Professional Documents
Culture Documents
CURS 1 Notiuni Introductive
CURS 1 Notiuni Introductive
CLINICA
Toate substantele sunt
toxice, nu exista nici
una care sa nu fie
toxica.
Numai doza diferentiaza
un toxic de un remediu
Paracelsus
1493-1541
EVOLUTIA TOXICOLOGIEI:
INTERRELATIILE SI APLICATIILE SALE
BIOLOGIE CHIMIE
ZOOLOGIE BIOCHIMIE BOTANICA
GENETICA FIZIOLOGIE
FARMACOLOGIE
TOXICOLOGIE
~ 1% DECESE
Plants 8 27 17 - - 25 15 3 - - 95 (2.4%)
Mushrooms 3 17 26 4 - 4 1 3 2 - 60 (1.5%)
POLIMEDICAMENTOASE 270 324 239 220 124 81 51 18 1327 91 218 110 79 29 12 15 1 555 1882
NEUROLEPTICE 13 15 10 6 12 5 0 0 61 7 16 7 3 6 0 0 0 39 100
TUBERCULOSTATICE 4 3 3 3 0 1 0 0 14 2 8 3 1 0 0 0 0 14 28
ETILENGLICOL 3 2 0 2 2 1 4 0 14 3 5 8 12 8 8 4 0 48 62
METANOL 1 0 0 1 1 0 0 0 3 1 1 5 4 1 1 0 0 13 16
COROZIVE / CAUSTICE 4 7 6 4 3 2 0 0 26 0 5 3 1 10 0 1 0 20 46
ANTICONVULSIVANTE 23 18 14 8 6 0 2 2 73 8 21 12 13 2 0 1 0 57 130
BETA-BLOCANTE 2 1 1 1 1 1 0 0 7 1 1 1 3 0 0 0 0 6 13
BLOCANTE DE CALCIU 1 2 1 4 2 4 0 0 14 3 2 4 0 6 3 0 0 18 22
PARACETAMOL 2 1 0 O O O O O 3 0 1 0 0 0 0 0 0 1 4
METALE 1 0 0 0 0 0 0 0 1 2 0 0 0 0 0 0 0 2 3
DIVERSE 116 144 100 131 101 99 109 16 816 30 94 73 92 100 76 71 16 552 1368
DECESE 7 4 2 14 1 12 16 11 67 2 11 15 14 13 18 13 8 94 161
CAUSE DISTRIBUTION OF ICU
HOSPITALIZED POISENED PATIENTS
OTHER CAUSES
BARBITURATES
POLIDRUGS
ETHILICS
WOMEN
ANTIDEPRESIVES
MEN
NEUROLEPTICS
UNDETERMINATED
BENZODIAZEPINES
Internal
Medicine Total STI: 1 000Women
Patients
70% 54%
Non-Drug
Men
46%
Drug
Intoxications
PATIENTS HOSPITALIZED IN
ICU
Men
35%
TOTAL HOSPITALIZED
PATIENTIS IN ICU 1000 Women
65%
Death
7%
70 PATIENTS DIED
Survive
93%
DRUG INTOXICATION
Polidrug
Barbiturates
Benzodiazepines
Neuroleptics
Triciclic antidepresive
Izoniazide
Anticonvulsivantes
Unexplained Substances
Ethanol+Drugs or Nondrugs
Ethanol
Detergents
Aniline
Mushrooms
Men
Insecticides
OPC
Methanol
Women
Solvents
CO
Ethilenglicol
Burns (acids)
Burns (bases)
140
120
100
80
60
40
20
0
Average annual percent distribution of type of poisoning-related
emergency department visits by urgency and hospital admission:
US, 1993 – 1996
(Source: CDC/NCHS, NHAMCS, 1993 - 1996)
80 75
70
60
45 47
50
40
30 22
17
20
6
10
0
Urgent Admitted
Death
1
Hospitalizations
13
Emergency
59 department visits
Poison exposures
147
The prevalence of drug addicts (overdose and
withdrawal syndrome) between 1989-2008
13%
12%
8% 14%
8%
12%
