PhD Department of Cell Biology Genetics Faculty of Science Palacky University Olomouc Intoxications Symptoms amp Therapy The dose makes the poison ID: 935036
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Slide1
TOXICOLOGY
Prof. RNDr. Zdeněk DVOŘÁK, DrSc., Ph.D.Department of Cell Biology GeneticsFaculty of Science, Palacky University Olomouc
Intoxications
:
Symptoms
&
Therapy
Slide2„
The dose makes the poison" Philippus Aureolus Theophrastus Bombastus von Hohenheim (Paracelsus) – Swiss-German philosopher, physician, botanist, astrologer, founder
of
toxicology (1493-1541)
„Sola dosis facit venenum“
„Alle Dinge sind Gift und nichts ist ohne Gift, allein die Dosis macht es, dass ein Ding kein Gift ist.“
DOSE
CLASSIFICATION
AccidentalHousehold products (cleaning, dyes, solvents, anti-cough drugs, paracetamol)Food-born (adulterants, illicit drugs, toxins)Inhalation (petroleum products, solvents – dyes, nailpolish, diesel exhausts)Industrial and environmental accidents, natural disasters
Intentional
Suicidal
Homicidal
Drug
and
alcohol
abuse
Slide3SYMPTOMS
Non-specificAcute disorders of consciousness, abnormal behaviour, coma, spasms, shock, respiratory distress, cardiac rhytm alterations, metabolic acidosis, diarrhoea, profuse vomiting OdoursBitter almonds = cyanideAcetone = methanol, acetylsalicylic acidGarlic = organophosphates, arsenic, phosphorusAlcohol = ethanol, methanolOil = kerosensSkin
Cyanosis
non-
responsive to oxygen = nitrites, nitrates, phenacetin, benzocainErythem = CO, cyanide
, anticholinergicsDry skin = anticholinergicsSweating = amphetamines, LSD, barbiturates, cocain, organophospatesIcterus = paracetamol, mashrooms, Fe, phosphorusBlood pressureHypertensis = sympathomimetics, amphetamine, organophosphatesHypotensis = narcotics, sedatives, hypnotics, b-blockers, Ca-channel blockers, TCAs
Slide4SYMPTOMS
Heart rate (pulse)Bradycardia = digitalis, hypnotics, b-blockers, Ca-channel blockersTachycardia = sympathomimetics, amphetamine, TCAs, cocain, alcohol, anticholinergicsCardiac arrhythmiaSupraventricular tachycardia = TCAs, anticholinergicsAtrial tachycardia = digitalis, TCAs, cocainGenerally = b-blockers, Ca-channel blockers, organophosphatesMucosaDry = anticholinergicsHypersalivation
=
organophosphates
, carbamatesLesis = acids, alkaline hydroxides
RespirationDepression = alcohol, narcotics, barbiturates, sedatives, hypnoticsTachypnea = salicylates, amphetamine, COPulmonary edema = organophospatesPneumonia = hydrocarbons, kerosensWheezing = organophosphatesKussmaul breathing = salicylates, methanol, ethylene glycol
Slide5SYMPTOMS
CNSSpasms = TCAs, cocain, phenothiazines, amphetamines, salicylates, organophosphatesMiosis = narcotics, phenothiazines, barbiturates, organophosphates, mushroomsMydriasis = anticholinergics, sympathomimetics, cocain, TCAs, LSD, methanolNystagmus = barbiturates, carbamazepine, alcohol, hidantoinesDelirium/psychosis = anticholinergics, sympathomimetics, alcohol phenothiazines, LSD, cocain, heroin, heavy metalsComa = alcohols, anticholinergics, narcotics, sedatives, hypnotics, CO, salicylates
Faintness
/
paralysis = organophosphates, carbamates, heavy metalsGITdiarrhoea
, vomiting = Fe, phosphorus, heavy metals, lithium, mushrooms, organophosphates
Slide6TOXIDROME
Toxic + SyndromesymptomsBlood pressureHeart rateRespiratory rateTemperaturePupil sizeBowel soundsDiaphoresis (sweating)Anticholinergic~↑~↑
↑
↓
↓
Cholinergic~~~~↓↑↑Hallucinogenic↑
↑↑~
↑↑~Sympathomimetic↑↑↑
↑↑↑↑Sedative-hypnotic↓↓
↓↓~↓↓
Slide7IDENTIFICATION OF NOXAE
Laboratory analyses – urine, blood, stomach content, (ev. faeces – mushrooms)Examination/inspection of the scene – drug or household containers…. MANAGEMENT/THERAPY
Maintenance
of vital functionsAntidotes
Elimination of noxae
Slide8ANTIDOTES
Only small number of poissons/drugs have appropriate antidoteMostly receptor antagonists or enzyme competitorsANTIDOTE INDICATION ATROPINE organophosphates, carbamates, nerve agents, mushroomsb-BLOCKERS theophyllineCALCIUM Ca-channel blockersCHELATORS (EDTA, BAL) heavy metalsAMYL NITRITE cyanideDEFEROXAMINE ironANTIBODIES digoxin, snake venomETHANOL ethylene glycol, methanolFLUMAZENIL benzodiazepinesNALOXONE opiatesN-ACETYLCYSTEINE paracetamolPHYSOSTIGMINE anticholinergic drugs
Slide9ELIMINATION OF NOXAE
Irrigation (lavage) – stomach, whole bowelActivated charcoal – not effective for strong acids and alkali, solvents, Fe, Li, AsHemodialysis – semipermeable membrane; extracorporeal device = salicylates, acetone, aniline, barbiturates, alcohols, toluenHemoperfusion – extracorporeal device; blood passes column with sorbent (active charcoal, resins) = small to medium-sized molecules that are
difficult
to
remove by hemodialysis; e.g. TCAs, chloropromazine, paracetamol, theophyllin, barbiturates
Forced diuresis: *most of drugs are weak acids or bases *when urine is alkaline, elimination of acidic drugs is increased *when urine is acidic, elimination of alkaline drugs is increased *adjustment of pH of plasma/urine by infusion, according to pK of drug
forced alkaline diuresis – pH ↑ bicarbonate = salicylates, barbiturates (acidic drugs)forced acidic diuresis
– pH ↓ ascorbate, NH4Cl = cocaine, quinidine, strychnine (alkaline d.)