Applied PK Lecture: Tsu (July 3rd)

What is the reversal agent for Digoxin?

Digoxin-specific antibody Fab fragments (DigiFab).

Why does DigiFab work effectively as a reversal agent for Digoxin?

It has a higher affinity to digoxin than the Na+/K+ ATPase digoxin receptor site and irreversibly binds to digoxin.

Can Digoxin levels be accurately measured immediately after DigiFab administration?

No because the levels are falsely elevated.

What should be monitored after administering DigiFab?

Monitor for resolution of arrhythmias and gastrointestinal (GI) adverse effects.

How is DigiFab administered?

DigiFab is administered intravenously (IV).

What is the onset of action for DigiFab?

The onset of action for DigiFab is approximately 20 minutes.

What is the average time to maximal response after administering DigiFab?

The average time to maximal response is about 90 minutes.

How is the dose of DigiFab determined when the digoxin dose and timing of toxicity are known?

For an acute known dose, the dose is calculated as digoxin load in mg / 0.5 mg digoxin bound per vial.

How many vials of DigiFab are administered for an acute unknown dose of digoxin?

For an acute unknown dose, 10-20 vials are administered, and the patient is monitored closely.

How many vials of DigiFab are administered for a chronic unknown dose of digoxin?

For a chronic unknown dose, 6 vials are administered, and the patient is monitored closely.

How is the DigiFab dose determined for a chronic known dose of digoxin?

The dose is calculated as (digoxin steady-state level x weight) / 100.

What is the primary indication for Lidocaine in this lecture?

Treatment of ventricular arrhythmias.

What class of antiarrhythmic is Lidocaine?

Class IB antiarrhythmic.

How is Lidocaine administered for the treatment of ventricular arrhythmias?

It is administered intravenously (IV) only.

What is the usual bolus dosing of Lidocaine for ventricular arrhythmias?

The usual bolus dose is 1 to 1.5 mg/kg.

What is the usual continuous infusion rate of Lidocaine after the bolus dose?

The continuous infusion rate is 1 to 4 mg/min.

What is the therapeutic concentration range for Lidocaine?

1 to 5 mg/L.

What minor CNS effects can be seen with Lidocaine concentrations of 3 to 5 mg/L?

Dizziness, mental confusion, and blurred vision.

At what concentration of Lidocaine have seizures been observed?

Seizures have been seen at concentrations greater than 9 mg/L.

What model is used to describe the volume of distribution (Vd) of Lidocaine following an IV bolus?

A two-compartment model.

When considering Lidocaine's volume of distribution, which compartment should include the myocardium?

The initial volume of distribution (Vi) should include the myocardium.

What body weight measure should be used for calculating the volume of distribution (Vd) of Lidocaine in obese patients?

Total body weight (TBW) should be used for obese patients.

How should the bolus dose (loading dose, LD) of Lidocaine be calculated compared to the total dose of lidocaine?

• Bolus dose should be calculated using the initial volume of distribution (Vi).

• Total dose should be calculated using the final volume of distribution (Vd).

What conditions can decrease the volume of distribution (Vd) of Lidocaine?

Congestive heart failure (CHF), severe trauma, and critically ill (ventilated) patients in the ICU.

What condition can increase the volume of distribution (Vd) of Lidocaine?

Chronic liver disease.

What is notable about Lidocaine's first-pass effect?

Lidocaine has a high first-pass effect.

What percentage of Lidocaine is cleared renally, and is there a need for dose adjustment in renal disease?

Less than 5% of Lidocaine is cleared renally, and no dose adjustment is necessary for renal disease

What is the bioavailability (F) of Lidocaine?

The bioavailability (F) of Lidocaine is 0.4, though it is usually variable.

What is the usual clearance rate of Lidocaine?

The usual clearance rate of Lidocaine is 10 mL/kg/min.

What is the clearance rate of Lidocaine in patients with congestive heart failure (CHF) or cirrhosis?

6 mL/kg/min

When is the appropriate time to sample Lidocaine levels after beginning therapy?

4 to 8 hours after beginning therapy.

What factors can alter the pharmacokinetics (PK) of Lidocaine?

Hint: Not renal dysfunction

Heart failure, liver dysfunction, severe trauma, critical illness, and concurrent medications.