J Pharmacol Exp Ther. 2005 Feb 17.
Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine co-administration during exercise testing in healthy premenopausal women.
Sharma A, Pibarot P, Pilote S, Dumesnil JG, Arsenault M, Belanger PM, Meibohm B, Hamelin BA.
Quebec Heart and Lung Institute and Faculty of Pharmacy, Laval University.
Premenopausal women may be most vulnerable to acute coronary syndromes at a point in their menstrual cycle when their plasma estrogen levels are the lowest during and immediately after menstruation. Metoprolol is a first line drug in the management of patients with acute coronary syndrome, however, when metoprolol was marketed (1982), women were largely excluded from clinical trials. Further, the over-the-counter antihistamine diphenhydramine inhibited the metabolism of the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and pharmacodynamic consequences. The pharmacokinetics and pharmacodynamics of metoprolol and its interaction with diphenhydramine were investigated in a randomized, double-blind, cross-over, placebo-controlled fashion in healthy, premenopausal extensive (EM; n=16) and poor metabolizer (PM; n=4) women immediately after menstruation. During the placebo phase, EMs had between 5.2-8.4 fold higher total clearance (CL/F) of R- and S-metoprolol compared to PMs while the latter had a 35% greater area under the effect curve (AUEC) and 60% greater EC50 for heart rate reduction than EMs (all p < 0.05). Diphenhydramine coadmininstration caused a 2.2-3.2 fold decrease in CL/F of metoprolol enantiomers with a resulting 21% increase in AUEC and 29% increase in EC50 for heart rate reduction in EMs (all p < 0.05). This is the first study to report an in-depth elucidation of metoprolol's pharmacokinetics and hemodynamics in premenopausal EM and PM women at a point in their menstrual cycle when vulnerability for acute coronary events may be greatest. Caution is warranted when the over-the-counter antihistamine diphenhydramine is part of a chronic therapeutic regimen.

J Neural Transm Suppl. 2003;(64):35-63.
Pharmacological approaches to migraine.
Diener HCh.
Department of Neurology, University Essen, Federal Republic of Germany. h.diener@uni-essen.de
Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. This review summarises new treatment options both for the therapy of the acute attack as well as for migraine prophylaxis. Analgesics like aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) are effective in treating migraine attacks. Few controlled trials were performed for the use of ergotamine or dihydroergotamine. These trials indicate inferior efficacy compared to serotonin (5-HT)1B/D-agonists (further on called "triptans"). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan) are highly effective. They improve headache as well as nausea, photo- and phonophobia. The different triptans have minor differences in efficacy, headache recurrence and adverse effects. The knowledge of their different pharmacological profile allows a more specific treatment of the individual migraine characteristics. Migraine prophylaxis is recommended, when more than 3 attacks occur per month, if attacks do not respond to acute treatment or if side effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol, the calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently antiepileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for the prophylaxis of migraine. The use of botulinum-toxin is under investigation.

Drugs Aging 2002;19(9):671-84
Optimising the Use of beta-Blockers in Older Patients with Heart Failure
Owen A
Kent and Canterbury Hospital, Canterbury, UK
Heart failure is predominantly a disease of the older person with half of all patients with the condition aged >75 years. Diuretics are the first-line symptomatic treatment for heart failure. beta-blockers should be initiated on an outpatient basis once the patient is stable, euvolaemic (by means of a diuretic) and established on an angiotensin converting enzyme (ACE) inhibitor. Large trials have demonstrated the beneficial effects of the beta-blockers carvedilol, metoprolol and bisoprolol in patients with heart failure, most of whom were also receiving ACE inhibitors. However, the mean age of patients in these trials was generally 60 to 65 years, with very few patients aged >75 years being recruited. It is, thus, not immediately clear how to apply these trial results to older patients with heart failure. Subgroup analyses from these large beta-blocker heart failure trials suggest that older patients gain similar benefit from beta-blocker treatment to younger patients. The trials, however, give no guidance as to whether older patients should receive the same target dosage or titration regimen as younger patients. It is suggested that a less aggressive titration regimen may be more appropriate for older patients while still attempting to achieve the trial target dosages. Titration can be safely achieved on an outpatient basis. In particular, a period of observation in the clinic after initiation of treatment does not appear to be necessary. The survival benefit resulting from the use of a beta-blocker in patients with heart failure is modest (months rather than years). It is, thus important not to neglect the effects of treatment on quality of life. A proportion of patients experience adverse effects with a beta-blocker. For such patients a balance needs to be made between the adverse effects on quality of life and the likely extension of life from the use of a beta-blocker. For patients who can tolerate a beta-blocker, the available evidence suggests that it can improve quality of life. The evidence currently available does not support the use of an angiotensin II receptor blocker (ARB) in addition to an ACE inhibitor and beta-blocker. For patients unable to tolerate an ACE inhibitor or beta-blocker, the use of an ARB may confer some advantage.

