Amlodipine Explained

Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure, coronary artery disease (CAD) and variant angina (also called Prinzmetal angina or coronary artery vasospasm, among other names).[1] It is taken orally (swallowed by mouth).

Common side effects include swelling, feeling tired, abdominal pain, and nausea. Serious side effects may include low blood pressure or heart attack. Whether use is safe during pregnancy or breastfeeding is unclear. When used by people with liver problems, and in elderly individuals, doses should be reduced. Amlodipine works partly by vasodilation (relaxing the arteries and increasing their diameter). It is a long-acting calcium channel blocker of the dihydropyridine type.

Amlodipine was patented in 1982, and approved for medical use in 1990.[2] It is on the World Health Organization's List of Essential Medicines.[3] It is available as a generic medication.[4] [5] In 2021, it was the fifth most commonly prescribed medication in the United States, with more than 73million prescriptions.[6] [7]

Medical uses

Amlodipine is used in the management of hypertension (high blood pressure)[8] and coronary artery disease in people with either stable angina (where chest pain occurs mostly after physical or emotional stress) or vasospastic angina (where it occurs in cycles) and without heart failure. It can be used as either monotherapy or combination therapy for the management of hypertension or coronary artery disease. Amlodipine can be administered to adults and to children 6–17 years of age.[9]

Calcium channel blockers, including amlodipine, may provide greater protection against stroke than beta blockers.[10] [11] Evidence from two meta-analyses has reported no significant difference between calcium channel blockers, ACE inhibitors, diuretics [12] and angiotensin receptor blockers in stroke protection while one 2015 meta-analysis has suggested that calcium channel blockers offer greater protection against stroke than other classes of antihypertensive.

Amlodipine along with other calcium channel blockers are considered the first choice in the pharmacological management of Raynaud's phenomenon.[13] [14]

Combination therapy

Amlodipine can be given as a combination therapy with a variety of medications:[15]

Contraindications

The only absolute contraindication to amlodipine is an allergy to amlodipine or any other dihydropyridines.

Other situations occur, however, where amlodipine generally should not be used. In patients with cardiogenic shock, where the heart's ventricles are not able to pump enough blood, calcium channel blockers exacerbate the situation by preventing the flow of calcium ions into cardiac cells, which is required for the heart to pump.[16] While use in patients with aortic stenosis (narrowing of the aorta where it meets the left ventricle) since it does not inhibit the ventricle's function is generally safe, it can still cause collapse in cases of severe stenosis.[17] In unstable angina (excluding variant angina), amlodipine can cause a reflex increase in cardiac contractility (how hard the ventricles squeeze) and heart rate, which together increase the demand for oxygen by the heart itself.[18] Patients with severe hypotension can have their low blood pressure exacerbated, and patients in heart failure can get pulmonary edema. Those with impaired liver function are unable to metabolize amlodipine to its full extent, giving it a longer half-life than typical.[19]

Amlodipine's safety in pregnancy has not been established, although reproductive toxicity at high doses is known. Whether amlodipine enters the milk of breastfeeding mothers is also unknown.

Those who have heart failure, or recently had a heart attack, should take amlodipine with caution.[20]

Adverse effects

Some common dose-dependent adverse effects of amlodipine include vasodilatory effects, peripheral edema, dizziness, palpitations, and flushing.[21] Peripheral edema (fluid accumulation in the tissues) occurs at rate of 10.8% at a 10-mg dose (versus 0.6% for placebos), and is three times more likely in women than in men. It causes more dilation in the arterioles and precapillary vessels than the postcapillary vessels and venules. The increased dilation allows for more blood, which is unable to push through to the relatively constricted postcapillary venules and vessels; the pressure causes much of the plasma to move into the interstitial space.[22] Amlodipine-association edema can be avoided by adding ACE inhibitors or angiotensin II receptor antagonist. Of the other dose-dependent side effects, palpitations (4.5% at 10 mg vs. 0.6% in placebos) and flushing (2.6% vs. 0%) occurred more often in women; dizziness (3.4% vs. 1.5%) had no sex bias.

