请输入您要查询的百科知识：

　

词条 Amlodipine
释义

  1. Medical uses

     Combination therapy 

  2. Contraindications

  3. Adverse effects

  4. Overdose

  5. Interactions

  6. Pharmacology

      Mechanism of action   Pharmacokinetics 

  7. History

  8. Veterinary use

  9. References

  10. External links

{{Use dmy dates|date=July 2013}}{{Drugbox
| verifiedrevid = 456689822
| IUPAC_name = (RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
| image = Amlodipine.svg
| width = 230
| image2 = Amlodipine 3D ball.png
| width2 = 200
| chirality = Racemic mixture
| pronounce = {{IPAc-en|æ|m|ˈ|l|oʊ|d|ɪ|ˌ|p|iː|n}}[1]
| tradename = Norvasc, others
| class = Calcium channel blocker
| Drugs.com = {{drugs.com|monograph|amlodipine-besylate}}
| MedlinePlus = a692044
| license_US = Amlodipine
| licence_EU = yes
| DailyMedID=Amlodipine
| pregnancy_AU = C
| pregnancy_US = C


| legal_status=Rx-only
| routes_of_administration = By mouth
| bioavailability = 64–90%
| protein_bound = 93% [2]
| metabolism = Liver
| metabolites = Various inactive pyrimidine metabolites
| onset = Highest availability 6–12 hours after oral dose
| elimination_half-life = 30–50 hours
| duration_of_action = At least 24 hours
| excretion = Urine
| IUPHAR_ligand = 6981
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 88150-42-9
| ATC_prefix = C08
| ATC_suffix = CA01
| PubChem = 2162
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00381
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2077
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 1J444QC288
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07450
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2668
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1491
| PDB_ligand = 6UB
| C=20 | H=25 | Cl=1 | N=2 | O=5
| molecular_weight = 408.879 g/mol
| smiles = Clc1ccccc1C2C(=C(/N/C(=C2/C(=O)OCC)COCCN)C)\\C(=O)OC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HTIQEAQVCYTUBX-UHFFFAOYSA-N
}}Amlodipine, sold under the brand name Norvasc among others, is a medication used to treat high blood pressure and coronary artery disease.[3] While not typically recommended in heart failure, amlodipine may be used if other medications are not sufficient for treating high blood pressure or heart-related chest pain.[2] It is taken by mouth and has an effect for at least a day.[3]

Common side effects include swelling, feeling tired, abdominal pain, and nausea.[3] Serious side effects may include low blood pressure or heart attack.[3] Whether use is safe during pregnancy or breastfeeding is unclear.[3] When used by people with liver problems, and in elderly individuals, doses should be reduced.[3] Amlodipine works partly by increasing the size of arteries.[3] It is a long-acting calcium channel blocker of the dihydropyridine type.[3]

Amlodipine was patented in 1982 and approved for medical use in 1990.[3] It is on the World Health Organization's List of Essential Medicines, which lists the most effective and safe medicines needed in a health system.[4] It is available as a generic medication.[5] Wholesale cost in the developing world is US$0.003 to 0.066 per day for a typical dose as of 2015.[6] In the United States, a month's supply costs less than $25.[7] In 2016, it was the 5th most prescribed medication in the United States, with more than 75 million prescriptions.[8]

Medical uses

Amlodipine is used in the management of hypertension[9] and coronary artery disease in people with either stable angina (where chest pain occurs mostly after physical or emotional stress)[10] 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 children 6–17 years of age.[11] Calcium channel blockers, including amlodipine, may provide greater protection against stroke than other classes of blood pressure-lowering drugs.[12]

Combination therapy

Amlodipine can be given as a combination therapy with a variety of medications:[5][13]

