Adalat (Nifedipine)

Adalat is the brand name under which the drug Nifedipine is sold. Nifedipine is most commonly used in the treatment and control of hypertension. It is part of a class of drugs called calcium channel blockers, because its main action is to slow the movement of calcium through the blood vessels and thus relax them so the heart can pump blood easier. This activity prevents blood pressure from rising abruptly by slowing down the heart beat and widening the arteries. Nifedipine can also be used in the treatment and prevention of angina because it reduces the amount of energy the heart uses and thus relieves chest pain. Studies have also shown that adalat is an effective remedy for Raynaud’s disease. Nifedipine is known to exhibit very few side effects, the most common of which dizziness due to low blood pressure. It should not be used on people with hypotension, liver disease or heart failure. Also, eating grapefruits or drinking grapefruit juice is not advisable while taking adalat because its blood levels may be altered.

Indian J Physiol Pharmacol. 2005 Jan;49(1):72-6.
Effects of calcium, strontium, and barium on isolated phrenic nerve-diaphragm preparation of rat and their interactions with diltiazem and nifedipine.
John P, Kaore S, Singh R.
Department of Pharmacologyy, M. G. Institute of Medical Sciences, Sewagram - 442 102. johnpremendran@yahoo.co.in

Calcium (Ca2+), strontium (Sr2+), and barium (Ba2+) are expected to exert similar chemical and pharmacological effects. The effects of barium, strontium and calcium were studied on the contractions of rat phrenic nerve-diaphragm preparations, following electrical stimulation and their interactions with nifedipine (nif) and diltiazem (DZM) were also studied. Low doses of strontium chloride (SrCl2), barium chloride (BaCl2) and calcium chloride (CaCl2) were able to increase the force of contraction of the rat diaphragm when actively stimulated. Diltiazem inhibited the stimulant effects of Sr2+, Ba2+, and Ca2+. On the other hand, nifedipine blocked the effects of Sr2+ and Ca2+ but potentiated the effects of Ba2+. Strontium, barium, and calcium restored the contractility of the muscle following electrical stimulation when the tissue was in biological fluid absolutely depleted of calcium. These findings suggest that Sr2+ and Ba2+ may be able to substitute Ca2+ in the rat diaphragm for its contractions and nifedipine and diltiazem may follow different mechanisms of actions or channels in their blocking effects.

Pediatr Nephrol. 2005 May 7;
Ventricular arrhythmia following short-acting nifedipine administration.
Castaneda MP, Walsh CA, Woroniecki RP, Del Rio M, Flynn JT.
Division of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA, jflynn@montefiore.org.

Short-acting nifedipine is still advocated for use in children with severe hypertension, but is no longer recommended for use in adults because of adverse effects from rapid blood pressure reduction. A 19 year-old adolescent with symptomatic, severe hypertension (blood pressure 180/120) received 10 mg of short-acting nifedipine sublingually for blood pressure reduction. Within minutes after the dose, the patient complained of palpitations. Tachycardia (heart rate 100 beats per minute) and bigeminy were noted on the cardiac monitor. The bigeminy resolved but premature ventricular contractions were noted for the duration of her hospital stay. We hypothesize that reflex sympathetic activation following an abrupt drop in blood pressure may cause arrhythmias because of elevated catecholamine levels. Given this, it may be more appropriate to treat severe hypertension in children with intravenous antihypertensive agents that can be titrated to produce controlled reductions in blood pressure.

Biomed Pharmacother. 2005 Jan-Feb;59(1-2):1-7. Epub 2005 Jan 20.
Effects of nifedipine, verapamil and diltiazem on serum biochemical parameters and aortic composition of atherosclerotic chickens.
Garcia-Perez B, Ayala I, Castells MT, Domenech G, Sanchez-Polo MT, Garcia-Partida P, Valdes M.
Universitary Clinical Hospital, Virgen de la Arrixaca, Murcia, Spain.

