Diltiazem indications

BK currents consisted of transient and steady-state components. The transient currents were abolished by ryanodine (10 fiM), indicating that they are activated by Ca2+ sparks. The lag from the onset of depolarization (activation of VDCCs) to the first transient BK current was around 50 ms. This delay is much too long to be attributed to local signalling from VDCCs to RyRs such as occurs in heart, and instead is consistent with the idea of loose coupling between VDCCs and RyRs (Fig. 1 A) (Collier et al 2000). Spark-activated transient BK currents remained in the presence of the VDCC antagonist diltiazem (50 //M). However, the frequency of... 

Diltiazem appears to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate control in atrial fibrillation. An intravenous form of diltiazem is available for the latter indication and causes hypotension or bradyarrhythmias relatively... 

These agents appear to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate control in atrial fibrillation. An intravenous form of diltiazem is available for the latter indication and causes hypotension or bradyarrhythmias relatively infrequently. Bepridil also has action potential- and QT-prolonging actions that theoretically may make it more useful in some ventricular arrhythmias but also create the risk of torsade de pointes. Bepridil is only rarely used, primarily to control refractory angina. 

K. Shivram, A. C. Shah, B. L. Newalhar, and B. V. Kamath, Stability indicating HPLC method for the assay of diltiazem hydrochloride in tablets, J. Liquid Chromatogr., 75 2417 (1992). 

Mibefradil is a tetralol derivative developed as a unique CCB. Its efficacy as an antihypertensive was demonstrated in phase III trials, where doses of 50 to 100 mg were compared to other CCBs (nifedipine SR, diltiazem CD, nifedipine GITS, amlodipine). Mibefradil was shown to be equally effective as or more effective than nifedipine SR, diltiazem CD, nifedipine GITS, or amlodipine in reducing blood pressure in mild to moderate hypertension. Average reductions of diastolic blood pressure of as much as 15 mmHg were seen with the 100-mg dose. It was also found to be effective in the treatment of chronic stable angina. Thus, it was indicated for use in hypertension and stable angina at doses of 50 or 100 mg once daily (15). 

Verapamil and diltiazem are prototypic calcium channel blockers. As indicated previously, these drugs influence cardiac function by blocking inward calcium movement through L channels. In so doing they block conduction velocity in SA and AV node cells. They are used therapeutically to treat reentry arrhythmias through the AV node as well as paroxysmal supraventricular tachycardias. In fact, verapamil has been reported to terminate 60-80 percent of paroxysmal supraventricular tachycardias within several minutes. However, because of their potent effect on AV conduction, these drugs are contraindicated in patients with preexisting conduction problems since they may produce complete AV block. 

Trade names Alti-Diltiazem Britiazem Calcicard Cardizem (Biovail) Cartia-XT Deltazen Dilacor XR (Watson) Dilrene Diltahexal Diltia-XT Nu-Diltiaz Presoken Teczem (Sanofi-Aventis) Tiamate Tiazac (Forest) Tilazem Tildiem Indications Angina, essential hypertension Category Antiarrhythmic class IV Calcium channel blocker Half-life 5-8 hours (for extended-release capsules)... 

Diltiazem hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium antagonist). It has generally been indicated for the treatment of angina and, more recently (2), hypertension. Diltiazem hydrochloride is a potent dilator of coronary arteries and has been shown to increase exercise tolerance in man. It is available for dosing as immediate release tablets and as extended or sustained release capsules and is usually well-tolerated. While some adverse reactions have been reported during diltiazem hydrochloride therapy, it is generally considered to be well-tolerated. In most cases, no causal relationship between the events and diltiazem hydrochloride use has yet to be established (1). 

Diltiazem hydrochloride has principal tradenames of Dilacor and Cardizem . It has also been known as CRD-401, RG 83606, Altiazem , Anginyl , Angize , Britiazi , Bruzen , Calcicard , Cardiem , Dilpral , Dilzem , Dilzene , Herbesser , Masdii and Tildiem . Diltiazem hydrochloride possesses two asymmetric carbons and is supplied as the dextrorotatory cis-isomer. Diltiazem, when referenced, indicates the free base (CAS registry number 42399-41-7). 

Thermogravimetric Analysis (TGA) of diltiazem hydrochloride tested under a nitrogen atmosphere indicates no weight loss until a temperature of - 230°C is reached. Significant weight loss is observed above 230°C due to decompo-sition/vaporization. A typical TGA curve is shown in Figure 11. The curve was obtained using a Perkin Elmer Series 7 TGA... 

The solubility of diltiazem hydrochloride in a variety of solvents is presented in Table IV (3). Note that solubilities are indicated in terms of current USP definitions (23). 

A stability-indicating HPLC procedure may be used for the identity testing of diltiazem hydrochloride. The retention time of the major peak in the sample chromatogram should correspond to that of the diltiazem hydrochloride reference standard (approxi-mately 5.5 minutes). The HPLC procedure is described under Section 9.2.1.1. 

A stability-indicating high performance liquid chromatographic method is available for the formulated product of diltiazem hydrochloride. Diltiazem hydrochloride is separated from its major potential degradate, desacetyl diltiazem using an isocratic HPLC method. The method utilizes a Phenomenex IB... 

CCBs are useful add-on agents for BP control in hypertensive patients with diabetes. Several studies have compared an ACE inhibitor with either a dihydropyridine CCB or a /8-blocker. In the studies comparing a dihydropyridine with an ACE inhibitor, the ACE inhibitor group had significantly lower rates of cardiovascular end points, including myocardial infarctions and all cardiovascular events. These data do not suggest that CCBs are harmful in diabetic patients but indicate that they are not as protective as ACE inhibitors. While data are limited, nondihydropyridine CCBs (diltiazem and verapamil) appear to provide more kidney protection than the dihydropyridines. ... 

Calcium channel antagonists and nitrates also may increase myocardial oxygen supply through coronary vasodilation. Diastolic function also may be improved with verapamil, nifedipine, and perhaps, diltiazem. These effects may vary from those indicated in the table depending on individual patient baseline hemodynamics. 

Class IB drugs act primarily on ventricular muscle and, in the case of lidocaine, concen- j trate in ischemic tissues. Adenosine is indicated for SVTs and nodal tachycardias. The primary actions of both beta blockers (esmolol) and CCBs (diltiazem) are at the AV node— they are not particularly effective in ventricular arrhythmias. Flecainide, a class IC drug, has been implicated in sudden deaths post-MI. 

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