gastrointestinal Issues: Nausea, vomiting, stomach cramping, or diarrhea.
• Photosensitivity: Your skin may become more sensitive to sunlight, leading to easier sunburns or rashes.
• Electrolyte Imbalances: Mild decreases in potassium (hypokalemia) or sodium (hyponatremia). You may feel slightly fatigued or experience minor muscle cramps.
• Hyperuricemia: An increase in uric acid levels in the blood, which can occasionally trigger a gout attack (joint pain, typically in the big toe).

• Aplastic Anemia: A rare blood disorder where the body stops producing enough new blood cells.
• Pancreatitis: Inflammation of the pancreas, characterized by severe upper abdominal pain.
• Necrotizing Angiitis: Inflammation of the blood vessels (vasculitis).
• Non-Melanoma Skin Cancer: Some long-term observational studies have suggested a small increased risk of squamous cell and basal cell carcinoma due to the drug's photosensitizing effects.

> Warning: Stop taking Hydrochlorothiazide and call your doctor immediately if you experience any of these serious symptoms:

• Severe Electrolyte Imbalance: Symptoms include extreme confusion, a very dry mouth, irregular heartbeat (arrhythmia), severe muscle weakness, or a 'floppy' feeling in the limbs.
• Allergic Reaction: Hives, difficulty breathing, or swelling of the face, lips, tongue, or throat (angioedema).
• Eye Pain or Vision Changes: Sudden decrease in vision or pain in the eye can be a sign of acute angle-closure glaucoma or transient myopia.
• Jaundice: Yellowing of the skin or the whites of the eyes, which may indicate liver problems.
• Severe Skin Reactions: Fever, sore throat, and a red or purple rash that spreads and causes blistering and peeling (Stevens-Johnson Syndrome).
• Kidney Problems: Little or no urination, or painful/difficult urination.

With prolonged use, hydrochlorothiazide can lead to metabolic changes that require ongoing monitoring:

• Glucose Intolerance: It may slightly raise blood sugar levels, which is particularly important for patients with pre-diabetes or diabetes.
• Lipid Changes: Some patients may see a temporary increase in cholesterol or triglyceride levels.
• Chronic Hypokalemia: Long-term low potassium can affect heart rhythm and muscle function; your doctor may prescribe a potassium supplement or a potassium-rich diet (e.g., bananas, orange juice).

No FDA black box warnings currently exist for Hydrochlorothiazide. However, it is important to note that it is often combined with other drugs (like ACE inhibitors or ARBs) that do carry black box warnings regarding fetal toxicity during pregnancy.

Report any unusual symptoms or side effects to your healthcare provider promptly to ensure your treatment remains safe and effective.

Hydrochlorothiazide is a potent medication that requires careful medical supervision. It is not a 'simple' water pill; it significantly alters the body's internal chemistry. Patients must be aware that while it is effective, it can lead to severe dehydration and mineral depletion if not monitored correctly.

There are no FDA black box warnings for Hydrochlorothiazide as a monotherapy. However, when Hydrochlorothiazide is used in combination with drugs like Lisinopril or Losartan, those combination products carry a Black Box Warning regarding Fetal Toxicity. Discontinue such combination products as soon as pregnancy is detected, as they can cause injury or death to the developing fetus.

• Sulfonamide Allergy: Hydrochlorothiazide is a sulfonamide derivative. If you have a known allergy to 'sulfa drugs' (such as Bactrim or Septra), you may be at risk for an allergic reaction to hydrochlorothiazide. Discuss this with your doctor before starting the medication.
• Systemic Lupus Erythematosus (SLE): Thiazide diuretics have been reported to activate or exacerbate systemic lupus erythematosus. If you have an autoimmune condition, inform your provider.
• Renal and Hepatic Risk: In patients with severe kidney disease, the drug may precipitate 'azotemia' (an accumulation of nitrogenous waste products). In patients with impaired liver function, even minor electrolyte shifts can lead to hepatic encephalopathy.
• Acute Myopia and Secondary Angle-Closure Glaucoma: Hydrochlorothiazide can cause an idiosyncratic reaction resulting in fluid buildup in the eye. Symptoms include the sudden onset of decreased visual acuity or ocular pain. This typically occurs within hours to weeks of starting the drug. If left untreated, it can lead to permanent vision loss.

Because hydrochlorothiazide affects fluid and mineral balance, your healthcare provider will require regular blood tests, especially during the first few months of treatment:

• Basic Metabolic Panel (BMP): To check levels of sodium, potassium, chloride, and bicarbonate.
• Renal Function Tests: Monitoring Creatinine and Blood Urea Nitrogen (BUN) to ensure the kidneys are handling the medication well.
• Blood Glucose: Periodic checks, especially for diabetic patients, as thiazides can interfere with insulin sensitivity.
• Uric Acid: To monitor for the risk of gout.