  • Amlodipine/atorvastatin, where amlodipine is given for hypertension or CAD and atorvastatin prevents cardiovascular events, or if the person also has high cholesterol.
  • Amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide if amlodipine alone cannot reduce blood pressure. Aliskiren is a renin inhibitor, which works to reduce primary hypertension (that with no known cause) by binding to renin and preventing it from initiating the renin–angiotensin system (RAAS) pathway to increase blood pressure. Hydrochlorothiazide is a diuretic and decreases overall blood volume.
  • Amlodipine/benazepril if either drug has failed individually, or amlodipine alone caused edema. Benazepril is an ACE inhibitor and blocks the conversion of angiotensin I to angiotensin II in the RAAS pathway.
  • Amlodipine/olmesartan or amlodipine/olmesartan/hydrochlorothiazide if amlodipine is insufficient in reducing blood pressure. Olmesartan is an angiotensin II receptor antagonist and blocks part of the RAAS pathway.
  • Amlodipine/perindopril if using amlodipine alone caused edema. Perindopril is a long-lasting ACE inhibitor.
  • Amlodipine/telmisartan, where telmisartan is an angiotensin II receptor antagonist.
  • Amlodipine/valsartan or amlodipine/valsartan/hydrochlorothiazide, where valsartan is an angiotensin II receptor antagonist.

Contraindications

The only absolute contraindication to amlodipine is an allergy to amlodipine or any other dihydropyridines.[14]

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.[15] 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.[16] 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.[17] 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.[14][18]

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.[14][18]

For those who have heart failure or recently had a heart attack, should take amlodipine with caution.[19]

Adverse effects

Some common dose-dependent adverse effects of amolodipine include vasodilatory effects, peripheral edema, dizziness, palpitations, and flushing.[14][20] 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.[11] 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.[21] Amlodipine-association edema can be avoided by adding ACE inhibitors or angiontensin II receptor antagonist.[5] 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.[11][14]

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 somnolence (1.4% vs. 0.6%).[14] Side effects occurring less than 1% of the time include: blood disorders, impotence, depression, peripheral neuropathy, insomnia, tachycardia, gingival enlargement, hepatitis, and jaundice.[14][22][23]

Amlodipine-associated gingival overgrowth is a relatively common side effect with exposure to amlodipine.[44] Poor dental health and build up of dental plaque is a risk factor.[24]

Amlodipine may increase the risk of worsening angina or acute myocardium infraction, 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 property that works directly on vascular smooth muscle causing reduction in peripheral vascular resistance and consequent reduction in blood pressure.[5]

Overdose

{{See also|Calcium channel blocker toxicity}}

Although rare,[25] amlodipine overdose toxicity can result in widening of blood vessels, severe low blood pressure, and fast heart rate.[26] Toxicity is generally managed with fluid replacement[27] 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.[11][26]

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.[11] 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).[28] When more than 20 mg of simvastatin, a lipid-lowering agent, are given with amlodipine, the risk of myopathy increases.[29] Giving amlodipine with Viagra increases the risk of hypotension.[11][5]

Pharmacology

Amlodipine is a long acting calcium channel antagonist that selectively inhibits calcium ion influx across cell membranes.[30] 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.[31][32] 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. [33] In turn, following treatment lasting a month, with amlodipine, cardiac output was significantly enhanced. [33] Unlike verapamil which has efficacy in moderation of emotional arousal and reduces cardiac load without lowering cardiac output demands, amlidpine, on the other hand, increases the cardiac output response concomitantly with increased functional cardiac load[33].

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.[5]

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.[34] 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.[35][36]

The mechanisms by which amlodipine relieves angina are:

  • Stable angina: amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, thereby lowering myocardial oxygen demand, at any given level of exercise.[37]
  • Variant angina: amlodipine blocks spasm of the coronary arteries and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.[38]

Amlodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.[39]

Pharmacokinetics

Amlodipine has been studied in healthy volunteers following oral administration of 14C-labelled drug.[41] 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%.[42] 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.[11] 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.[43] 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.[44] 20-25% of the drug is excreted in the faeces.[45]

