Describe some pharmacokinetic features of Digoxin:
Bioavailability? Volume of distribution? Elimination half-life (in the absence of renal impairment)?
Bioavailability ~70%. Volume of distribution = 500L/70kg person (i.e. 7.14L/kg body wt), this mainly reflects its distribution in skeletal and cardiac muscular tissue. Elimination half-life ~35hrs.
Which important cardiac drug can be inactivated by gut flora?
What is the therapeutic range of Digoxin?
Therapeutic range is 1-2mcg/L, which is the same as 1-2ng/mL
What is the fundamental molecular mechanism that digoxin uses to exert its effects?
Binds to and inhibits the Na+/K+/ATPase pump in the cell membrane, causing increased intracellular Na+, and decreased intracellular K+. This leads to reduced expulsion of Ca2+ from the cell via the Ca2+/Na+ exchange pump, so there is increased intracellular Ca2+.
What happens to the cardiac muscle’s intracellular levels of Ca2+ and K+ in patients taking Digoxin, and what effect does this have on cardiac function?
Increased intracellular Ca2+, in the vicinity of the contractile proteins, producing increased contractility. Decreased intracellular K+, causing decreased automaticity, slowed AV conduction, shortened action potential, shortened refractory period.
What effect does hyperkalaemia have on Digoxin toxicity, and why?
K+ competes with digoxin for binding to the Na+/K+/ATPase pump, and so moderate hyperkalaemia can reduce the toxic effects of digoxin. But note that hyperkalaemia is one of the first signs of digoxin toxicity.
What kind of arrhythmias can arise in digoxin toxicity?
Extrasystoles, bijeminy, tachycardia, fibrillation, arrest at extremely high doses.
Apart from cardiac effects, what are some other manifestations of digoxin toxicity?
Nausea, vomiting, diarrhoea, drowsiness, headache.
What is an important early sign (on laboratory investigations) of digoxin toxicity?
Name some drugs that may potentiate the effect of digoxin, and explain how they do this.
Verapamil and Amiodarone reduce the clearance of digoxin.
Some antibiotics alter the gut flora, and thereby reduce the gut flora's inactivation of digoxin, increasing the bioavailability of digoxin.
Frusemide, quinidine, NSAIDs.