Perindopril

Perindopril belongs to the group of ACE inhibitors (angiotensin-converting enzyme inhibitors). It is used to treat high blood pressure and heart failure. Perindopril is a prodrug, a substance which is activated to its pharmacologically active form only after absorption into the body.

Use and indications

It is used to treat high blood pressure (hypertension), heart failure and to reduce cardiac events in patients with coronary heart disease. In patients who have had a heart attack in the past, perindopril may also be used to reduce the risk of cardiac events. Perindopril may also be used in combination with other medications, especially those that lower blood lipid levels and blood pressure.

Perindopril is generally taken orally, as a tablet or melting tablet.

History

Perindopril was first developed by Servier in 1987 and is now marketed as a generic by many other companies. It was first approved in France and has since proven to be an effective drug in many countries.

Pharmacodynamics and mechanism of action

Perindoprilat, the active form of perindopril, is a potent competitive inhibitor of ACE (angiotensin converting enzyme). ACE is the enzyme responsible for converting angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). The RAA system is a homeostatic mechanism regulating hemodynamics, water and electrolyte balance, and thus is also a regulator of blood pressure.

Pharmacokinetics

Perindopril is rapidly absorbed, with maximum plasma concentrations reached approximately 1 hour after oral administration. Bioavailability is 65-75%. After absorption, perindopril is hydrolyzed to perindoprilat, which has an average bioavailability of 20%. The rate and extent of absorption is not affected by concomitant dietary intake. Perindoprilat is 10-20% bound to plasma proteins. Perindopril is extensively metabolized in the liver; therefore, only 4-12% of the dose is recovered in urine after oral administration. Perindoprilat has a very long half-life of 30 to 120 hours. This is due to its slow dissociation from ACE binding sites.

Drug Interactions

Interactions may occur with the following drugs:

• Lithium
• Gold injections in the treatment of arthritis.
• Potassium-sparing diuretics such as spironolactone, amiloride, and triamterene
• When combined with a diuretic and a so-called NSAID (non-steroidal anti-inflammatory drug) with perindopril, very severe kidney damage or even kidney failure may occur. This combination is also called "triple whammy".

Contraindications

• Perindopril should not be used in case of hypersensitivity to the active substance or other ACE inhibitors.
• Perindopril should not be used in patients with severe kidney disease.
• Perindopril should not be given in children and pregnant women.

Side effects

The most common side effects of Perindopril are:

• Tiredness
• Dizziness
• Headache
• Cough
• Sleep disturbances
• Slight mood swings
• Back pain

Less common side effects:

• Digestive problems such as diarrhea
• Nausea
• Taste disturbances
• Rashes
• Abdominal pain

Pregnancy and lactation

Perindopril should not be used during pregnancy and lactation.