History

Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.[46] 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. The efficacy and tolerability of a fixed-dose combination of amlodipine and perindopril, an angiotensin converting enzyme inhibitor, have recently been confirmed in a prospective, observational, multicentre trial of 1250 hypertensive patients.[47]

The medical form comes as besylate, mesylate or maleate.[48]

Veterinary use

Amlodipine is most often used to treat systemic hypertension in cats and dogs.[49] In cats, it is the first line of treatment due to its efficacy and few side effects.[50] 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.[51] 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.[52] By decreasing resistance to forward flow in the systemic circulation it results in a decrease in regurgitant flow into the left atrium.[53] 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.[54]

References

1. ^{{cite web|title=Medical Definition of AMLODIPINE|url=https://www.merriam-webster.com/medical/amlodipine|website=www.merriam-webster.com|accessdate=5 July 2017|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20161108030935/http://www.merriam-webster.com/medical/amlodipine|archivedate=8 November 2016|df=dmy-all}}
2. ^{{cite book|title=The ESC Textbook of Preventive Cardiology: Clinical Practice|date=2015|publisher=Oxford University Press|isbn=9780199656653|page=261|ref=https://books.google.ca/books?id=MmXiBwAAQBAJ&pg=PA261}}
3. ^{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=465 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA465 |language=en}}
4. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=dmy-all}}
5. ^1 2 3 4 5 6 7 8 9 10 11 12 13 {{cite web|title=Amlodipine Besylate|url=https://www.drugs.com/monograph/amlodipine-besylate.html|website=Drugs.com|publisher=American Society of Hospital Pharmacists|accessdate=22 July 2016|deadurl=no|archiveurl=https://web.archive.org/web/20160604161825/http://www.drugs.com/monograph/amlodipine-besylate.html|archivedate=4 June 2016|df=dmy-all}}
6. ^{{cite web|title=Amlodipine|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=1029&searchYear=2015|website=International Drug Price Indicator Guide|accessdate=23 July 2016|deadurl=no|archiveurl=https://web.archive.org/web/20170811011446/http://mshpriceguide.org/en/single-drug-information/?DMFId=1029&searchYear=2015|archivedate=11 August 2017|df=dmy-all}}
7. ^{{cite book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia | edition= Deluxe Lab-Coat|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=154}}
8. ^{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=clincalc.com |accessdate=22 December 2018}}
9. ^{{cite journal | last=Wang|first=JG| title = A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention| journal = Vascular Health and Risk Management |volume=5 | issue= | pages = 593–605|year=2009 | pmid=19688100|doi= 10.2147/vhrm.s6203 | pmc=2725792}}
10. ^{{MedlinePlusEncyclopedia|000198|Stable angina}}
11. ^1 2 3 4 5 6 7 8 9 10 {{Cite web|url =http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf|title =Norvasc Prescribing Information|date =|accessdate =3 July 2017|website =|deadurl =no|archiveurl =https://web.archive.org/web/20170216181729/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf|archivedate =16 February 2017|df =dmy-all}}
