Calcium channel blocker adverse effects

Throbbing headache, facial warmth and flushing, and dizziness are minor complaints associated with the use of calcium channel blockers these effects are beheved to be caused by inhibitory actions on smooth muscle (20). Palpitation, muscle cramps, and pedal edema also occur (21-27). Dizziness, facial flushing, leg edema, postural hypotension, and constipation have been reported in up to one-third of patients. They are rarely severe and often abate on continued therapy. More serious adverse effects, mainly those affecting cardiac conduction, are much less common, and only rarely is withdrawal necessary. 

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. 

Adverse effects and contraindications of calcium channel blockers are described in Table 5-2. Verapamil, diltiazem, and first-generation dihydropyridines should also be avoided in patients with acute decompensated heart failure or left... 

The calcium channel blockers have been associated with both prolonged pregnancy and decreased neonatal morbidity.36,42 when compared with P-mimetics (e.g., terbutaline) and magnesium, they show better neonatal outcome and a lower incidence of serious maternal side effects.42 Potential minor maternal adverse effects include headache, flushing, dizziness, and transient hypotension.41... 

Cytochrome P450 inhibition Coadministration of delavirdine tablets with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, calcium channel blockers, ergot alkaloid preparations, amphetamines, and cisapride may result in potentially serious or life-threatening adverse events caused by possible effects of delavirdine on the hepatic metabolism of certain drugs metabolized by CYP3A and... 

TABLE 19.3 Adverse Effects of Calcium Channel Blockers... 

All of the following adverse effects are likely to occur with long-term use of calcium channel blockers EXCEPT... 

Most types of smooth muscle are dependent on transmembrane calcium influx for normal resting tone and contractile responses. These cells are relaxed by the calcium channel blockers (Figure 12-3). Vascular smooth muscle appears to be the most sensitive, but similar relaxation can be shown for bronchiolar, gastrointestinal, and uterine smooth muscle. In the vascular system, arterioles appear to be more sensitive than veins orthostatic hypotension is not a common adverse effect. Blood pressure is reduced with all calcium channel blockers. Women may be more sensitive than men to the hypotensive action of diltiazem. The reduction in peripheral vascular resistance is one mechanism by which these agents may benefit the patient with angina of effort. Reduction of coronary artery tone has been demonstrated in patients with variant angina. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

The adverse effects of atazanavir include fever, jaundice/scleral icterus, myalgia and diarrhea. Its coadministration is not recommended with the drugs that induce cytochrome P-450 isoenzyme CYP3A4. Ritonavir increases plasma concentrations of atazanavir. It is an inhibitor of isoenzymes CYP3A4, CYP2C8 and UGT1A1. The coadministration of atazanavir with calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants and phosphodiesterase 5 inhibitors should be carefully monitored. 

The mechanism for this adverse effect is unclear and has not been reported with other calcium channel blockers. 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

CALCIUM CHANNEL BLOCKERS MACROLIDES t plasma concentrations of felodipine when co-administered with erythromycin cases of adverse effects of verapamil (bradycardia and 1 BP) with both erythromycin and clarithromycin Erythromycin inhibits CYP3A4-mediated metabolism of felodipine and verapamil. Clarithromycin and erythromycin inhibit intestinal P-gp, which may t the bioavailability of verapamil Monitor PR and BP closely watch for bradycardia and 1 BP. Consider reducing the dose of calcium channel blocker during macrolide therapy... 

CALCIUM CHANNEL BLOCKERS GRAPEFRUIT JUICE t bioavailability of felodipine and nisoldipine (with reports of adverse effects), and t bioavailability of isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine and verapamil (without reported adverse clinical effects) Postulated that flavonoids in grapefruit juice (and possibly Seville oranges and limes) inhibit intestinal (but not hepatic) CYP3A4. They also inhibit intestinal P-gp, which may t the bioavailability of verapamil Avoid concurrent use of felodipine and nisoldipine and grapefruit juice... 

SSRIs CALCIUM CHANNEL BLOCKERS Reports oft serum levels of nimodipine and episodes of adverse effects of nifedipine and verapamil (oedema, flushing, l BP) attributed to t levels when co administered with fluoxetine Fluoxetine inhibits the CYP3A4-mediated metabolism of calcium channel blockers. It also inhibits intestinal P-gp, which may T bioavailability of verapamil Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.). Consider reducing the dose of calcium channel blocker or using an alternative antidepressant... 

OMEPRAZOLE CALCIUM CHANNEL BLOCKERS - NIFEDIPINE Possible T efficacy and adverse effects Small t bioavailability possible via T intragastric pH Unlikely to be clinically significant... 

Adverse effects are rmcommon, but include transient hepatitis and hypokalaemia. Prolonged use may lead to cardiac failure, especially in those with preexisting cardiac disease. Co-administration of a calcium channel blocker adds to the risk. 

---