Verapamil toxicity

Price WA, Shalley JE. Lithium-verapamil toxicity in the elderly. J Am Geriatr Soc 1987 35(2) 177-8. 

Competitive albumin binding of drugs with high serum protein affinity can increase pharmacologically active unbound concentrations and enhance the metabolism of low clearance drugs. Acute verapamil toxicity with ceftriaxone and clindamycin may be explained by this mechanism (210). 

A 15-year-old woman survived a total of 65 minutes cardiac arrest after taking 7200 mg of verapamil and 240 mg of paroxetine, which potentiates verapamil toxicity (19). Despite the length of cardiopulmonary resuscitation, with evidence of subsequent myocardial damage and renal impairment, she was discharged 17 days after admission, having made a full recovery, without evidence of neurological impairment. 

Vetter FJ, Simons SB, Mironov S, Hyatt CJ, Pertsov AM (2005) Epicardial fiber organization in swine right ventricle and its impact on propagation. Cite Res 96 244-251 Vick JA, Kandil A, Herman EH, Balazs T (1983) Reversal of propranolol and verapamil toxicity by calcium. Vet Hum Toxicol 25 8-10... 

Kishore K, Raina A, Misra V, Jonas E. Acute verapamil toxicity in a patient with chronic toxicity possible interaction with ceftriaxone and clindamycin. Arm Pharmacother (1993) 27, 877-80,... 

Erythromycin markedly increases the bioavailability of felodipine. isolated reports describe increased felodipine, nifedipine or verapamil effects and toxicity in patients also given erythromycin. There are also a few reports of verapamil toxicity with clarithromycin, and one with telithromycin. 

ReedM, WallGC, ShahNP, Heun JM,HicklinGA. Verapamil toxicity resultii from a probable interaction with teUthromycin. Atm Pharmaco er (2005) 39,357-60. 

The side effects and toxic reactions to verapamil iaclude upper GI upset, constipation, di22iaess, headaches, flushing and burning, edema, hypotension, bradycardia, and various conduction disturbances. Verapamil has negative iaotropic activity and may precipitate heart failure ia patients having ventricular dysfunction (1,2). 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

Calcium is contraindicated in patients with hypercalcemia or ventricular fibrillation and in patients taking digitalis. Calcium is used cautiously in patients with cardiac disease. Hypercalcemia may occur when calcium is administered with the thiazide diuretics. When calcium is administered with atenolol there is a decrease in Hie effect of atenolol, possibly resulting in decreased beta blockade. There is an increased risk of digitalis toxicity when digitalis preparations are administered with calcium. The clinical effect of verapamil may be decreased when the drug is administered with calcium. Concurrent ingestion of spinach or cereal may decrease file absorption of calcium supplements. 

The toxic mechanism of action of these various jellyfish venoms is complex. The cardiotoxic reaction seems to focus on calcium transport and is blocked by the prior or post administration of therapeutic doses of verapamil (7J). In neuronal tissue, Chrysaora venom induces large cationic selective channels which open and close spontaneously. These channels are permeable to Na , Li, K, and Cs but not and the channels are present in spite of the treatment with sodium and potassium inhibitors such as tetrodotoxin and tetraethylammonium (14). 

Certain medications (e.g., cimetidine, diltiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefazodone, propoxyphene, and verapamil) added to carbamazepine therapy may cause carbamazepine toxicity. 

Negre-Salvayre, A., and Salvayre, R., 1992, Protechon by Ca channel blockers (nifedipine, chltiazem and verapamil) against the toxicity of oxidized low density hpoprotein to cultured lymphoid cells, Br. J. Pharmacol. 107 738-744. 

Maintenance dose 0.125-0.25 mg PO/IV qd low potassium or magnesium levels potentiate toxicity reduce dose in renal failure toxicity indicated by nausea, headache, visual disturbances (yellow-green halos), ventricular arrhythmias. Quinidine, verapamil, and amiodarone elevate digoxin level. 

The metabolism of ciclosporin is inhibited by diltiazem, verapamil, azole antifungal agents, erythromycin and clarithromycin with resultant potential for renal, hepatic and CNS toxicity. These interactions have been investigated as a cost saving device in organ transplant recipients, with the aim of using a lower dose of ciclosporin to achieve immunosuppression. 

Quinidine inhibits the tubular secretion of digoxin which consequently raises the plasma digoxin concentration, which may be associated with toxicity. Certain other drugs also increase the digoxin concentration like verapamil, amiodarone, spironolactone etc. 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

Other reported potentially significant drug interactions include the combination of verapamil or nifedipine with CBZ, which, at times, can lead to toxicity secondary to increases in CBZ levels, and neurotoxic reactions when verapamil or diltiazem is combined with lithium. 

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... 

Nifedipine (a dihydropyridine) Block of vascular L-type calcium channels > cardiac channels Like verapamil and diltiazem less cardiac effect Prophylaxis of angina, hypertension Oral, duration 4-6 h Toxicity Excessive hypotension Interactions Additive with other vasodilators... 

Verapamil Calcium channel (ICa-i type) blockade Slows SA node automaticity and AV nodal conduction velocity decreases cardiac contractility t reduces blood pressure Supraventricular tachycardias Oral, IV hepatic metabolism caution in patients with hepatic dysfunction Toxicity Interactions See Chapter 12... 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

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