Toxicology I. Márton Zoltán Department of Pharmacology and Pharmacotherapy Poision - definition • Poison: Any substance that can cause severe organ damage or death if ingested, breathed in, or absorbed through the skin. • Many substances that normally cause no problems, including water and most vitamins, can be poisonous if taken in excessive quantity. There are may agents and factors that can cause intoxication: • • • • • drugs chemical substances mushrooms plants, herbs poisonous animals Most common cases of intoxication • Overdose e.g.: multiple administration resulting from carelessness • Misuse e.g.: exchange of similar containers by parents, nurses • Recklessness the improper storage of dangerous agents causes 85-90 % of childhood intoxicatons • Accident e.g.: animal poisoning General diagnosis of intoxication • poisoning should be considered if the apparently healthy patient suddenly gets sick, or produce symptoms of acute illness • acute symptoms: - vomiting, diarrhea, difficulty swallowing, mouth and oral mucosa sore, increased or irregular heart rate, respiratory distress, low or high RR, low or high body temperature, various skin disorders, neurological disorders General diagnosis of intoxication • chronic symptoms : – poisoning identified based on general condition, and symptoms – and justified by examination of urine, feces or other secretions What to do in case of poisoning • • • • • prevent the further effect of the poison removal of unabsorbed toxin treatment of dysfunction caused by toxins speed up the the excretion of poison prevention of adverse reactions Poisoning with acids Acid poisoning SYMPTOMS Acute: coagulating necrosis at areas exposed to acid - inhalation: spasm of glottis, glottisedema, suffocation - pain, shock, bleeding - serious vomiting, coffee-ground vomit - corrosion and perforation of esophagus, stomach, peritonitis - acidosis, anuresis, coma Chronic: - bleeding - cicatrization - strictures THERAPY CI: gastric lavage, vomiting, administration of alkalines diluting: water, milk mouth, pharynx and stomach mucous membrane anaesth. - lidocain analgesia: opioid analgesics; antibiotics for prevention antiemetic: atropine i.v. shock: transfusion, excessive infusion alkalisation: HCO3-, Na-lactate infusion conicotomy if necessary gastric strictures - probe therapy, correctional operations Alkaline poisoning SYMPTOMS Acute: colliquative necrosis at areas exposed to alkaline (soap like touch) - inhalation, aspiration: spasm of glottis, glottisedema, suffocation - collapse, shock, perforation of esophagus and stomach, - bleeding, peritonitis, mediastinitis - alkalosis, Ca2+ ionisation ↓, tetany, seizures - oliguresis, lethal vasomotor center paralysis Chronic: - bleeding - cicatrization, - strictures THERAPY CI: gastric lavage, induction of vomiting, neutralization diluting: water, milk (perforation!) mouth, pharynx and stomach anaesthetization - lidocain anaesthesia: opioid analgesics; antibiotics as prevention antiemetic: atropine i.v. shock: transfusion, excessive infusion conicotomy if needed gastric strictures - probe therapy, correctional operations CO poisoning MECHANISM OF ACTION COHb forms, O2 carrying capacity of blood ↓ Direct effect on neurons SYMPTOMS Acut poisoning (exacerbated by: anaemia, physical activity) - 1st stage (15-20%): weakness of lower extremities, headache, vertigo, tinnitus, nausea, vomiting, dizziness - 2nd stage (20-60%): unconsciousness, trismus, increased ventilation, fast heart rate, seizures, acidosis - 3rd stage (above 60%): areflexia, paralysis of respiration, coma, cardiovascular collapse 10-30% of survivors acquire delayed neuropsychiatric sequelae (DNS) Chronic poisoning Symptoms: chronic fatigue, headache, sleep disturbances, vertigo, memory deficits, difficulty working, abdominal pain, diarrhea Smoking → COHb level ↑ → workplace exposure THERAPY: - O2 inhalation, O2 with overpressure - trismus → diazepam Cyanide poisoning MECHANISM OF ACTION - firm binding to enzymes containing Fe3+ (ferri) ions, mainly to cytochrome oxydases → cytotoxic anoxia SYMPTOMS - almond smell of breath, salivation, nausea without vomiting, - hyperaemic face, headache, vertigo, anxiety - tachycardia, hypertension, - dyspnea, asphyxic seizures, fixed and dilated pupils, hypoventilation - coma, paralysis of respiration, heart block, ventricular arrhythmias THERAPY - inhalation → fresh air, 100% O2 - per os → gastric lavage (Carbo Med.) - methaemoglobin formation → 4-dimethylaminophenol i.v. - methaemoglobin formation → sodium nitrite, amyl nitrite i.v. - thiocyanate forming → sodium-thiosulphate i.v. - complex forming → Co2-EDTA, hydroxocobalamin Poisoning with nitrites and nitrates Mechanism of action: Nitrits are formed from nitrates as well, causing methemoglobinamia O2 carrying capacity of blood ↓ • Increased risk in case of infants under age of three months, because: 1. nitrit is absorbed just from the upper section of the GI, in adults there are no nitrit forming bacteria ↔ infants 2. haemoglobin F binds nitrites better 3. the infant kidney is unable to repidly excrete nitrates • Nitrozamines are also formed, which are carcinogenous in stomach, lungs and liver Sympthoms: somnolence, lethargy, concentration difficulty, mental and physical performance degradation, cyanosis, respiratory distress Treatment: Methylene-blue, ascorbic acid Arsenic poisoning MECHANISM OF ACTION paralyzing SH containing enzymes - cytotoxic effect pyruvate oxydase, succin acid dehydrogenase ACUT POISONING Symptoms (min. 3 hours latency): - GI effects (unstoppable vomiting, cholera - like diarrhea) - CV effects (exsiccosis, oliguresis, hypotension, arrhythmias) - haematopoetic effects (anaemia, leukopenia, granulocytopenia) - coma, shock, brain anoxia, death Therapy: - dimercaprol, gastric lavage (Carbo Med. + MgO) - palliative: liquid, supporting circulation CHRONIC POISONING Symptoms: - cumulation in bones, nails, hair - symmetric hyperkeratosis on palm and sole, exsiccated mucous membranes - loss of appetite, anaemia, edemas, polyneuritis - peripheral vascular disease (→ blackfoot disease) Therapy - dimercaprol before irreversible damage Mercury poisoning ACUT POISONING Inorganic mercury salts: - vomiting, diarrhae, haemorrhagic necrosis, gastroenteritis - acut tubular necrosis, oliguric renal failure, hypovolemic shock Organic mercury salts : - central neurotoxic efect (paraesthesia, neurasthenia, ataxia, tremor, visual -, hearing disturbance, spasticity, coma, death) - peripheral neuropathy, renal failure Therapy : - gastric lavage, milk, egg white (Hg-albuminat), Na-tiosulfat (insoluble HgS), symptomatic - dimercaprol, penicillamin, - hemodialysis, extracorporal dialysis CHRONIC POISONING Elementary mercury: - fatigue, tachycardia,tremor, gingivitis, swollen -, bleeding gums - insomnia, memory loss, emotional instability, depression, anorexia, vasomotor disturbance (erethism), goitre Therapy: - dimercaprol, penicillamin Lead poisoning ACUT POISONING (rare) GI symptoms: pain, vomiting, diarrhae, shock Absorbed Pb: see Chronic poisoning Therapy: - Ca-EDTA, D-penicillamin, - symptomatic (painkilling, fluid therapy) CHRONIC POISONING Hypochrom mycrocytaer anaemia metal taste, grey-blue line along the margin of the gums „Burton line” GI: abdominal pain, constipation, diarrhea, vomiting, poor appetite Peripheral motoneuron damage: muscular weakness CNS symptoms (mainly in children): lead-encephalopathy - intracrainal pressure ↑, cerebral edema - irritability, decreased attentiveness - vomiting, altered consciousness, intractable seizures and coma - mental retardation, seizure disorders, aggressive behavior disorders, developmental regression Therapy: - Ca-EDTA, D-penicillamin, dimercaprol - symptomatic (anticonvulsants, mannitol)
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