How Amlodipine and Atorvastatin works (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.
Atorvastatin selectively brings about the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Atorvastatin primarily acts in the liver, where it increases the hepatic uptake of dietary cholesterol and reduces the hepatic cholesterol levels and plasma cholesterol levels. Atorvastatin is a selective, competitive inhibitor of the HMG-CoA reductase enzyme of cholesterol biosynthesis pathway.
HMG-CoA reductase is involved in the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate. It is the key rate-limiting enzyme in cholesterol biosynthesis via the mevalonate pathway. Due to the inhibition of HMG-CoA reductase, hepatic cholesterol level decreases which stimulate the upregulation of hepatic low-density lipoproteins cholesterol (LDL-C) receptors on cell surface.
As a result, hepatic uptake of low-density lipoproteins cholesterol increases and serum LDL cholesterol concentration decreases. Atorvastatin also decreases the level of very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) and produce variable increase in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1.
Can both Amlodipine and Atorvastatin be taken together in combination?
Yes, Amlodipine can be used in combination with Atorvastatin to treat hypertension (high blood pressure) and to lower the risk of associated complications such as chest pain (angina), stroke, heart attack. The combination is also used to reduce the risk of heart complications in people with type 2 diabetes, coronary heart disease, or other risk factors.
Since, Amlodipine (calcium channel blocker) helps to relaxes the blood vessels and therefore improves blood flow and reduces blood pressure. In comparison, Atorvastatin (HMG CoA reductase inhibitors, or “statins’) reduces levels of “bad” cholesterol or so called low-density lipoprotein, and triglycerides in the blood. Besides this Atorvastatin increasing levels of “good” cholesterol so called high-density lipoprotein, or HDL.
The Amlodipine and Atorvastatin combination is available as tablets for oral administration under brand name Caduet. Caduet tablets are available in different strengths that contains a combination of Amlodipine besylate equivalent to 2.5, 5 mg or 10 mg of Amlodipine, and 10 mg, 20 mg, 40 mg or 80 mg of Atorvastatin .
The strength of Amlodipine and Atorvastatin combinations are as such 2.5/5 mg, 2.5/10 mg, 2.5/20 mg, 2.5/40 mg, 5/10 mg, 5/20mg, 5/40 mg, 5/80 mg. Caduet tablets are recognized or differentiated by tablet color/size and are engraved with a unique number on one side.
Combinations of atorvastatin with 2.5 mg amlodipine are round and film-coated white, combinations of atorvastatin with 5 mg amlodipine are oval and film-coated white, and combinations of atorvastatin with 10 mg amlodipine are oval and are film-coated blue.
Safety and precautions while taking Amlodipine + Atorvastatin combination
- The usual dose of the Amlodipine and Atorvastatin may vary depending upon the age, disease status and the drug efficacy in a particular individual.
- Do not use the Amlodipine and Atorvastatin, alone or in combination if you are hypersensitive or allergic to any of the ingredients of Amlodipine and Atorvastatin.
- The use of Amlodipine is contraindicated in case of hypotension (low blood pressure) and liver disease.
- The drug Amlodipine is contraindicated with other drugs such as vasodilator agents, calcium channel blockers , CYP3A4 inhibitors , antihypertensive drugs , antifungal agents and macrolide antibiotics.
- The use of Amlodipine is contraindicated in children and elderly people, therefore care should be taken while prescribing Amlodipine for children (under the age of 6 years) and elderly people.
- Do not use high salt diet and grapefruit products while taking Amlodipine.
- Before taking Amlodipine and Atorvastatin inform your physician about your past medical history, most notably about heart problem or ever had heart failure or liver disease.
- Avoid smoking and alcohol use while taking Amlodipine or Atorvastatin alone or in combination.
- Do not use any herbal products or prescription and non-prescription drugs while taking Amlodipine and Atorvastatin. If you are using them inform your doctor immediately.
- The use of Atorvastatin is not recommended in patients with hepatitis, hepatic encephalopathy, cholestasis and jaundice.
- The use of Atorvastatin is not recommended with drugs such as Cimetidine, Ketoconazole, , Spironolactone, HIV protease inhibitor drugs , oral contraceptives, medications that suppress immune system and cholesterol lowering medications.
- Use of grapes or grapefruit juice is prohibited while taking Atorvastatin.
- Consult with your doctor and pharmacist about what prescription and non-prescription medications, vitamins, and nutritional supplements you are taking or plan to take.
- Use of high salt, high fat and high cholesterol diet is strictly prohibited while taking Amlodipine and Atorvastatin.
- It is highly advisable to form your Physician if you are pregnant or plan or become pregnant or breast feeding.
- Grapefruit juice is also avoided because its components are known inhibitors of intestinal CYP3A4.
- Use of vitamin D supplements is contraindicated if you are taking Atorvastatin. Since, use of the supplements can affect the stability of Atorvastatin and its active metabolites.
- It is advisable to inform your healthcare provider if you are alcoholic or diabetic or hypothyroidic while taking Amlodipine and Atorvastatin.