Nifedipine is a drug used to lower blood pressure, the action of which is based on the inhibition of calcium influx into the smooth muscle cells. The active ingredient belongs to the group of calcium antagonists of the 1,4-dihydropyridine type. The drug, which used to be widely used for high blood pressure, has largely lost its importance today because of its short duration of action and some side effects.
What is nifedipine?
Nifedipine belongs to the dihydropyridine group of substances. Representatives of this class of drugs lower blood pressure by inhibiting calcium influx into smooth muscle calcium channels. The active ingredient nifedipine is considered the lead substance for one of the three structural types of calcium antagonists. These are the nifedipine-type antihypertensives. The other two calcium antagonists belong to the phenylalkylamines (verapamil type) and the benzothiazepines (diltiazem type). The mechanisms of action of these three types differ. The dihydropyridines provide vasodilatation, while the phenylalkylamines decrease heart rate and the benzothiazepines combine both mechanisms. Nifedipine is a water-insoluble, yellowish powder. The substance is also highly photosensitive. In the liver, the drug is rapidly degraded by the enzyme CYP3A4 and thus is subject to a significant limitation of bioavailability due to high first-pass metabolism.
Pharmacologic Action
The action of nifedipine is based on inhibition of calcium influx into vascular smooth muscle cells through calcium channels. Nifedipine thus acts as a calcium antagonist. The influx of calcium ions into the muscle cells changes the electrical voltage state and the muscles undergo contraction. With regard to the vascular muscles, this means a constriction of the blood vessels with an increase in blood pressure. This calcium influx is part of the normal regulatory system within the blood circulation. However, if essential hypertension (high blood pressure) or other diseases based on circulatory disorders exist, only a widening and relaxation of the blood vessels can ensure a normalization of blood pressure. This relaxation of the vascular muscles is achieved by inhibiting calcium influx into the vascular muscle cells. Nifedipine inhibits only the L-type calcium channels. The L-type calcium channel is voltage-dependent and is located in the cell membrane of the T-tubules of muscle cells. The influx of calcium ions into the cytoplasm of muscle cells is controlled by depolarization of the cell membrane via activation of the ryanodine receptor. Since the ryanodine receptor is closely related to the dihydropyridine receptor, dihydropyridines can stop calcium influx into the cell. Because deactivation of the channel is slow, it is called a longlasting or L channel. Nifedipine mainly affects vascular muscle cells, but not cardiac muscle cells. However, the organism tries to counteract a reduction in blood pressure as part of its regulatory mechanisms. This can lead to side effects that can be dangerous in the case of an unstable circulatory situation.
Medical application and use
Because of its antihypertensive effect, nifedipine is used in essential hypertension, hypertensive emergencies, Raynaud’s syndrome, and stable angina. This drug is also frequently used in preterm labor. Furthermore, it can also be used in creams for anal fissures. In this case, the creams contain 0.2 percent of nifedipine. Essential hypertension, also called essential hypertension, exists without an identifiable cause. Nifedipine helps very well here by relaxing the vascular muscles. In a hypertensive emergency, severe high blood pressure suddenly occurs, which can even lead to damage to internal organs. In this threatening condition, blood pressure must be lowered quickly to prevent further damage. Nifedipine is best suited for this purpose. Hypertensive crisis, a preliminary stage of hypertensive emergency, is manifested by angina pectoris, dizziness, breathing difficulties, nosebleeds, states of confusion up to coma, urinary behavior and visual disturbances. Raynaud’s syndrome, on the other hand, involves arterial circulatory disorders in the fingers. The fingertips are white and cold because their blood flow is disturbed by spasm of the vascular muscles. The use of nifedipine has proven effective in Raynaud’s syndrome.Nifedipine can also be used for the treatment of stable angina pectoris. To achieve a long-lasting effect, nifedipine is now administered in sustained-release form. With sustained-release tablets, the slow release of nifedipine is ensured so that new active ingredient is always available after the rapid drop in effect due to the first-pass effelt.
Risks and side effects
In the past, nifedipine was mainly used to lower blood pressure. In the meantime, however, nifedipine has lost its outstanding importance because, on the one hand, in the sustained-release form it has only a short-term effect due to the first-pass mechanism and, on the other hand, its side effects and contraindications have been increasingly recognized. Although the active ingredient acts exclusively in relaxing the vascular muscles, it has no significant effect on heart rate. However, due to the strong onset of the drug, there is a rapid reduction in blood pressure, which provokes counter-reactions of the organism. Thus, nifedipine is contraindicated in unstable angina because reflex tachycardia develops, which can become life-threatening in this condition. Today, second-generation calcium antagonists are widely used, which are stored in the membranes due to their lipid solubility and thus are released more slowly. The lower kindling of these drugs also reduces the risk of reflex tachycardia. In addition to unstable angina, nifedipine is also contraindicated in myocardial infarction, high-grade aortic valve stenosis, shock, or when certain drugs such as rifampicin are administered. Common side effects when taking nifedipine include headache, flushing (flushing), and general feeling of weakness. Less common are abdominal pain, flatulence, constipation, nervousness, anorexia, sweating, muscle cramps, fever, polyuria, or visual disturbances. Reflex tachycardia is also among the less common side effects.
