1. Intoxications, antidote therapy

2. 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

3. 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 %

4. Diagnosis of poisoning anamnesis foétor ex ore skin inspection body temperature muscular tonus spasms pupil biologic material (blood, urine, gastric content, vomit)

5. 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 )

6. 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 !!!

7. 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

8. 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)

9. 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)

10. 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)

11. Drug intoxications intentional (suicidal behaviour) unintentional (e.g. medical mistake) accidental (at children)

12. 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

13. 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

14. 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

15. 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%)

16. 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.

17. Psychopharmacons TCA:  clinically: hypotension, conscioussnes disorders, spasms, fatal arrhythmias !!!  risk: ↑ age, cardial disease  prognosis: not good, elimination methods uneffective  Th: symptomatic (fyzostigmine, vital ff.)

18. 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.

19. 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)

20. 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 ‰)

21. 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

22. 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!!!

23. Giving informations (24 hous consultations – intoxications) National Toxicologic Information Center, Limbová 5, FNsP Bratislava (Clinic of Occupational Medicine) phone = + 421 2 5477 4166