HCTZ

HCTZ Uses, Dosage, Side Effects, Food Interaction and all others data.

Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

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

Trade Name HCTZ
Availability Prescription only
Generic Hydrochlorothiazide
Hydrochlorothiazide Other Names HCTZ, Hidroclorotiazida, Hydrochlorothiazide, Hydrochlorothiazidum
Related Drugs Prolia, amlodipine, lisinopril, metoprolol, losartan, furosemide, spironolactone, atenolol, alendronate, Lasix
Weight 12.5mg, 12.5mg, 25mg, 50mg
Type Oral capsule, oral tablet
Formula C7H8ClN3O4S2
Weight Average: 297.739
Monoisotopic: 296.964474846
Protein binding

Hydrochlorothiazide is 40-68% protein bound in plasma. Hydrochlorothiazide has been shown to bind to human serum albumin.

Groups Approved, Vet approved
Therapeutic Class Thiazide diuretics & related drugs
Manufacturer
Available Country United States
Last Updated: September 19, 2023 at 7:00 am
HCTZ
HCTZ

Uses

HCTZ is used for-

  • Edema associated with congestive heart failure, hepatic cirrohosis, various forms of renal dysfunction and corticosteroid and estrogen therapy
  • Management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe form of hypertension
  • Management of diabetes insipidus
  • Management of proximal renal tubular acidosis
  • Idiopathic hypercalciuria and calcium nephrolithiasis, osteoporosis and exercise induced hyperkalemia

HCTZ is also used to associated treatment for these conditions: Acidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsia

How HCTZ works

HCTZ 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.

HCTZ 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.

Dosage

HCTZ dosage

Adults-

For Edema: The usual adult dosage is 25 to 100 mg daily as a single or divided dose.

For Control of Hypertension: The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium. In some patients (especially the elderly) an initial dose of 12.5 mg daily may be sufficient.

Infants and children-

For diuresis and for control of hypertension: The usual pediatric dosage is 1 to 2 mg/kg/day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 3 mg/kg/day in two divided doses may be required.

Side Effects

Generally, HCTZ is well tolerated. However, a few side effects may occur like weakness, restlessness, dizziness, headache, fever, diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, and hypotension. In rare case hyperglycemia, glycosuria, hyperuricemia and muscle spasm may occur.

Toxicity

The oral LD50 of hydrochlorothiazide is >10g/kg in mice and rats.

Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.

Precaution

Thiazides should be used with caution in patients with severe renal disease, impaired hepatic function or progressive liver disease and gout.

Interaction

Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur.

Antidiabetic Drugs (oral agents and insulin): Thiazides can impair control of diabetes mellitus by diet and antidiabetic Drugs. Antihypertensive Drugs: Additive effect or potentiation.

Food Interaction

  • Avoid alcohol. Alcohol may potentiate orthostatic hypotension.
  • Avoid multivalent ions. Take this medication 2 hours before or after the administration of antacids, calcium supplements, or iron supplements to avoid decreased absorption of hydrochlorothiazide.
  • Avoid natural licorice. Licorice potentiates the hypokalemic effect of hydrochlorothiazide.
  • Increase consumption of potassium-rich foods. This medication may cause potassium depletion. Foods containing potassium include bananas and orange juice.
  • Limit salt intake. Avoid excessive salt, unless recommended by a physician.
  • Take with or without food.

HCTZ Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

HCTZ Cholesterol interaction

[Moderate] Thiazide diuretics may increase serum triglyceride and cholesterol levels, primarily LDL and VLDL.

Whether these effects are dose-related and sustained during chronic therapy are unknown.

Patients with preexisting hyperlipidemia may require closer monitoring during thiazide therapy, and adjustments made accordingly in their lipid-lowering regimen

Volume of Distribution

The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.

Elimination Route

An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a Tmax of 1-5 hours, and a Cmax of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, Cmax is 20% lower, and Tmax increases from 1.6 to 2.9 hours.

Half Life

The plasma half life of hydrochlorothiazide is 5.6-14.8h.

Clearance

The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.

Elimination Route

HCTZ is eliminated in the urine as unchanged hydrochlorothiazide.

Pregnancy & Breastfeeding use

Pregnancy: Evidence of fetal risk in hydrochlorothiazide therapy is found, but it is indicated if benefits outweigh risks. Thiazides are indicated in pregnancy when edema is due to pathologic causes.\

Lactation: Neonatal side effects have been seen incase of hydrochlorothiazide therapy and therefore it is not recommended.

Contraindication

HCTZ is contraindicated to the patients of anuria and those who are sensitive to hydrochlorothiazide or to other sulfonamide-derived drugs. Therapy is not to be initiated in diabetes mellitus.

Special Warning

Elderly: in some patients specially the elderly an initial dose of 12.5 mg daily may be sufficient.

Children: An initial dose for children has been 1 to 2 mg per kg body-weight in 2 divided doses. Infants under 6 months may need doses upto 3 mg per kg daily.

Acute Overdose

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Rarely, autoimmune hemolytic anemia and other hypersensitivity reactions may complicate the picture.

In the event of over dosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. Hemodialysis can be used successfully to treat severe intoxication.

Storage Condition

Store between 15-30°C. Protect from light, moisture and freezing.

Innovators Monograph

You find simplified version here HCTZ

HCTZ contains Hydrochlorothiazide see full prescribing information from innovator HCTZ Monograph, HCTZ MSDS, HCTZ FDA label

http://classyfire.wishartlab.com/tax_nodes/C0000000
http://classyfire.wishartlab.com/tax_nodes/C0000002
http://classyfire.wishartlab.com/tax_nodes/C0000224
http://classyfire.wishartlab.com/tax_nodes/C0000308
http://classyfire.wishartlab.com/tax_nodes/C0004292
http://classyfire.wishartlab.com/tax_nodes/C0002458
http://classyfire.wishartlab.com/tax_nodes/C0001585
http://classyfire.wishartlab.com/tax_nodes/C0002448
http://classyfire.wishartlab.com/tax_nodes/C0001030
http://classyfire.wishartlab.com/tax_nodes/C0003137
http://classyfire.wishartlab.com/tax_nodes/C0004139
http://classyfire.wishartlab.com/tax_nodes/C0004557
http://classyfire.wishartlab.com/tax_nodes/C0001516
http://classyfire.wishartlab.com/tax_nodes/C0003940
http://classyfire.wishartlab.com/tax_nodes/C0004150
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5778
http://www.hmdb.ca/metabolites/HMDB0001928
http://www.genome.jp/dbget-bin/www_bget?drug:D00340
http://www.genome.jp/dbget-bin/www_bget?cpd:C07041
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3639
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504440
https://www.chemspider.com/Chemical-Structure.3513.html
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=13076
https://mor.nlm.nih.gov/RxNav/search?searchBy=RXCUI&searchTerm=5487
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=5778
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL435
https://zinc.docking.org/substances/ZINC000000896569
http://bidd.nus.edu.sg/group/cjttd/ZFTTDDRUG.asp?ID=DAP000750
http://www.pharmgkb.org/drug/PA449899
https://www.ebi.ac.uk/pdbe-srv/pdbechem/chemicalCompound/show/HCZ
http://www.rxlist.com/cgi/generic/hctz.htm
https://www.drugs.com/hctz.html
https://en.wikipedia.org/wiki/Hydrochlorothiazide
*** Taking medicines without doctor's advice can cause long-term problems.
Share