45 Questions
What are the two main clinical indications for digoxin?
Congestive heart failure and atrial fibrillation
What is the mechanism of action of digoxin in congestive heart failure?
Binds to Na+/K+ ATPase in myocytes, increasing intracellular Na+ and Ca2+ to enhance myocardial contractility
How does digoxin exert a negative chronotropic effect in atrial fibrillation?
Increases parasympathetic activity and vagal tone to slow conduction and decrease ventricular heart rate
What is the primary site of absorption of digoxin?
Small intestine
Which factor can increase the bioavailability of digoxin?
Inhibition of p-glycoprotein
Where does digoxin concentrate in the body?
Heart and kidneys
How is the pharmacokinetics of digoxin affected by obesity?
Not affected due to its large binding to skeletal muscle
What is the primary site of metabolism of digoxin?
Liver
Which statement about the distribution volume (VD) of digoxin is correct?
VD is 5-9 L/kg, with an average of 7 L/kg
What is the effect of E. lentum on the absorption of digoxin?
It inactivates digoxin in the gut
What is the therapeutic range of digoxin concentrations for patients with atrial fibrillation?
0.8-1.5 ng/mL
Which condition is associated with a decrease in digoxin non-renal clearance?
Moderate/severe heart failure
What is the recommended treatment for digoxin overdose?
Digoxin immune Fab (DigiFab)
Which drug inhibits renal/extrarenal digoxin clearance and increases digoxin concentration by 50-75%?
Verapamil
What percentage of digoxin is eliminated unchanged by glomerular filtration rate (GFR) and active tubular secretion?
75%
What is the half-life of digoxin for creatinine clearance greater than 80 mL/min?
24-48 hours
What is the primary cause of digoxin toxicity?
Hypokalemia
Which electrolyte disturbance is associated with an increased pharmacologic response to digoxin?
Hypokalemia
What is the maintenance dose of digoxin for heart failure?
0.125-0.25 mg/daily
What is the loading dose of digoxin for atrial fibrillation?
No loading doses
What is the primary clinical use of lithium?
Treatment for acute mania and maintenance treatment of bipolar I and II
How does lithium affect suicide risk in patients?
It reduces suicide risk
What is the mechanism of action of lithium?
It is unknown, but it is thought to modulate neurotransmission at both the neuronal and intracellular levels
What is the bioavailability of immediate-release lithium?
95 to 100%
Where is lithium almost completely absorbed from?
The small intestine
What is the primary site of absorption of lithium?
Small intestine
What is the effect of food on the absorption of lithium?
Food does not affect absorption
What is the peak concentration of lithium carbonate regular-release tablets/capsules?
Varies
What is the peak concentration of lithium for immediate release?
Varies
What is the peak concentration of lithium for extended release?
Varies
What is the primary form of absorption of lithium after oral administration?
Complete dissociation to the lithium cation
What is the primary mechanism of absorption of lithium from the small intestine?
Passive diffusion
What is the bioavailability of oral syrup lithium?
~100%
What is the primary route of elimination for lithium?
Renal
At what time post-dose should blood samples be drawn for accurate lithium levels?
12 hours
What is the therapeutic range for lithium concentrations?
0.6-1.5 mEq/L
How long does it take to reach steady state for lithium?
5 days
What is the starting dose range for lithium in bipolar disorder?
600-900 mg/day
Which organs preferentially take up lithium during distribution?
Brain, kidney, thyroid, and bone
What factor affects lithium levels among others?
Sodium intake
What type of tablets have a peak concentration of lithium at 4 to 12 hours?
Extended-release tablets
How is clearance of lithium related to renal function?
Proportional to glomerular filtration rate (GFR)
What is the dosing adjustment increment typically made for lithium?
300 mg
What should be maintained to avoid lithium toxicity?
Consistent salt intake
What is essential for monitoring when using lithium?
Regular monitoring of lithium levels, baseline labs, and vital signs
Study Notes
Lithium Pharmacokinetics and Clinical Considerations
- Lithium has different peak concentrations and absorption times depending on the formulation: extended-release tablets (4 to 12 hours), citrate solution (15 to 60 minutes).
- Distribution of lithium occurs in a two-compartment model and is preferentially taken up by specific organs such as the brain, kidney, thyroid, and bone.
- The elimination of lithium is mainly renal (95%) and it is not metabolized by the liver. Clearance is proportional to glomerular filtration rate (GFR) and blood flow to the kidney.
- Lithium levels are affected by various factors including drug interactions, renal function, and sodium intake, and baseline labs and vitals are necessary for monitoring.
- The therapeutic range for lithium is generally 0.6-1.5 mEq/L, with different ranges for acute mania (0.8-1.2 mEq/L) and maintenance (0.6-1.0 mEq/L) based on clinical situations.
- Lithium dosing for bipolar disorder typically starts at 600-900 mg/day and can be titrated based on response and tolerability by 300 to 600 mg every 1 to 5 days.
- It takes approximately 5 days to reach steady state for lithium, and dose adjustments are usually made in 300 mg increments with monitoring of serum levels.
- Lithium toxicity occurs at levels greater than 1.5 mEq/L, and dosing adjustments should be made in elderly patients who may experience toxicity at lower levels.
- Counseling points for lithium use include taking it with or without food, maintaining consistent salt intake, and avoiding excessive caffeine and dehydration.
- Regular monitoring of lithium levels, baseline labs, and vital signs is essential, and blood samples need to be drawn 12 hours post-dose for accurate levels.
- The complex concentration-time curve of lithium concentrations requires careful patient adherence to dosing instructions and consideration of individual variability in distribution.
- It is important to consider individual patient factors, clinical response, tolerability, and serum concentration when making dose adjustments for lithium in bipolar disorder.
Test your knowledge of digoxin with this quiz covering its two main clinical indications, mechanism of action, and the positive inotropic effects it has on congestive heart failure and atrial fibrillation.
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