Index
It is a dihydropyridine calcium channel blocker, used alone or with an angiotensin-converting enzyme inhibitor to treat hypertension.
It is also used to treat angina, chronic stable angina, and variant angina.
It is similar to other peripheral vasodilators.
Nitrendipine inhibits the influx of extracellular calcium through the membranes of vascular and myocardial smooth muscle cells, possibly deforming the channel, inhibiting the control mechanisms of ion control, and interfering with the release of calcium from the sarcoplasmic reticulum.
The decrease in intracellular calcium inhibits the contractile processes of myocardial smooth muscle cells, causing dilation of coronary and systemic arteries, increased oxygen supply to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and fall in afterload.
Mechanism of action
Once nitrendipine is ingested, it is absorbed by the intestine and metabolized by the liver before entering the systemic circulation to reach the cells of the smooth muscles and the heart muscle cells.
Due to its lower membrane potential at rest binds more efficiently with the L-type calcium channels in smooth muscle cells.
Nitrendipine diffuses into the membrane and binds to its high-affinity binding site in the inactivated L-type calcium channel between the four intermembrane components of the α1 subunit.
The exact mechanism of action of nitrendipine is unknown. Still, it is thought to have significant tyrosine and threonine residues in its binding pocket, and its critical interferes with the voltage sensor and the channel activation mechanism.
It is believed to have a domain interface link model.
In hypertension, nitrendipine binding causes a decrease in the likelihood of opening L-type calcium channels and reduces the influx of calcium into the blood.
Reduced calcium levels prevent the contraction of smooth muscle within these muscle cells.
The prevention of muscle contraction in the heart allows the dilatation of the smooth muscle.
Dilatation of the vasculature reduces total peripheral resistance, which decreases the workload on the heart and prevents the formation of scars in the heart or heart failure.
It has also been found that nitrendipine acts as a mineralocorticoid receptor antagonist or an antimineralocorticoid.
Pharmacodynamic properties
As with other calcium entry blockers, nitrendipine inhibits the entry of calcium from the “slow” channel into cardiac and vascular tissue.
As stated above, it has been shown that nitrendipine possesses a high degree of selectivity for vascular smooth muscle.
Therefore, its main effect is to decreases peripheral vascular resistance with subsequent blood pressure reduction.
In vitro investigations in the animal coronary artery and aorta demonstrate that nitrendipine blocks the contractions induced by potassium, calcium chloride, and barium, and the calcium agonist Bay K 8644 in a measure similar to nicardipine, nisoldipine, and nimodipine, and with more force than nifedipine, verapamil and diltiazem.
However, nitrendipine does not alter conduction through the sinus or atrioventricular nodules, unlike these last three medications.
In patients with mild to moderate hypertension, it has been shown that a single oral dose of 20 mg of nitrendipine decreases the systolic and diastolic pressure by approximately 15 to 20% within 1 to 2 hours after administration.
This effect is maintained during the more extended-term administration of nitrendipine, generally 20 to 40 mg/day.
The effects of nitrendipine on resting blood pressure appear to be greater than its effects on elevated blood pressures during submaximal exercise.
Although most pharmacodynamic studies have used nitrendipine in dosing regimens twice daily, it has also been shown that a daily dose effectively maintains reductions in blood pressure.
Elderly patients and those with low baseline plasma renin activity tend to respond better to nitrendipine than their younger counterparts and those with high plasma renin activities.
However, a close correlation between high blood pressure before treatment and the degree of response to the drug has not been convincingly demonstrated.
In normotensive subjects, blood pressure remains the same or may decrease after nitrendipine.
In contrast, nitrendipine initially increases the heart rate in normotensive and hypertensive subjects, but this effect decreases with continuous treatment.
Although nitrendipine significantly reduces systemic vascular resistance, alterations in cardiac output and decreases in left ventricular filling pressure have not been consistently observed.
In addition, although cardiac output and left ventricular ejection time have increased in some short-term studies, these effects are probably not significant in the long term.
Some hypertensive patients have experienced decreased left ventricular hypertrophy during treatment with nitrendipine. Still, a correlation between these reductions and the decrease in blood pressure in humans has not yet been demonstrated.
In a single study, nitrendipine reduced cardiac workload during exercise and prolonged time until the onset of angina.
