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The main pharmacological effects of Generic Digiter are on the heart. Extracardiac effects are responsible for many of the adverse effects (see below).

Its main cardiac effects are: A decrease of conduction of electrical impulses through the AV node, making it a commonly used drug in controlling the heart rate during atrial fibrillation or atrial flutter. An increase of force of contraction via inhibition of the Na+/K+ ATPase pump (see below).

Generic Digiter binds to a site on the extracellular aspect of the a-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased Na+ levels, which in turn slows down the extrusion of Ca2+ via the Na+/Ca2+ exchange pump. Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by Generic Digiter. This is a different mechanism from that of catecholamines.

Generic Digiter also increases vagal activity via its central action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. This is important for its clinical use in different arrhythmias (see below).

Today, the most common indications for Generic Digiter are probably atrial fibrillation and atrial flutter with rapid ventricular response. High ventricular rate leads to insufficient diastolic filling time. By slowing down the conduction in the AV node and increasing its refractory period, Generic Digiter can reduce the ventricular rate. The arrhythmia itself is not affected, but the pumping function of the heart improves owing to improved filling.

The use of Generic Digiter in congestive heart failure during sinus rhythm is controversial. In theory the increased force of contraction should lead to improved pumping function of the heart, but its effect on prognosis is disputable and Generic Digiter is no longer the first choice for congestive heart failure. However, it can still be useful in patients who remain symptomatic despite proper diuretic and ACE inhibitor treatment.

Generic Digiter is usually given by mouth, but can also be given by IV injection in urgent situations (the IV injection should be slow, heart rhythm should be monitored). The half life is about 36 hours, Generic Digiter is given once daily, usually in 125 µg or 250 µg dosing. In patients with decreased kidney function the half life is considerably longer, calling for a reduction in dosing or a switch to a different glycoside (digitoxin).

Effective plasma levels are fairly well defined, 1-2.6 nmol/l. In suspected toxicity or ineffectiveness, Generic Digiter levels should be monitored. Plasma potassium levels also need to be closely controlled (see side effects below).

The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity). Adverse effects are concentration-dependent, and are rare when plasma Generic Digiter concentration is <0.8 µg/L (Rossi, 2006). They are also more common in patients with low potassium levels (hypokalemia), since Generic Digiter normally competes with K+ ions for the same binding site on the Na+/K+ ATPase pump.

Common adverse effects (=1% of patients) include: loss of appetite, nausea, vomiting, diarrhoea, blurred vision, visual disturbances (yellow-green halos), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression. Less frequent adverse effects (0.1%–1%) include: acute psychosis, delirium, amnesia, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, heart block (Rossi, 2006).

The pharmacological actions of Generic Digiter usually results in electrocardiogram (ECG) changes, including ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of Generic Digiter toxicity. Additionally, increased intracellular Ca2+ may cause a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation.

An often described but rarely seen adverse effect of Generic Digiter is a disturbance of colour vision (mostly yellow and green colour) called xanthopsia.

Generic Digiter has potentially dangerous interaction with verapamil, amiodarone and erythromycin.

In an overdose, the usual supportive measures are needed. Generic Digiter cannot be removed by hemodialysis, the antidote is antiGeneric Digiter (antibody fragments against Generic Digiter, trade name Digibind).

Some physical properties of Generic Digiter are water solubility of 64.8 mg/L at 25 C and melting point at 249.3 C.