Metoprolol adverse effects

The adverse effects noted with metoprolol result from the -adrenoceptor blocking actions and are similar to those noted for propranolol... 

For highly potent APIs, profound effects can occur at low ng levels, the adverse effect of ethynylestradiol on fish populations is one example [107]. Another example is the development of resistant bacterial strains induced by the release of antibiotics into the environment [112, 113]. Dome et al. [114] concluded that fluoxetine, ibuprofen, diclofenac, propranolol and metoprolol exhibit relatively high acute toxicity to aquatic species. In addition, due to the inherent properties of these chemicals, pharmacodynamic effects were observed in the heart rate of Daphnia magna for the (3-blockers propranolol and metoprolol. 

Trials of 3-blocker therapy in patients with heart failure are based on the hypothesis that excessive tachycardia and adverse effects of high catecholamine levels on the heart contribute to the downward course of heart failure patients. The results clearly indicate that such therapy is beneficial if initiated very cautiously at low doses, even though acutely blocking the supportive effects of catecholamines can worsen heart failure. Several months of therapy may be required before improvement is noted this usually consists of a slight rise in ejection fraction, slower heart rate, and reduction in symptoms. As noted above, not all 3 blockers have proved useful, but bisoprolol, carvedilol, and metoprolol have been shown to reduce mortality. Trials are underway with the newer 13 blocker, nebivolol. 

Adverse effects The adverse events associated with (3 blockers may be avoided by starting treatment at very low doses. However, treatment can be associated with complaints of fatigue and weakness, which usually resolve in a few weeks, Sometimes it is necessary to decrease the dose of the (3 blocker or diuretic. Symptomatic bradycardia is another serious adverse effect of (3 blockers, and requires a decrease in the dose or sometimes cardiac pacing to allow the use of this vital medication, Hypotension is another potential side effect however, it is rarely seen as the therapy is started with a very low dose (3,25 mg twice a day for carvedilol, I mg for bisoprolol and 12,5 mg for extended release metoprolol). The administration of ACE inhibitor and diuretic at a different time of day than the (3 blocker can... 

BETA-BLOCKERS RITONAVIR, TIPRANAVIR t adverse effects of carvedilol, metoprolol, propanolol and timolol Inhibition of CYP2D6-mediated metabolism of these beta-blockers and CYP2C19-mediated metabolism of propanolol Use an alternative beta-blocker if possible if not, monitor closely... 

Beta-adrenoceptor blockers. The realisation that the coiuse of chronic heart failure can be adversely affected by activation of the renin-angiotensin-aldosterone and sympathetic nervous systems led to exploration of possible benefit from P-adrenoceptors in a condition where, paradoxically, such drugs can have an adverse effect. Clinical trials have, indeed, shown that bisoprolol, carvedilol or metoprolol lower mortality and decrease hospitalisation when added to diuretics, digoxin and an ACE inhibitor (see below). 

Many beta-adrenoceptor antagonists undergo substantial first-pass hepatic metabolism these include alprenolol, metoprolol, oxprenolol, and propranolol. Hepatic cirrhosis, with consequent portosystemic shunting, can therefore result in increased systemic availability and higher plasma concentrations, perhaps resulting in adverse effects. Beta-blockers may also reduce liver blood flow and cause interactions with drugs with flow-dependent hepatic clearance. 

In the treatment of hypertension, a major use of beta-blockers is in combination with hydralazine. The direct vasodilators bring about reflex cardiac stimulation, and beta-blockers prevent these adverse effects (see also Figure 67). Beta-blockers also reduce blood pressure by exerting a central effect or a peripheral action, or both, which decreases renin activity. Metoprolol and atenolol are beta selective, and they are safer agents in patients with asthma, diabetes mellitus, or low-renin hypertension. Some beta-blocking agents such as pindolol have intrinsic sympathomimetic activity and may be used in the treatment of pronounced bradycardia (sick sinus syndrome). Unlike propranolol, metoprolol is not a very lipid-soluble... 

Retrospective analysis of a large multinational study in patients given terazosin 5 or 10 mg daily found that terazosin only affected the blood pressure of patients taking beta blockers (atenolol, labetalol, metoprolol, sotalol, and timolol) if the blood pressure was uncontrolled. No change in blood pressure was seen in those with normal blood pressure (i.e. those without hypertension and those with hypertension controlled by beta blockers). The most common adverse effect in the 10-week terazosin phase was dizziness, and the incidence of this appeared to be lower in those taking antihypertensives (13 to 16%) than those not (21 to 25%)."... 

A matched study in 51 cardiac patients taking a variety of beta blockers (including propranolol, metoprolol, timolol, pindolol) found no significant differences in either total or free concentrations of lidocaine during a lidocaine infusion, but there was a trend towards an increase in the adverse effects of lidocaine (bradycardias) with concurrent beta blocker treatment. ... 

A double-blind, crossover study in 8 healthy subjects found that over a 5-day period, metoprolol 100 mg twice daily did not affect the pharmacokinetics of felodipine 10 mg twice daily. On the other hand, the bioavailability and peak plasma levels of metoprolol were increased by 31% and 38%, respectively. Another study in 10 healthy subjects given felodipine 10 mg with either metoprolol 100 mg, pindolol 5 mg, propranolol 80 mg, or timolol 10 mg found no changes in heart rate, PR interval or blood pressure that might be considered to be harmful to patients with hypertension or angina. However, 7 of the 10 subjects reported some inerease in adverse effects. ... 

Kirch W, Spahn H, Kbhler H, Mutschler E. Accumulation and adverse effects of metoprolol and propranolol after concurrent adm inistration of cimetidine. Arch Toxicol (1983) (Suppl 6),... 

Information is limited but the interaetion would seem to be established. Concurrent use need not be avoided but antieipate the need to reduce the dosage of metoprolol and propranolol. Monitor closely because some patients may experience adverse effects. If the suggested mechanism of interaction is correct it is possible (but not confirmed) that other beta blockers that undergo liver metabolism will interact similarly but not those largely excreted unchanged in the urine. See Table 22.1 , (p.833) for the metabolism of some commonly used beta blockers. Also note that propafenone and the beta blockers have negative inotropic effects, which could be additive and result in unwanted cardiodepression. 

A study in 9 healthy subjects found that sulfinpyrazone 4(X) mg twice daily did not affect the pharmacokinetics of metoprolol 1(X) mg twice daily. No adverse effects were noted in healthy subjects during concurrent... 

A woman taking metoprolol 50 mg daily and felodipine 5 mg daily for hypertension developed bilateral leg oedema, orthostatic hypotension, and other symptoms including dizziness and fatigue, 3 days after starting HAART following a needle-stick injury. The antiretroviral therapy included zidovudine, lamivudine, and nelfinavir 2 g daily. Antihypertensive treatment was stopped and the adverse effects abated within 3 days. The patient was then successfully switched to a diuretic-based regimen without recurrence of oedema. ... 

Nervous system Sleepwalking is as a rare adverse effect of metoprolol, possibly facilitated by a history of childhood somnambulism [IS ]. 

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