Common but not dose-related adverse effects are fatigue (4.5% vs. 2.8% with a placebo), nausea (2.9% vs. 1.9%), abdominal pain (1.6% vs. 0.3%), and drowsiness (1.4% vs. 0.6%). Side effects occurring less than 1% of the time include: blood disorders, impotence, depression, peripheral neuropathy, insomnia, tachycardia, gingival enlargement, hepatitis, and jaundice.[23] [24]

Amlodipine-associated gingival overgrowth is a relatively common side effect with exposure to amlodipine. Poor dental health and buildup of dental plaque are risk factors.[25]

Amlodipine may increase the risk of worsening angina or acute myocardial infarction, especially in those with severe obstructive coronary artery disease, upon dosage initiation or increase. However, depending on the situation, amlodipine inhibits constriction and restores blood flow in coronary arteries as a result of its acting directly on vascular smooth muscle, causing a reduction in peripheral vascular resistance and a consequent reduction in blood pressure.[4]

Amlodipine and other dihydropyridine calcium channel blockers are associated with primary open angle glaucoma.[26]

Overdose

See also: Calcium channel blocker toxicity. Although rare,[27] amlodipine overdose toxicity can result in widening of blood vessels, severe low blood pressure, and fast heart rate.[28] Toxicity is generally managed with fluid replacement[29] monitoring ECG results, vital signs, respiratory system function, glucose levels, kidney function, electrolyte levels, and urine output. Vasopressors are also administered when low blood pressure is not alleviated by fluid resuscitation.

Interactions

Several drugs interact with amlodipine to increase its levels in the body. CYP3A inhibitors, by nature of inhibiting the enzyme that metabolizes amlodipine, CYP3A4, are one such class of drugs. Others include the calcium-channel blocker diltiazem, the antibiotic clarithromycin, and possibly some antifungals. Amlodipine causes several drugs to increase in levels, including cyclosporine, simvastatin, and tacrolimus (the increase in the last one being more likely in people with CYP3A5*3 genetic polymorphisms).[30] When more than 20 mg of simvastatin, a lipid-lowering agent, are given with amlodipine, the risk of myopathy increases.[31] The FDA issued a warning to limit simvastatin to a maximum dose of 20 mg if taken with amlodipine based on evidence from the SEARCH trial.[32] Giving amlodipine with Viagra increases the risk of hypotension.

Pharmacology

Amlodipine is a long-acting calcium channel antagonist that selectively inhibits calcium ion influx across cell membranes.[33] It targets L-type calcium channels in muscle cells and N-type calcium channels in the central nervous system which are involved in nociceptive signalling and pain perception.[34] [35] Amlodipine has an inhibitory effect on calcium influx in smooth muscle cells to inhibit contraction.

Amlodipine ends up significantly reducing total vascular resistance without decreasing cardiac output expressed by pressure-rate product and cardiac contractability in comparison with verapamil, a non-dihydropyridine.[36] In turn, following treatment lasting a month, with amlodipine, cardiac output is significantly enhanced. Unlike verapamil which has efficacy in moderation of emotional arousal and reduces cardiac load without lowering cardiac output demands, amlodipine increases the cardiac output response concomitantly with increased functional cardiac load.

Mechanism of action

Amlodipine is an angioselective calcium channel blocker and inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth muscle cells. Amlodipine inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells. This causes vasodilation and a reduction in peripheral vascular resistance, thus lowering blood pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries.[4]

Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Among the two stereoisomers [''R''(+), ''S''(–)], the (–) isomer has been reported to be more active than the (+) isomer.[37] Serum calcium concentration is not affected by amlodipine. And it specifically inhibits the currents of L-type Cav1.3 channels in the zona glomerulosa of the adrenal gland.[38] [39]

The mechanisms by which amlodipine relieves angina are:

Amlodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.[42]

Pharmacokinetics

Amlodipine has been studied in healthy volunteers following oral administration of 14C-labelled drug.[43] Amlodipine is well absorbed by the oral route with a mean oral bioavailability around 60%; the half-life of amlodipine is about 30 h to 50 h, and steady-state plasma concentrations are achieved after 7 to 8 days of daily dosing. In the blood it has high plasma protein binding of 97.5%. Its long half-life and high bioavailability are largely in part of its high pKa (8.6); it is ionized at physiological pH, and thus can strongly attract proteins. It is slowly metabolized in the liver by CYP3A4, with its amine group being oxidized and its side ester chain being hydrolyzed, resulting in an inactive pyridine metabolite.[44] Renal elimination is the major route of excretion with about 60% of an administered dose recovered in urine, largely as inactive pyridine metabolites. However, renal impairment does not significantly influence amlodipine elimination.[45] 20-25% of the drug is excreted in the faeces.[46]

