Metoprolol dosage

There are pharmacokinetic differences among /1-blockers in first-pass metabolism, serum half-lives, degree of lipophilicity, and route of elimination. Propranolol and metoprolol undergo extensive first-pass metabolism. Atenolol and nadolol have relatively long half-lives and are excreted renally the dosage may need to be reduced in patients with moderate to severe renal insufficiency. Even though the half-lives of the other /J-blockers are much shorter, once-daily administration still may be effective. /J-Blockers vary in their lipophilic properties and thus CNS penetration. 

Compounds that exhibit roughly the same affinity to and j32 rsceptors independent of dosage such as nadolol, propranolol, pindolol, timolol, and labetalol (combined a- and j3-adrenoblocker) are classified as nonselective blockers. Drugs which in therapeutic doses have higher affinity to -receptors than to j32-receptors such as acebutol, atenolol, metoprolol, and esmolol, are called selective or cardioselective j3-adrenoblockers. 

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. 

Atenolol is not extensively metabolized and is excreted primarily in the urine with a half-life of 6 hours it is usually dosed once daily. Recent studies have found atenolol less effective than metoprolol in preventing the complications of hypertension. A possible reason for this difference is that once-daily dosing does not maintain adequate blood levels of atenolol. The usual dosage is 50-100 mg/d. Patients with reduced renal function should receive lower doses. 

G. Ramana Rao, G. Raghuveer, and P. Khadgapathi, High-performance liquid chromatographic determination of metoprolol tartrate and hydrochlorothiazide in dosage forms, Indian Drugs, 25 39(1985). 

Very limited drug absorption due to the lack of microvilli and the more viscous and semisolid nature of the lumen contents. A few drugs such as theophylline and metoprolol are absorbed in this region. Drugs that are absorbed well in this region are good candidates for an oral sustained-release dosage form... 

Martin A, Browning RC (1985) Metoprolol in the aged hypertensive a comparison of two dosage schedules. Postgraduate Medical Journal 61 225-227. 

Preliminary results of a study in 6 healthy subjects found that long-term treatment with propranolol [period and dosage not stated] increased the procainamide half-life from 1.71 to 2.66 hours and reduced the plasma clearance by 16%. However, a later study in 8 healthy subjects found that the pharmacokinetics of a single 500-mg dose of procainamide were only slightly altered by propranolol 80 mg three times daily or metoprolol 100 mg twice daily. The procainamide half-life of 1.9 hours increased to 2.2 hours with propranolol, and to 2.3 hours with metoprolol, but no sig-ni ficant changes in total clearance occurred. No changes in the AUC of the metabolite A-acetylprocainamide were seen. It seems unlikely that a clinically important adverse interaction normally occurs between these drugs. 

The manufacturers of bupropion have predicted this interaction and recommend that if metoprolol is added to treatment with bupropion, doses at the lower end of the range should be used. If bupropion is added to existing treatment, decreased dosages of metoprolol should be considered. ... 

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. 

Information seems to be limited. If sulfinpyrazone is given to patients taking oxprenolol for hypertension, the effects should be monitored. It seems likely that this interaetion eould be aeeommodated by raising the dosage of the oxprenolol but this needs eonfirmation. The effect of this interaction on cardiac workload appears to be less important, but it would still be prudent to monitor coneurrent use if oxprenolol is used for angina. Metoprolol may be a suitable alternative to oxprenolol as it does not appear to interact with sulfinpyrazone. 

Metoprolol isasefifectiveaspropranololanddoesnotslowmefoyhcndvneeaTe-tion. The si ested dosage is 0uO4-Oj06 mg/1% intravenous, tfawthnesdafly. 

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