12. ^{{cite journal |vauthors=Mukete BN, Cassidy M, Ferdinand KC, Le Jemtel TH |title=Long-Term Anti-Hypertensive Therapy and Stroke Prevention: A Meta-Analysis |journal=Am J Cardiovasc Drugs |volume=15 |issue=4 |pages=243–57 |date=August 2015 |pmid=26055616 |doi=10.1007/s40256-015-0129-0 |url=}}
13. ^{{Cite journal|title = Atorvastatin calcium plus amlodipine for the treatment of hypertension|journal = Expert Opinion on Pharmacotherapy|date = 1 December 2012|issn = 1465-6566|pages = 2673–2685|volume = 13|issue = 18|doi = 10.1517/14656566.2012.742064|pmid = 23140185|first = Antonia|last = Delgado-Montero|first2 = Jose L.|last2 = Zamorano}}{{closed access}}
14. ^1 2 3 4 5 6 {{Cite web|title = Amlodipine besylate tablet|url = http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1cec7a02-b7a5-49e1-ab64-3a4dab4149d2|website = DailyMed|accessdate = 5 November 2015|publisher = US National Library of Medicine|deadurl = no|archiveurl = https://web.archive.org/web/20151029071325/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1cec7a02-b7a5-49e1-ab64-3a4dab4149d2|archivedate = 29 October 2015|df = dmy-all}}
15. ^{{Cite web | title=Amlodipine Disease Interactions | work=Drugs.com | accessdate=4 July 2017 | url=https://www.drugs.com/disease-interactions/amlodipine.html | deadurl=no | archiveurl=https://web.archive.org/web/20170811011628/https://www.drugs.com/disease-interactions/amlodipine.html | archivedate=11 August 2017 | df=dmy-all }}
16. ^{{Cite journal | last1=Grimard | first1=Brian H. | last2=Safford | first2=Robert E. | last3=Burns | first3=Elizabeth L. | title=Aortic Stenosis: Diagnosis and Treatment | journal=American Family Physician | date=2016 | url=http://www.aafp.org/afp/2016/0301/p371.html | issn=0002-838X | volume=93 | issue=5 | pages=371–378 | deadurl=no | archiveurl=https://web.archive.org/web/20170811010658/http://www.aafp.org/afp/2016/0301/p371.html | archivedate=11 August 2017 | df=dmy-all }}
17. ^{{Cite book | last1=Hitchings | first1=Andrew | last2=Lonsdale | first2=Dagan | last3=Burrage | first3=Daniel | last4=Baker | first4=Emma | title=The Top 100 Drugs e-book: Clinical Pharmacology and Practical Prescribing | page=90 | date=2014 | publisher=Elsevier Health Sciences | isbn=9780702055157 | url=https://books.google.com/books?id=oeYjAwAAQBAJ&pg=PA90 | deadurl=no | archiveurl=https://web.archive.org/web/20170908192420/https://books.google.com/books?id=oeYjAwAAQBAJ&pg=PA90 | archivedate=8 September 2017 | df=dmy-all }}
18. ^1 {{Cite web | title=Amlodipine 5mg Tablets | work=emc | accessdate=3 July 2017 | date=30 May 2017 | url=https://www.medicines.org.uk/emc/medicine/26288 | deadurl=no | archiveurl=https://web.archive.org/web/20170714204439/http://www.medicines.org.uk/emc/medicine/26288 | archivedate=14 July 2017 | df=dmy-all }}
19. ^{{cite web | title=Amlodipine: medicine to treat high blood pressure | website=nhs.uk | date=2018-08-29 | url=https://www.nhs.uk/medicines/amlodipine/ | access-date=2019-02-07}}
20. ^{{Cite journal | last=Russell | first=R. P. | title=Side effects of calcium channel blockers. | journal=Hypertension | date=1988 | pmid=3280492 | doi=10.1161/01.HYP.11.3_Pt_2.II42 | issn=0194-911X | volume=11 | issue=3 Pt 2 | pages=II42–4 | df=dmy-all }}