History

Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.[47] A number of generic versions are available. In the United Kingdom, tablets of amlodipine from different suppliers may contain different salts. The strength of the tablets is expressed in terms of amlodipine base, i.e., without the salts. Tablets containing different salts are therefore considered interchangeable. Fixed-dose combination of amlodipine and perindopril, an angiotensin converting enzyme inhibitor are also available.[48]

The medical form comes as besilate, mesylate, or maleate.[49]

Society and culture

Brand names

In the US, Norvasc is marketed by Viatris after Upjohn was spun off from Pfizer.[50] [51]

Veterinary use

Amlodipine is most often used to treat systemic hypertension in both cats and dogs.[52] In cats, it is the first line of treatment due to its efficacy and few side effects.[53] Systemic hypertension in cats is usually secondary to another abnormality, such as chronic kidney disease, and so amlodipine is most often administered to cats with kidney disease.[54] While amlodipine is used in dogs with systemic hypertension, it is not as efficacious. Amlodipine is also used to treat congestive heart failure due to mitral valve regurgitation in dogs.[55] By decreasing resistance to forward flow in the systemic circulation it results in a decrease in regurgitant flow into the left atrium.[56] Similarly, it can be used on dogs and cats with left-to-right shunting lesions such as ventricular septal defect to reduce the shunt. Side effects are rare in cats. In dogs, the primary side effect is gingival hyperplasia.[57]

