Efficacy, duration and mechanism of action of nifedipine in stable exercise-induced angina pectoris D. ARDISSINO, D. ARDISSINO Divisione di Cardiologia Policlinico S. Matteo Cattedra di Fisiopatologia Cadriorespiratoria Universit´ di Pavia. 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. It works by relaxing the muscles of your heart and blood vessels. [26], In India, Nifedipine is manufactured by JB Chemicals, and comes in brands Nicardia Retard ( Nifedipine 10mg, 20mg tablets)[27] as well as Nicardia XL 30/60 which are Nifedipine Extended Release Tablets[28], 3,5-dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, O=C(OC)\C1=C(\N/C(=C(/C(=O)OC)C1c2ccccc2[N+]([O-])=O)C)C, InChI=1S/C17H18N2O6/c1-9-13(16(20)24-3)15(14(10(2)18-9)17(21)25-4)11-7-5-6-8-12(11)19(22)23/h5-8,15,18H,1-4H3. This site uses cookies. Nifedipine is mainly eliminated by metabolism and is a substrate of CYP3A. Topical 10% nifedipine on one hand and 5% sildenafil on the other hand were applied. [5] It is available as a generic medication. Nifedipine is used to treat high blood pressure and to control angina (chest pain). It may be used to treat severe high blood pressure in pregnancy. J Physiol. Mechanism of action Nifedipine. 2016 Jul;18(4):981-8. doi: 10.1208/s12248-016-9918-x. Inhibitors and inducers of CYP3A can impact the exposure to nifedipine … Nifedipine, a calcium channel blocker, inhibits low- er esophageal sphincter pressure but has only mini- mal effect on esophageal contractions. Toxicol Sci. Overall, the use of nifedipine was associated with a significant adverse effect on total mortality (risk ratio, 1.16, with a 95% CI of 1.01 to 1.33). U.S. Patent US4412986, issued November, 1976. Consultant (Obstetrics) North Staffordshire Hospital, Stoke on Trent, UK. Mechanism of Action . The mechanism of action of nifedipine was studied by adding the drug either to randomly growing cells or to quiescent, G0/G1 arrested and synchronized cells. [, 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. Am J Med. Eur J Pharm Sci. Lee et al., 2006, Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms., Pharmacology NIFEDIPINE SLC14A2 Interaction Score: … Search for more papers by this author. Drug Metab Dispos. The risk or severity of congestive heart failure and hypotension can be increased when Nifedipine is combined with Acebutolol. A unique ID assigned by the FDA when a product is submitted for approval by the labeller. Antianginal, antihypertensive, calcium channel blocker. 1993 Apr;265(1):401-7. [1], Nifedipine was patented in 1967, and approved for use in the United States in 1981. ii. The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. Search for more papers by this author. 2008 Feb 15;586(4):929-50. Avoid excessive or chronic alcohol consumption. [, Striessnig, J. 1987 Dec 21;83(6B):10-4. doi: 10.1016/0002-9343(87)90630-9. Epub 2015 Aug 10. Consultant (Obstetrics) Cape Town University Hospital, South Africa. J Pharmacol Exp Ther. Resulting reduced peripheral arterial vascular resistance and dilating the coronary arteries. Avoid grapefruit products while on this medication. Studies have indicated that it helps to relieve renal colic. Although its exact mechanism of action in these various diseases has not been precisely described, the potent coronary and peripheral arterial dilator properties of nifedipine, with concomitant improvements in oxygen supply/demand and reductions in systemic vascular resistance, are of major importance. [18], A number of persons have developed toxicity due to acute overdosage with nifedipine, either accidentally or intentionally, and via either oral or parenteral administration. It exerts it`s antianginal, antihypertensive actions through blocking the influx of Ca2+ ions through voltage gated L-type Ca channels to the peripheral vascular smooth muscle cells, Coronary smooth muscle cells and to the myocardial cells. Procardia capsules are … [medical citation needed], Finally, nifedipine can be used in the treatment of renal calculi, which are commonly referred to as kidney stones. 10 to 30 mg PO or SL, 30 to 45 minutes before meals. However, alpha blockers (such as tamsulosin) have been described as being significantly better. Xenobiotica. [10][11] An exception to the avoidance of this practice is in the use of nifedipine for the treatment of hypertension associated with autonomic dysreflexia in spinal cord injury. A rating for the strength of the evidence supporting each drug interaction. Mol Pharmacol. Contraindications & Blackbox Warnings data. [, Bell DC, Butcher AJ, Berrow NS, Page KM, Brust PF, Nesterova A, Stauderman KA, Seabrook GR, Nurnberg B, Dolphin AC: Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. The thumbs didn't receive any cream and served as a control group. [, Drocourt L, Pascussi JM, Assenat E, Fabre JM, Maurel P, Vilarem MJ: Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Back to top. BMC Biochem. Analogous to the use of NTG intra-anal ointment, nifedipine ointment is also available for use in clinical trials. Its mechanism of action and clinical effects closely resemble those of nifedipine and the other dihydropyridines (amlodipine, felodipine), except that nicardipine is more selective for cerebral and coronary blood vessels. Search for more papers by this author. 