Contents
What is Amlodipine?
Amlodipine is an antihypertensive drug that is used in treatment of high blood pressure and chest pain, It may also be used for heart failure. The drug is available under generic name Amlodipine and brand name Norvasc.
Initially, Pfizer Pharmaceuticals was responsible for its manufacture and distribution. Later, the drug was manufactured under various brand names by other pharmaceutical companies such as Teva pharmaceuticals, Synthon pharmaceuticals, Upsher smith laboratories and Matrix Laboratories after the expiration of Pfizer’s patent in 2007.
The drug is synthetic (man-made) pharmaceutical calcium channel blocker that lowers blood pressure by widening of blood vessels and prevents angina by increasing blood flow to the heart muscle to relieve pain. Amlodipine plays a key role in the treatment of high blood pressure (hypertension), chronic stable angina, vasospastic angina (prinzmetal’s or variant angina), and coronary artery disease.
Amlodipine chemically belongs to the class of organic compounds which are known as Dihydropyridine carboxylic acids and derivatives characterized by dihydropyridine moiety bearing a carboxylic acid group. Chemically, Amlodipine is 1, 4-dihydropyridine and mainly available as besylate salt and maleate salt.
It is a synthetic pharmaceutical aromatic heteromonocyclic compound with a molecular formula C20H25ClN2O5 and molecular weight 876 g/mol. Chemically, name of Amlodipine is 3-ethyl 5-methyl 2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate. Amlodipine is white and crystalline powder and has water solubility of 0.0074 mg/mL.
The drug Amlodipine is available in tablet form for oral administration with or without food. Amlodipine tablets are available in different strength of 2.5 mg, 5mg and 10 mg/tablet.
Amlodipine tablets contain Amlodipine besylate as active ingredient and magnesium stearate, microcrystalline cellulose, calcium hydrogen phosphate anhydrous and sodium starch glycolate type-A as inactive ingredients. The drug is taken once a day. The dose of the drug varies with the diseased state and the age of the patient. The drug is started at a lower dose and can be increased later.
What is Perindopril?
Perindopril is a non sulfhydryl prodrug that belongs to the class of ACE (angiotensin-converting enzyme) inhibitor. The drug is used to treat various diseases such as stable coronary artery disease, high blood pressure and heart failure. The drug is also used to treat hypertension and to reduce the risk of stroke in both hypertensive and nonhypertensive individuals with a history of stroke or transient ischemic attack.
The drug is available under generic name Perindopril arginine (under brand names including Coversyl, Coversum) or Perindopril erbumine (brand name Aceon). The drug is available as tablet for oral administration through mouth. The initial daily doses of Perindopril for hypertension is 5 mg Perindopril arginine (or 4 mg Perindopril erbumine) once daily.
The dosage may be increased to 10 mg Perindopril arginine (or 8 mg Perindopril erbumine) after one month of treatment. After oral administration, Perindopril is rapidly metabolized in the liver to perindoprilat, an active metabolite of Perindopril.
Chemically, Perindopril belongs to the class of organic compounds known as peptides that contain an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a peptide bond. Perindopril is chemically known as (2S,3aS,7aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxopentan-2-yl]amino}propanoyl]-octahydro-1H-indole-2-carboxylic acid.
The empirical formula and molecular weight of Perindopril is C19H32N2O5 and 368.4678 g/mol. Chemically, Perindopril is a pro drug that is the free acid form of Perindopril erbumine. Following administration, Perindopril is metabolized in vivo by hydrolysis of the ester group to form perindoprilat, the biologically active metabolite.
Perindopril erbumine is a white, crystalline powder which is freely soluble in water (60% w/w), alcohol and chloroform. The drug is available as tablet for oral administration through mouth. Perindopril is available in 2 mg, 4 mg and 8 mg strengths for oral administration. In addition to Perindopril erbumine, each tablet contains magnesium stearate, colloidal silica (hydrophobic), microcrystalline cellulose and lactose as an inactive ingredients.
How Amlodipine and Perindopril work (mode of action)?
Amlodipine is a slow but long-acting calcium channel blocker or calcium antagonist. It acts by inhibiting the calcium ion influx through L-type calcium channel across the cell membrane. After entering in the cell, calcium ions binds to calmodulin and form calcium bound calmodulin complex.
This calcium-calmodulin complex activates the myosin light chain kinase (MLCK) which catalyses a key step in muscle contraction that is the phosphorylation of regulatory light chain subunit of myosin. Inhibition of calcium ion influx results in the decreased contractile activity of arterial smooth muscle cells.
This reduction in contractile activity of arteries can cause the vasodilation. Effect of vasodilation finally results in lowering the blood pressure. It is also supposed that Amlodipine inhibits the activity of carbonic anhydrase I in vascular smooth muscle. Therefore, it causes the increase in pH which may be involved in the regulation of intracellular influx of calcium.
