Metoprolol toxicity

PROPAFENONE METOPROLOL, PROPANOLOL t plasma levels of propranolol and metoprolol Propafenone is extensively metabolized by CYP2D6 enzymes and interferes with the metabolism of propranolol and metoprolol Watch for propranolol and metoprolol toxicity 1 doses accordingly... 

METOPROLOL SSRIs T plasma concentrations of metoprolol SSRIs inhibit metabolism of metoprolol (paroxetine, fluoxetine, sertraline, fluvoxamine via CYP2D6, and (es)citalopram via mechanism uncertain at present) Monitor PR and BP at least weekly watch for metoprolol toxicity, in particular loss of its cardioselectivity... 

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. 

Finally, the toxicity of some effective drugs prevents their use at maximally effective dosage. The widespread indiscriminate use of 3 blockers has been criticized because several large clinical trials indicate that some members of the group, eg, metoprolol and carvedilol, have a greater benefit than others, eg, atenolol. However, all 3 blockers appear to have similar benefits in reducing mortality after myocardial infarction, so these drugs are particularly indicated in patients with an infarct and hypertension. 

BETA-BLOCKERS CYTOTOXICS Imatinib may cause an t in plasma concentrations of metoprolol, propanolol and timolol, with a risk of toxic effects Imatinib is a potent inhibitor of CYP2D6 isoenzymes, which metabolize beta-blockers Monitor for clinical efficacy and toxicity of beta-adrenergic blockers... 

METOPROLOL ARTEMETHER/ LUMEFANTRINE t risk of toxicity Uncertain Avoid co-administration... 

BETA-BLOCKERS DRUG DEPENDENCE THERAPIES - BUPROPION t plasma concentrations of metoprolol, propranolol and timolol, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose... 

IMATINIB 1. ANTIARRHYTHMICS -flecainide, mexiletine, propafenone 2. ANTIDEPRESSANTS - fluoxetine, paroxetine, TCAs, trazodone, venlafaxine 3. ANTIPSYCHOTICS -clozapine, haloperidol, perphenazine, risperidone, thioridazine 4. BETA-BLOCKERS - metoprolol, propanolol, timolol 5. DONEPEZIL 6. METHAMPHETAMINE Imatinib may cause t plasma concentrations of these drugs, with a risk of toxic effects Inhibition of CYP2D6-mediated metabolism of these drugs Watch for early features of toxicity of these drugs... 

Drugs that are metabolized by the cytochrome P-450 (CYP) isoenzymes CYP2D6, CYP2C9, and CYP2C19 also exhibit genetic polymorphisms. An example of CYP2D6 metabolism is debrisoquine. In about 5-10 /o of Caucasians in North America and Europe and about 1% of Asians, 4-hydroxylation of debrisoquine is reduced, and such individuals are at increased risk for toxicity (orthostatic hypotension). Beta blockers (metoprolol and timolol), antiarrhythmic drugs (encainide and flecainide), tricyclic antidepressants... 

Figure 6-7 Structure-toxicity relationships with -adrenoceptor antagonists practolol, atenolol, and metoprolol.

Ingestion is the most common route for both accidental and intentional exposures to the beta blockers. Esmolol, labetalol, metoprolol, and propranolol are all available for parenteral administration therefore, toxicity can occur via this route. Beta blockers are also administered as ocular medications and systemic toxicity can occur following administration by this route. 

As many as 40% of patients complain of headache, memory impairment, confusion, poor concentration, and impaired motor performance. A fine hand tremor may be evident in np to 50% of patients. Stress, concomitant nse of antidepressants or antipsychotics, caffeine, sympathomimetics, and impending toxicity may exacerbate the tremor. Strategies to rednce the tremor inclnde standard approaches or adding a /3-adrenergic antagonist (e.g., propranolol 20 to 120 mg/day, atenolol 50 mg/day, or metoprolol 20 to 80 mg/day). 

B. Clinical Uses and Toxicities Esmolol, a very short-acting beta-blocker for intravenous administration, is used exclusively in acute arrhythmias. Propranolol, metoprolol. and timolol are commonly used as prophylactic drugs in patients who have had a myoeardial infarction. These drugs provide a protective effect for 2 years or longer after the infarct. 

In Fig. 14B, the EC50 values of the parent compounds were normalized with the TPmixture- For a better appreciation of the effect, the negative logarithm of this ratio is plotted, i.e. a higher number relates to higher toxicity. The parent compound propranolol is much more toxic than metoprolol and atenolol. Consequently, despite the fact that metabolism results in quite a dramatic reduction of the toxic potential, propranolol remains the most ecotoxic of the three 6-blockers even if metabolism is included in the toxicity analysis. 

The plasma levels of lidocaine after intravenous, and possibly oral, use can be increased by propranolol. Isolated cases of toxicity attributed to this interaction have been reported. Nadolol and penbutolol possibly interact similarly, but there is uncertainty about metoprolol. Atenolol and pindolol appear not to interact. 

Plasma metoprolol and propranolol levels can be markedly raised (two to fivefold) by propafenone. Toxicity may develop. 

Identical oxidation byproducts detected for both anodes and J. Faster degradation rates for and higher J. Abundant formati(Hi of Cr and Br by-products of model compound metoprolol. Increase in toxicity by V.fischeri and Pseudokirchneriella subcapitata (Vtot = 10 L)... 

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