Methyclothiazide

log Kow = 1.42 at pH 6.5

0.6

0.6

Crystals form alcohol and water

White or practically white, crystalline powder

Slightly soluble in alcohol; freely soluble in acetone, pyridine; sparingly soluble in methanol; very slightly soluble in water, benzene, chloroform, isopropyl alcohol.

8.24e-01 g/L

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Thiazide Diuretics

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

225 °C

225 °C

9.4

pKa = 9.4

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methylclothiazide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Many diabetic patients regulated by chlorpropamide or other sulfonylureas exhibit impaired diabetic control when any thiazide diuretic is added to the drug regimen. ... This drug interaction may occur with acetohexamide, tolazamide, and tolbutamide. /thiazide diuretics/

Thiazides enhance the antihypertensive action of guanethidine, allowing the dose of guanethidine to be reduced and decr the incidence of adverse reactions. ... Bethanidine and debrisoquin are chemically and Pharmacologically related to guanethidine and may be expected to interact with hydrochlorothiazide. /thiazide diuretics/

Chlorothiazide and other thiazide diuretics enhance the cardiotoxic and neurotoxic effects of lithium and these drugs should not be administered concurrently. /thiazide diuretics/

...Disruption of uricosuric therapy by admin of diuretic which increases plasma uric acid levels (thiazides) ... /thiazide diuretics/

For more Interactions (Complete) data for METHYCLOTHIAZIDE (16 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Methyclothiazide

Ambiguous-DILI-concern

2

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Did not impair fertility in rats receiving up to 4 mg/kg/day.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies performed in rats and rabbits at doses up to 4 mg/kg/day have revealed no evidence of harm to the fetus due to methyclothiazide.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

LD50 Rat ip 2000 mg/kg

LD50 Mouse ip 870 mg/kg

LD50 Mouse iv 400 mg/kg

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methylclothiazide, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

C - Cardiovascular system

QC - Cardiovascular system

Methyclothiazide, a diuretic-antihypertensive agent, is a member of the benzothiadiazine (thiazide) class of drugs. Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic/natriuretic effects. Like other benzothiadiazines, methyclothiazide also has antihypertensive properties, and may be used for this purpose either alone or to enhance the antihypertensive action of other drugs.

Methyclothiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, methyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like methyclothiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of methyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.

Acute admin of thiazides increases the excretion of uric acid. However, uric acid excretion is reduced following chronic admin... . The acute effects of inhibitors of Na+-Cl- symport on Ca2+ excretion are variable; when admin chronically, thiazide diuretics decr Ca2+ excretion. The mechanism is unknown but may involve increased proximal reabsorption due to volume depletion as well as direct effects of thiazides to incr Ca2+ reabsorption in the /distal convoluted tubule/. Thiazide diuretics may cause a mild magnesuria by a poorly understood mechanism, and there is increasing awareness that long-term use of thiazide diuretics may cause magnesium deficiency, particularly in the elderly. /Thiazide diuretics/

Thiazides inhibit reabsorption of sodium and ...chloride in distal segment. ... As /a/ class...have important action on excretion of potassium that results from increased secretion of cation by distal tubule. ... Glomerular filtration rate may be reduced by thiazides, particularly with iv admin for exptl purposes. /thiazide diuretics/

Nature of chemical interaction between thiazides and specific renal receptors responsible for chloruretic effect is not known; no critical enzymatic reactions have been identified. /thiazides/

Thiazide diuretics increase urinary excretion of sodium and water by inhibiting sodium reabsorption in the early distal tubules. They increase the rate of delivery of tubular fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma volume contraction increases aldosterone production. The increased delivery and increase in aldosterone levels promote sodium reabsorption at the distal tubules, thus increasing the loss of potassium and hydrogen ions. /Thiazide diuretics/

The antidiuretic effect of thiazide diuretics is a result of mild sodium and water depletion leading to increased reabsorption of glomerular filtrate in the proximal renal tubule and reduced delivery of tubular fluid available for excretion. /Thiazide diuretics/

L3H46UAC61

METHYCLOTHIAZIDE

Physiologic Effects [PE] - Increased Diuresis

Established Pharmacologic Class [EPC] - Thiazide Diuretic

Chemical Structure [CS] - Thiazides

Methyclothiazide is a Thiazide Diuretic. The physiologic effect of methyclothiazide is by means of Increased Diuresis.

Agents that promote the excretion of urine through their effects on kidney function.

Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.

Rapidly absorbed following oral administration.

Thiazides are absorbed from GI tract and owe their usefulness largely to their effectiveness by oral route. Absorption is relatively rapid. Most agents show demonstrable diuretic effect within hr after oral administration. /thiazide diuretics/

In general, thiazides with relatively long durations of action show proportionately high degrees of both binding to plasma proteins and reabsorption by renal tubules. ... Drug passes readily through placental barrier to fetus. All thiazides probably undergo active secretion in proximal tubule. /thiazide diuretics/

Methyclothiazide is absorbed from the GI tract. Little information is available on the extent of absorption and the distribution of methyclothiazide in the body. Methyclothiazide is excreted unchanged in urine.

Close et al, J Am Chem Soc 82, 1132 (1960).

By process analagous to that for chlorothiazide, 4-amino-6-chloro-n(3)-methyl-m-benzenedisulfonamide is cyclized through condensation with monochloroacetaldehyde or an acetal thereof. US patent 3,163,644.