by egpat 28 May 2024
Amlodipine is one of the calcium channel blockers, commonly known as CCB, but this drug can be differentiated from the other calcium channel blockers by its few structural features. We can split the name into three parts: the prefix "AM-" indicates this drug has some amino group attached to ethoxy, so an aminoethoxy group is present in the amlodipine. The infix "-LO-" indicates this drug has a chloro group. Finally, the suffix "-DIPINE" indicates this drug is a dihydropyridine. From the term dihydropyridine, we can take the suffix dipine. So amlodipine is a dihydropyridine with an amino-ethoxy moiety and a chloro group within the structure.
Amlodipine can block the L-type calcium channels present in the cardiac muscle as well as in the vascular smooth muscle. Particularly, dihydropyridines are more selective towards the vascular smooth muscle, so amlodipine shows more affinity towards the L-type calcium channels present on the vascular smooth muscle compared with the cardiac muscle. However, it can show action on both cardiac muscle as well as vascular smooth muscle.
Within the cardiac muscle, different types of ion channels are present. One of the important ion channels is the sodium channel, so through this voltage-gated sodium channel, sodium can enter the membrane, which produces the depolarization of the cardiac muscle. When the sodium ions are entered, the action potential is going to be propagated into the T-tubules. Upon reaching this action potential in the T-tubules, calcium channels are going to be activated.
Now the calcium ions can enter through these L-type calcium channels, and then they can activate the store-operated calcium channels. These store-operated calcium channels are nothing but the rhinodine receptors, which, when activated, can release a large amount of calcium into the cytoplasm. In this way, when the L-type calcium channels are activated, it results in increased intracellular calcium levels within the cardiac muscle, which results in the contraction of the cardiac muscle.
Amlodipine that is administered in the body can be protonated within the plasma. Within this protonated form, it can act on the L-type calcium channels. Amlodipine can bind to one of the binding sites, called the dihydropyridine binding site. Upon binding to this site, it inhibits L-type calcium channel activity. This prevents contraction of the cardiac muscle. In this way, amlodipine can reduce the rate of contraction as well as the force of contraction in the heart.
Vascular smooth muscle is again equipped with L-type calcium channels, through which calcium enters the cytoplasm. However, the contractile mechanism is somewhat different. Calcium can bind with calmodulin, forming a complex. This complex activates the myosin light chain kinases (MLCK). Normally, this MLCK is required for phosphorylation of the myosin light chains (MLC). Within this phosphorylated form, MLC can combine with the actin filament, such that they are going to form an actomyosin complex. This results in the contraction of the vascular smooth muscle.
Amlodipine can bind these L-type calcium channels at the dihydropyridine binding site. Just like the cardiac muscle, amlodipine again inhibits L-type calcium channel activity, thereby inhibiting the contraction of the vascular smooth muscle.
The important side effects are headaches and edema. These two side effects are mainly related to vasodilation as well as increased capillary permeability. The headache is because of cerebral vasodilation, and the edema is because of the accumulation of body fluids. Apart from these two side effects, amlodipine can also produce a few other side effects, like fatigue, nausea, and abdominal pain. It can also produce somnolence and a few of the vasodilatory symptoms, like dizziness and flushing. Amlodipine can also produce palpitations because of the reflex mechanism.
Amlodipine reduces the force of contraction in the heart. Therefore, it reduces cardiac output and can aggravate the anginal attack. It can increase the risk of myocardial infarction, particularly in patients who have an obstruction in the cardiac conduction system. So amlodipine should be carefully given to patients who have angina and myocardial infarctions, along with obstructions in the cardiac conduction system.
Amlodipine is converted to metabolites within the liver. This drug is long-acting with a half-life of 56 hours, but in patients with severe hepatic failure, this metabolism may be impaired, which may result in an increased half-life of amlodipine. So in such patients, there may be an accumulation of amlodipine levels within the plasma, which should be carefully monitored.
Amlodipine is going to produce vasodilation, thereby producing hypotension. Even though it is not producing acute hypotension, any symptoms of hypotension like flushing, dizziness, and headache should be carefully monitored.
Amlodipine is metabolized within the liver by CYP3A4. A few of the drugs, like ketoconazole, itraconazole, and ritonavir, are strong CYP3A4 inhibitors that can inhibit the metabolism of amlodipine, resulting in increased levels of this drug.
Since amlodipine is a vasodilator, it is particularly used in the treatment of hypertension. It can be given alone or in combination for the treatment of hypertension. Similarly, this drug can also act on the heart, and it can also reduce afterload, so this drug is useful in the treatment of vasospastic angina as well as chronic stable angina.
Sometimes amlodipine can also be given for coronary artery disease in patients who are not associated with heart failure. Because in heart failure, cardiac output is already reduced, amlodipine reduces the force of contraction, which further reduces the cardiac output. So in patients who are having heart failure, particularly those who have a lower ejection fraction, amlodipine should not be used.
Amlodipine is available as a tablet in different doses, like 2.5 mg, 5 mg, and 10 mg. The correct dose of amlodipine depends on various factors, like patient conditions, age, hepatic function, and comorbid conditions. Typically, the initial dose is started at 5 mg per day, and the maximum dose that can be administered is 10 mg. But in patients who have severe hepatic impairment, the dose may be reduced, so the initial dose may be reduced to 2.5 mg.
Amlodipine is a calcium channel blocker with an amino ethoxy group as well as a chloro group within the structure. This drug can act on both cardiac muscle and vascular smooth muscle, with more affinity for the vascular smooth muscle. Since this drug acts as a vasodilator, it can be used in the treatment of hypertension as well as vasospastic and chronic stable angina, and it can also be given in a few cases of coronary artery disease in patients who are not associated with heart failure. This drug is protonated within the plasma, and it can block the L-type calcium channels by binding to that dihydropyridine binding site. Headache and edema are the two important side effects that can be produced by this amlodipine.