Flashcards in Clinical Toxicology 2 Deck (26):
what are the 3 categories which antidotes fall into ?
formation of inert complexes
regeneration of and/or protection of target
how are most cases of poisoning treated ?
managed in a supportive manner and dont require antidotal treatment
what are some examples of pharmacological reversal ?
- atropine can block affects of cholinergic toxidrome by blocking AChE and acetylcholinesterase inhibitors for anticholinesterase poisonings
- naloxone is used for reversal of opiate overdose
- flumazenil is used for benzodiazepam overdose
- vitamin K is used for treatment of warfarin overdose
- leucovorin and folate rescue methotrexate induced toxicity- methotrexate is used in cancer therapy
- ethanol/fomepizole is used for treatment of methanol and ethylene glycol poisoning
-hyperbaric oxygen therapy is used for carbon monoxide poisoining
what are some examples of formation of inert complexes?
-dimercaptrol and dimercaptosuccinic acid for heavy metal poisoning = forms an inert water soluble compound
-calcium EDTA and dimercaptosuccinic acid for lead poisoning - cheating agents
-deferoxamine for iron toxicity
-penicillamine for copper poisoning
- thiosulphate for cyanide poisoning
-antibodies for digoxin and snake bites
what happens when methanol is consumed ?
undergoes metabolism to form formaldehyde and formic acid which are toxic
formic acid- causes acidosis and mitochondrial dysfunction- this dysfunction will increase anaerobic atp production leading to more lactic acid production and further acidosis
what is a lethal dose of methanol?
what is the aim of treatment for methanol treatment ?
inhibit alcohol dehydrogenase
- use ethanol or 4-methylpyrazole fomepizole = these block metabolism of methanol
what is a lethal dose of ethylene glycol ?
it is sweet so animals find it appealing
what is the affects of ethylene glycol consumption ?
metabolism leads to the production of oxalic acid which will cause acidosis and leads to damage to the kidneys - it combined with calcium in the renule tubule fluid
this can cause obstructive renal failure
what are some examples of regeneration/protection of target ?
oxime treatment of anticholinesterase poisoning - regenerates AChE
methylene blue reversal of met Hb- regenerates target
sodium nitrite therapy for cyanide poisoning - protects main target that cynaide interacts with
methionine and n-acetylcysteine treatment of paracetamol overdose
what are the effects of an opiate overdose ?
CNS depression, repsiratory depression, pinpoint pupils and coma
bradycardia, hypotension and decreased gastrointestinal motility
often present hypothermia ad hypoglycaemia
what symptoms occur by benzodiazepine overdose?
ataxia, drowsiness and coma
what do organophosphates bind to ?
covalently bind to serine of AChE
this bond can be displaced if you act quickly
what used in treatment of organophosphate poisoning?
oxime as an antidote
it binds closely with hydroxyl of itself and the phosphte so organophosphate is displaced onto oxime
why do you have to act quickly with organophosphate poisoning ?
the organophophate goes through an ageing process in which chemical changes occur and this causes the AChE to not be able to br regenerated by oximes
this can happen as little as 30 mins to an hour
what does the ageing process of organosphosphates cause?
resistance to dephosphorylation
what can cause oxidation of Hb and what does this cause ?
anilline and nitrobenzene
it produces met Hb which has an fe 3+ ion instead of fe 2+ so it cannot bind oxygen as efficiently
what reduces fe 3+ back to fe 2+?
NADH restores binding capacity of Hb
what enzyme converts metHb to Hb ?
met Hb reductase
young and neonates have low levels of this enzyme so they are most at risk
what is the treatment for met Hb ?
methylene blue reductase
what is a treatment for cyanide poisoning ?
infusion of met Hb
cyanide binds strongly to it so you produce a dummy target preventing cyanide binding to cytochrome oxidase
what substance can be infused into blood to produce met Hb ?
No2- and 4--DMAP
what happens when normal doses of paracetamol arre taken ?
the hydroxyl group undergoes sulphation or glucuronidation - making it more water soluble and less toxic so more excretable
what happens in paracetamol overdose ?
sulpahation and glucuronidation pathways become saturate so it causes paracetamol to undergo another pathway in which it is oxidise to produce a metbaolically active substance that depletes liver cells antioxidant gluutathione
this depletion may be responsible for killing liver cells
what helps with synthesis of glutathione?