Notes and References

  1. Book: Goldman's Cecil Medicine . Boden WE . 2012 . Saunders . 978-1-4377-1604-7 . 24th . Dihydropyridine calcium-channel blockers (e.g., amlodipine, 5 to 10 mg orally per day) are preferred in patients with Prinzmetal's angina. . 26 August 2023 . https://web.archive.org/web/20230826150455/https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/variant-angina-pectoris . 26 August 2023 . live.
  2. Book: Analogue-based Drug Discovery . Fischer J, Ganellin CR . 2006 . John Wiley & Sons . 9783527607495 . 465 . 1 June 2020 . https://web.archive.org/web/20210827213813/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA465 . 27 August 2021 . live.
  3. Book: World Health Organization . The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) . ((World Health Organization)) . World Health Organization . 2023 . Geneva . 10665/371090 . WHO/MHP/HPS/EML/2023.02 . free.
  4. Web site: Amlodipine Besylate . live . https://web.archive.org/web/20160604161825/http://www.drugs.com/monograph/amlodipine-besylate.html . 4 June 2016 . 22 July 2016 . Drugs.com . American Society of Hospital Pharmacists.
  5. Web site: 29 June 2023 . Competitive Generic Therapy Approvals . live . https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals . 29 June 2023 . 29 June 2023 . U.S. Food and Drug Administration (FDA).
  6. Web site: The Top 300 of 2021 . live . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . 15 January 2024 . 14 January 2024 . ClinCalc.
  7. Web site: Amlodipine - Drug Usage Statistics . live . https://web.archive.org/web/20200411192007/https://clincalc.com/DrugStats/Drugs/Amlodipine . 11 April 2020 . 14 January 2024 . ClinCalc.
  8. Wang JG . 2009 . A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention . Vascular Health and Risk Management . 5 . 593–605 . 10.2147/vhrm.s6203 . 2725792 . 19688100 . free.
  9. Web site: 14 March 2019 . Norvasc- amlodipine besylate tablet . live . https://web.archive.org/web/20200610221323/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=abd6a2ca-40c2-485c-bc53-db1c652505ed . 10 June 2020 . 29 December 2019 . DailyMed.
  10. Chen GJ, Yang MS . 6 March 2013 . The effects of calcium channel blockers in the prevention of stroke in adults with hypertension: a meta-analysis of data from 273,543 participants in 31 randomized controlled trials . PLOS ONE . 8 . 3 . e57854 . 2013PLoSO...857854C . 10.1371/journal.pone.0057854 . 3590278 . 23483932 . free.
  11. Mukete BN, Cassidy M, Ferdinand KC, Le Jemtel TH . August 2015 . Long-Term Anti-Hypertensive Therapy and Stroke Prevention: A Meta-Analysis . American Journal of Cardiovascular Drugs . 15 . 4 . 243–257 . 10.1007/s40256-015-0129-0 . 26055616 . 33792903.
  12. Iyengar SS, Mohan JC, Ray S, Rao MS, Khan MY, Patted UR, Gaurav K . December 2021 . Effect of Amlodipine in Stroke and Myocardial infarction: A Systematic Review and Meta-analysis . Cardiology and Therapy . 10 . 2 . 429–444 . 10.1007/s40119-021-00239-1 . 8555097 . 34480745.
  13. Baumhäkel M, Böhm M . April 2010 . Recent achievements in the management of Raynaud's phenomenon . Vascular Health and Risk Management . 6 . 207–214 . 10.2147/vhrm.s5255 . 2856576 . 20407628 . free.
  14. Book: StatPearls . Musa R, Qurie A . 2024 . StatPearls Publishing . Treasure Island (FL) . Raynaud Disease . 29763008 . Dihydropyridine calcium channel blockers (DHP CCBs) are the first-line pharmacologic treatment for Raynaud phenomenon. DHP CCBs include amlodipine and nifedipine..
  15. Delgado-Montero A, Zamorano JL . December 2012 . Atorvastatin calcium plus amlodipine for the treatment of hypertension . Expert Opinion on Pharmacotherapy . 13 . 18 . 2673–2685 . 10.1517/14656566.2012.742064 . 23140185 . 43250258.
  16. Web site: Amlodipine Disease Interactions . live . https://web.archive.org/web/20170811011628/https://www.drugs.com/disease-interactions/amlodipine.html . 11 August 2017 . 4 July 2017 . Drugs.com.
  17. Grimard BH, Safford RE, Burns EL . March 2016 . Aortic Stenosis: Diagnosis and Treatment . live . American Family Physician . 93 . 5 . 371–378 . 26926974 . https://web.archive.org/web/20170811010658/http://www.aafp.org/afp/2016/0301/p371.html . 11 August 2017.
  18. Book: The Top 100 Drugs e-book: Clinical Pharmacology and Practical Prescribing . Hitchings A, Lonsdale D, Burrage D, Baker E . 2014 . Elsevier Health Sciences . 9780702055157 . 90 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=oeYjAwAAQBAJ&pg=PA90 . 8 September 2017 . live.
  19. Web site: 28 September 2020 . Istin 5 mg Tablets - Summary of Product Characteristics (SmPC) . live . https://web.archive.org/web/20220620032313/https://www.medicines.org.uk/emc/product/1069/smpc . 20 June 2022 . 19 June 2022 . (emc).
