[6][7], The approved uses are for the long-term treatment of hypertension and angina pectoris. class. A rating for the strength of the evidence supporting each drug interaction. Richard Johanson. Nifedipine blocked all contractile activity. It was once frequently prescribed on an as-needed basis to patients taking MAOIs for real or perceived hypertensive crises. Recent trials of any calcium antagonist and formulation were also reviewed for information about the possible mechanisms of action that might increase mortality. Nifedipine is a dihydropyridine calcium channel blocking agent. [, Lee SJ, Bell DA, Coulter SJ, Ghanayem B, Goldstein JA: Recombinant CYP3A4*17 is defective in metabolizing the hypertensive drug nifedipine, and the CYP3A4*17 allele may occur on the same chromosome as CYP3A5*3, representing a new putative defective CYP3A haplotype. Nifedipine (10, 20, 30 mg] or placebo was ingested as capsules in a double-blind design on 4 separate days. Avoid excessive or chronic alcohol consumption. Nifedipine inhibits the entry of calcium ions by blocking these voltage-dependent L-type calcium channels in … [, Raemsch KD, Sommer J: Pharmacokinetics and metabolism of nifedipine. Mechanism of Action. i. Nifedipine block the voltage gated L-type Ca +2 channels in the myocardial cells and vascular smooth muscles. The drug may be quantified in blood or plasma to confirm a diagnosis of poisoning, or to assist in a medicolegal investigation following death. Talk to your doctor before using this form of nifedipine if you have galactose intolerance, or severe problems with lactose (milk sugar). U.S. Patent US4412986, issued November, 1976. [, Vater W, Kroneberg G, Hoffmeister F, Saller H, Meng K, Oberdorf A, Puls W, Schlossmann K, Stoepel K: [Pharmacology of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (Nifedipine, BAY a 1040)]. John Anthony. Contraindications & Blackbox Warnings data. Although nifedipine and other dihydropyridines are commonly regarded as specific to the L-type calcium channel, they also possess nonspecific activity towards other voltage-dependent calcium channels. Their mechanism of action in tocolysis involves the blockade of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. C. The mechanism by which nifedipine reduces arterial blood press… Generic name: Nifedipine. If you are breastfeeding, discuss with your doctor if you should either discontinue breastfeeding or stop using this medicine while breastfeeding. [2][3][4] It is on the World Health Organization's List of Essential Medicines. Nifedipine is in a class of medications called calcium-channel blockers. These two compounds interact in a … Nifedipine, or BAY a 1040, is a first generation dihydropyridine L-type calcium channel blocker, similar to nicardipine.3,10,11,13 Nifedipine was developed by Bayer and first described in the literature, along with other dihydropyridines, in 1972.11,12 Since nifedipine's development, second and third generation dihydropyridines have been developed with slower onsets and longer durations of action.10 The most popular of the third generation dihydropyridines is amlodipine.10, Nifedipine was granted FDA approval on 31 December 1981.13, Nifedipine capsules are indicated to treat vasospastic angina and chronic stable angina.13 Extended release tablets are indicated to treat vasospastic angina, chronic stable angina, and hypertension.14,15, Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart.1 Immediate release nifedipine's duration of action requires dosing 3 times daily.13 Nifedipine dosing is generally 10-120mg daily.13 Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.13, Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells.1 This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries.1 These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina.1, Sublingual dosing leads to a Cmax of 10ng/mL, with a Tmax of 50min, and an AUC of 25ng*h/mL.9 Oral dosing leads to a Cmax of 82ng/mL, with a Tmax of 28min, and an AUC of 152ng*h/mL.9, Nifedipine is a Biopharmaceutics Classification System Class II drug, meaning it has low solubility and high intestinal permeability.8 It is almost completely absorbed in the gastrointestinal tract but has a bioavilability of 45-68%, partly due to first pass metabolism.3,8, The steady state volume of distribution of nifedipine is 0.62-0.77L/kg and the volume of distribution of the central compartment is 0.25-0.29L/kg.3, Nifedipine is 92-98% protein bound in serum.13 Nifedipine is 97±12% bound in a 40g/L solution of pure albumin.2 Nifedipine is 51.4±5.9% protein bound in a 50mg/100mL solution of alpha-1-acid glycoprotein, and 75.5±3.5% protein bound in a 150mg/mL solution.2, Nifedipine is predominantly metabolized by CYP3A4.1,8,13,14,15 Nifedipine is predominantly metabolized to 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3-carboxylic acid, and then further metabolized to 2-hydroxymethyl-pyridine carboxylic acid.6 Nifedipine is also minorly metabolized to dehydronifedipine.7, Hover over products below to view