AMRINONE LACTATE

Chemistry - Unrelated structurally to cardiac glycosides or catecholamines, amrinone is abipyrdine cardiac inotropic agent. It occurs as a pale yellow, crystalline powder and is insoluble inwater and slightly soluble in alcohol. The commercially available injection has a pH adjusted to 3.2-4 and an osmolality of 101 mOsm/L.

Storage, Stability, Compatibility

The commercially available injection should be stored at roomtemperature and protected from light. It is stable for 2 years after manufacture.
Amrinone lactate for injection is reportedly compatible with 0.45% or 0.9% sodium chlorideinjection, propranolol HCl, verapamil HCl. It is reportedly incompatible with solutions containingdextrose or sodium bicarbonate. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references (e.g., Handbook on
Injectable Drugs by Trissel; see bibliography) for more specific information.

Pharmacology - AMRINONE LACTATE

The exact mechanisms of amrinone's cardiac effects are not well understood. It isthought the primary effects are due to its vasodilatory effects, thereby reducing both preload andafterload. Because it inhibits phosphodiesterase, it may also directly stimulate cardiac contractility.

Uses, Indications

Amrinone is considered to be a second line agent for the short term management of CHF.

Pharmacokinetics - AMRINONE LACTATE

Although no commercial dosage forms are available, amrinone is rapidlyabsorbed after oral administration. After initial intravenous injection, effects begin within 2-3 minutes and peak effects occur within 10 minutes. Cardiac effects generally correlate with thedrug's serum level. Amrinone's distribution characteristics are not well described. In humans, it has an apparent volume of distribution of 1.2 L/kg. It exhibits low to moderate protein binding (10-49%). It is unknown if it crosses the placenta, blood-brain barrier or enters into maternal milk.
Amrinone is eliminated primarily via the kidneys. About 63% of a dose is excreted (10-40% unchanged) into the urine. The duration of effect (in humans) is dose related with a single doselasting from 30 minuets after a 0.75 mg/kg IV dose to 2 hours after a 3 mg/kg dose. Plasma half lives may be prolonged in patients with CHF.

Contraindications, Precautions, Reproductive Safety

Amrinone is considered contraindicatedwhen severe aortic or pulmonic valve disease is present or in patients hypersensitive to it orbisulfites. The potential risks versus benefits of therapy with amrinone should be carefully considered in patients with hypertrophic cardiomyopathy. Reproductive safety data are conflicting; use only when benefits outweigh risks.

Adverse Effects, Warnings

Use in domestic animals is limited. Adverse effects that potentiallycould be seen include arrhythmias (drug is not inherently arrhythmogenic, but CHF patients aremore susceptible to arrhythmias secondary to any drug), hypotension, GI effects (vomiting, diarrhea), thrombocytopenia (particularly with prolonged therapy), hepatotoxicity, and hypersensitivityreactions (variable symptomatology: pericarditis to myositis, etc.). Amrinone should only be used insettings where appropriate monitoring may be employed.

Overdosage, Acute Toxicity

Only one case (human) of accidental massive overdose resulting indeath has been reported (causal relationship not unequivocally established). Because hypotension isthe primary problem that would generally be seen, circulatory support should be instituted.

Drug Interactions

Digoxin and other inotropic cardiac glycosides have an additive effect withamrinone. This is generally considered to be a positive drug interaction. Disopyramide may causeexcessive hypotension when used with amrinone.