Week 20 Pharmacology - Toxicology Flashcards
What effect does large volume of distribution have on ability for drug to be cleared via dialysis?
Large Vd = not readily cleared by dialysis
i.e. antidepressants, amphetamines, benzodiazepines, CCB, digoxin, beta blockers, opioids
What drugs have low Vd and are well cleared via dialysis?
Salicylates, ethanol, lithium, phenytoin, valproate, phenobarbital
What is the RRISDEAD acronym?
Resuscitation
Risk assessment
Supportive care
Investigations
Decontamination
Enhanced elimination
Antidotes
Disposition
What does the risk assessment in toxicology assessment entail?
What drug, coingestions
Time since ingestion
Amount taken
Formulation/route
What drug/toxin should be suspected with tachycardia, hypertension?
Amphetamines
Cocaine
Anticholinergic drugs
What drug/toxin should be suspected with bradycardia, hypotension?
CCBs
Beta blockers
Clonidine
Sedative hypnotics
What drug/toxin should be suspected with tachycardia and hypotension?
TCAs
Beta-agonists
Quetiapine
Vasodilators (I,e, GTN, hydralazine)
What ingestions can cause miosis?
Opioids
Clonidine
Cholinesterase inhibitors
What ingestions can cause mydriasis?
Amphetamines
Anticholinergic drugs
What ingestion classically causes tachypnoea and respiratory alkalosis?
Salicylates
What are common causes of prolonged QT interval in overdose?
TCAs, antipsychotics, lithium, anti-arrhythmic, macrolides
What is the most common cause of death in overdose?
Airway compromise, due to respiratory depression, loss of airway protective reflexes, aspiration of gastric contents, obstruction with flaccid tongue
What are the causes of mortality in overdose RE cardiovascular system?
- CVS collapse/toxicity due to cardiac depression, hypovolaemia due to vomiting, blockade of peripheral alpha 1 receptors
- Cardiac arrhythmia: VT or VF secondary to either cardiac active drugs (adrenaline, amphetamines, cocaine, digoxin) and non CVS drugs (TCA, antidepressants, anti-histamines)
What agents can causes seizures?
Antidepressants
Amphetamines
Ioniazid
Withdrawal from EtOH
What is the toxic effect of paraquat?
Generation of reactive oxygen species, causing alveolar fibrosis , poor prognosis
What is the pathway of metabolism of paracetamol, and what are the toxic metabolites?
95% of Paracetamol is metabolised via glucouronidation and sulfation reactions into harmless metabolites.
5% is metabolised via YP450-dependent metabolic pathway, which generates NAPQI + superoxide anions. Normal conditions, NAPQI is rapidly conjugated with glutathione. Superoxide anions can cause oxidative stress.
Where in excess, glutathione stores are exhausted and NAPQI concentration increases.
How does NAPQI cause toxic effect?
Uncoupling of oxidative phosphorylation via inhibition of cytochrome enzymes, lactic acidosis, release of intracellular calcium stores and apoptosis –> massive liver injury and cell death
What is the approach to treatment of methamphetamine induced seizure, hyperthermia, rhabdomyolysis?
IV benzodiazepines, cooling techniques for hyperthermia
What is anticholinergic syndrome?
Red as a beet
Hot as a hare
Dry as a bone
Mad as a hatter
Blind as a bat
What are common features of clinical findings for someone with anticholinergic poisoning?
Sinus tachycardia
Mydriasis
Urinary retention
Agitated delirium
What are general principles of anticholinergic poisoning management?
Supportive cares
Benzodiazepines
Urinary catheterisation
+/- consideration of anticholinesterase inhibitor (physostigmine)
What are the general principles of managing anti-depressant overdose? (TCA in particular)
MoA = anticholinergic, antihistamine, Na+ channel blockage
Supportive therapy = mainstay, important to obtain ECG and administer sodium bicarbonate if widening QRS
If hypotension, IVF and consideration of noradrenaline
What is a toxic dose of aspirin/salicylate?
> 200mg/kg
What is the mechanism of toxicity in aspirin?
Uncoupling oxidative phosphorylation, metabolic disruption.
How does aspirin overdose present?
Initially increased RR and respiratory alkalosis, followed by profound metabolic acidosis and lactaemia
What form of enhanced elimination can be considered in aspirin overdose?
Sodium bicarbonate to increase urinary alkalisation and trap salicylic acid in ionic form.
Also haemodialysis can be effective in severe cases.
Are beta blockers selective for B1/B2 in high doses?
No, lose selectivity
What physical observations and ECG findings are associated with beta blocker OD?
Bradycardia
Hypotension
Wide QRS complex on ECG
What is the treatment for ethylene glycol/methanol OD?
IV Fomepizole, an alcohol dehydrogenase inhibitor
Less commonly, IV ethanol
What does activated charcoal NOT work for?
Anything on the periodic table! Also corrosive mineral acids and alkali
What time frames would be considered for administering activated charcoal?
2 hours immediate release, 4 hours modified
Using ADME framing, what are pharmacokinetic changes associated with ageing?
A: minimal (can be altered by antacid, laxative use, nutritional habits, changes in gastric emptying)
D: Reduced lean body mass, body water, and have increased fat percentage. Reduced serum albumin, usually = increased free drug circulating
M: Liver capacity decines with age (reduced clearance of benzos, barbiturates, propranolol, theophylline) - greatest impact on phase I reactions (P450)
E: Age related decline in creatinine clearance
What are the criteria for classification of a teratogen?
1) Result in characteristic set of malformations
2) Exert effect at particular stage of foetal development
3) Dose dependent incidence
What are some examples of drugs unsafe in pregnancy?
ACEi –> renal injury
Warfarin
NSAIDs
Phenytoin
Valproate
Carbamazepine
Lithium
What syndrome is precipitated by lack of VitB1?
Wenicke’s Encephalopathy –> Thiamine
What is pellagra caused by?
Vit B3 deficiency (Niacin)
Dementia
Diarrhoea
Dermatitis
Death
What is the clinical triad of serotonin syndrome?
- Mental state changes: agitation, anxiety, delirium
- Autonomic changes/instability: inc. temp, tachycardia, HTN, diaphoresis
- Neuromuscular abnormalities: hyperreflexia, clonus
What is neuroleptic malignant syndrome precipitated by?
Dopamine antagonism:
- Antiemetics: metoclopramide, promethazine
- Antipsychotis: haloperidol, chlorpromazine, clozapine, risperidone
What are the features of NMS?
Muscle rigidity/bradykinesia
Febrile
Tachycardia