Principally, ACE inhibitors inhibit the angiotensin-converting enzyme (ACE), an important component of the renin–angiotensin–aldosterone system. This system is involved in homeostatic mechanism for regulating water and electrolyte balance and hemodynamics.
In the blood stream, renin cleaves circulating angiotensinogen to angiotensin I (ATI), which is subsequently cleaved to angiotensin II (ATII) by angiotensin converting enzymes (ACE). This ATII subsequently increases body oxygen demand and blood pressure. Perindopril belongs to the class of ACE (Angiotensin Converting Enzyme) inhibitors.
ACE inhibitors bind and inhibit the activity of angiotensin converting enzyme. This results in relaxation of blood vessels, decreased blood volume, and lower blood pressure. As a consequence, heart oxygen demand is decreased significantly.
The active metabolite of Perindopril (Perindoprilat) competes with ATI for binding to ACE and inhibits the enzymatic proteolysis of ATI to ATII. Besides this, Perindopril also enhances plasma renin activity possibly due to loss of feedback inhibition mediated by ATII .
Can both Amlodipine and Perindopril be taken together in combination?
Yes, Amlodipine is commonly used in combination with Perindopril to treat high blood pressure (hypertension) and prevention of heart attacks, stroke and kidney problems. The combination product is available under brand name Coveram and contains 2 medications: Perindopril (angiotensin-converting enzyme (ACE) inhibitor) and Amlodipine (calcium channel blocker).
The mode of action of the two drugs is different but both of them work effectively to relax the blood vessels and overall blood flow. The combination of Amlodipine and Perindopril is used when individual drug alone is unable to control blood pressure.
Clinical studies of Amlodipine –Perindopril combination have suggested the impact and relevance in situations of increased central pulse pressure, such as elderly populations or patients with chronic kidney disease. Furthermore, studies also suggested improved therapeutic benefits of fixed combination of Amlodipine-Perindopril combination in management of hypertension.
The drugs combination is available in tablet form for oral administration through mouth. Coveram tablets are available in different strengths that contain a combination of Amlodipine besylate equivalent to 5 mg or 10 mg of Amlodipine, and Perindopril. The strength of Perindopril and Amlodipine combinations are as such 5/5 mg, 5/10 mg, 10/5 mg, 10/10 mg.
Safety and precautions while taking Amlodipine : Perindopril combination
- Do not use the medicine if you are hypersensitive or allergic to any of the ingredients of Amlodipine and Perindopril.
- Amlodipine is not used in patients of hypotension (low blood pressure). The drug is also withheld in case of aortic stenosis (narrowing of the left ventricle exit of the heart) and liver disease.
- Use of Amlodipine is contraindicated with other calcium channel blockers and vasodilator agents.
- Amlodipine together with CYP3A4 inhibitors such as ketoconazole and clarithromycin is contraindicated because these compounds may increase the plasma concentration of Amlodipine.
- Use of antihypertensive drugs with Amlodipine is also contraindicated because it may decrease the serum concentration of Amlodipine.
- Amlodipine is also contraindicated with the antifungal agents such as itraconazole and voriconazole because they may enhance the toxic effects of the drug.
- Amlodipine together with macrolide antibiotics such as sulfisoxazole is also contraindicated because these compounds may decrease the metabolism of the calcium channel blocking agents.
- Take low-salt diet or as prescribed by your doctor otherwise follow usual diet.
- Before taking Amlodipine, and Perindopril combination tell your doctor about your medical history preferentially if you have any kind of liver disease.
- Grapefruit or grapefruit juice should be avoided because it may increase the level of active Amlodipine in the blood which may cause toxicity.
- Consult with your doctor and pharmacist if you are taking any prescription and non-prescription medications or herbal products.
- Do not use Perindopril if you have a history of angioedema caused by treatment with an ACE angioedema.
- Perindopril may interact with following medical conditions and therefore it is advisable to tell your doctor or pharmacist if you have any of these medical conditions including pregnancy, breast-feeding, heart problems , blood vessel problems, liver problems, diabetes, or kidney problems, autoimmune disease (eg, lupus, scleroderma) etc.
- It has been observed that Perindopril may interact with some of the medications therefore it is advisable to discuss with your healthcare provider, if you are taking any of the following medicines. Following is a list of medications that interact with Perindopril:
- Cyclosporine, spironolactone, triamterene (potassium-sparing diuretics), eplerenone, potassium supplements, or trimethoprim.
- Diuretics (eg, furosemide, hydrochlorothiazide) and Dextran sulfate
- Everolimus or sirolimus, Aliskiren or angiotensin receptor blockers (eg, valsartan)
- Lithium or sulfonylureas (eg, glyburide), gold-containing medicines (eg, auranofin) and nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, celecoxib, ibuprofen, indomethacin) etc.
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