Hydrochlorothiazide can cause dizziness, especially during the first few days of treatment or when the dose is increased. Do not drive, operate heavy machinery, or engage in dangerous activities until you know how this medication affects you.

Alcohol can increase the blood-pressure-lowering effect of hydrochlorothiazide, which may lead to severe dizziness or fainting (syncope). It is best to limit alcohol consumption while taking this medication.

Do not stop taking hydrochlorothiazide abruptly without consulting your doctor. Stopping the medication suddenly can cause a 'rebound' effect, where blood pressure rises quickly or edema returns rapidly. Your doctor will likely provide a tapering schedule if you need to stop the drug.

> Important: Discuss all your medical conditions, including history of gout, diabetes, or kidney disease, with your healthcare provider before starting Hydrochlorothiazide.

• Dofetilide: Hydrochlorothiazide can increase the blood levels of dofetilide (an anti-arrhythmic), which significantly increases the risk of a life-threatening heart rhythm called Torsades de Pointes. This combination is generally strictly avoided.

• Lithium: Hydrochlorothiazide reduces the renal clearance of lithium. This means the kidneys cannot get rid of lithium as effectively, leading to potentially toxic levels of lithium in the blood. Symptoms of lithium toxicity include tremors, vomiting, and confusion.
• Digoxin: While there is no direct interaction between the drugs themselves, hydrochlorothiazide causes low potassium (hypokalemia). Low potassium levels significantly increase the risk of digitalis toxicity, which can cause dangerous heart arrhythmias.
• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Drugs like ibuprofen (Advil/Motrin) and naproxen (Aleve) can reduce the diuretic and antihypertensive effects of hydrochlorothiazide. Furthermore, the combination can increase the risk of acute kidney injury.

• Antidiabetic Medications: Hydrochlorothiazide may increase blood sugar levels, necessitating an adjustment in the dosage of insulin or oral diabetes medications like metformin or glipizide.
• Corticosteroids (e.g., Prednisone): These can increase the risk of severe potassium depletion when taken with hydrochlorothiazide.
• Other Antihypertensives: While often used together intentionally, the combination with other blood pressure drugs (like beta-blockers or ACE inhibitors) increases the risk of hypotension (excessively low blood pressure).
• Cholestyramine and Colestipol: These cholesterol-lowering resins can bind to hydrochlorothiazide in the gut, reducing its absorption. Hydrochlorothiazide should be taken at least 4 hours before or 4 hours after these medications.

• Salt Substitutes: Many salt substitutes contain potassium chloride. Since hydrochlorothiazide lowers potassium, some patients might think these are beneficial; however, if you are also taking an ACE inhibitor or ARB, using salt substitutes could lead to dangerously high potassium (hyperkalemia). Always check with your doctor.
• Licorice: Natural black licorice contains glycyrrhizic acid, which can further deplete potassium levels when combined with diuretics.

• St. John’s Wort: May increase the risk of photosensitivity (sun sensitivity).
• Ginkgo Biloba: Some studies suggest it may interfere with blood pressure control.
• Calcium Supplements: Hydrochlorothiazide reduces the amount of calcium the kidneys excrete. Taking high doses of calcium supplements alongside this drug could lead to hypercalcemia (excessively high blood calcium).

• Thyroid Function Tests: Hydrochlorothiazide may interfere with tests for parathyroid function, as it affects calcium metabolism. It should be discontinued before carrying out tests for parathyroid function.
• Doping Tests: Hydrochlorothiazide is on the World Anti-Doping Agency (WADA) prohibited list because it can be used as a 'masking agent' to hide the presence of other performance-enhancing drugs in the urine.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, as many interactions are manageable with proper dose adjustments and monitoring.

There are specific circumstances where hydrochlorothiazide must NEVER be used due to the risk of life-threatening complications:

• Anuria: This is a condition where the kidneys are not producing any urine. Since hydrochlorothiazide works by acting on the kidneys to increase urine production, it is completely ineffective and potentially toxic in patients whose kidneys have failed to this extent.
• Hypersensitivity (Allergy): Patients with a known severe allergy to hydrochlorothiazide or other sulfonamide-derived drugs (sulfa drugs) should not take this medication. Reactions can range from severe skin rashes to anaphylaxis.

These are conditions where the drug may be used, but only with extreme caution and frequent monitoring by a healthcare professional:

• Severe Renal Impairment: If the Creatinine Clearance is less than 30 mL/min, the drug is unlikely to be effective and may worsen renal function.
• Active Gout: Because hydrochlorothiazide increases uric acid levels, it can trigger or worsen a gout flare. Providers may choose an alternative antihypertensive (like Losartan) in these patients.
• Diabetes Mellitus: While not a strict contraindication, the risk of increased blood sugar requires very close monitoring of glucose levels.
• Electrolyte Imbalance: Patients with pre-existing low potassium (hypokalemia), low sodium (hyponatremia), or high calcium (hypercalcemia) should have these conditions corrected before starting therapy.