  20. Web site: 29 August 2018 . Amlodipine: medicine to treat high blood pressure . live . https://web.archive.org/web/20190209180234/https://www.nhs.uk/medicines/amlodipine/ . 9 February 2019 . 7 February 2019 . nhs.uk.
  21. Russell RP . March 1988 . Side effects of calcium channel blockers . Hypertension . 11 . 3 Pt 2 . II42–II44 . 10.1161/01.HYP.11.3_Pt_2.II42 . 3280492 . free . doi.
  22. Sica D . 1 July 2003 . Calcium channel blocker-related periperal edema: can it be resolved? . Journal of Clinical Hypertension . 5 . 4 . 291–4, 297 . 10.1111/j.1524-6175.2003.02402.x . 8099365 . 12939574 . 38027134 . free . doi.
  23. Book: Handbook of Pediatric Cardiovascular Drugs . Munoz R, Vetterly CG, Rother SJ, Da Cruz EM . 18 October 2007 . Springer Science & Business Media . 9781846289538 . 96 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=NiTR3Uzp_jMC&pg=PA96 . 8 September 2017 . live.
  24. Ono M, Tanaka S, Takeuchi R, Matsumoto H, Okada H, Yamamoto H, Makiyama Y, Hirayama T, Sakamaki T, Fujii A, Akimoto Y . 2010 . Prevalence of Amlodipine-induced Gingival Overgrowth . International Journal of Oral-Medical Sciences . 9 . 2 . 96–100 . 10.5466/ijoms.9.96 . free . doi.
  25. Gaur S, Agnihotri R . June 2018 . Is dental plaque the only etiological factor in Amlodipine induced gingival overgrowth? A systematic review of evidence . Journal of Clinical and Experimental Dentistry . 10 . 6 . e610–e619 . 10.4317/jced.54715 . 6005094 . 29930781.
  26. Kastner A, Stuart KV, Montesano G, De Moraes CG, Kang JH, Wiggs JL, Pasquale LR, Hysi P, Chua SY, Patel PJ, Foster PJ, Khaw PT, Khawaja AP . October 2023 . Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants . JAMA Ophthalmology . 141 . 10 . 956–964 . 10.1001/jamaophthalmol.2023.3877 . 10485742 . 37676684 . 7 September 2024.
  27. Book: Side Effects of Drugs Annual 35 . Aronson J . Elsevier . 2014 . 978-0-444-62635-6.
  28. Book: Modern Medical Toxicology . Pillay V . Jaypee . 2013 . 978-93-5025-965-8 . 4th.
  29. Book: Approach to Internal Medicine: A Resource Book for Clinical Practice . Hui D . Springer . 2015 . 978-3-319-11820-8 . 4th.
  30. Zuo XC, Zhou YN, Zhang BK, Yang GP, Cheng ZN, Yuan H, Ouyang DS, Liu SK, Barrett JS, Li PJ, Liu Z, Tan HY, Guo R, Zhou LY, Xie YL, Li ZJ, Li J, Wang CJ, Wang JL . 2013 . Effect of CYP3A5*3 polymorphism on pharmacokinetic drug interaction between tacrolimus and amlodipine . live . Drug Metabolism and Pharmacokinetics . 28 . 5 . 398–405 . 10.2133/dmpk.DMPK-12-RG-148 . 23438946 . https://web.archive.org/web/20170811010432/https://www.jstage.jst.go.jp/article/dmpk/28/5/28_DMPK-12-RG-148/_pdf . 11 August 2017.
  31. Web site: Center for Drug Evaluation and Research . 15 December 2017 . FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury . live . https://web.archive.org/web/20130106223019/https://www.fda.gov/Drugs/DrugSafety/ucm256581.htm . 6 January 2013 . 30 April 2019 . Drug Safety and Availability . FDA.
  32. Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Peto R, Collins R . November 2010 . Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial . Lancet . 376 . 9753 . 1658–1669 . 10.1016/s0140-6736(10)60310-8 . 2988223 . 21067805.
  33. Book: Profiles of Drug Substances, Excipients, and Related Methodology . Ananchenko G, Novakovic J, Lewis J . 1 January 2012 . Academic Press . 9780123972200 . Profiles of Drug Substances, Excipients and Related Methodology . 37 . 31–77 . Amlodipine Besylate . 10.1016/b978-0-12-397220-0.00002-7 . 22469316 . 205142025.
  34. Web site: Amlodipine . live . https://web.archive.org/web/20190131040154/https://www.drugbank.ca/drugs/DB00381 . 31 January 2019 . 30 January 2019 . www.drugbank.ca.
  35. Book: Calcium Channel Blockers: Current Controversies and Basic Mechanisms of Action . Clusin WT, Anderson ME . 1 January 1999 . Academic Press . 9780120329472 . Advances in Pharmacology . 46 . 253–296 . 10.1016/s1054-3589(08)60473-1 . 10332505.
  36. Nazzaro P, Manzari M, Merlo M, Triggiani R, Scarano AM, Lasciarrea A, Pirrelli A . September 1995 . Antihypertensive treatment with verapamil and amlodipine. Their effect on the functional autonomic and cardiovascular stress responses . European Heart Journal . 16 . 9 . 1277–1284 . 10.1093/oxfordjournals.eurheartj.a061086 . 8582392.
  37. Karmoker JR, Joydhar P, Sarkar S, Rahman M . 2016 . Comparative in vitro evaluation of various commercial brands of amlodipine besylate tablets marketed in Bangladesh . dead . Asian Journal of Pharmaceutical and Health Sciences . 6 . 1384–1389 . https://web.archive.org/web/20160701194238/http://www.ajphs.com/journals/02_AJPHS_Jan-Mar_2016_738.pdf . 1 July 2016 . 29 May 2016.
