Toxicology

Question 1

Why is therapeutic drug monitoring used?

Answer 1

To assess therapeutic compliance so if the patient is taking their medication appropriately or not.
Efficacy, if the drug is actually working this is important if the medication has a narrow therapeutic window.

Question 2

What is pharmacokinetics?

Answer 2

Relates the dose, dosing interval and route of administration of the drug in the blood.

Question 3

What is pharmacodynamics?

Answer 3

Relates the drugs concentration at the site of action to the observed magnitude of the drugs effect.

Question 4

What is subtherapeutic?

Answer 4

Means the drug is not effective

Question 5

What influences peaks of troughs of drug monitoring?

Answer 5

The route of the dose, if administered through IV it will have sharp peaks and troughs.

Question 6

What factors should you consider when doing therapeutic drug monitoring?

Answer 6

Drug factors
Details of interest
Patient factors

Question 7

What drug factors should you consider when therapeutic drug monitoring?

Answer 7

Absorption
Distribution
Metabolism
Excretion

Question 8

What details of interest should you consider when therapeutic drug monitoring?

Answer 8

Dose
Timing between doses
Drug half life

Question 9

What patient factors should you consider when therapeutic drug monitoring?

Answer 9

Age
Gender
Ethnicity
Genetics
Health
Other medications

Question 10

What is considered when a drug is chosen for therapeutic drug monitoring?

Answer 10

Is the drug used chronically
Variable pharmacokinetics
Narrow therapeutic index
Severity of failed therapy or toxicity
Problem with compliance.

Question 11

What is Digoxin?

Answer 11

A drug that treats heart failure (atrial fibrillation). It increases Na and Ca concentrations in the cells of the heart causing it to contract correctly.

Question 12

How do levels of digoxin in the blood relate to levels in the tissue?

Answer 12

Levels are 15-30 times higher in the tissue, accumulation in the tissue lags behind the blood. It peaks 2-3 hours in blood compared to 6-10 hours in tissue.

Question 13

How is digoxin measured?

Answer 13

Immunoassay.

Question 14

How is digoxin metabolised?

Answer 14

50-70% is excreted unchanged in the urine, some is metabolised to dihydrodigoxin and excreted in the kidneys and the rest excreted in the stool. Children can tolerate higher doses.

Question 15

What are the symptoms of digoxin toxicity?

Answer 15

Nausea, vomiting, anorexia, tachycardia, fibrillation and arrhythmia’s.

Question 16

What are some things you need to consider with digoxin toxicity?

Answer 16

The dose route, dose, timing of last dose, DLIS, potassium and magnesium levels.

Question 17

What are DLIS?

Answer 17

Digoxin like immunoreactive substances, they are substances they can give false positive results, they can either be internal or external from the patient or medications.

Question 18

Why do you need to test for potassium and magnesium during digoxin toxicity?

Answer 18

Low magnesium and sodium increases sensitivity to digoxin so you need a lower dose.

Question 19

Where is paracetamol metabolised?

Answer 19

In the liver

Question 20

How does paracetamol cause hepatocellular toxicity?

Answer 20

Too much paracetamol produces too much NAPQ1 which quenches GSH, the pathway to metabolise paracetamol. This leads to hepatocyte necrosis.

Question 21

Why isn’t everyone with paracetamol toxicity treated?

Answer 21

Because the treatment can sometimes do more harm than good so the situation needs to be assessed. People with risk factors need to be treated before others.

Question 22

What is the treatment of paracetamol overdose?

Answer 22

L-cysteine, methionine, N-acetyl cysteine and cysteamine containing agents.

Question 23

What level of paracetamol in the blood would warrant treatment?

Answer 23

200mg/L after 4 hours.

Question 24

What half life of paracetamol would warrant treatment?

Answer 24

2-4 hours.

Question 25

Why are liver function tests performed in paracetamol overdose?

Answer 25

They can give you an indication of how long ago the overdose occurred due to the amount of necrosis present.

Question 26

How do you calculate the osmolarity gap?

Answer 26

2(sodium + potassium) + glucose + urea

Question 27

How do you calculate the anion gap?

Answer 27

sodium - (chloride + bicarbonate)

Question 28

How do you measure ethanol?

Answer 28

Measure osmolarity gap and breakdown metabolites of alcohol ethyl glucuronide and ethyl sulfate.

Question 29

What does methanol metabolise to?

Answer 29

Formic acid which can cause serious acidosis and optic neuropathy leading to blindness or death.