Hydrochlorothiazide

Hydrochlorothiazide is a drug that facilitates the elimination of water and salts (in particular, sodium and potassium) from the body by increasing the production and elimination of urine (a diuretic drug). It is used to lower blood pressure when it is too high (“arterial hypertension”) and to eliminate the collection of liquids that can form in the tissues (edema), due to various diseases. The drug does not cure hypertension but serves to keep it under control.

Hydrochlorothiazide is used in the treatment of edema of cardiac origin (mild or moderate congestive heart failure), ascites resulting from liver cirrhosis, and renal diabetes insipidus. Hydrochlorothiazide both in monotherapy and in combination with other antihypertensive drugs – can also be used in the treatment of hypertension.

Hydrochlorothiazide starts to carry out its diuretic action after about 2 hours and achieving maximum effectiveness at the fourth hour, can be taken easily by mouth. The diuretic effect of Hydrochlorothiazide is due to the presence of hydrochlorothiazide, the active ingredient benzothiazidic able to mainly increase the excretion of sodium and chlorine, but in second analysis also of potassium and magnesium, inhibiting the sodium / chlorine transporter expressed on the surface apical of the cells of the distal convoluted tubule of the nephron.

The diuretic action of Hydrochlorothiazide is generally followed by a direct antihypertensive action on the vascular smooth muscle, mediated by the increase in the exchange activity of the sodium / calcium channel. The increased flow of this element from the muscle cell to the blood, accompanied by a reabsorption of cellular sodium, guarantees a better control of the spastic contraction of my arterial fibrillary cells.

After its action, which lasted for about 6/12 hours, the hydrochlorothiazide is eliminated via the kidneys.

It should be taken preferably in the morning, after breakfast. If a second dose is needed, it can be taken in the early hours of the afternoon, unless otherwise advised by the doctor. If you miss a dose, see to it as soon as possible; however, if the next dose is due, leave the forgotten dose and continue following the prescribed schedule. Do not stop therapy without first consulting your doctor. Antihypertensive treatment may need to be continued throughout life.

Administration and usual doses

Hydrochlorothiazide inhibits sodium reabsorption in the distal tubule, causing an increase in the excretion of sodium and water as well as potassium and hydrogenions. The diuretic effect is established within 1-2 hours of administration and lasts 6-12 hours. Absorption after oral administration is 50-80%. It is 68% bound to plasma proteins and has a plasma half-life of 5.6-14.8 hours. It is not metabolised and is excreted as such in urine.

In addition to the beneficial effects, each drug can have some side effects. This drug is generally well tolerated; however, sometimes disorders such as: dry mouth, intense thirst, feeling of tiredness (which is generally reduced with the continuation of treatment), stomach pain, nausea, diarrhea, feeling of dizziness and empty head, increased sensitivity to light solar (erythema), rarely impotence (talk to your doctor if this disorder occurs and causes you to quit therapy). Contact your doctor if you notice signs of excessive loss of potassium salts, such as: irregular heartbeats, mood changes, cramps or muscle pain, fatigue and weakness or other disorders. Report any other effects deemed to be attributable to the drug to the doctor.

Hydrochlorothiazide, like other thiazides, can cause the following side effects:

• postural hypotension
• modest gastrointestinal effects
• hypokalemia
• hypomagnesaemia
• hyponatremia
• hypercalcaemia
• hypochloraemic alkalosis
• hyperuricemia
• gout
• hyperglycemia

The drug may cause changes in plasma lipid concentrations. The incidence of sexual dysfunctions (eg difficulty in erection) is greater with thiazides than with other antihypertensive agents, but generally does not require suspension of treatment. Less commonly, hydrochlorothiazide can induce rash, photosensitivity and haematological disorders. Pancreatitis, intrahepatic cholestasis and hypersensitivity reactions (including pneumonias, pulmonary edema and severe skin reactions) have also been described.

Like in case with all diuretics, it is advisable to assess the plasma levels of the electrolytes before proceeding with the administration of Hydrochlorothiazide, and if necessary, correct them.

In diabetic patients it is necessary to administer the drug with particular care, as it may be required to adjust the dose of the hypoglycemic drug, given the hyperglycaemic effect of hydrochlorothiazide. In hyperuremic patients, the haemoconcentration effect following the administration of Hydrochlorothiazide could lead to an increase in gout attacks.

Given the increased secretion of potassium, determined by the saluretic effect of hydrochlorothiazide, to avoid episodes of hypokalemia, with consequent associated symptoms, it could be useful to add a diet rich in potassium to pharmacological therapy.

It is also necessary to consider that diuretics, and in particular thiazide ones, expose the patient to potential hypokalemia, with symptoms characterized by a significant decrease in perceptive and reactive capacities, which could make driving or the use of machinery dangerous.

Pregnancy and breastfeeding

The use of diuretics such as hydrochlorothiazide, could determine an alteration of the normal blood flow to organs important for the growth of the fetus, compromising their development; therefore the use of this drug is not recommended during the first trimester of pregnancy, and subsequently only under strict medical supervision. Instead it would be necessary to suspend breastfeeding during the therapeutic protocol.

Pay attention to the following drug interactions:

Hydrochlorothiazide could increase the side effects of lithium salts, reducing their excretion, and curare derivatives.

The hypotensive action of this drug could be enhanced by the concomitant administration of other antihypertensives, alcohol or barbiturates, and inhibited by the simultaneous administration of non-steroidal anti-inflammatory drugs.

Concomitant use of corticosteroids, on the other hand, could increase potassium loss and expose the patient to more or less severe symptoms depending on the extent of the loss.

Refractory hypokalaemia, hyponatremia, hypercalcaemia; severe liver and kidney failure; symptomatic hyperuricemia, Addison’s disease; hypersensitivity to the drug, to thiazides, to sulfonamide derivatives.

Report all the medications you are taking to your doctor, if you have serious kidney or liver diseases or if you suffer from other important diseases; signal if diarrhea or persistent vomiting appear which can lead to a further and excessive loss of water and salts. Report if you have ever suffered from “allergies” to drugs or diseases such as eczema, asthma, hives.

Do not take Hydrochlorothiazide alongside:

• with NSAIDs: increased risk of NSAID nephrotoxicity; NSAIDs, in particular indomethacin and ketorolac antagonize the diuretic effect
• with hypoglycemic agents: the hypoglycemic effect is antagonized by thiazide diuretics
• with cardioactive glycosides: their toxicity can be increased if the diuretic induces hypokalemia or hypomagnesemia
• with lithium salts: thiazides reduce the renal excretion of lithium, increasing the risk of the appearance of toxic effects. Concomitant use must therefore presuppose constant monitoring of lithium levels.
• with ion exchange resins: the absorption of the diuretic can be reduced (the administrations of the two drugs must be spaced between them for at least two hours
• CNS depressive drugs: drug-induced orthostatic hypotension can be accentuated by alcohol, barbiturates and drugs.

• Aquazidea – Sun Pharmaceuticals Industries Ltd.
• Bpzide – Stadmed Pvt. Ltd.
• Hydride – Micro Labs Ltd (Cardicare)
• Klorzidea – Zydus Cadila Healthcare Ltd.
• Xenia – US Vitamins Limited