Calcium channel blockers selectivity

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. 

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 is a calcium-channel blocker that blocks the intracellular movement of calcium ions and hence slows the contractility of the myocardium and relaxes the vascular smooth muscle. The negative inotropic effects are rarely seen at therapeutic doses since amlodipine has a greater selectivity for vascular smooth muscle than for the myocardium. 

Ziconotide (45 Prialt ) Ziconotide (45) Peptide NP Animal Pain Acts as a selective /V-type voltage-gated calcium channel blocker 417 28... 

Important differences in vascular selectivity exist among the calcium channel blockers. In general, the dihydropyridines have a greater ratio of vascular smooth muscle effects relative to cardiac effects than do diltiazem and verapamil. Furthermore, the dihydropyridines may differ in their potency in different vascular beds. For example, nimodipine is claimed to be particularly selective for cerebral blood vessels. Splice variants in the structure of the cq channel subunit appear to account for these differences. 

Important differences between the available calcium channel blockers arise from the details of their interactions with cardiac ion channels and, as noted above, differences in their relative smooth muscle versus cardiac effects. Sodium channel block is modest with verapamil, and still less marked with diltiazem. It is negligible with nifedipine and other dihydropyridines. Verapamil and diltiazem interact kinetically with the calcium channel receptor in a different manner than the dihydropyridines they block tachycardias in calcium-dependent cells, eg, the atrioventricular node, more selectively than do the dihydropyridines. (See Chapter 14 for additional details.) On the other hand, the dihydropyridines appear to block smooth muscle calcium channels at concentrations below those required for significant cardiac effects they are therefore less depressant on the heart than verapamil or diltiazem. 

So-called bradycardic drugs, relatively selective If sodium channel blockers (eg, ivabradine), reduce cardiac rate by inhibiting the hyperpolarization-activated sodium channel in the sinoatrial node. No other significant hemodynamic effects have been reported. Ivabradine appears to reduce anginal attacks with an efficacy similar to that of calcium channel blockers and 3 blockers. The lack of effect on gastrointestinal and bronchial smooth muscle is an advantage of ivabradine, and FDA approval is expected. 

Bowersox, S.S., Gadbois, Th., Singh, T., Pettus, M., Wang, Y.-X., Luther, R.R. Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX - 111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain, J. Pharmacol. Exper. Ther. 1996, 279, 1243-1249. 

Aryl-1,4-dihydropyridines.2 These compounds are important calcium channel blockers or enhancers depending on the stereochemistry at C4. An enaritio-selective synthesis of the (S)-isomers (blockers) is based on addition of an aryl-lithium to achiral 3-dihydrooxazolyl-5-methoxycarbonylpyridine (2). Thus addition... 

In a retrospective case-control study, a primary diagnosis of hypoglycemia was identified in 413 patients registered as diabetic in 1993 (164). Five controls of the same age and sex, without hypoglycemia, were selected for each case from the same cohort. The relative risks of hypoglycemia with ACE inhibitors, beta-blockers, calcium antagonists, and salicylates were determined. There was an association between enalapril and sulfonylureas. However, other ACE inhibitors could not be identified as a risk factor. There was no interaction with beta-blockers, calcium channel blockers, or salicylates. 

The resolution of certain calcium channel blockers was optimized by temperature variations on cellulose tris(4-chlorophenylcarbamate) CSP coated on silica gel [150]. The van t Hoff plots for retention were curved, while those for selectivity were linear. 

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