Toxicology I.

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:
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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
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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)