  38. Book: Pharmacotherapeutics for Advanced Practice: A Practical Approach . Arcangelo VP, Peterson AM . Lippincott Williams & Wilkins . 2006 . 9780781757843 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=EaP1yJz4fkEC&pg=PA252 . 8 September 2017 . live.
  39. Book: A Textbook of Clinical Pharmacology and Therapeutics . Ritter J, Lewis L, Mant T, Ferro A . CRC Press . 2012 . 9781444113006 . 5 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=TD59BgAAQBAJ&pg=PA191 . 8 September 2017 . live.
  40. Book: Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based Therapeutics . Li YR . 2015 . John Wiley & Sons . 9780470915370 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=rXy0BgAAQBAJ&pg=PA189 . 8 September 2017 . live.
  41. Book: 2013 Nurse's Drug Handbook . Jones & Bartlett Publishers . 2012 . 9781449642846 . https://web.archive.org/web/20170908192421/https://books.google.com/books?id=ckdTGZe7aRAC&pg=PA73 . 8 September 2017 . live.
  42. Luther JM . September 2014 . Is there a new dawn for selective mineralocorticoid receptor antagonism? . Current Opinion in Nephrology and Hypertension . 23 . 5 . 456–461 . 10.1097/MNH.0000000000000051 . 4248353 . 24992570.
  43. Beresford AP, McGibney D, Humphrey MJ, Macrae PV, Stopher DA . February 1988 . Metabolism and kinetics of amlodipine in man . Xenobiotica; the Fate of Foreign Compounds in Biological Systems . 18 . 2 . 245–254 . 10.3109/00498258809041660 . 2967593.
  44. Book: Amlodipine . Nayler WG . 2012 . Springer Science & Business Media . 9783642782237 . 105 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=Z5T0BwAAQBAJ&pg=PT105 . 8 September 2017 . live.
  45. Book: Profiles of Drug Substances, Excipients and Related Methodology . Brittain HG . Academic Press . 2012 . 9780123977564 . https://web.archive.org/web/20170908192420/https://books.google.com/books?id=ew_MiZ_xBdcC&pg=PA68 . 8 September 2017 . live.
  46. Murdoch D, Heel RC . March 1991 . Amlodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease . Drugs . 41 . 3 . 478–505 . 10.2165/00003495-199141030-00009 . 1711448 . 195693179.
  47. News: 22 March 2007 . Pfizer loses court ruling on Norvasc patent . live . https://web.archive.org/web/20080803060500/http://www.marketwatch.com/news/story/pfizer-loses-court-ruling-norvasc/story.aspx?guid=%7B9819D67E-B76B-431D-835C-FB8D6D8327B7%7D . 3 August 2008 . MarketWatch . Kennedy VB.
  48. on amlodipine and perindopril. Accessed 28 February 2020.
  49. Book: Intracellular Calcium . Campbell AK . 14 October 2014 . John Wiley & Sons . 9781118675526 . 68 . 10 August 2016 . https://web.archive.org/web/20210101093831/https://books.google.com/books?id=aDbcBAAAQBAJ&pg=PA68 . 1 January 2021 . live.
  50. Web site: 16 November 2020 . Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan . 17 June 2024 . Pfizer . Business Wire.
  51. Web site: Norvasc . 17 June 2024 . Pfizer.
  52. Book: Saunders Handbook of Veterinary Drugs . Papich MG . 2007 . Saunders/Elsevier . 9781416028888 . 2nd . St. Louis, Mo . 26–27 . Amlodipine Besylate.
  53. Henik RA, Snyder PS, Volk LM . 28 August 2014 . Treatment of systemic hypertension in cats with amlodipine besylate . Journal of the American Animal Hospital Association . 33 . 3 . 226–234 . 10.5326/15473317-33-3-226 . 9138233.
  54. Web site: Amlodipine in Veterinary Medicine . live . https://web.archive.org/web/20170811011323/http://www.diamondbackdrugs.com/treating-high-blood-pressure-with-amlodipine/ . 11 August 2017 . 29 June 2017 . Diamondback Drugs.
  55. Atkins C, Bonagura J, Ettinger S, Fox P, Gordon S, Haggstrom J, Hamlin R, Keene B, Luis-Fuentes V, Stepien R . 1 November 2009 . Guidelines for the diagnosis and treatment of canine chronic valvular heart disease . live . Journal of Veterinary Internal Medicine . 23 . 6 . 1142–1150 . 10.1111/j.1939-1676.2009.0392.x . 19780929 . https://web.archive.org/web/20240110170518/https://rvc-repository.worktribe.com/preview/1650595/10.1016%20j%20jevs%202023%20104896.pdf . 10 January 2024 . 13 January 2024 . free . doi.
  56. Suzuki S, Fukushima R, Ishikawa T, Yamamoto Y, Hamabe L, Kim S, Yoshiyuki R, Machida N, Tanaka R . September 2012 . Comparative effects of amlodipine and benazepril on left atrial pressure in dogs with experimentally-induced mitral valve regurgitation . BMC Veterinary Research . 8 . 166 . 10.1186/1746-6148-8-166 . 3489586 . 22989022 . free.
  57. Web site: Amlodipine for Veterinary Use . live . https://web.archive.org/web/20170627172329/http://www.wedgewoodpetrx.com/learning-center/professional-monographs/amlodipine-for-veterinary-use.html . 27 June 2017 . 29 June 2017 . Wedgewood Pharmacy . Forney B.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Amlodipine".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.