Drug information

GENERIC NAME: metoprolol
BRAND NAMES: Lopressor, Toprol XL

DRUG CLASS AND MECHANISM: Metoprolol is a beta-adrenergic blocking agent. Metoprolol blocks the action of the sympathetic nervous system, a portion of the involuntary nervous system. The sympathetic nervous system stimulates the pace of the heart beat. By blocking the action of these nerves, metoprolol reduces the heart rate and is useful in treating abnormally rapid heart rhythms. Metoprolol also reduces the force of heart muscle contraction and lowers blood pressure. By reducing the heart rate and the force of muscle contraction, metoprolol reduces heart muscle oxygen demand. Since angina occurs when oxygen demand of the heart exceeds supply, metoprolol is helpful in treating angina.

PREPARATIONS: Tablets: 50 mg, 100 mg, 200 mg.

STORAGE: Tablets should be stored at room temperature in a tightly closed container.

PRESCRIBED FOR: Metoprolol is prescribed for patients with high blood pressure (hypertension). It is also used to treat chest pain (angina pectoris) related to coronary artery disease. Metoprolol is also useful in slowing and regulating certain types of abnormally rapid heart rates (tachycardias). Other uses for metoprolol include the prevention of migraine headaches and the treatment of certain types of tremors (familial or hereditary essential tremors).

DOSING: Should be taken before meals or at bedtime.

DRUG INTERACTIONS: Metoprolol can aggravate breathing difficulties in patients with asthma, chronic bronchitis, or emphysema. In patients with existing slow heart rates (bradycardias) and heart blocks (defects in the electrical conduction of the heart), metoprolol can cause dangerously slow heart rates, and even shock. Metoprolol reduces the force of heart muscle contraction and can aggravate symptoms of heart failure. Calcium channel blockers and digoxin (Lanoxin) can cause lowering of blood pressure and heart rate to dangerous levels when administered together with metoprolol. In patients with coronary artery disease, abruptly stopping metoprolol can suddenly worsen angina, and occasionally precipitate heart attacks. If it is necessary to discontinue metoprolol, its dosage can be reduced gradually over several weeks.

Metoprolol can mask the early warning symptoms of low blood sugar (hypoglycemia), and should be used with caution in patients receiving treatment for diabetes. Safe use of metoprolol in children has not been established. It is not habit forming.

PREGNANCY: Safe use of metoprolol during pregnancy has not been established.

SIDE EFFECTS: Metoprolol is generally well tolerated, side effects are mild and transient. Rare side effects include abdominal cramps, diarrhea, constipation, fatigue, insomnia, nausea, depression, dreaming, memory loss, fever, impotence, lightheadedness, slow heart rate, low blood pressure, cold extremities, sore throat, and shortness of breath or wheezing.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov (1)
www.nlm.nih.gov (2)

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METOPROLOL
Generic name: metoprololium tartaricum
Brand name: Betaloc
Manufacturer: Astra (Sweden license)

Metoprolol is used for chest pain (angina),
high blood pressure and irregular heartbeats.

Health information and news

Dosage	Packing	Price	Pay now
50 mg	100 tab	USD 19.00
100 mg	60 tab	USD 34.00