14.1 Poisoning Flashcards
What can be poisonous?
Anything
Water can be poisonous at large volumes
Give some examples of pharmacological toxicity
- Warfarin - excessive bleeding
- Insulin - hypoglycaemia
- Loop diuretics - electrolyte imbalance
- ACEi - movement disorders
What is secondary pharmacological toxicity?
Secondary effects of a drug are toxic, not the drug itself
Give some examples of secondary pharmacological toxicity
- Statins - myalgia/rhabdomyolysis
- Thalidomide - teratogenic
- B-agonist - tachycardia
- B-blocker - bronchoconstriction
What are drugs with secondary effects usually prescribed with?
- Chemotherapy drugs - often causes secondary vomiting, so anti-emetic given
- Methotrexate - dihydrofolate reductase inhibitor, so folic acid given
What effects are often seen only with large overdoses of drugs?
- Myocardial depression - B-blocker and CCB together
- Respiratory depression - Opioid overdose, benzodiazepines, anti-epileptic (carbamazepine), barbiturates
What is biochemical toxicity?
Drug or metabolite which causes cellular damage eg macromolecules including structural proteins and enzymes
Are many drugs on the market biochemically toxic?
No - most drugs have been tested extensively for toxicity
At supra-therapeutic levels (overdose or high levels) toxic metabolites build up when they are usually converted to inactive metabolites
What dictates harm a drug can cause?
Balance of elimination of a drug or metabolites, can be toxic
How is biochemical toxicity caused by overdose treated?
- Thiol groups on glutathione can prevent cell damage
- Glutathione can get overwhelmed due toxic metabolite build-up
- Can give n-acetylcysteine - replenishes thiols
What regime is n-acetylcysteine given in when treating paracetamol overdose?
Three successive infusions at different concentrations over 21 hours
What evidence is there for n-acetylcysteine working in the mechanism of donating thiols?
- Studies shown n-acetylcysteine is beneficial in hepatic necrosis
- CYP inducers which damage the liver can have their effect reduced by NAC if they are hepatotoxic
- Patients with low hepatic reserves of glutathione
What part of metabolism does N-acetylcysteine work on in liver?
Phase 2
Increases production of glutathione by donating thiol groups
What is the biological toxicity of cyclophosphamide?
- Highly toxic metabolites eliminated in urine
- Can cause haemorrhagic cystitis due to damaging cells in bladder
When is cyclophosphamide prescribed?
Severe rheumatic disease
How do we prevent the biological toxicity of cyclophosphamide?
- Use Mesna or excessive hydration
- Mesna - thiol group and is polar so cannot cross tubular cells and is excreted in urine - protects bladder epithelia
Where can you find information on managing poisoning?
- BNF
- Toxbase
- UK National Poisons service information
- Local guidelines - eg paracetamol
What are the management principles for posioning?
- Prevent absorption
- Immediate actions - are they in danger?
- Antidotes
- Enhance elimination
- Supportive measures
What are some immediate actions for someone who has been poisoned?
- Stop contact with poison
- Vital signs and assess injury
- History - from patient if possible, who they are with, evidence, packaging, written notes
What are some supportive measures for poisoning?
Manage:
- Hypoxia
- Myocardial depression
- Cardiac toxicity
- Nephro/hepatotoxicity
How can we prevent poison absorption?
- Gastric lavage - stomach pumping, not reccomended due to risk of aspiration
- Activated charcoal - need a lot, 10:1 of drug
What are the problems with using activated charcoal?
- Need to use a lot
- Timing of overdose makes efficacy unpredictable
- Not suitable for drowsy or if comatosed
- Can affect absorption of therapeutic drugs
How can we increase speed of poison elimination?
- Continued activated charcoal - can be used up to 36hrs for some poisonings, normally needs to be used quickly
- Sodium bicarbonate - causes alklaine diuresis by increasing pH (still <7.5 though), often used in aspirin poisoning
- Haemodialysis -if drug has small Vd
- Forced diuresis -not recommended as causes serious electrolyte imbalances
What two examples of competitive antagonist antidotes?
- Naloxone - opioid receptor antagonist
- Atropine - muscarinic antagonist, organophosphate poisoning
What happens in organophosphate poisoning?
- Organophosphate binds to AChE and inhibits it
- This severely reduces how much ACh broken down
- ACh continues to bind to muscarinic receptors
- SLUDGE
What are some other examples of antidotes?
- Chelating agents -forms a complex with poison, reduces free drug e.g. cyanide, lead and iron poisoning
- Manipulating drug metabolism-Fomepizole, acetylcysteine
- Antibodies-antivenom, digoxin-specific antibody
How does Fomepizole work?
- Inhibits alcohol dehydrogenase
- Decreased toxic metabolites, formeldehyde (acidosis, retinal damage) and oxalic acid (acidosis, nephrotoxic)
- These build up from methanol or ethylene glycol (anti-freeze) poisoning
What is STOPP START?
- Screening tool for the older peoples prescriptions (STOPP)
- Screening tool to alert to right treatment (START)
Why is medicine optimisation so important?
- Polypharmacy
- Every drug may be necessary- but check
- Ensures right patient receives right drugs
- Improves clinical outcomes
- Economic
What patients should be particularly targeted for review of medications (STOPP START review)?
- Older people
- Co-morbidities
- Polypharmacy
- High risk medications-narrow therapeutic index, known serious side effects
What are some pharmacokinetic and pharmacodynamic changes that occur in older people meaning they need STOPP START review?
- Body composition - increased fat, decreased body water and lean mass
- Reduced renal function
- Hepatic function
- GI absorption/GI bleed risk
- Baroreceptor sensitivity reduced - not as much response from HR
- Reduced first pass metabolism
- Protein binding
- Receptor expression changes
- Psychotropic drugs and extra pyramidal effects
What needs to be considered in medication review STOPP START?
- Is medication right for patient?
- Time limited medications - used for discharge but not needed now
- Age - life expectancy and risk/benefit if only short time left
- Is medication effective - measurable outcome eg HbA1c, BP, cholesterol, symptomatic relief
- Cost
- ADRs and DDIs
Who is STOPP START used for?
Older patients - 65 and above
What is the aim of STOPP START?
Highlight and prevent inapproriate prescribing to reduce DDI and adverse reactions
