Calcium channel-blocking drugs toxicity

Ethosuximide, USE. Ethosuximide. 2-ethyl-2-methyl succinimide (Zarontin), conforms very well to the general structural pattern for antiabsence activity. The drug is more active and less toxic than trimelhadione. It is a calcium T channel-blocking drug. Toxicity primarily involves the. skin and blood. 

Prenylamine is a coronary vasodilator that depletes myocardial catecholamine stores and has some calcium-channel blocking activity. It has been used in the treatment of angina pectoris, but it often causes ventricular dysrhythmias and has been superseded by less toxic drugs. 

C. Clinical Use and Toxicities Calcium channel blockers are effective for converting atrioventricular nodal reentry (also known as nodal tachycardia) to normal sinus rhythm. Their major use is in the prevention of these nodal arrhythmias in patients prone to recurrence. These drugs are orally active verapamil is also available for parenteral use (Table 14—2). The most important toxicity of verapamil is excessive pharmacologic effect, since cardiac contractility, AV conduction, and blood pressure can be significantly depressed. See Chapter 12 for additional discussion of toxicity. Amiodarone has moderate calcium channel-blocking activity. 

Amiodarone (Cordarone) is an iodine-containing benzo-furan derivative identified as a class III agent because it predominantly prolongs action potentials. Amiodarone also blocks sodium and calcium channels and is a noncompetitive p-receptor blocker. Amiodarone is effective for the treatment of most arrhythmias. Toxicity associated with amiodarone has led the U. S. Food and Drug Administration (FDA) to recommend that it be reserved for use in patients with life-threatening arrhythmias. 

Verapamil, diltiazem Nonselective block of L-type calcium channels in vessels and heart Reduced vascular resistance, cardiac rate, and cardiac force results in decreased oxygen demand Prophylaxis of angina, hypertension, others Oral, IV, duration 4-8 h Toxicity Atrioventricular block, acute heart failure constipation, edema Interactions Additive with other cardiac depressants and hypotensive drugs... 

Increased risk of toxicity with drugs that alter serum electrolytes (potassium -depleting diuretics, corticosteroids, thiazide and loop diuretics, amphotericin B, quinidine, amiodarone). Blockers of p adrenergic receptors, calcium channels, or acetylcholinesterase increase risk of complete AV block. Drugs which alter Gl absorption may alter bioavallabillty. 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

Amiodarone, a special case Amiodarone is effective in most types of arrhythmias and is considered the most efficacious of all antiarrhythmic drugs. This may be because it has a broad spectrum it blocks sodium, calcium, and potassium channels and beta adrenoceptors. Because of its toxicities, however, amiodarone is usually reserved for use in arrhythmias that are resistant to other drugs. 

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