Calcium appears to be involved in many of the cellular events, which are thought to be important in atherogenesis. In this study, we examine the effects of three calcium entry blockers (nifedipine, verapamil, and diltiazem at clinical and higher doses) on serum biochemical parameters and aortic calcium, cholesterol and triglyceride concentrations of atherosclerotic egg-fed chickens. All egg-fed chickens (treated and non-treated) showed an increase in serum total cholesterol, LDL-cholesterol and triglycerides without significant effect when calcium entry blockers were used. Increased HDL values were observed in clinical and high-dose nifedipine and clinical dose verapamil groups. The high-dose diltiazem group presented increased zinc values with respect to the clinical dose diltiazem and control groups. The sodium concentrations were significantly decreased in all the groups of animals treated with calcium entry blockers at high-doses and nifedipine at clinical doses. Measurements of aortic calcium concentration showed a significant decrease in the high-dose nifedipine and verapamil groups. Calcium channel blockers had a tendency to decrease total cholesterol in aortas. The values were statistically significant for the high-dose verapamil, and nifedipine groups. Only nifedipine showed a significant decrease for this parameter at clinical dosages. Triglyceride concentrations in aortas were significantly low in animals fed an atherogenic diet and treated with calcium channel blockers, without differences between drugs or dosages used in the experiment. In addition, the chicken atherosclerosis model has proved itself useful and very suitable for in vivo drug intervention studies.

BJOG. 2005 Mar;112 Suppl 1:79-83.
Nifedipine trials: effectiveness and safety aspects.
Geijn HP, Lenglet JE, Bolte AC.
Department of Obstetrics and Gynaecology, Vrije Universiteit Medical Center (VUmc), De Boelelaan, Amsterdam, The Netherlands.

Nifedipine (Adalat) is marketed as an anti-hypertensive agent. Nifedipine inhibits voltage-dependent L-type calcium channels, which leads to vascular (and other) smooth muscle relaxation and negative inotropic and chronotropic effects on the heart. Vasodilation, followed by a baroreceptor-mediated increase in sympathetic tone then results in indirect cardiostimulation. Nifedipine was introduced as a tocolytic agent at a time when beta-agonists and magnesium sulphate dominated the arena for the prevention of preterm birth. The oral administration route, the availability of immediate and slow-release preparations, the low incidence of (mild) side effects, and its limited costs explain the attraction to this medication from the obstetric field and its rapid and widespread distribution. Currently, over 40 studies have been published on nifedipine's tocolytic effectiveness, including seven meta-analyses. The quality of the studies suffers particularly from performance bias because the majority of them failed to ensure adequate blinding to treatment both for providers and patients. Concerns about other methodological flaws include measurements, outcome assessment and attrition bias. In particular, the safety aspects of nifedipine for tocolysis have been underassessed. Conclusions from the meta-analyses, favouring the use of nifedipine as a tocolytic agent, are not supported by close examination of the data. The tocolytic effectiveness and 'safety' of nifedipine has been studied primarily in normal pregnancies. Based on its pharmacological properties, one should be cautious to administer nifedipine when the maternal cardiovascular condition is compromised, such as with intrauterine infection, twin pregnancy, maternal hypertension, cardiac disease, etc. Life-threatening pulmonary oedema and/or cardiac failure are definite risks and have been reported. Under such circumstances, the baroreceptor-mediated increase in sympathetic tone may not balance the cardiac-depressant activity of nifedipine.

Pharmazie. 2003 Sep;58(9):645-50.
Particular features of photolabile substances in tablets.
Aman W, Thoma K.
Department of Pharmaceutical Technology, Ludwig-Maximilians-University Munich, Germany.

Nifedipine and molsidomine tablets are extremely photolabile drug preparations, even at cool room light. Compared to solutions the light spectrum responsible for photodegradation is moved towards the long-wavelength range corresponding to the bathochromic shift of light absorption in the solid state. In the case of nifedipine tablets light up to 500 nm, especially the range between 400-420 nm, is degrading. Molsidomine tablets are affected only by ultraviolet light, but not by visible light. In both cases light penetrates less than 1 mm into the tablets. For nifedipine tablets the exact penetration depth could be determined due to the discolouration of the drug substance upon irradiation. It varied from 360 microm to 880 microm depending on the drug content. Since the decomposition products of nifedipine act as photostabilizers by spectral overlay, light penetration and photodegradation in nifedipine tablets are limited. The formation of gaseous and liquid decomposition products in molsidomine tablets enhances photodegradation. Changes of the tablet structure as well as dissolution and migration processes are discussed. Furthermore the degradation products donot photostabilize the drug substance due to the missing light absorption above 300 nm.

