Poisioning Flashcards
What is the apparent volume of distribution of digoxin?
Over 200L - large
What is the half life of digoxin?
40 hours
How long would it take for digoxin to reach a steady state?
Over a week
What is the consequence of digoxin taking over a week to reach a steady state?
You need loading doses to achieve a rapid therapeutic effect
Why is it important to use a loading dose with digoxin?
As you need to achieve satisfactory control of atrial fibrillation quickly
How does the loading dose of digoxin compare to the maintenance dose?
It is 4-8x as much
Other than taking a long time to reach a steady state, what is the other consequence of the long half life of digoxin?
It takes a long time to eliminate
How long does it take to reduce the concentration of digoxin by 50% in a patient with normal GFR?
40 hours
What happens to the clearance of digoxin in a patient with renal failure?
The clearance is reduced and so the half life will be increased
What is the result of the increase in half life of digoxin in a patient with renal failure?
It takes longer for the concentration of drug to return to therapeutic levels if the patient becomes digitoxic
What is digoxin predominantly excreted by?
Kidneys
What needs to be done to maintanance doses of digoxin in renal failure?
Needs reducing, as the renal failure leads to reduced clearance
What happens to loading doses of digoxin in renal failure?
They remain much the same, unless renal failure is very severe
What kind of kinetics does digoxin show?
First order kinetics
What will the clinical effectiveness of digoxin after it is stopped depend on?
- Therapeutic window
- Minimal effective plasma drug concentration
What are the symptoms of a digitoxic patient?
- Bradycardia
- Xanthopsia
- Vomiting
What needs to be done when a patient presents as digitoxic?
Need to give a drug that binds digoxin to eliminate it
What is paracetamol metabolised into at normal doses?
- 60% is converted to paracetamol glucuronide
- 30% is converted to paracetamol sulfate
- 10% is ungergoes P460 oxidation to NAPQI
What happens to the NAPQI produced as a result of paracetamol metabolism?
It is conjugated with glutathione to inactive metabolites
What inactive metabolites are formed when NAPQI is conjugated with glutathione?
Cysteine and mercapturic acid
What happens in substantial paracetamol overdose?
The conjugation of NAPQI is saturated, leading to increased toxic levels of NAPQI
What is the treatment for paracetamol overdose?
To replace glutathione, e.g. with N-acetylcysteine