reaction partners, Nifedipine is 60-80% recovered in the urine as inactive water soluble metabolites, and the rest is eliminated in the feces as metabolites.14, The terminal elimination half life of nifedipine is approximately 2 hours.3,8, The total body clearance of nifedipine is 450-700mL/min.3, The oral LD50 in rats is 1022mg/kg and in mice is 202mg/kg.16, Patients experiencing an overdose may present with hypotension, sinus node dysfunction, atrioventricular node dysfunction, and reflex tachycardia.4,5 Overdose may be managed by monitoring cardiovascular and respiratory function; elevating extremities; and administering vasopressors, fluids, and calcium infusions.13. This group reduces the absorption of calcium by the myocardial cells and blood vessels – all as a result of the blockage of voltage-dependent calcium channels. J Pharmacol Exp Ther. Inhibitors and inducers of CYP3A can impact the exposure to nifedipine … By continuing to browse the site you are agreeing to our policy on the use of cookies. [, Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T: The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. [2] It may be used to treat severe high blood pressure in pregnancy. Drug Metab Rev. [24], The use of nifedipine and related calcium channel antagonists was much reduced in response to 1995 trials that mortality was increased in patients with coronary artery disease who took nifedipine. [2] It is a calcium channel blocker of the dihydropyridine type. 2010 Jun;38(6):981-7. doi: 10.1124/dmd.110.032094. The metabolism of Nifedipine can be increased when combined with Acalabrutinib. Rcsmoak. 2002;18(4):221-33. iii. Patricia Smith. [, Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. 3. Know how this interaction affects the subject drug. Procardia® (nifedipine) is an antianginal drug belonging to a class of pharmacological agents, the calcium channel blockers. Mechanism of action Nifedipine. Am J Med. [1], Nifedipine was patented in 1967, and approved for use in the United States in 1981. The precise means by which this inhibition relieves angina has not been fully determined, but includes at least the following two mechanisms: 1) Relaxation and Prevention of Coronary Artery Spasm. Mechanism Of Action. The serum concentration of Nifedipine can be increased when it is combined with Abiraterone. Nucleic Acids Res. It can cause an uncontrollable decrease in blood pressure, reflex tachycardia, and a steal phenomenon in certain vascular beds. Although nifedipine and other dihydropyridines are commonly regarded as specific to the L-type calcium channel, they also possess nonspecific activity towards other voltage-dependent calcium channels. Epub 2016 Apr 22. In vivo, there is minimal effect on the cardiac conducting system. NIFEDIPINE AND ADENOSINE: BASIC SCIENCE We feel nifedipine exerts part of its action via an interaction with endogenously produced adenosine. 23 results found < Page ; 1; of ; 1 > Adalat LA 30 mg prolonged-release tablets nifedipine Bayer plc. [, Godfraind T: Discovery and Development of Calcium Channel Blockers. The effects of varying the duration of drug treatment were also examined. 5 History.Nifedipine given as sublingual administration has previously been used in hypertensive emergencies. We investi- gated the effects of nifedipine on esophageal contractions in 5 healthy volunteers and 10 patients with the nutcracker esophagus. [, Patki KC, Von Moltke LL, Greenblatt DJ: In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Classification Nifedipine. Conclusions: We believe that both tamsulosin and nifedipine prevent the disorganized antiperistalsis associated with ureteral spasm while allowing some degree of antegrade fluid-bolus (stone) propagation. Therapeutic doses range from 10-30 mg orally every 6-8 hours. Eur J Pharm Sci. It is one of the treatments of choice for Prinzmetal angina. Nifedipine is a medicine used to treat high blood pressure.. [, Ramachandran SD, Vivares A, Klieber S, Hewitt NJ, Muenst B, Heinz S, Walles H, Braspenning J: Applicability of second-generation upcyte(R) human hepatocytes for use in CYP inhibition and induction studies. Mol Pharmacol. Abacavir may decrease the excretion rate of Nifedipine which could result in a higher serum level. Hypersensitivity to nifedipine or other calcium-channel blockers. [8], Nifedipine given as sublingual administration has previously been used in hypertensive emergencies. Mechanism of Action of Nifedipine Nifedipine is a dihydropyridine Ca channel blocker. [, Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. An effect category for each drug interaction. [, Waller DG, Renwick AG, Gruchy BS, George CF: The first pass metabolism of nifedipine in man. Nicardipine was approved by the FDA in December 1988. [, Takara K, Sakaeda T, Tanigawara Y, Nishiguchi K, Ohmoto N, Horinouchi M, Komada F, Ohnishi N, Yokoyama T, Okumura K: Effects of 12 Ca2+ antagonists on multidrug resistance, MDR1-mediated transport and MDR1 mRNA expression. 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