Br J Clin Pharmacol. 1993 Oct;36(4):315-21.
A comparison of the acute haemodynamic effects of nisoldipine and nifedipine during treatment with atenolol in patients with coronary artery disease.
Donaldson KM, Dawkins KD, Waller DG.
Clinical Pharmacology Group, Southampton General Hospital, Southampton.

1. The acute haemodynamic effects of intravenous nisoldipine (1, 2, 4 microg kg(-1)) and nifedipine (2.5, 5, 10 microg kg(-1)) were compared in a randomised, within-patient crossover study. Fifteen male patients with stable angina pectoris treated with atenolol were studied after undergoing routine cardiac catheterisation. 2. Nisoldipine caused a dose-related fall in systemic vascular resistance (maximum 22%) associated with an increase in heart rate and cardiac index (18%) and a fall in mean arterial pressure (7%). 3. By contrast, nifedipine was associated with a significant increase in heart rate but systemic vascular resistance, cardiac index and mean arterial pressure remained unaltered. 4. At doses with equivalent effects on heart rate (2 microg kg(-1) nisoldipine; 10 microg kg(-1) nifedipine) acute dosing with nisoldipine caused a significantly greater fall in systemic vascular resistance and increase in cardiac index, whilst nifedipine caused a greater reduction in stroke volume index and left ventricular stroke work index. 5. The results suggest that, when combined with atenolol, acute dosing with nisoldipine may have a more complementary haemodynamic profile than nifedipine. The implications of this finding for chronic oral dosing in patients with impaired left ventricular function should be evaluated.

Br J Clin Pharmacol. 1993 Nov;36(5):460-3.
Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice.
Rashid J, McKinstry C, Renwick AG, Dirnhuber M, Waller DG, George CF.
Clinical Pharmacology Group, University of Southampton, Bassett Crescent East, Southampton SO9 3TU, UK.

Quercetin, a flavonoid present in various fruits, is a potent in vitro inhibitor of CYP3A. Its role in the reported interaction between grapefruit juice and nifedipine has been determined in vivo in humans. Eight healthy volunteers were given in random order 10 mg nifedipine orally, either alone or with 200 ml double strength grapefruit juice, or with 400 mg quercetin. The area under the plasma concentration-time curve (AUC) for nifedipine with grapefruit juice (mean 320 ng ml(-1) h) was increased significantly (P < 0.01) compared with the AUC when nifedipine was given alone (mean 218 ng ml(-1) h). The time to peak plasma concentration for nifedipine with grapefruit juice (1.5 h) was also increased (P < 0.05) compared with control (0.5 h) suggesting delayed absorption. Although quercetin delayed the time to peak nifedipine concentration (1.3 h) it did not alter the AUC of either the parent drug (mean 209 ng ml(-1) h) or its first-pass metabolite. The results suggest that quercetin does not contribute to the effects of grapefruit juice (which contains <10 mg of quercetin 200 ml(-1)) on the metabolism of nifedipine. Oral doses of quercetin, similar to those possible from the ingestion of other fruits such as strawberries, do not produce in vivo inhibition of CYP3A mediated metabolism of nifedipine.

J Clin Hypertens (Greenwich). 2003 Jul-Aug;5(4):249-53.
Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study.
Romito R, Pansini MI, Perticone F, Antonelli G, Pitzalis M, Rizzon P.
Sezione di Malattie dell'Apparato Cardiovascolare, Dipartimento di Metodologia Clinica e Tecnologie Medico-Chirurgiche, Universita degli Studi di Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.

This multicenter, double-blind, parallel-group study compared the effects of three dihydropyridine calcium channel blockers (lercanidipine, felodipine, and nifedipine gastrointestinal therapeutic system) on blood pressure and heart rate in 250 patients with mild to moderate hypertension (diastolic blood pressure > or =95 and 109 mm Hg). Patients were randomized to 4 weeks of treatment with once-daily doses of lercanidipine 10 mg, felodipine 10 mg, or nifedipine gastrointestinal therapeutic system 30 mg. After 4 weeks of treatment, the dose was doubled in nonresponding patients. At 8 weeks, no significant differences in blood pressure were observed among the three groups. Increases in heart rate in all three groups induced by stressful conditions before and after treatment were not exacerbated during active treatment. The incidence of adverse drug reactions was lower in the lercanidipine and nifedipine groups than in the felodipine group (p<0.05); in particular, the incidence of edema for lercanidipine was 5.5% vs. 13% for felodipine and 6.6% for nifedipine.