21. ^{{Cite journal | last=Sica | first=Domenic A. | title=Calcium Channel Blocker-Related Peripheral Edema: Can It Be Resolved? | journal=The Journal of Clinical Hypertension | date=1 July 2003 | doi=10.1111/j.1524-6175.2003.02402.x | issn=1751-7176 | volume=5 | issue=4 | pages=291–295 | df=dmy-all }}
22. ^{{Cite book|title = Handbook of Pediatric Cardiovascular Drugs|url = https://books.google.com/books?id=NiTR3Uzp_jMC&pg=PA96|publisher = Springer Science & Business Media|date = 18 October 2007|isbn = 9781846289538|first = Ricardo|last = Munoz|first2 = Carol G.|last2 = Vetterly|first3 = Stephen J.|last3 = Roth|first4 = Eduardo da|last4 = Cruz|page = 96|deadurl = no|archiveurl = https://web.archive.org/web/20170908192420/https://books.google.com/books?id=NiTR3Uzp_jMC&pg=PA96|archivedate = 8 September 2017|df = dmy-all}}
23. ^{{cite journal |last1=Ono |first1=M. et. al |date=2010 |title=Prevalence of Amlodipine-induced Gingival Overgrowth |journal=Int J Oral-Med Sci |volume=9 |issue=2 |pages=96–100 |doi=10.5466/ijoms.9.96 }}
24. ^1 {{cite journal |vauthors=Gaur S, Agnihotri R |title=Is dental plaque the only etiological factor in Amlodipine induced gingival overgrowth? A systematic review of evidence |journal=J Clin Exp Dent |volume=10 |issue=6 |pages=e610–e619 |date=June 2018 |pmid=29930781 |pmc=6005094 |doi=10.4317/jced.54715 |url=}}
25. ^{{Cite book|title = Side Effects of Drugs Annual 35|last = Aronson|first = J|publisher = Elsevier|year = 2014|isbn = 978-0-444-62635-6|location = |pages = }}
26. ^1 2 3 {{Cite book|title = Modern Medical Toxicology |edition=4th |last = Pillay|first = V|publisher = Jaypee|year = 2013|isbn = 978-93-5025-965-8|location = |pages = }}
27. ^{{Cite book|title = Approach to Internal Medicine: A Resource Book for Clinical Practice | edition=4th|last = Hui|first = David|publisher = Springer|year = 2015|isbn = 978-3-319-11820-8|location = |pages = }}
28. ^{{Cite journal|title = Effect of CYP3A5*3 Polymorphism on Pharmacokinetic Drug Interaction between Tacrolimus and Amlodipine|url = https://www.jstage.jst.go.jp/article/dmpk/28/5/28_DMPK-12-RG-148/_pdf|journal = Drug Metabolism and Pharmacokinetics|date = 2013|pages = 398–405|volume = 28|issue = 5|doi = 10.2133/dmpk.DMPK-12-RG-148|pmid = 23438946|first = Xiao-cong|last = Zuo|first2 = Ya-nan|last2 = Zhou|first3 = Bi-kui|last3 = Zhang|first4 = Guo-ping|last4 = Yang|first5 = Ze-neng|last5 = Cheng|first6 = Hong|last6 = Yuan|first7 = Dong-sheng|last7 = Ouyang|first8 = Shi-kun|last8 = Liu|first9 = Jeffrey S.|last9 = Barrett|deadurl = no|archiveurl = https://web.archive.org/web/20170811010432/https://www.jstage.jst.go.jp/article/dmpk/28/5/28_DMPK-12-RG-148/_pdf|archivedate = 11 August 2017|df = dmy-all}}
29. ^{{Cite web|work = Drug Safety and Availability|title = FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury|url = http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm|publisher = FDA|accessdate = 5 November 2015|author = Center for Drug Evaluation and Research|deadurl = no|archiveurl = https://web.archive.org/web/20130106223019/http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm|archivedate = 6 January 2013|df = dmy-all}}
30. ^{{cite journal |last1=Ananchenko |first1=Gennady |last2=Novakovic |first2=Jasmina |last3=Lewis |first3=Johnathan |title=Chapter 2 - Amlodipine Besylate |journal=Profiles of Drug Substances, Excipients and Related Methodology |date=1 January 2012 |volume=37 |pages=31–77 |doi=10.1016/b978-0-12-397220-0.00002-7 |pmid=22469316 |publisher=Academic Press|isbn=9780123972200 }}
