intoxications, antidote therapy. toxic substance (poison) hard to define substance, which in...
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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!!!