Diltiazem Beta blockers

BETA-BLOCKERS DILTIAZEM t hypotensive and bradycardic effects cases of severe bradycardia and AV block when both drugs are administered concurrently in the presence of pre-existing heart failure or conduction abnormalities Additive effects on conduction diltiazem causes bradycardia, sinoatrial block and AV block. Also, diltiazem inhibits CYP1A2-mediated metabolism of propanolol Monitor PR, BP and ECG at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

The incidence of atrioventricular block has been reported in 600 consecutive patients who underwent stress myocardial perfusion imaging with adenosine (140 micrograms/kg/minute for 6 minutes), and of whom 43 had first-degree heart block before adenosine and 557 had a baseline PR interval less than 200 ms (Table 1) (31). The heart block in all cases was of short duration, was not associated with any specific symptoms, and in no case required specific treatment. The risk of atrioventricular block during adenosine infusion was not increased by the presence of other drugs that might have caused atrioventricular block (digitalis, beta-blockers, diltiazem, verapamil). 

Yust I, Hoffman M, Aronson RJ, Life-threatening bradycardic reactions due to beta blocker-diltiazem interactions, IsrJMedSci (1992) 28, 292-4,... 

Calcium-channel blockers ACE inhibitors Alpha blockers Angiotensin II receptor antagonists Beta blockers + Dihydropyridines Beta blockers + Diltiazem Beta blockers + Verapamil Calcium-channel blockers Diuretics Glyceryl trinitrate (Nitroglycerin) Nitrates... 

IV diltiazem and IV beta-blockers should not be administered together or in close proximity (within a few hours). 

Concomitant use of calcium channel blockers (atenolol) Bradycardia and heart block can occur and the left ventricular end diastolic pressure can rise when beta-blockers are administered with verapamil or diltiazem. Patients with preexisting conduction abnormalities or left ventricular dysfunction are particularly susceptible. Recent acute Ml (sotalol) Sotalol can be used safely and effectively in the long-term treatment of life-threatening ventricular arrhythmias following an Ml. However, experience in the use of sotalol to treat cardiac arrhythmias in the early phase of recovery from acute Ml is limited and at least at high initial doses is not reassuring. 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Diltiazem (Cardizem, Dilacor). Like the other calcium channel blockers, diltiazem is able to vasodilate the coronary arteries and the peripheral vasculature. Diltiazem also produces some depression of electrical conduction in the sinoatrial and atrioventricular nodes, an effect that may cause slight bradycardia. This bradycardia can be worsened by beta blockers or in patients with myocardial conduction problems, and diltiazem should probably be avoided in these individuals.32,45... 

Because of effects on smooth muscle, the calcium channel blockers (particularly verapamil (96) but also diltiazem) can cause constipation. This may be due to colonic motor activity inhibition (97). Gastroesophageal reflux can also occur, and the calcium channel blockers should be avoided in patients with symptoms suggestive of reflux esophagitis (98). Calcium channel blockers (verapamil, diltiazem, and nifedipine) can also be associated with an increased incidence of gastrointestinal bleeding, as reported in a prospective cohort study in 1636 older hypertensives, with a relative risk of 1.86 (95% Cl = 1.22, 2.82) compared with beta-blockers (7). However, this finding was not confirmed in other retrospective studies (13,99,100). 

The effects of antihypertensive agents have been evaluated in patients taking ciclosporin. Collectively, dihydropyridine calcium channel blockers that do not affect ciclosporin blood concentrations substantially or at all (felodipine, isradipine, and nifedipine) are usually considered to be the drugs of choice. However, the risk of gingival hyperplasia with nifedipine, which ciclosporin also causes, should be borne in mind. Combination therapy with angiotensin-converting enzyme inhibitors or beta-blockers, or the use of other calcium channel blockers (verapamil or diltiazem) should also be considered, but careful monitoring of ciclosporin blood concentrations is recommended with the latter because they inhibit ciclosporin metabolism. 

The nondihydropyridine calcium channel blockers, such as verapamil and diltiazem, have efficacy rates similar to that of adenosine, but are considered second line. Intravenous calcium channel blockers have a few disadvantages. In contrast to adenosine, caution should be taken in hypotensive patients. Adenosine may cause hypotension, but appears to be safe in patients who present with hypotension due to the short half-life. In addition, calcium channel blockers also should be used with caution in patients with systolic heart failure, patients receiving concurrent beta-blocker therapy, and in those with accessory pathways. 

Case Conclusion Diuretics and beta-blockers are first-line agents for treating HTN. Because this patient has asthma, beta-blockers should be avoided. Calcium channel blockers are favorable therapeutic options in patients with both angina and HTN. Because her heart rate is low, diltiazem and verapamil are not optimal choices because they can slow down AV nodal conduction. A long-acting dihydrof ridine, amlodipine, was started. 

