Actions and Spectrum:

captopril is an angiotensin-converting enzyme (ACE) inhibitor. It works by blocking the action of ACE (it is an enzyme which converts angiotensin I to angiotensin II). Angiotensin II is a potent vasoconstrictor, meaning it causes the blood vessels to narrow and raise blood pressure. By inhibiting ACE, captopril reduces the production of angiotensin II, leading to vasodilation and lower blood pressure.

hydrochlorothiazide is a thiazide diuretic. It works by inhibiting the reabsorption of sodium and chloride in the distal tubule. This leads to a decrease in blood volume and lower blood pressure.

Together, captopril and hydrochlorothiazide work to lower blood pressure through different mechanisms, making them a popular combination therapy for hypertension.

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency Defined

Captopril

1-10%

Hypotension (1-3%)

Cough (1-2%)

Dysgeusia (2-4%)

Chest pain (1%)

Hypersensitivity reactions

Hypotension (1-3%)

Hyperkalemia (1-11%)

Palpitations (1%)

Tachycardia (1%)

Pruritis rash (2%)

<1%

ARF if renal artery stenosis

Angioedema

Impotence

Photosensitivity

Neutropenia

Black Box Warning

The black box warning for the combination drug captopril/hydrochlorothiazide (brand name Capozide) is for fetal toxicity.

Contraindication/Caution:

Contraindications:

• Allergy: This medication should not be used if you are allergic to captopril, hydrochlorothiazide, or any other ingredients present in the formulation.
• Angioedema: Individuals with a history of angioedema or who have developed it after taking ACE inhibitors (a class of drugs that captopril belongs to) should not take this medication.
• Pregnancy: captopril/hydrochlorothiazide is not recommended during pregnancy, especially during the second and third trimesters, as it may harm the fetus.

Caution:

• Kidney disease: Individuals with kidney disease should use this medication with caution as it can affect the kidneys’ functioning.
• Liver disease: captopril/hydrochlorothiazide should be used with caution in individuals with liver disease as it can cause liver damage.
• Diabetes: This medication may affect blood sugar levels, so it should be used with caution in individuals with diabetes.
• Gout: captopril/hydrochlorothiazide can increase the risk of gout attacks in individuals with a history of gout.
• Dehydration: This medication can cause dehydration, so it should be used with caution in individuals who are dehydrated or at risk of dehydration.
• Surgery: captopril/hydrochlorothiazide should be stopped at least 24 hours before surgery as it can cause low blood pressure during anesthesia.

Pregnancy warnings:   

Pregnancy category: C in 1st trimester and D in 2nd and 3rd trimester

Lactation: Excreted into human milk is known

Pregnancy Categories:     

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology:

captopril and hydrochlorothiazide are two medications commonly used together to treat hypertension (high blood pressure). captopril is an angiotensin-converting enzyme (ACE) inhibitor, while hydrochlorothiazide is a diuretic.

Pharmacodynamics:

captopril works by inhibiting the action of ACE, a enzyme. This leads to a decrease in the production of angiotensin II, which results in the dilation of blood vessels, reducing blood pressure. captopril also increases the levels of bradykinin, a vasodilator, further reducing blood pressure.

hydrochlorothiazide works by reducing the reabsorption of sodium and water in the kidneys, leading to increased urine output and decreased blood volume. This also helps to lower blood pressure.

The combination of captopril and hydrochlorothiazide produces a synergistic effect, as they work through different mechanisms to lower blood pressure. The two medications are usually taken orally in tablet form and are available in various strengths, depending on the severity of hypertension.

Pharmacokinetics:

Absorption

Both captopril and hydrochlorothiazide are rapidly absorbed from the gastrointestinal tract after oral administration. captopril has a bioavailability of approximately 75%, while hydrochlorothiazide has a bioavailability of around 70%.

Distribution

Both drugs are distributed widely throughout the body, and they are highly bound to plasma proteins. captopril has a volume of distribution of 0.6 L/kg, while hydrochlorothiazide has a volume of distribution of 0.8 L/kg.

Metabolism

captopril is rapidly metabolized in the liver to its active metabolite, captopril disulfide. Hydrochlorothiazide is not extensively metabolized in the liver but is eliminated unchanged in the urine.

Elimination and Excretion

Both drugs are primarily eliminated by the kidneys. The elimination half-life of captopril is approximately 2 hours, while the elimination half-life of hydrochlorothiazide is approximately 6-15 hours.

Administration:

The dosage of captopril/hydrochlorothiazide will depend on the severity of hypertension and the patient’s medical history. The usual starting dose is one tablet (50 mg/25 mg) once daily. If the patient’s blood pressure is not adequately controlled, the dosage may be increased to two tablets (100 mg/50 mg) once daily.

captopril/hydrochlorothiazide should be taken with or without food, at the same time every day. It is important to take this medication regularly and as directed by the doctor.

Patient information leaflet

Generic Name: captopril/hydrochlorothiazide

Why do we use captopril/hydrochlorothiazide?

captopril/hydrochlorothiazide is used to treat hypertension (high blood pressure) in adults. This medication is a combination of two drugs, captopril, an ACE inhibitor, and hydrochlorothiazide, a diuretic.