VIVA: Pharmacology - Toxicology Flashcards
Describe the metabolism of methanol
What specific modalities of treatment are available for the treatment of severe methanol poisoning?
EtOH* as alcohol dehydrogenase substrate (acts as competitive antagonist)
Fomepizole (alcohol dehydrogenase antagonist)
Correction of acid/base status (should be a priority because serious metabolic acidosis is common and pH <7 is associated with poor prognosis)
Need to add adjuncts to minimise accumulation of formic acid (e.g. folic acid, which acts as a cofactor in the conversion of formic acid to carbon dioxide to enhance methanol elimination)
Dialysis
- needed to pass + one other
In a poisoned patient what modalities are available for decontamination?
3/5 needed to pass
Skin:
- Remove clothes, wash contaminated skin
GIT:
- Emesis
- Gastric lavage
- Activated charcoal and cathartics (accelerates defaecation; no longer recommended) / whole bowel irrigation
How does activated charcoal work?
Adsorption due to large surface area
Name some drugs or agents that activated charcoal is NOT effective in adsorbing
2 needed to pass:
- Ions: iron, lithium, potassium
- Alcohols
- Cyanide
- Corrosives (acids and alkalis)
Name a drug where repeated doses of activated charcoal may assist in elimination of the drug
1 needed to pass:
- Carbamazepine
- Dapsone
- Theophylline
What is the mechanism of action of N-acetylcysteine in paracetamol overdose?
In overdose:
- Paracetamol metabolism by hepatic glucuronidation/sulphation is saturated, resulting in increased metabolism via cytochrome P450 system to form N-acetylbenzoquinoneimine (a toxic intermediate*)
- Elevated NAPQI production leads to depletion of hepatic glutathione stores, resulting in hepatotoxicity
NAC prevents hepatotoxicity by four possible mechanisms:
- Increased glutathione availability / sulfhydryl donor*
- Direct binding to NAPQI
- Provision of inorganic sulphate
- Reduction of NAPQI back to paracetamol
- needed to pass
Name an adverse effect of N-acetylcysteine
Mild anaphylactoid reactions* (15-20%) with mild flushing, rash and angioedema
- needed to pass
What is the mechanism of action of naloxone?
Pure opioid antagonist* binds to mu-opioid binding sites
- needed to pass
What is the time to onset and duration of action when administered IV?
Rapid onset 1-3mins
Duration 1-2hrs
What problems may be associated with naloxone administration?
Opioid withdrawal
Resedation
How can these problems be minimised or avoided?
Smaller/titrated doses*
Infusion
Route of administration
- needed to pass
What is the mechanism of action of flumazenil?
Antagonist at the benzodiazepine binding site on the GABA-A receptor (ligand-gated chloride channel)*
Decreases the binding of GABA
Blocks GABA-induced increase in Cl- permeability and influx of Cl- into the cell causing hyperpolarisation and decreased excitability of the neuron
- needed to pass
What are the indications for flumazenil use?
Avoid intubation or ICU admission in benzodiazepine overdose
Reverse benzodiazepine sedation* after procedures
Diagnostic role
- needed to pass
What potential problems should be anticipated when using flumazenil?
Precipitate seizures* in mixed overdoses with benzodiazepines and proconvulsants
Precipitates seizures* in patients taking benzodiazepines to control epilepsy
Precipitate withdrawal symptoms and seizures* in benzodiazepine-dependent patients
Duration of action is only 1-3hrs thus repeated administration may be necessary*
Reversal of benzodiazepine-induced respiratory depression has not been demonstrated, so respiratory and CV support may be required
Adverse effects including headache, visual disturbance, increased anxiety, nausea, light-headedness
- needed to pass
