Poisons and Poisoning Flashcards
Define a poison:
Any substance which destroys life or injures health
Define an antidote
A medicine given to counteract the influence of poison, or an attack of disease
What are the stratagies to counteract poisoning?
Using Pharmacodynamics and pharmacokinetics:
- Decrease absorption
- ‘Neutralize’ the chemical or metabolite so it cannot react with endogenous targets
- Enhance elimination
- Antagonize the effect
- Replace the activity
Usually used in combination i.e attempt to decrease absoprtion and neutralize activity
Whats a drug that attempts to decrease absorption?
Ipecac:
- Ipecac consists of Cephaeline which stimulates the central vomiting center
- Bad cause vomiting is damaging
- Not proven to improve patient outcome
- Increases risk of aspiration
Will affect the absorption of other antidotes
Whats another example of a drug that decreases absorption?
Activated charcoal
- Charcoal may absorb drug
- Can create concentration gradient across mesenteric vasculature so that the drug is eliminated faster
- Useful on drugs that undergo enterohepatic recirculation, small volume of distribution, low protein binding
- Dose 1-2g/kg orally or nasogastric tube
Multiple doses may be given
What is an example of a drug used to neutralize the chemical?
Ingestion of large amounts of iron is toxic (60mg/kg) is life threatening
- When serum binding levels exceed the capacity of the binding protein transferrin, severe toxicity may occur, secondary to deposition of iron in soft tissue.
Deferoxamine is used to treat
How does deferoxamine work?
Free iron generates oxygen free radicals which are severely damaging.
stage one = vomiting and diarrhea + tachycardia
stage two = major organ failure
Deferoxamine chelates the free iron to form feroxamine but does not remove iron from proteins (great!) i.e transferrin, ferritin, cytochromes and haemoglobin
Feroxamine is excreted in the urine
Which drug is most commonly seen in overdoses?
Paracetamol
What are the stats of paracetamol overdose in NZ?
172/879 overdoses are paracetamol related
- 86.2% self harm, of these 80% female
How is paracetamol overdose treated?
N-actetyl cysteine
What is the action of N-actetyl cysteine in paracetamol overdose?
precursor for glutathione synthesis and so boosts resynthesis allowing deactivation of metabolite
or
The sulfhydryl group of N-actetyl cysteine may bind and detoxify the metabolite directly
or
Act as an antioxidant and block reactive oxygen species dependent cell death
What is an example of enhanced elimination?
Salicylate is excreted more by urinary alkalisation
What is salicylate and why is it a problem?
Aspirin is readily hydrolyzed to salicylate which,
- Stimulates medullary resp center = resp akalosis and eventually metabolic acidosis
- Produces tinnitus, nausea, vomiting, ataxia, coma and hyperthermia
How much aspirin must be ingested to be toxic?
> 300mg/kg serious toxic reactions
>500mg/Kg potentially toxic
How is aspiring overdose treated/
Salicylate toxicity is remedied by:
- Sodium Bicarbonate is used to raise urinary pH (>7.5)
- Weak acids that undergo renal excretion become trapped
- Useful for salicylate, herbicide
- Used in conjunction with activated charcoal
What may happen with poor perfusions of sodium bicarbonate?
May produce too higher pH which impairs cardiac contractility, hypernatremia, and fluid overload may occur.
Whats an example of pharmacodynamic intervention?
Heroin and Naloxone
How is heroin generally toxic?
When overdoses, used normally in conjunction with alcohol, benzodiazapines, cannabis and anphetamine
What does heroin do?
Heroin produces typical narcotic effects as it is converted into morphine
- euphoria
Associated with coma, seizures, and delayed encephelopathy in overdose.
Can the lethal dose of heroin be defined?
No its hard to define
- death may be sudden in massive overdose
- Complicated by administration of other drugs
What is often the cause of heroin related death?
Friends-
- Advise sleeping it off = coma and resp depression
- Give milk as antidote
- Use cold shower potential hypotension
- Using more drugs
What is naloxone?
An antagonist at the beta, K and delta opoid receptors
How is nalaxone administered?
I.m
S.C
endotracheal etc
What is bad about nalaxone?
It has a shorter half life than heroin therefore relapse may occur.
May also precipitate heroin withdrawl
Whats an example of replace activity poison + antidote?
Warfarin and vitamin K
What is warfarin?
Used in the prophylaxis and treatment of venous thrombosis + Pulmonary embolism
- Inhibits the synthesis of vitamin K dependent coagulation factors
- This results in a sequential depression of factors
How does warfarin overdose present?
Blood in stools, urine, excessive menstrual bleeding
Can lead to gangrene necrosis
Death
Whats the normal dose of vitmamin K?
1microgram
What happens at higher vitamin K dosing?
At higher concentrations Vitamin k is reduced to hydroquinone by another warfarin- insensitive liver reductase
How is warfarin overdose countered?
Vitamin K therapy may be required for weeks or months until prothrombrin time (coagulation) returns to normal
What receptors do organophosphate poisons act on?
Nicotinic receptors:
- Muscle weakness
- Hypertension
- tachycardia
CNS effects:
- Confusion
- Seizures
Muscunaric effects
- Salivation
- Urination
- Defacation
What method is used to relieve organophosphate poisoning?
Regenerate effect
What does the regenerate effect involve and whats an example?
Give a combination of drugs to prevent symtoms i.e
Give atropine to antagonise ACh then pralidoxime.
Pralidoxime can remove a phosphate group from ACh esterase, to regenerate catalytic activity
- effects at nicotinic>muscunaric
- Effect is great if erythrocyte esterase is given soon after toxicity
- Reactivation of plasma cholinesterase is minimal