C Diltiazem. Quinidine can be used to maintain normal sinus rhythm (NSR) after cardioversion of atrial fibrillation. Metoprolol is commonly used to control ventricular rate before conversion to NSR. However, this patient has two contraindications (COPD and diabetes) for beta-blocker use. Unlike diltiazem, amlodipine and nimodipine do not block AV nodal conduction therefore, they would be ineffective at rate control. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

Class IB drugs act primarily on ventricular muscle and, in the case of lidocaine, concen- j trate in ischemic tissues. Adenosine is indicated for SVTs and nodal tachycardias. The primary actions of both beta blockers (esmolol) and CCBs (diltiazem) are at the AV node— they are not particularly effective in ventricular arrhythmias. Flecainide, a class IC drug, has been implicated in sudden deaths post-MI. 

All calcium-channel blockers cause vasodilatation, but the cardiac response to the decrease in peripheral resistance is variable. An initial reflex increase in heart rate usually occurs with the dihydropyridines (nifedipine, nicardipine, isradipine, and felodipine) verapamil and diltiazem cause little or no change in heart rate. Verapamil and diltiazem can, however, slow atrioventricular (AV) conduction and should be used with caution in patients also taking a beta-blocker dihydropyridines generally do not affect AV conduction and can be used with a beta-blocker, which decreases reflex tachycardia. All calcium-channel blockers should be used with caution in patients with heart failure. 

Beta-adrenergic blocking agents are effective for the prophylactic therapy of exertional angina pectoris by reducing heart rate and the force of myocardial contraction. However, verapamil, nifedipine, and diltiazem are also effective for the prophylactic treatment of stable exertional angina. The combination therapy with beta-blockers and calcium-entry blockers is well tolerated, effective, and safe. 

PO. 50% bioavailability after oral dose. 75% protein bound, half-life=3 hrs, metabolites are active. Reduce dose in patients with renal dysfunction. AV node block, sick sinus syndrome, hypotension, pulmonary congestion. Beta-blockers and digoxin increase A-V conduction time. Diltiazem increases propranolol levels. Cimetidine and drugs metabolized by P-450 increase diltiazem levels. ... 

Kim MH, Rachwal W, McHale C, Bruckman D, Decena BF, Rushan P, MoratfyF, Eagle KA. Effect of amiodarone diltiazem beta blocker on frequency of atrial fibrill on, length of ho italization, and hospital costs after coronary artery bypass graftii. Am J Carrol (2002) 89,1126-28... 

Beta blockers + Calcium-channel blockers Diltiazem... 

The cardiac depressant effects of diltiazem and beta blockers are additive, and although concurrent use can be beneflcial, close monitoring is recommended. A number of patients, (usually those with pre-existing ventricular failure or conduction abnormalities) have developed serious and potentially life-threatening bradycardia. Diltiazem increases the serum levels of propranolol and metoprolol, but not those of atenolol, but these changes are probably not clinically important. 

The bradycardic effects of the beta blockers can be additive with the delay in conduction through the atrioventricular node caused by diltiazem. This advantageously increases the antianginal effects in most patients, but in a few these effects may exacerbate existing cardiac abnormalities. Diltiazem apparently also inhibits the metabolism of propranolol and metoprolol, but the exact mechanism for this is not clear. ... 

Concurrent use is unquestionably valuable and uneventful in many patients, but severe adverse effects can develop. This is well established. A not dissimilar adverse interaction can occur with verapamil , (p.841). On the basis of 6 reports, the incidence of symptomatic bradyarrhythmia was estimated to be about 10 to 15%. It can occur with different beta blockers, even with very low doses, and at any time from within a few hours of starting treatment to 2 years of concurrent use. The main risk factors seem to be ventricular dysfunction, or sinoatrial or AV nodal conduction abnormalities. Note that these are usually contraindications to the use of diltiazem. Patients with normal ventricular function and no evidence of conduction abnormalities are usually not at risk. Concurrent use should be well monitored for evidence of adverse effects. Changes in the pharmacokinetics of the beta blockers may also occur, but these changes are probably not clinically important. 

Sagie A Strasberg B, Kusnieck J, Sclarovsky S, Symptomatic bradycardia induced by the combination of oral diltiazem and beta blockers, Clin Cardiol (1991) 14, 314-16,... 

Hassell AB, Creamer JE, Profound bradycardia after the addition of diltiazem to a beta-blocker. 5A77 (1989) 298, 675. 

A patient who had marked hypotension and bradycardia when erythromycin was added to verapamil and propranolol (see under verapamil, below) had previously taken erythromycin with diltiazem and a beta blocker witiiout any reported adverse effects. ... 

However, in some cases combining two or more antihypertensives has led to severe, first-dose hypotension, see Alpha blockers + ACE inhibitors , p.84. Further, life-threatening bradycardia, asystole and sinus arrest can occur when antihypertensives that cause cardiodepression are given together (see beta blockers and diltiazem , (p.840)). 

---