Clinical Toxicology 2

Question 0

how are most cases of poisoning treated ?

Answer 0

managed in a supportive manner and dont require antidotal treatment

Question 1

what are the 3 categories which antidotes fall into ?

Answer 1

pharmacological reversal
formation of inert complexes
regeneration of and/or protection of target

Question 2

what are some examples of pharmacological reversal ?

Answer 2

• 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

Question 3

what are some examples of formation of inert complexes?

Answer 3

• 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

Question 4

what happens when methanol is consumed ?

Answer 4

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

Question 5

what is a lethal dose of methanol?

Answer 5

30-240ml

Question 6

what is the aim of treatment for methanol treatment ?

Answer 6

inhibit alcohol dehydrogenase

- use ethanol or 4-methylpyrazole fomepizole = these block metabolism of methanol

Question 7

what is a lethal dose of ethylene glycol ?

Answer 7

about 100ml

it is sweet so animals find it appealing

Question 8

what is the affects of ethylene glycol consumption ?

Answer 8

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

Question 9

what are some examples of regeneration/protection of target ?

Answer 9

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

Question 10

what are the effects of an opiate overdose ?

Answer 10

CNS depression, repsiratory depression, pinpoint pupils and coma
bradycardia, hypotension and decreased gastrointestinal motility
often present hypothermia ad hypoglycaemia

Question 11

what symptoms occur by benzodiazepine overdose?

Answer 11

ataxia, drowsiness and coma

Question 12

what do organophosphates bind to ?

Answer 12

covalently bind to serine of AChE

this bond can be displaced if you act quickly

Question 13

what used in treatment of organophosphate poisoning?

Answer 13

oxime as an antidote

it binds closely with hydroxyl of itself and the phosphte so organophosphate is displaced onto oxime

Question 14

why do you have to act quickly with organophosphate poisoning ?

Answer 14

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

Question 15

what does the ageing process of organosphosphates cause?

Answer 15

resistance to dephosphorylation

Question 16

what can cause oxidation of Hb and what does this cause ?

Answer 16

anilline and nitrobenzene

it produces met Hb which has an fe 3+ ion instead of fe 2+ so it cannot bind oxygen as efficiently

Question 17

what reduces fe 3+ back to fe 2+?

Answer 17

NADH restores binding capacity of Hb

Question 18

what enzyme converts metHb to Hb ?

Answer 18

met Hb reductase

young and neonates have low levels of this enzyme so they are most at risk

Question 19

what is the treatment for met Hb ?

Answer 19

methylene blue reductase

Question 20

what is a treatment for cyanide poisoning ?

Answer 20

infusion of met Hb

cyanide binds strongly to it so you produce a dummy target preventing cyanide binding to cytochrome oxidase

Question 21

what substance can be infused into blood to produce met Hb ?

Answer 21

No2- and 4–DMAP

Question 22

what happens when normal doses of paracetamol arre taken ?

Answer 22

the hydroxyl group undergoes sulphation or glucuronidation - making it more water soluble and less toxic so more excretable

Question 23

what happens in paracetamol overdose ?

Answer 23

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

Question 24

what helps with synthesis of glutathione?

Answer 24

methionine

Question 25

what can be used as an antiote for paracetamol overdose for up to 20 hurs ?

Answer 25

n- acetylcysteine