31. ^{{cite web |title=Amlodipine |url=https://www.drugbank.ca/drugs/DB00381 |website=www.drugbank.ca |accessdate=30 January 2019}}
32. ^{{cite journal |last1=Clusin |first1=William T. |last2=Anderson |first2=Mark E. |title=Calcium Channel Blockers: Current Controversies and Basic Mechanisms of Action |journal=Advances in Pharmacology |date=1 January 1999 |volume=46 |pages=253–296 |doi=10.1016/s1054-3589(08)60473-1 |publisher=Academic Press|isbn=9780120329472 }}
33. ^1 2 {{cite | last=Nazzaro | first=P | last2=Manzari | first2=M | last3=Merlo | first3=M | last4=Triggiani | first4=R | last5=Scarano | first5=AM | last6=Lasciarrea | first6=A | last7=Pirrelli | first7=A | title=Antihypertensive treatment with verapamil and amlodipine. Their effect on the functional autonomic and cardiovascular stress responses. | journal=European heart journal | volume=16 | issue=9 | year=1995 | issn=0195-668X | pmid=8582392 | pages=1277–84}}
34. ^{{cite journal |last1=Karmoker |first1=J.R. |last2=Joydhar |first2=P. |last3=Sarkar |first3=S. |last4=Rahman |first4=M. |year=2016 |title=Comparative in vitro evaluation of various commercial brands of amlodipine besylate tablets marketed in Bangladesh |journal=Asian Journal of Pharmaceutical and Health Sciences |volume=6 |pages=1384–1389 |url=http://www.ajphs.com/journals/02_AJPHS_Jan-Mar_2016_738.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20160701194238/http://www.ajphs.com/journals/02_AJPHS_Jan-Mar_2016_738.pdf |archivedate=1 July 2016 |df=dmy-all }}
35. ^{{Cite book|title = Pharmacotherapeutics for Advanced Practice: A Practical Approach|url = https://books.google.com/books?id=EaP1yJz4fkEC&pg=PA252|publisher = Lippincott Williams & Wilkins|year = 2006|isbn = 9780781757843|first = Virginia Poole|last = Arcangelo|first2 = Andrew M.|last2 = Peterson|deadurl = no|archiveurl = https://web.archive.org/web/20170908192420/https://books.google.com/books?id=EaP1yJz4fkEC&pg=PA252|archivedate = 8 September 2017|df = dmy-all}}
36. ^{{Cite book|title = A Textbook of Clinical Pharmacology and Therapeutics|edition = 5|url = https://books.google.com/books?id=TD59BgAAQBAJ&pg=PA191|publisher = CRC Press|year = 2012|isbn = 9781444113006|first = James|last = Ritter|first2 = Lionel|last2 = Lewis|first3 = Timothy|last3 = Mant|first4 = Albert|last4 = Ferro|deadurl = no|archiveurl = https://web.archive.org/web/20170908192420/https://books.google.com/books?id=TD59BgAAQBAJ&pg=PA191|archivedate = 8 September 2017|df = dmy-all}}
37. ^{{Cite book|title = Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based Therapeutics|url = https://books.google.com/books?id=rXy0BgAAQBAJ&pg=PA189|publisher = John Wiley & Sons|date = 2015|isbn = 9780470915370|first = Y. Robert|last = Li|deadurl = no|archiveurl = https://web.archive.org/web/20170908192420/https://books.google.com/books?id=rXy0BgAAQBAJ&pg=PA189|archivedate = 8 September 2017|df = dmy-all}}
38. ^{{Cite book|title = 2013 Nurse's Drug Handbook|url = https://books.google.com/books?id=ckdTGZe7aRAC&pg=PA73|publisher = Jones & Bartlett Publishers|year = 2012|isbn = 9781449642846|first = Jones|last = Learning|first2 = Bartlett|last2 = Learning|deadurl = no|archiveurl = https://web.archive.org/web/20170908192421/https://books.google.com/books?id=ckdTGZe7aRAC&pg=PA73|archivedate = 8 September 2017|df = dmy-all}}