Studies in hypertensive patients investigating the effects of nitrendipine on the peripheral vascular circulation have shown that the drug causes significant dilatation of the small and large arteries resulting in a decrease in total peripheral vascular resistance of about 20%.
The renal effects of nitrendipine have not been fully elucidated. Still, it has been observed that the drug does not produce consistent changes in animal renal perfusion or renal blood flow, renovascular resistance, or glomerular filtration rate in humans.
Diuresis observed after acute doses of nitrendipine has not persisted with long-term use.
A significant loss of potassium with nitrendipine is unlikely, but it was shown that urinary excretion of aldosterone increases during a 6-month study.
In addition, most tests indicate that the drug initially increases plasma renin activity, but this effect may decrease with prolonged treatment.
In animal models, nitrendipine dilates cerebral blood vessels, as do other dihydropyridine derivatives, and reduces pulmonary artery vasoconstriction with subsequent decreases in pulmonary artery pressure.
A single study in patients with pulmonary hypertension showed similar effects.
More studies are needed on the effect of nitrendipine in pulmonary hypertension.
In addition to its relaxing effects on vascular smooth muscle, nitrendipine inhibits tracheobronchial and uterine contractions in animal models in vitro.
However, the clinical implications of these findings are uncertain.
There have been no changes in fasting blood glucose or plasma lipids in patients receiving nitrendipine.
Therapeutic trials
Open trials of 1 to 12 months have shown that nitrendipine (usually 10 to 40 mg daily) reduces systolic and diastolic pressures within normal limits in 45 to 86% of patients with mild to moderate hypertension.
These response rates can be further increased by adding a β-blocker or a diuretic.
A few comparative trials indicate that nitrendipine allows a significantly greater number of patients to achieve target blood pressure than placebo and is as effective as hydralazine, hydrochlorothiazide, beta-blockers, and nifedipine.
In addition, when nitrendipine is combined with beta-blockers, a diuretic, or captopril, the expected antihypertensive response is often achieved in patients who previously did not respond to nitrendipine monotherapy.
Although recent evidence indicates that the antihypertensive effect of nitrendipine persists during prolonged treatment, more long-term studies are needed to adequately assess the potential, if any, for the development of drug tolerance.
Dosage and administration
Nitrendipine therapy should be initiated with a dose of 10 mg administered once a day. The amount should be adjusted to individual patient responses for several weeks up to 40 mg/day in 1 or 2 doses.
Elderly patients may respond to lower daily doses (5 to 10 mg/day). Dose adjustments may be necessary for the presence of liver but not renal failure.
It is advisable to take it during or after meals.
Side effects
The most common side effects caused by nitrendipine (headache, flushing, edema, and palpitations) arise from the vasodilator properties of the medication.
Despite their relatively frequent occurrence, these adverse reactions are usually mild and disappear with continuous treatment.
Only 5% of patients require the withdrawal of treatment.
However, some patients may need analgesics, diuretics, or a beta-blocker if the initial headache, edema, or tachycardia persists.
Overdose
The overdose with this clinical product is characterized mainly by the unwanted development of hypertension.
The severity of this condition depends on the amount of Nitrendipine that the patient used excessively.
In such cases, the individual should be transported immediately to the nearest medical center to receive adequate supportive symptomatic therapy.
If the patient does not receive the therapeutic approach necessary for his condition (overdose of Nitrendipine), severe and potentially fatal consequences can arise.
Interactions
Interaction with the following medications has been reported:
- Acetazolamide.
- Amphotericin B.
- Corticosteroids
- Dichlorphenamide.
- Diuretics.
- Metazolamida.
- Betabloqueantes: acebutolol, atenolol, betaxolol, carteolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol.
- Carbamazepine.
- Cyclosporine.
- Procainamide.
- Quinidine: the effects of these drugs may increase if they are used together with calcium channel blockers.
- Digitalis glycosides: the effects of these drugs can be enhanced if they are used with calcium channel blockers.
- Disopyramide: the effects of calcium channel blockers on the heart can be improved.
Warnings
- Caution should be exercised in patients with a history of liver failure and the elderly.
- Dizziness or drowsiness may occur, do not drive a car or operate machinery while taking this medication.
- Avoid the intake of grapefruit while taking this medication.
