Amlodipine

CAS Registry No. 88150-42-9 (amlodipine), 111470-99-6 (amlodipine besylate), 88150-47-4 (amlodipine maleate) 

Sample preparation Condition a 3 mL 100 mg Bond Elut C2 SPE cartridge with 2 mL MeCN, 1 mL water, and 1 mL buffer. Add 500 p-L buffer, 50 p,L 200 ng/mL IS in MeOH water 50 50, 1 mL plasma, and 500 pL buffer sequentially to the SPE cartridge. Wash with 2 mL MeCN water 20 80, wash with 1 mL MeCN, elute with 1 mL 2.5% ammonia in MeCN. Evaporate the eluate to dryness under reduced pressure, reconstffute with 50 pL MeOH 100 mM pH 4.0 acetate buffer 50 50, inject an aliquot. (Buffer was 25 mM pH 7.0 phosphate buffer.) 

Mobile phase MeOH 100 mM pH 4.0 acetate buffer containing 2 mM sodium dodeqrl sulfate and 1 mg/L EDTA 

Detector E, Antec Decade, Antec VT-03 analytical cell with 50 pm spacer 0.95 V, ESA 5020 guard cell 0.5 V 

Internal standard 2-[ 2-aminoethoxy)methyl]-4-(2,3-dichlorophenyl)-l,4-dihydro-6-meth-yl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (UK52.829) (13) 

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Widely used DHPs are nifedipine, amlodipine, nitrendipine, nisoldipine, nicardipine, and isradipine. They directly bind to and stabilize the inactivated state of the... 

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

Calcium channel blocking drug s—for example, amlodipine (Norvasc) and diltiazem (Cardizem)... 

Lotensin (Ciba)-comb. with Hydrochlorothiazide Lotrel (Ciba)-comb. with Amlodipine... 

C7H5CIO 89-98-5) see Amlodipine Clobenzorex Clopidogrel hydrogensulfate Cloxacillin 4-chlorobenzaldehyde... 

C H,202 22286-82-4) see Bomaprine Tilidine ethyl 4-(2-azidoethoxy)acetoacetate (CJH13N3O4 88150-45-2) see Amlodipine ethyl 3-azido-2,3,4,S-tetrahydro-2-oxo-lif-l-benzazepin-... 

C5H(jN02 14205-39-1) see Amlodipine Aranidipine Barnidipine Benidipine Isradipine Lercanidipinc hydrochloride Manidipine Nicardipine Nisoldipine Nitrendipine... 

Caron, G., Ermondi, G., Damiano, A., Novaroli, L., Tsinman, O., Ruelle, J. A., Avdeef, A. Ionization, lipophilidty, and molecular modeling to investigate permeability and other biological properties of amlodipine. Eioorg. Med. Chem. 2004, 22, 6107-6118. 

Isoptin SR, Verelan) 180-480 Amlodipine (Norvasc) 5-10 Nifedipine long-acting (Adalat CC, Procardia XL) 30-90 Diltiazem sustained-release (Cardizem SR) 180-360 Diabetes... 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

DW, a 78-year-old Caucasian man, presents to the emergency room with complaints of a headache persisting over the last 3 days. Repeated blood pressure measurements average 200/11 0 mm Hg. He reports no other symptoms and physical examination and laboratory tests are unremarkable as is his past medical history with the exception of hypertension diagnosed in his early 60s. DW reports that he is struggling on a fixed retirement income with no prescription coverage and takes "what I can afford." Blood pressure medications are carvedilol 25 mg twice daily, amlodipine 10 mg once daily, torsemide (Demadex )... 

Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine the VALUE randomised trial. Lancet 2004 363(9426) =2022-2231. 

Treatment with nondihydropyridine calcium channel blockers (diltiazem and verapamil) may worsen HF and increase the risk of death in patients with advanced LV dysfunction due to their negative inotropic effects. Conversely, dihydropyridine calcium channel blockers, although negative inotropes in vitro, do not appear to decrease contractility in vivo. Amlodipine and felodipine are the two most extensively studied dihydropyridine calcium channel blockers for systolic H F.39 4() These two agents have not been shown to affect patient survival, either positively or negatively. As such, they are not routinely recommended as part of a standard HF regimen however, amlodipine and felodipine can safely be used... 

STE ACS class lla recommendation and NSTE ACS class I recommendation for patients with ongoing ischemia who are already taking adequate doses of nitrates and P-blockers or in patients with contraindications to or intolerance to P-blockers (diltiazem or verapamil for STE ACS and diltiazem, verapamil, or amlodipine for NSTE ACS). 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

Amlodipine Hypotension, dependent peripheral edema, gingival hyperplasia BP every shift during oral administration during hospitalization, then every 6 months following hospital discharge dental exam and teeth cleaning every 6 months... 

Atorvastatin 40 mg PO once daily Hydrochlorothiazide 25 mg PO once daily Amlodipine 5 mg PO once daily Lantus insulin 30 units per day Multivitamin 1 tablet daily Pantoprazole 40 mg PO once daily Maalox 15 mL PO 4 times daily as needed for heartburn/stomach upset... 

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