Nifedipine Beta blockers

Vetrovec GW, Parker VE. Nifedipine, beta blocker interaction effect on left ventricular function. C/mRes (1984) 32, 833A. 

Nifedipine is a calcium-channel blocker of the dihydropyridine group. It relaxes smooth muscle and dilates both coronary and peripheral arteries by interfering with the inward displacement of calcium-channel ions through the active cell membrane. Unlike verapamil, nifedipine can be given with beta-blockers. Long-acting formulations of nifedipine are preferred in the long-term treatment of hypertension. 

Drugs that affect all phosphodiesterase type 5 inhibitors include the following alcohol, amlodipine, angiotensin II receptor blockers, antacids, bendroflumethiazide, beta blockers, cimetidine, diuretics, enalaphl, metoprolol, nifedipine, rifampin, tacrolimus. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Propranolol is a beta blocker, and nifedipine is a calcium-channel blocker. 

Acute intoxication with amphetamine is associated with tremor, confusion, irritability, hallucinations and paranoid behaviour, hypertension, sweating and occasionally cardiac arrhythmias convulsions and death may occur. The cardiovascular effects of the stimulants may be treated by beta-blockers, or by the combined alpha- and beta-blocker labetalol calcium channel antagonists such as nifedipine may correct the arrhythmias, while intravenous diazepam is of value in attenuating seizures. 

BETA-BLOCKERS DIHYDROPYRI DINES Rare cases of severe 1 BP and heart failure when nifedipine and nisoldipine are given to patients on beta-blockers It is uncertain why this severe effect occurs Monitor PR, BP and ECG at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

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). 

Vetrovec GW, Parker VE. Alternative medical treatment for patients with angina pectoris and adverse reactions to beta blockers. Usefulness of nifedipine. Am J Med 1986 81(4A) 20-7. 

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. 

Tobacco smoke reduces serum levels of a wide range of drugs and dose adjustment may be necessary when smokers have given up, particularly with theophylline, beta-blockers, adrenergic agonists, nifedipine, tricyclic antidepressants, phenothiazines, benzodiazepines and insulin. 

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. 

If the combination of a beta-blocker and a diuretic does not produce sufficient lowering of pressure, a calcium channel blocker (e.g., verapamil, nifedipine) may be used. This class of drugs blocks type L calcium channels in the myocardium and peripheral vasculature in a dose-depen-dent manner, resulting in decreased cardiac output and peripheral resistance (see chapter 12 for a full discussion of calcium channel blockers). The individual drugs within the class vary as to effect on cardiac muscle and/or vasculature. Therefore, the drug used dictates the relative decrease in cardiac output and/or TPR. 

A PO/sublingual. Rapid, complete absorption of sublingual dose. 98% protein bound. Metabolites are inactive, half-life = 3 hrs. Hypotension. Beta blockers increase risk of severe hypotension, heart failure, and angina. Nifedipine increases effects of oral anticoagulants. Cimetidine elevates nifedipine levels. Inttiai doses may exacerbate angina. Reduce dose in patients with liver dysfunction. 

The use of beta blockers with felodipine, isradipine, lacidipine, nicardipine, nimodipine and nisoldipine normally appears to be useful and safe. However, severe hypotension and heart failure have occurred rarely when a beta blocker was given with nifedipine or nisoldipine. Changes in the pharmacokinetics of the beta blockers and calcium-channel blockers may also occur on concurrent use, but they do not appear to be clinically important. 

Nifedipine 10 mg three times daily did not alter the pharmacokinetics of atenolol 100 mg daily, betaxolol, metoprolol 100 mg twice daily 47 or propranolol 80 mg twice daily. A single-dose study also found no pharmacokinetie interaetion between nifedipine and atenolol. However, another study found that nifedipine 10 mg three times daily eaused an inerease in the peak plasma level and AUC of propranolol 80 mg twiee daily of 56% and 23%, respectively. Another study found that the absorption of a single-dose of propranolol appeared to be faster, leading to higher initial eoncentrations, when it was given after nifedipine. Regardless of the pharmacokinetic changes, none of these studies in healthy subjeets found any adverse haemodynamic effects from the eombination of nifedipine and these beta blockers. - ... 

Not understood. Where pharmaeokinetie ehanges are seen, a possible reason is that the metabolism of the beta bloekers is altered by changes in blood flow through the liver. The pharmacodynamic changes with nifedipine may be explained by the fact that nifedipine reduces the contractility of the heart muscle. This is counteracted by a sympathetic reflex increase in heart rate due to nifedipine-induced peripheral vasodilation, so that the ventricular output stays the same or is even improved. The presence of a beta blocker may oppose this to some extent by slowing the heart rate, which allows the negative inotropic effects of nifedipine to go unchecked. 

Silke B, Verma SP, Guy S. Hemodynamic interactions of a new beta blocker, celiprolol, with nifedipine in angina pectoris. Cardiovasc Drugs Ther (1991) 5,681-8. 

Co-codamol is a combination of paracetamol (nonnapioid analgesic) and codeine (opioid analgesic). One of the side-effects of opioids is constipation. Naprosyn is a proprietary (trade name) preparation of the non-steroidal antiinflammatory drug naproxen Adalat is a proprietary preparation of the calcium-channel blocker nifedipine Amoxil is a proprietary preparation of the beta-lactam amoxicillin and Dulco-lax is the brand name of the stimulant laxative bisacodyl. 

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