Atorvastatin, Perindopril arginine, Amlodipine besilate

Indications

Atorvastatin, Perindopril arginine, Amlodipine besilate is used for: Atorvastatin
Atorvastatin is approved for the treatment of several types of dyslipidemias including: - Primary hyperlipidemia and mixed dyslipidemia in adults. - Hypertriglyceridemia. - Primary dysbetalipoproteinemia. - Homozygous familial hypercholesterolemia. - Heterozygous familial hypercholesterolemia in adolescent patients with failed dietary modifications.[A177397] Dyslipidemia is defined as an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.[L6025] Atorvastatin is indicated, in combination with dietary modifications, to prevent cardiovascular events in patients with cardiac risk factors and/or abnormal lipid profiles.[A177397] Atorvastatin can be used as a preventive agent for myocardial infarction, stroke, revascularization, and angina, in patients without coronary heart disease but with multiple risk factors, and in patients with type 2 diabetes without coronary heart disease but multiple risk factors.[A177397] Atorvastatin can also be used as a preventive agent for non-fatal myocardial infarction, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure and angina in patients with coronary heart disease.[A177397] The term cardiovascular events correspond to all the incidents that can produce damage to the heart muscle including the interruption of blood flow.[L6028]
Perindopril
For the treatment of mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease.
Amlodipine
Amlodipine may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of the following conditions [FDA label]: B Hypertension B Coronary artery disease B Chronic stable angina B Vasospastic angina (PrinzmetalBs or Variant angina) B Angiographically documented coronary artery disease in patients without heart failure or an ejection fraction < 40%

Adult Dose

Child Dose

Renal Dose

Administration

Contra Indications

Precautions

Pregnancy-Lactation

Interactions

Adverse Effects

Side effects of Atorvastatin, Perindopril arginine, Amlodipine besilate :

Mechanism of Action

Atorvastatin
Atorvastatin is a reversible competitor of the 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA).[A177388] It acts by binding to the critical catalytic site of the enzyme.[T568] The HMG-CoA reductase is an enzyme that catalyzes the reduction of HMG-CoA to mevalonate which is a rate-limiting step in the cholesterol synthesis in the liver.[A177415] Hence, the blockade of this enzyme later reduces _de novo_ cholesterol production.[A177397] As part of atorvastatin's effects, it has been observed an increase in the number of LDL receptors on the surface of the hepatic cells.[A177397] As well, as atorvastatin presents a reduction on cholesterol levels which are required for the secretion of very-low-density lipoprotein; hence, the secretion and formation of this cholesterol isotype is significantly reduced which in order reduces the level of circulating triglycerides.[A177436] The mechanism of the increase in the level of high-density lipoprotein cholesterol is still unknown.[A177436]
Perindopril
There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Perindoprilat, the active metabolite of perindopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Perindopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.
Amlodipine
**Mechanism of action on blood pressure** Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both _dihydropyridine_ and _nondihydropyridine_ binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells [FDA label]. Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure [F3757]. **Mechanism of action in angina** The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold: Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements [F3757]. Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking [F3757].