Calcium channel blocker drugs

Kizer JR and Kimmel SE. Epidemiologic review of the calcium channel blocker drugs An up-to-date perspective on the proposed hazards. Arch Intern Med 2001 161 1145-1158. 

Fig. 3.20 Comparison of the perturbation effect of calcium channel blocker drugs on parameter S of 16-PC in liposomal membranes at 25 and 37 °C. Co, control NIF, nifedipine ...

Wikel JH, Bemis KG, Kurz K, Denney ML, Main BW, Moore RA, et al. Comparative QSAR studies of two series of 1,4-dihydropyridines as slow calcium channel blockers. Drug Des Discov 1994 11 1-14. 

Members of the dihydropyridine class of calcium channel blocker drugs (e.g., nifedipine, nisoldipine) have intrinsically less effect on the cardiac conduction system than other classes. In particular, verapamil has a high degree of SA nodal and AV nodal blockade, and diltiazem has a somewhat lower effect. Bepridil blocks both sodium and potassium channels, and also causes both SA nodal and AV nodal blockade. 

Collins WCJ, Cullen MJ, Feely J. Calcium channel blocker drugs and diabetic CCTitrol. Clin Pharmacol Ther 9ZT) 42,420-3. 

Dietary products - e.g. grapefruit juice is an enzyme inhibitor and increases plasma concentrations of some calcium channel blockers, drugs which are used to treat hypertension and angina. 

The separation of four calcium channel blocker drugs (diltiazem, verapamil, nifedipine, nitrendipine) and five metabolites (e.g., demethyldiltiazem, norverapa-mil) was accomplished on a C,g column (2 = 230nm) using a 2/2/1/0.04 methanol/water (40 mM ammonium acetate pH 7.9)/acetonitrile/triethylamine mobile phase. Elution was complete in 11 min. A plot of the effect of pH from 6.9 to 7.9 on retention is shown. Linear ranges were generated from 10 to 5000ng/mL and detection limits of 8ng/mL were reported [579]. 

Six calcium channel blocker drugs (atenolol, amlodipine, nifedipine, nitrendipine, nimodipine, felodipine) were separated on a Cjg colunm (A = 250nm) using a 50/50 acetonitrile/water (lOmM phosphate at pH 4.5) mobile phase [1488]. Note that the choice of pho hate generates a system with little buffer capacity (halfway between pK and pATj)- Baseline resolution, excellent peak shape and elution time of 13 min were all obtained. Linear ranges fix>m 25 to 3200 ng/mL and detection limits of 15 ng/mL were reported. 

The so-called calcium channel blockers constitute a class of cardiovascular agents that have gained prominence in the past few years. These drugs, which obtund contraction of arterial vessels by preventing the movement of calcium ions needed for those contractions, have proved especially useful in the treatment of angina and hypertension. Dihydropyridines such as nifedipine (30) are par-... 

The selectivity of another cellulose-based CSP, Chiralcel OJ, has also been examined in SFC [60]. Separations of racemic drugs such as benoxaprofen, temazepam, and mephobarbital were obtained. Acetonitrile proved to be a better modifier than methanol for some of the compounds investigated. The four optical isomers of a calcium channel blocker were resolved by Siret et al. on the Chiralcel OJ CSP [30]. In LC, two CSPs were required to perform the same separation. 

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. 

FIGURE 41 -1. Calcium channel blockers inhibit the movement of caldum ions across the cell membrane. When calcium channels are blocked by drug molecules, musde contraction is decreased, causing the smooth musdes of the arteries and arterioles to dilate. 

The nurse takes Hie patient s vital signs before die drug is administered and frequentiy during administration of die antiaiiginals or die calcium channel blockers. If die heart rate is below 50 bpm or die systolic blood pressure is below 90 mm Hg, the drug is widiheld and die primary health care provider notified. A dosage adjusdnent may be necessary. 

ADMINISTERING CALCIUM CHANNEL BLOCKERS The nurse may give these dru without regard to meals. If gastrointestinal upset occurs, the drug may be administered... 

Benzothiazepines belong to the three classes of calcium channel blockers which are important cardiovascular drugs in the management of angina pectoris and hypertension. A diastereoselective one-pot synthesis of the trans-and ds-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-l,5-benzothiazepin-4-one nucleus, a key intermediate in the preparation of the calcium channel blocker Diltiazem, was carried out under microwave irradiation in an open vessel (Scheme 25). Control of the diastereoselectivity was achieved by vary-... 

Other drugs such as the neuroleptic, haloperidol, inhibit the induction of hsp70 mRNA in rodent neurons (Sharp et al.. 1992). Although this observation needs to be confirmed in the human population, it raises the possibility that an age-dependent defect in the production of HS proteins is exacerbated by a drug which is commonly used in demented elderly patients. The potential for certain pharmacologic agents to inhibit the HS response could increase the risk for untoward effects of atherosclerosis and hypoxia. A similar concern may be raised with certain calcium channel blockers which also have been found to reduce the synthesis of HS proteins in cardiac myocytes (Low-Friedrich and Schoeppe, 1991). 

Ondrias, K., Misik, V., Gergel, D. and Stasko, A. (1989). Lipid peroxidation of phosphatidylcholine liposomes depressed by the calcium channel blockers nifedipine and verapamil and by the antiarrhythmic-antihypoxic drug stobadine. Biochim. Biophys. Acta 1003, 238-245. 

---