39. ^{{cite journal|last1=Luther|first1=James M.|title=Is there a new dawn for selective mineralocorticoid receptor antagonism?|journal=Current Opinion in Nephrology and Hypertension | volume=23 | issue=5 | year=2014 | pages=456–461 | issn=1062-4821 | doi=10.1097/MNH.0000000000000051 | pmc=4248353 | pmid=24992570}}
40. ^{{Cite journal | last1=Zhu | first1=Yanlin | last2=Wang | first2=Fen | last3=Li | first3=Quan | last4=Zhu | first4=Mingshe | last5=Du | first5=Alicia | last6=Tang | first6=Wei | last7=Chen | first7=Weiqing | title=Amlodipine Metabolism in Human Liver Microsomes and Roles of CYP3A4/5 in the Dihydropyridine Dehydrogenation | journal=Drug Metabolism and Disposition | date=1 February 2014 | pmid=24301608 | doi=10.1124/dmd.113.055400 | issn=0090-9556 | volume=42 | issue=2 | pages=245–249 | df=dmy-all }}
41. ^{{Cite journal | last1=Beresford | first1=A. P. | last2=McGibney | first2=D. | last3=Humphrey | first3=M. J. | last4=Macrae | first4=P. V. | last5=Stopher | first5=D. A. | title=Metabolism and kinetics of amlodipine in man | journal=Xenobiotica | date=1 January 1988 | doi=10.3109/00498258809041660 | issn=0049-8254 | volume=18 | issue=2 | pages=245–254 | pmid=2967593}}{{closed access}}
42. ^{{cite web |title=Amlodipine |url=https://www.drugbank.ca/drugs/DB00381 |website=www.drugbank.ca |accessdate=30 January 2019}}
43. ^{{Cite book | last=Nayler | first=Winifred G. | title=Amlodipine | date=2012 | publisher=Springer Science & Business Media | page=105 | isbn=9783642782237 | url=https://books.google.com/books?id=Z5T0BwAAQBAJ&pg=PT105 | deadurl=no | archiveurl=https://web.archive.org/web/20170908192420/https://books.google.com/books?id=Z5T0BwAAQBAJ&pg=PT105 | archivedate=8 September 2017 | df=dmy-all }}
44. ^{{Cite book|title = Profiles of Drug Substances, Excipients and Related Methodology|url = https://books.google.com/books?id=ew_MiZ_xBdcC&pg=PA68|publisher = Academic Press|year = 2012|isbn = 9780123977564|first = Harry G.|last = Brittain|deadurl = no|archiveurl = https://web.archive.org/web/20170908192420/https://books.google.com/books?id=ew_MiZ_xBdcC&pg=PA68|archivedate = 8 September 2017|df = dmy-all}}
45. ^{{cite journal |last1=Murdoch |first1=David |last2=Heel |first2=Rennie C. |title=Amlodipine |journal=Drugs |date=March 1991 |volume=41 |issue=3 |pages=478–505 |doi=10.2165/00003495-199141030-00009|pmid=1711448 }}
46. ^{{Cite news| author = Kennedy VB| title = Pfizer loses court ruling on Norvasc patent| work = MarketWatch| date = 22 March 2007| url = http://www.marketwatch.com/news/story/pfizer-loses-court-ruling-norvasc/story.aspx?guid=%7B9819D67E-B76B-431D-835C-FB8D6D8327B7%7D| deadurl = no| archiveurl = 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| archivedate = 3 August 2008| df = dmy-all}}
47. ^{{cite journal |vauthors=Bahl VK, Jadhav UM, Thacker HP | title = Management of hypertension with the fixed combination of perindopril and amlodipine in daily clinical practice: results from the STRONG prospective, observational, multicenter study | journal = Am J Cardiovasc Drugs | volume = 9 | issue = 3 | pages = 135–42 | year = 2009 | pmid = 19463019 | doi = 10.2165/00129784-200909030-00001 | doi-broken-date = 2019-03-14 }}
