Calcium antagonists toxicity

The side effects or toxic effects that the calcium antagonists have in common are hypotension, facial flushing, headache, di22iness, weakness, sedation, skin rash, edema, constipation, and abdominal discomfort (nausea, vomiting, and epigastric pressure). 

Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers. 

Calcium antagonist prolonged peak effect of di-vasid and ouabain and reduced their toxicity 482... 

Quinidine [KWIN i deen] is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. Because of quinidine s toxic potential, calcium antagonists, such as verapamil, are increasingly replacing this drug in clinical use. 

Calcium-channel blockers increase the toxicity of lithium, which has calcium antagonist effects itself. 

I. Mechanism of toxicity. Calcium antagonists slow the influx of calcium through cellular calcium channels. Currently marketed agents act primarily on vascular smooth muscle and the heart. They result in coronary and peripheral vasodilation, reduced cardiac contractility, slowed (AV) nodal conduction, and depressed sinus node activity. Lowering of blood pressure through a fall in peripheral vascular resistance may be offset by reflex tachycardia, although this reflex response may be blunted by depressant effects on contractility and sinus node activity. Table 11-17 summarizes usual doses, sites of activity, and half-lives of common calcium antagonists. 

Taxine I and II are extremely toxic. This activity may arise because these alkaloids are effective calcium antagonists (Blechert and Guenard, 1990). 

In addition to angina, calcium channel blockers have well-documented efficacy in hypertension (see Chapter 11) and supraventricular tachyarrhythmias (see Chapter 14). They also show moderate efficacy in a variety of other conditions, including hypertrophic cardiomyopathy, migraine, and Raynaud s phenomenon. Nifedipine has some efficacy in preterm labor but is more toxic and not as effective as atosiban, an investigational oxytocin antagonist (see Chapter 17). 

Iodinated radiographic contrast media can cause acute renal insufficiency, perhaps as a result of reduced renal blood flow, an intrarenal osmotic effect, or direct tubular toxicity (58). Diuretics, calcium channel blockers, adenosine receptor antagonists, acetylcysteine, low-dose dopamine, the dopamine Di receptor agonist fenoldopam, endothelin receptor antagonists, and captopril have all been used to prevent contrast nephropathy. 

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