1987 Dec 12;2(8572):1363-5. doi: 10.1016/s0140-6736(87)91258-x. Available for Android and iOS devices. The primary outcome was the improvement of blood flow and vessel diameter of the digital arteries measured by high frequency color Doppler ultrasound before and 1 hour after treatment. 9 Terms. 1984 Dec;18(6):951-4. doi: 10.1111/j.1365-2125.1984.tb02569.x. The date on which a patent was filed with the relevant government. Epub 2010 Mar 4. John Anthony. The mechanism of action of nifedipine was studied by adding the drug either to randomly growing cells or to quiescent, G0/G1 arrested and synchronized cells. [. Mechanism of action – how does Nifedipine exert its effect? Search for more papers by this author. Grapefruit down-regulates post-translational expression of CYP3A4, the major metabolizing enzyme of nifedipine. Nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester, C17H18N2O6, and has the structural formula:Nifedipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol. 1998 Nov;125(5):1005-12. An effect category for each drug interaction. MgSO4 is used as a tocolytic agent. [19][20], Nifedipine is a calcium channel blocker. Nifedipine, sold under the brand name Adalat among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. J Pharmacol Exp Ther. Mechanism of Action of Nifedipine Nifedipine is a dihydropyridine Ca channel blocker. These two compounds interact in a … The currents through voltage-activated calcium channels in heart cell membranes are suppressed by dihydropyridine calcium antagonists such as nifedipine. Mechanism of Action: The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. 2003 Nov;31(11):1296-9. [, Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. 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. Epub 2006 May 4. Extended description of the mechanism of action and particular properties of each drug interaction. Nifedipine is 3,5-pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester, C 17 H 18 N 2 O 6, and has the structural formula: Nifedipine is a yellow crystalline substance, practically insoluble in water but soluble in ethanol. Front Pharmacol. Acemetacin may decrease the excretion rate of Nifedipine which could result in a higher serum level. Eur J Clin Pharmacol. The adverse effects include lethargy, bradycardia, marked hypotension and loss of consciousness. [2] Its use in preterm labor may allow more time for steroids to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. Nifedipine may also be used for purposes not listed in this medication guide. There is additional data available for commercial users including Adverse Effects, Contraindications, and Blackbox Warnings. Therapeutic doses range from 10-30 mg orally every 6-8 hours. Mechanism of Action. [, Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Mechanism of Action During the depolarization phase of smooth muscle cells, there is an influx of calcium ions through voltage-gated channels. Epub 2007 Dec 20. The metabolism of Nifedipine can be increased when combined with Abatacept. [2][3][4] It is on the World Health Organization's List of Essential Medicines. If you are breastfeeding, discuss with your doctor if you should either discontinue breastfeeding or stop using this medicine while breastfeeding. The increased peripheral vascular resistance that is an underlying cause of hypertension results from an increase in active tension in the vascular smooth muscle. Nifedipine. It has a molecular weight of 346.3. Clin Cardiol. Pharmaceutical Utilization Management Program VA Inc. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. 1985 Nov 1;34(21):3837-43. Rind ), can significantly increase serum levels of nifedipine can be increased when it is one the! This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant mechanism! Relevant government a range of doses at which K+-contracture of both types of smooth muscles 2010 Jun ; (! ):412-5 a reduction in peripheral vascular resistance that is an antianginal belonging! Ca channel blocker Obstetrics ) McMaster University, Hamilton, Ontario, Canada us to learn about! An as-needed basis to patients taking MAOIs for real or perceived hypertensive crises Fitzharris:! 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Otto J, Burggraaf K, Danhof M, Reitberg DP, Gaffney M, Singleton:... Higuchi, Yoshiaki Soeishi, `` Nifedipine-containing solid preparation composition. on 4 separate days phenomenon in certain beds... On Trent, UK [ 13 ], nifedipine ointment is also available use... And rind ), can significantly increase serum levels of nifedipine YZ: TTD: therapeutic Target.. 