METOPROLOL TARTRATE, METOPROLOL SUCCINATE

Chemistry - A beta1 specific adrenergic blocker, metoprolol tartrate occurs as a white, crystallinepowder having a bitter taste. It is very soluble in water. Metoprolol succinate occurs as a white, crystalline powder and is freely soluble in water.

Storage, Stability, Compatibility

Store all products protected from light. Store tablets in tight, light-resistant containers at room temperature. Avoid freezing the injection.

Pharmacology - METOPROLOL TARTRATE, METOPROLOL SUCCINATE

Metoprolol is a relatively specific beta1 blocker. At higher dosages this specificitymay be lost and beta2 blockade can occur. Metoprolol does not possess any intrinsic sympathomimetic activity like pindolol nor does it possess membrane stabilizing activity like pindolol or propranolol. Cardiovascular effects secondary to metoprolol's negative inotropic and chronotropic actions include: decreased sinus heart rate, slowed AV conduction, diminished cardiac output at rest and during exercise, decreased myocardial oxygen demand, reduced blood pressure, and inhibition of isoproterenol-induced tachycardia.

Uses, Indications

Because metoprolol is relatively safe to use in animals with bronchospasticdisease, it is often chosen over propranolol. It may be effective in supraventricular tachyarrhythmias, premature ventricular contractions (PVC's, VPC's), systemic hypertension and in treating cats withhypertrophic cardiomyopathy.

Pharmacokinetics - METOPROLOL TARTRATE, METOPROLOL SUCCINATE

Metoprolol tartrate is rapidly and nearly completely absorbed from the GItract, but it has a relatively high first pass effect (50%) so systemic bioavailability is reduced. Thedrug has very low protein binding characteristics (5-15%) and is distributed well into most tissues.
Metoprolol crosses the blood-brain barrier and CSF levels are about 78% of those found in theserum. It crosses the placenta and levels in milk are higher (3-4X) than those found in plasma.
Metoprolol is primarily biotransformed in the liver; unchanged drug and metabolites are thenprincipally excreted in the urine. Reported half lives in various species:

Dogs:

1.6 hours; Cats: 1.3hours; Humans 3-4 hours.

Contraindications, Precautions, Reproductive Safety

Metoprolol is contraindicated in patientswith overt heart failure, hypersensitivity to this class of agents, greater than first degree heart block, or sinus bradycardia. Non-specific beta-blockers are generally contraindicated in patients with CHFunless secondary to a tachyarrhythmia responsive to beta-blocker therapy. They are also relativelycontraindicated in patients with bronchospastic lung disease.
Metoprolol should be used cautiously in patients with significant hepatic insufficiency. It shouldalso be used cautiously in patients with sinus node dysfunction.
Metoprolol (at high dosages) can mask the symptoms associated with hypoglycemia. It can alsocause hypoglycemia or hyperglycemia and, therefore, should be used cautiously in labile diabeticpatients.
Metoprolol can mask the symptoms associated with thyrotoxicosis, but it may be used clinically totreat the symptoms associated with this condition.
Safe use during pregnancy has not been established, but adverse effects to fetuses have apparentlynot been documented.

Adverse Effects, Warnings

It is reported that adverse effects most commonly occur in geriatricanimals or those that have acute decompensating heart disease. Adverse effects considered to beclinically relevant include: bradycardia, lethargy and depression, impaired AV conduction, CHF orworsening of heart failure, hypotension, hypoglycemia, and bronchoconstriction (less so with beta1specific drugs like metoprolol). Syncope and diarrhea have also been reported in canine patientswith beta blockers.
Exacerbation of symptoms have been reported following abrupt cessation of beta-blockers inhumans. It is recommended to withdraw therapy gradually in patients who have been receiving thedrug chronically.
Overdosage - There is limited information available on metoprolol overdosage. Humans haveapparently survived dosages of up to 5 grams. The most predominant symptoms expected would beextensions of the drug's pharmacologic effects: hypotension, bradycardia, bronchospasm, cardiacfailure and potentially hypoglycemia.
If overdose is secondary to a recent oral ingestion, emptying the gut and charcoal administration may be considered. Monitor ECG, blood glucose, potassium, and, if possible, blood pressure.
Treatment of the cardiovascular effects are symptomatic. Use fluids, and pressor agents to treat hypotension. Bradycardia may be treated with atropine. If atropine fails, isoproterenol given cautiously has been recommended. Use of a transvenous pacemaker may be necessary. Cardiac failure can be treated with a digitalis glycosides, diuretics, and oxygen. Glucagon (5-10 mg IV - Human dose) may increase heart rate and blood pressure and reduce the cardiodepressant effects of metoprolol.

Drug Interactions

Sympathomimetics (metaproterenol, terbutaline, beta effects of epinephrine, phenylpropanolamine, etc.) may have their actions blocked by metoprolol and they may, in turn, reduce the efficacy of metoprolol. Additive myocardial depression may occur with the concurrentuse of metoprolol and myocardial depressant anesthetic agents. Phenothiazines given withmetoprolol may exhibit enhanced hypotensive effects. Furosemide and hydralazine or otherhypotensive producing drugs may increase the hypotensive effects of metoprolol. Metoprolol mayprolong the hypoglycemic effects of insulin therapy. Concurrent use of beta blockers withcalcium channel blockers (or other negative inotropics should be done with caution; particularlyin patients with preexisting cardiomyopathy or CHF.