There is a theoretical risk of cross-sensitivity between hydrochlorothiazide and other sulfonamides, such as sulfonylureas (used for diabetes) or certain antibiotics. While many patients with a sulfa-antibiotic allergy can tolerate thiazide diuretics, it is a risk that must be discussed with an allergist or primary care physician.

> Important: Your healthcare provider will evaluate your complete medical history, including your kidney function and allergy profile, before prescribing Hydrochlorothiazide.

Hydrochlorothiazide is generally classified as Pregnancy Category B (under the old FDA system). This means that animal studies have not shown a risk to the fetus, but there are no adequate, well-controlled studies in pregnant women.

• Trimester Risks: Use during the second and third trimesters can lead to decreased placental perfusion (blood flow to the baby) and may cause fetal or neonatal jaundice, thrombocytopenia (low platelets), and electrolyte imbalances.
• Clinical Use: It is generally not used to treat the normal swelling that occurs during pregnancy. It should only be used if the potential benefit justifies the potential risk to the fetus.

Hydrochlorothiazide is excreted in human breast milk. While it is generally considered compatible with breastfeeding by the American Academy of Pediatrics, there are two concerns:

1. 1Milk Supply: High doses of diuretics can sometimes decrease the volume of breast milk produced.
2. 2Infant Exposure: While the amount the baby receives is small, they should be monitored for signs of dehydration or electrolyte issues.

Hydrochlorothiazide is approved for use in children for the treatment of hypertension and edema. However, long-term safety data in the pediatric population is more limited than in adults. Dosing must be carefully managed by a pediatric specialist, and regular monitoring of electrolytes is mandatory.

Older adults (65+) are at a significantly higher risk for complications from hydrochlorothiazide:

• Hyponatremia: Seniors are much more likely to develop dangerously low sodium levels, which can lead to confusion and seizures.
• Fall Risk: Dizziness from blood pressure changes increases the risk of hip fractures and other fall-related injuries.
• Renal Clearance: As kidney function naturally declines with age, the drug may become less effective or accumulate in the body.

In patients with mild to moderate renal impairment, hydrochlorothiazide can still be used, but it is less effective as the Glomerular Filtration Rate (GFR) drops. It is generally considered ineffective when the GFR is below 30 mL/min. In these patients, 'loop diuretics' are the standard of care.

Patients with liver cirrhosis or other severe hepatic diseases must be monitored closely. Thiazides can cause sudden shifts in fluid that may lead to 'hepatic coma' (a loss of brain function when the liver can't remove toxins).

> Important: Special populations require individualized medical assessment and more frequent laboratory monitoring to ensure safety.

Hydrochlorothiazide is a thiazide diuretic that acts on the distal convoluted tubule of the nephron. Its primary molecular target is the NCC (Sodium-Chloride Symporter). By binding to the chloride site of this transporter, hydrochlorothiazide inhibits the reabsorption of sodium and chloride ions from the tubular fluid back into the epithelial cells. This increase in luminal osmolarity (saltiness of the urine) prevents water reabsorption, leading to diuresis (increased urine output). Additionally, hydrochlorothiazide indirectly increases potassium excretion by increasing the delivery of sodium to the collecting duct, where sodium is exchanged for potassium.

• Onset of Action: Diuresis typically begins within 2 hours of oral administration.
• Peak Effect: The maximum effect is reached at approximately 4 to 6 hours.
• Duration: The clinical effect lasts for 6 to 12 hours, though the blood-pressure-lowering effect may last longer.
• Dose-Response: There is a 'ceiling effect' with hydrochlorothiazide; increasing the dose beyond 50 mg often increases side effects without providing significant additional diuresis or blood pressure reduction.

| Parameter | Value |

|---|---|

| Bioavailability | 60% - 80% |

| Protein Binding | 40% - 68% |

| Half-life | 6 - 15 hours |

| Tmax | 2 - 5 hours |

| Metabolism | Minimal (Not CYP-dependent) |

| Excretion | Renal >95% (Unchanged) |

• Molecular Formula: C7H8ClN3O4S2
• Molecular Weight: 297.74 g/mol
• Solubility: Slightly soluble in water; soluble in sodium hydroxide solution.
• Structure: It is a benzothiadiazine 1,1-dioxide derivative with a sulfonamide group.

Hydrochlorothiazide is the prototypical Thiazide Diuretic. It is related to other thiazides like Chlorthalidone and Indapamide (though these are technically 'thiazide-like' diuretics). It is chemically distinct from 'loop diuretics' (like Furosemide) and 'potassium-sparing diuretics' (like Spironolactone).