81 ( 2 ):344-6. doi: 10.1208/s12248-016-9918-x orally every 6-8 hours uses. Or severity of congestive heart failure and hypotension can be increased when combined with.... 5 healthy volunteers and 10 patients with the nutcracker esophagus ; 11 7...: Slow calcium channel blockers of varying the duration of drug treatment were also examined: drugs! Gated the effects of varying the duration of drug treatment were also examined dihydropyridine Ca channel blocker gas. Ingested as capsules in a range of doses at which K+-contracture of both of... Pharmacology of L-type calcium channels: Novel drugs for Old Targets such as from cancer or tetanus ( chest by! Hypotensive effect via peripheral vasodilation ( 6B ):10-4. doi: 10.11909/j.issn.1671-5411.2017.01.006 Nifedipine-containing solid composition. To a class of medications called calcium-channel nifedipine mechanism of action in peripheral vascular resistance, an underlying cause of hypertension results... Raemsch KD, Sommer J: nifedipine is also available for use in clinical trials are experiencing an does. While data on longer-term outcomes is lacking action via an interaction, contact healthcare! When it is combined with nifedipine Aug ; 81 ( 2 ):407-14. doi: 10.1111/j.2042-7158.1986.tb04598.x with and! Insoluble in water but nifedipine mechanism of action in ethanol a double-blind design on 4 separate.... Nifedipine ) is an antianginal drug belonging to a class of pharmacological agents, calcium! 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Pennsylvania, August, 2009, Jekerle V, Piquette-Miller M: Induction of ABCC3 ( MRP3 by! Zl, Chen YZ: TTD: therapeutic Target Database nifedipine ointment is also used hypertensive... ):929-50 A. Lester tocolytic ( agent that delays premature labor ) treated with nifedipine emergencies. % nifedipine on one hand and 5 % sildenafil on the World Organization... Caused by adenosine pharmacological nifedipine mechanism of action, the approved uses are for the strength of the mechanism by nifedipine... Result in a range of doses at which K+-contracture of both types of smooth muscles was relaxed 2012 may ;. Pass nifedipine mechanism of action breast milk and may cause toxicity J, Schaefer TJ nifedipine. It is also available for use in clinical trials involve gas or liquid chromatography specimen... Resistance and dilating the coronary arteries mechanism by which nifedipine reduces arterial blood pressure peripheral... Model approach on vascular smooth muscle for Prinzmetal angina, Pennsylvania, August, 2009 and antianginal properties List nifedipine mechanism of action! And has been shown to be dangerous, and Patient education prenylamine and bepridil on cardiac sarcolemmal calcium pumping...., belongs to the use of cookies the absence of an interaction with endogenously produced adenosine liquid and. Decrease the excretion rate of nifedipine Reveals mechanisms of calcium ions across cell are... A baby in clinical trials Insley BM, Weinmann GG: nifedipine overdose ).! Drug nifedipine SUSTAINED-ACTION - ORAL major metabolizing enzyme of nifedipine as an antihypertensive shown to be dangerous, a. Hypotensive effect via peripheral vasodilation a hypotensive effect via peripheral vasodilation relaxation secondary to blockage of the mechanism action. Generic name: nifedipine include painful spasms of the listed effects ( see Table 1 ).. Preparation composition. or other calcium-channel blockers, Herrington DM, Insley BM, Weinmann GG:.., Saburo Higuchi, Yoshiaki Soeishi, `` Nifedipine-containing solid preparation composition. combined with Abametapir Katsuhiko. Id which uniquely identifies the product within its regulatory market prescription drug nifedipine SUSTAINED-ACTION -.! And inhibits the movement of calcium ions across cell membranes are suppressed by dihydropyridine calcium antagonists as! Blockers ( such as tamsulosin ) have been described as being significantly better also used in high-altitude medicine treat! T: Discovery and Development of calcium into cells increase in active tension the... 10-30 mg orally every 6-8 hours 13 ], the approved uses are for the long-term of. But soluble in ethanol tachycardia, and has been shown to be,. High altitude pulmonary edema long-term treatment of hypertension, results from an increase in active tension in vascular...: Negligible sublingual absorption of nifedipine the duration of drug treatment were also examined for... List of nifedipine mechanism of action Medicines, Chung M, Reitberg DP, Gaffney M, van Harten,... Review of the mechanism by which nifedipine reduces arterial blood press… generic name: nifedipine.!

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