Toxicology Flashcards
During a risk assessment of a recently poisoned individual, what factors need to be considered for treatment?
What is the substance Dose ingested Weight of the patient Time since ingestion Symptoms and clinical signs Co-morbidities What treatments are available at the receiving hospital
How can oral absorption of a drug be affected during overdose?
Oral absorption is a saturable process
Anticholinergics will slow absorption from the gut
Hypotensives with reduce blood flow and delay absorbtion
Solubility of the gut lumen
However, this may worsen toxicity due to delay of onset and duration, eg: carbamezapine toxicity
How can drug distibution be affected during overdose?
Some drugs (eg: aspirin) may secondly distribute into the CNS and mitochondria - away from active site - delaying their active effect.
How can drug metabolism be affected during overdose?
Hepatic metabolism may be saturable at high concentrations, leading to overdose, particularly for drugs with high first pass metabolism and narrow TI
Bioactivation may lead to the production of toxic metabolites, eg: paracetamol
Methods of gut decontamination (methods of removing drug from gut BEFORE adsorbtion)
Gastric lavage
Emesis
Activated charcoal - Must be with 1hr and only suitable for drugs with no known antidote/treatment
Whole bowel irrigation - Uaing PEGylated solutions
Methods to increase elimination
Activated charcoal - Repeated every 2hrs
Urinary alkalisation - Alkalise drugs in the urine to increase likelyhood of excretion
Extracorporeal elimination - ie: haemodialysis (requires low Vd)
Methods of ECR (extracoporeal elimination)
Haemodialysis (HD) - Movement of solute over a semipermeable membrane from patient’s blood into the dialysate (by diffusion)
Haemoperfusion (HP) - Adsorption of solutes intoa bed of activated charcoal
Continuous Renal Replacement Therapy (CRRT) - Movement of solute over a semipermeable membrane from patient’s blood into the dialysate (by hydrostatic pressure gradient - blood is kept at higher pressure so solutes are “pushed” out)
Indications for each type of ECR:
Haemodialysis (HD)
Haemoperfusion (HP)
Continuous Renal Replacement Therapy (CRRT)
Haemodialysis (HD) - effective for particular toxins and corrects eloctrolyte imbalances, requires no protein binding
Haemoperfusion (HP) - Can remove protein bound drugs
Continuous Renal Replacement Therapy (CRRT) - Can remove protein bound drugs, larger MW drugs/complexes
Indications for ECR
Known toxic dose
Co-existing fluid abnormalites
Non-responsive to alternative therapies
Explain paracetamol poisoning and its antidote
Paracetamol typically metabolised by CYP450 enzymes to harmless product. When saturated, may be metabolised by alternative pathway to produce toxic product - NAPQI. The “bad” enzyme may induced by chronic alcoholism and decreased glutathione (malnutrition)
Antidote: Activated charcoal if very early, also use NAC - a glutathione donor which competes for metabolism
Explain benzodiazepine poisoning and its antidote
Benzodiazepines induce sedatory effects - CNS, respiratory depression
Antidote: Flumazeniil - Inhibits the binding site of benzodiazepines at GABA
Explain opioid poisoning and its antidote
Opioids induce sedatory effects - CNS, respiratory depression
Antidote: Naloxone, opioid antagonist
Explain SSRI poisoning and its antidote
Serotonin Syndrome - muscle rigidity, hyperthermia, altered concious state, seizures, hypertension
Treatment: Prevent complications of hyperthermia - ie: rapid cooling, diazepam and 5HT2a antags to depress excited state
Explain TCA poisoning and its antidote
Anticholinergic psychosis, coma, seizures
Antidote - Block reuptake of NA and serotinin
