Verapamil disordering

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Nimodipine may be more effective than verapamil for rapid-cycling bipolar disorder because of its anticonvulsant properties, high lipid solubility, and good penetration into the brain. 

Calcium Channel Blockers. The calcium channel blockers work by blocking the influx of calcium, an excitatory ion, into the cell. The first calcium channel blocker, verapamil (Calan), was introduced in the 1960s. Others, including diltiazem, nifedipine, and nimodipine, are now available. The calcium channel blockers have been used to treat a variety of medical conditions including high blood pressure, cardiac pain (angina) and arrhythmias, migraines, seizure disorders, and premature labor. 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Antiadrenergic] Uses HTN Action Centrally acting antihypCTtensive Dose Adults. 250-500 mg PO bid-tid (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 doses (max 40 mg/kg/24 h q6-12h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20 0 mg/kg/24 h X in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine initial transient sedation/drowsiness frequent, edema, hemolytic anemia, hepatic disorders Interactions T Effects W/ anesthetics, diuretics, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide effects W/amphetamines, Fe, phenothiazine, TCAs ... 

Controlled and uncontrolled or open studies of the CCBs in affective illness are reviewed in Table 6-3. Initial open and blind studies of the phenyl-alkylamine L-type CCB verapamil were positive in the affective disorders, particularly in the treatment of acute mania. However, some preliminary controlled data are negative (Janicak et al. 1998) these data are highly subject to a type II error with the design used, the relatively small numbers of patients randomly selected for verapamil and placebo, and the associated relatively high placebo response rate in acute mania observed in many controlled studies... 

FKiURE 6 5C. Efficacy of dihydropyridine L-type calcium channel blockers. Mean deviation from euthymia ratings (number of days in parentheses) in a patient with bipolar 11 disorder with ultra-ultrarapid cycling showing the following efficacy of nimodipine monotherapy efficacy of nimodipine-carbamazepine combination therapy unsuccessful transition from nimodipine to verapamil successful reinstitution of nimodipine-carbamazepine combination therapy and, finally, successful transition to isradipine-carbamazepine combination therapy. P <. 05 "nimodipine slowly tapered to zero. 

Hoschl C Verapamil for depression Am J Psychiatry 140 1100, 1983 Hoschl C, Kozeny J Verapamil in affective disorders a controlled, double-blind study. Biol Psychiatry 25 128-140, 1989... 

CCAs (channel blockers influx inhibitors) have been used primarily for the treatment of cardiovascular disorders (e.g., supraventricular arrhythmias, angina, and hypertension). Agents such as verapamil exert their effects by modulating the influx of Ca across the cell membrane, thus interfering with calcium-dependent functions. Based partly on the common effects of lithium and this class of drugs (e.g., effects on Ca "" activity), the CCAs have been studied as a potential treatment for mania. Janicak et al. (251) reported the results of a 3-week, double-blind comparison of verapamil versus placebo, which did not demonstrate a beneficial effect for verapamil (up to 480 mg/day) in 33 acutely manic hospitalized patients. 

Verapamil has been shown to block the P-glycoprotein responsible for the transport of many foreign drugs out of cancer (and other) cells (see Chapter 1) other calcium channel blockers appear to have a similar effect. This action is not stereospecific. Verapamil has been shown to partially reverse the resistance of cancer cells to many chemotherapeutic drugs in vitro. Some clinical results suggest similar effects in patients (see Chapter 54). Animal research suggests possible future roles of calcium blockers in the treatment of osteoporosis, fertility disorders and male contraception, immune modulation, and even schistosomiasis. 

Verapamil causes peripheral vasodilation, which may be beneficial in hypertension and peripheral vasospastic disorders. Its effects on smooth muscle produce a number of extracardiac effects (see Chapter 12). 

Verapamil (Calan and others) is a calcium channel blocker used for the treatment of cardiac disorders that has also been used off-label as a mood leveler. It can produce a variety of cardiovascular side effects. 

Systematic studies of fluoxetine as monotherapy have not shown evidence of QTC prolongation. It is possible in this case that fluoxetine interacted with verapamil to produce a conduction disorder. 

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