Intoxications, antidote therapy

Toxic substance (poison)

• hard to define substance, which in relatively small amounts harms the organism

usually dose dependence

• according to site of toxicity = hemato-, hepato-, nefro-, neuro-, pneumotoxic, multiple toxicity

• intoxication = accidental or intentional ingestion                           of poison

Intoxications (datas from toxicol. inf. center)

1. Medicaments = 52 %2. Commercial preparations = 30 %3. Plants = 8 %4. Chemical substances = 5 %5. Mushrooms = 2 %6. Narcotics = 1 %7. Animals = 1 % 8. Others = 1 %

Diagnosis of poisoning

• anamnesis• foétor ex ore• skin inspection• body temperature• muscular tonus• spasms • pupil• biologic material (blood, urine, gastric content,

vomit)

Intoxication therapy – general rules

prevention of poison resorption: = induction of vomiting (risk of aspiration!!)

= gastric lavage (only till 1 hour !!)

= charcoal – powder form,1g/kg bolus, than repeadly 10 g every 4 hours per os or with gastric probe (adsorption of toxins, intestinal dialysis) = laxatives – MgSO4 + hydratation

= open lavage of small intestine (organophosphates)

KI of gastric lavage and induction of vomiting!!!

• poisoning by hydrocarbons, corrosive substances (acids, bases), unconsciousness

• Induction of vomiting : standardly not recommended, only in acute poisoning by a highly toxic substance!!!

Therapy of intoxication– general rules

elimination methods

remove already resorbed venom from the circulation hemodialysis, hemoperfusion, forsed diuresis

(furosemide)

ensure vital functions:

respiratory support (artificial ventilation)

circulation support (analeptic drugs, volum-expansion)

internal balance (acidobasis, minerals)

give antidote

Antidotes

• substances capable specifically abolish toxic effect of poison

• give as soon as possible after diagnosis

• mechanism of action:

competition on receptor

chelation of molecules (EDTA)

reactivation of enzyme (organophosphates)

reactivation of SH group (acetylcysteine)

Antidotes

• N-acetylcysteine (paracetamol)

• dimercaprol, EDTA (heavy metals)

• obidoxim, atropine (organophosphates)

• ethanol, fomepizol (metanol, ethylene glycol) • flumazenil (benzodiazepines)• naloxone (opiates)• glucagon (beta-blockers)• digidot – monoclon. antibody (digoxin)

Antidotes

• protamine (heparin)• plazma, vit. K (warfarin)• deferoxamine (iron)• paraffine (organic solvents) • silibinin, penicillin-G (Amanita phalloides) • partially fyzostigmine (TCA, neuroleptics ) • 40 % gluc., glucagon (insulin-hypoglycaemia)

Drug intoxications

• intentional (suicidal behaviour)

• unintentional (e.g. medical mistake)

• accidental (at children)

Drug intoxications

• ↑↑↑ risk of intoxication =

drugs with narrow therapeutic margin (digoxin,

warfarin, teophyllin, lithium, peroral antidiabetics, antiepileptics)

polypharmacy (interactions !!!)

dysfunction of elimination organs

geriatric patients, children

wrong dose, dosage interval, drug

Drug intoxications - prevention

• right drug, dose, interval, patient• clinical monitoring of patient (digoxin - ECG)• TDM (= monitoring of drug levels): digoxin, lithium, teophylline aminoglykosides, vankomycine cyklosporine A antiepileptics methotrexate• take into consideration interaction potential of

drug

Organophosphate intoxication (insekticides, chemical weapons)

= cholinergic syndrome: slacrimation, salivation, sweatting, diarrhoea, relaxation of sfincters, bradycardia, miosis, rhonchus, cyanosis, spasms, paralysis of breathing

• therapy: rinse affected with water (gloves!!!), ensure vital functions, atropine + obidoxime i.v. as antidote as soon as possible!!! (reactivator of Ach esterase), open lavage of small intestine

Amanita phalloides

• toxins: amanitin, faloidin (hepatotoxicity – inhibition of proteosynthesis)

• clinially: latention of symptoms > 4 hours, than nausea, vomitting, ↑ ALT, AST, icterus later

• Th: charcoal, hemoperfusion (till 24 hours),

silibinin i.v. (Legalon SIL), alternative

penicillin G i.v. (megadoses = 1.5 mil.u./kg!!!),

liver transplantation (factor V < 20%)

Psychopharmacons

• Benzodiazepines (↑biologic halflife = cumulation)

clinically:attenuation, hypotonia, hypotension,

hypothermia, conscioussnes disorders, attenuation of breathing,

prognosis: usually good, lethal dose

(LD50) high

interactions: alcohol, other psychopharmacons

Th: flumazenil, ensure vital ff.

Psychopharmacons

• TCA: clinically: hypotension, conscioussnes

disorders, spasms, fatal arrhythmias !!! risk: ↑ age, cardial disease

prognosis: not good, elimination methods

uneffective

Th: symptomatic (fyzostigmine, vital ff.)

Psychopharmacons

• opiates: clinically: miosis, conscioussnes disorders,

attenuation of breathing risk of interactions: other depressing

substances prognosis: lethal dose individ.

Th: repeatedly naloxone i.v., ensure vital ff.

Paracetamol

• in England the main reason of acute hepatal failure (usually suicidal)

• at respecting recommended doses safe drug• ↑ risk: hepatal disease, alcohol abuse

• toxic dose(cca): adults = 150 mg/kg

children = 200 mg/kg

• antidote: N-acetylcysteine i.v. (donor of SH groups for regeneration of glutathion in liver)

Ethylalcohol

• stages of intoxication: excitation (0.5 ‰)

hypnotic

narcotic

asfyctic (> 4 ‰)

• risk of death: respiratory failure, aspiration of

vomitting (carefull interactions !!!)

• Th: 20-40 % glucose, in case of spasms diazepam, if

coma with acidosis – hemodialysis (> 4 ‰)

Methylalcohol

• poisoning: domestic poorly burned alcohol, additive of chemical substances• toxic metabolites = formaldehyd, formic acid• typical latency of symptoms, missing is

excitation stage• toxicity: vision disorders (↓ visual acuity, skotoms), damage of vision, kidneys, liver, acidosis• Th: 40 % ethanol (2 ml/kg per os), fomepizol (competitive antagonist of ADH in liver), hemodialysis

Ethylene glycol

• ingredient in car antifreeze mixtures

• ↑ toxicity: metabolit oxalic acid, damage of renal tubules (oxalate crystalls) = acute renal failure,

damage of liver, acidosis

• Th: as at methylalcohol

• prognosis of poisoning with methanol and ethylene glycol = good only at early initiation of therapy!!!

Giving informations (24 hous consultations – intoxications)

• National Toxicologic Information Center, Limbová 5, FNsP Bratislava (Clinic of Occupational Medicine)

• phone = + 421 2 5477 4166