Lecture 24 Flashcards
What are the strategies which use pharmacokinetics to counteract poisons?
Decrease absorption
Neutralise the chemical or metabolite so that it cannot react with endogenous targets
Enhance elimination
What are the strategies which use pharmacodynamics?
Replace the activity
Antagonise the effect
How does Ipecac use a strategy to counteract poison?
Ipecac is used to decrease absorption as it is made of cephaline which stimulates the central vomiting centre and emetine which activates sensory receptors in the proximal small intestine
This can be very useful but has a limited use as there is a short time frame
This can also have the downside of affecting the absorbance of orally given antidotes or if the poison is caustic then it might damage the throat as it is vomited out
How does activated charcoal use a strategy to counteract poisons?
Absorption of the toxin can occur as it may adsorb onto the charcoal
Can help to create a concentration gradient across the mesenteric vasculature, so the drug or metabolite is eliminated faster
This can be used for toxins which have a small volume of distribution, low protein binding, have substantial enterohepatic recirculation and are highly adsorbed by charcoal
How can iron cause toxicity?
Ingestion of a large amount of iron overwhelms the gastrointestinal regulatory mechanisms resulting in massive iron absorption so it exceeds the volume of the transferring binding protein leading to iron deposition in of iron in soft tissues this causes toxicity by directly injuring the intestinal mucosa and generating free radicals
What occurs in stage 1 of iron toxicity?
There is a 30min-2 hour period of vomiting or diarrhoea, persistent tachycardia, hypotension and altered mental state
What occurs in stage 4 of iron toxicity?
2 to 4 days post ingestion, characterized by major organ failure, predominantly hepatic necrosis, renal failure, metabolic acidosis, bleeding diathesis, pulmonary distress syndrome, coma and death
How does deferoxamine detoxify iron overdose?
Deferoxamine mesylate chelates the free iron to feroxamine which is excreted in urine and does not remove the iron groups which are essential to protein function such as Hb
How can N-Acetyl Cysteine be used as an antidote to paracetamol overdose?
Acts as a precursor to glutathione synthesis boosting synthesis of this compound to prevent liver damage as the sulfhydryl group may bind and detoxify the metabolite directly or it can act as an antioxidant and block reactive oxygen species dependent cell death
What doses of N-Acetyl Cysteine are used to treat paracetamol overdose?
There is an initial infusion of 150 mg/kg in 200 mL of 5% glucose over the next 4 hours followed by a continuous infusion of 50 mg/kg NAC in 500 mL of 5% glucose
How can aspirin cause toxicity?
It can be readily hydrolysed to salicylate which will stimulate the medullary respiratory centre to produce heyper ventilation and respriatory alkalosis eventually leading to metabolic acidosis
It can uncouple oxidative phosphorylation increasing gluconeogenesis and lipid metabolism
Can produce tinnitus, nausea, vomiting, ataxia, coma and hyperthermia
How can sodium bicarbonate be used to counteract the toxic effect of salicylate?
Can be used to raise the urinary pH to greater than 7.5 which means that weak acids with a pKa less than 7 such as salicylic acid become trapped in the tubular fluid increasing their excretion
Can also be used for phenobarbital, chlorpropamide and 2,4-dichlorophenoxyacetic acid
This strategy must be carefully monitored as if the pH is too high then cardiac contractility is impaired and hypernatremia and fluid overload may occur
can be used in conjunction with activated charcoal
How can heroin lead to toxicity?
Produces typical narcotic effects as it is converted to morphine leading to shallow and decreased breathing which can cause coma, seizures and delayed encephalopathy in overdose
How can naloxone help be used to combat the toxicity of heroin?
Acts as an antagonist at mirco, kappa sigma opioid receptors
May be necessary to administer through intramuscular, subcutaneous, endotracheal or intralingual routes as the veins are often damaged by the user
Naloxone has a shorter half-life so relapse may occur
Naloxone may also precipitate heroin withdrawal
How can warfarin cause toxicity?
In an overdose there is blood in the stools or urine, haematuria and excessive menstrual bleeding as well as excessive bruising or persistent oozing from superficial injuries
There can then be necrosis and/or gangrene of kin and other tissues which may require amputation as well as death