48. ^{{cite book|last1=Campbell|first1=Anthony K.|title=Intracellular Calcium|publisher=John Wiley & Sons|isbn=9781118675526|page=68|url=https://books.google.com/books?id=aDbcBAAAQBAJ&pg=PA68|date=2014-10-14}}
49. ^{{Cite book | last=Papich | first=Mark G. | title=Saunders Handbook of Veterinary Drugs | chapter=Amlodipine Besylate | location=St. Louis, Mo | date=2007 | edition=2nd | publisher=Saunders/Elsevier | isbn=9781416028888 | pages=26–27}}
50. ^{{Cite journal|last=Henik|first=RA|last2=Snyder|first2=PS|last3=Volk|first3=LM|date=28 August 2014|title=Treatment of systemic hypertension in cats with amlodipine besylate|journal=Journal of the American Animal Hospital Association|language=en|volume=33|issue=3|pages=226–234|doi=10.5326/15473317-33-3-226|pmid=9138233}}
51. ^{{Cite web | last=Diamondback Drugs | title=Amlodipine in Veterinary Medicine | accessdate=29 June 2017 | url=http://www.diamondbackdrugs.com/treating-high-blood-pressure-with-amlodipine/ | deadurl=no | archiveurl=https://web.archive.org/web/20170811011323/http://www.diamondbackdrugs.com/treating-high-blood-pressure-with-amlodipine/ | archivedate=11 August 2017 | df=dmy-all }}
52. ^{{Cite journal|last=Atkins|first=C.|last2=Bonagura|first2=J.|last3=Ettinger|first3=S.|last4=Fox|first4=P.|last5=Gordon|first5=S.|last6=Haggstrom|first6=J.|last7=Hamlin|first7=R.|last8=Keene|first8=B.|last9=Luis-Fuentes|first9=V.|date=1 November 2009|title=Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease|journal=Journal of Veterinary Internal Medicine|language=en|volume=23|issue=6|pages=1142–1150|doi=10.1111/j.1939-1676.2009.0392.x|pmid=19780929|issn=1939-1676}}
53. ^{{Cite journal|last=Suzuki|first=Shuji|last2=Fukushima|first2=Ryuji|last3=Ishikawa|first3=Taisuke|last4=Yamamoto|first4=Yuta|last5=Hamabe|first5=Lina|last6=Kim|first6=Soomin|last7=Yoshiyuki|first7=Rieko|last8=Machida|first8=Noboru|last9=Tanaka|first9=Ryou|date=18 September 2012|title=Comparative effects of amlodipine and benazepril on Left Atrial Pressure in Dogs with experimentally-induced Mitral Valve Regurgitation|journal=BMC Veterinary Research|volume=8|pages=166|doi=10.1186/1746-6148-8-166|pmid=22989022|pmc=3489586|issn=1746-6148}}
54. ^{{Cite web | last=Forney | first=Barbara | title=Amlodipine for Veterinary Use | work=Wedgewood Pharmacy | accessdate=29 June 2017 | url=http://www.wedgewoodpetrx.com/learning-center/professional-monographs/amlodipine-for-veterinary-use.html | deadurl=no | archiveurl=https://web.archive.org/web/20170627172329/http://www.wedgewoodpetrx.com/learning-center/professional-monographs/amlodipine-for-veterinary-use.html | archivedate=27 June 2017 | df=dmy-all }}

External links

  • U.S. National Library of Medicine: Drug Information Portal - Amlodipine
{{Navboxes
| title = Pharmacodynamics
| titlestyle = background:#ccccff
| list1 ={{Ion channel modulators}}{{Mineralocorticoid receptor modulators}}{{Xenobiotic-sensing receptor modulators}}
}}{{portal bar|Pharmacy and pharmacology|Medicine}}

12 : Antimineralocorticoids|Amines|Calcium channel blockers|Carboxylate esters|Dihydropyridines|Ethers|Chloroarenes|World Health Organization essential medicines|Ethyl esters|Methyl esters|Pfizer products|RTT
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/10 15:58:08