6.70%
4% 5% 10%
4%
3% 4%
2% 2% 2% 2% 2% 2% 8%
2.70%
0% 1%1% 6%
4%
2%
0%
19 89 19 90 19 91 19 92 19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06 20 07 20 08
PARAMETRII CANTITATIVI AI TOXICITATII
DL 50 (EXPERIMENTAL) mg/kg
mM/kg
mg/m2
DML (DOZA MINIMA LETALA OM)
Cl 50
CLt 50
CONCENTRATIA ATMOSFERICA – EXPUNERI PROFESIONALE
ppm SAU g/m3
Mortalitate (%)
Doza (mg/kg)
Doza medie letalã pentru diverse
substante
Compusul Specia Dl50 (mg/kg, Masa moleculara DL 50 (mM/kg)
parenteral) (g/mol)
ETANOL SOARECE 10000 46 0.2173
CATEGORIA DL50
METABOLISM
XENOBIOTICE
DETOXIFIEREA
ECHILIBRU FRAGIL PLURIFACTORIAL
BIOACTIVAREA
CITOTOXICITATE
CARCINOGENEZA
METABOLIZAREA XENOBIOTICELOR DE
CATRE FLORA INTESTINALA
• HIDROLIZA
• GLUCURONIZI
• GLICOZIZI
• SULFAMATI – CICLAMAT
• AMIDE – METOTREXAT
• ESTERI – ACETILDIGOXINA
• NITRATI – PENTAERITR. TETRANITRAT
• DEHIDROXILARE
• DECARBOXILARE AMINOACIZI
• DEAMINARE AMINOACIZI
• DEHIDROGENARE COLESTEROL, ACIZI BILIARI
• DEHALOGENARE DDT
• REDUCERE
• GRUPARE NITRO ACID P-NITROBENZOIC
• LEGATURI DUBLE ACIZI GRASI NESATURATI
• ALDEHIDE BENZALDEHIDE
• ALCOOLI ALCOOLI BEZILICI
• ALTE REACTII
• FORMARE NITROZAMINE DIMETILNITROZAMINA
• AROMATIZAREA ACID CHINIC
• ACETILAREA HISTAMINA
• ESTERIFICAREA ACID GALIC
METABOLIZAREA XENOBIOTICELOR
REACTII FAZA I
OXIDAREA HIDROLIZA
• MONOOXIGENAZE (P450) • HIDROLIZA ESTERILOR
• XANTINOXIDAZE • CARBOXILESTERAZE
• PEROXIDAZE • AMIDAZE
• AMINOXIDAZE
• MAO
• DIOXIGENAZE
REDUCEREA
• MONOOXIGENAZE (P450)
• CETOREDUCTAZE
• GLUTATIONPEROXIDAZE
• EPOXIDHIDROLAZE
• SOD
REACTII FAZA II
• GLUCURONILTRANSFERAZA (GLUCURONIDAREA)
• SULFOTRANSFERAZA (SULFOCONJUGAREA)
• TIOLTRANSFERAZA
• METILTRANSFERAZA (METILAREA)
• N-ACETILTRANSFERAZA (ACETILAREA)
• SULFTRANSFERAZA (RODANAZA)
ENTITATI TOXICE CONSECUTIVE
METABOLIZARI UNOR COMPUSI
▪ EPOXIZI ▪ COMPUSI N-HIDROXILATI
▪ RADICALI LIBERI ▪ NITROZAMINE
AFLATOXINA B1
BENZEN, BROMBENZEN
EPOXIZI FUROSEMID
OLEFINE
BIFENILI POLICLORURATI SI POLIBROMATI
TRICLORETILENA
CLORURA DE VINIL
TETRACLORURA DE CARBON
RADICALI LIBERI HALOTAN
BROMTRICLORMETAN
PARAQUAT
UNELE ALIMENTE
RADIATII IONIZANTE
INFLAMATIE
PROCESE PATOGENICE
PARACETAMOL
COMPUSI N-HIDROXILATI URETAN
AMINE
NITROZAMINE
(tub digestiv) NITRITI
Compusi bioactivi
(modificat dupa Frank Lu, 1991)
Compusul initial Metabolit toxic Mecanismul toxicitatii Consecinte organo-functionale
Acetaminofen Derivat N-hidroxi Legatura covalenta Necroza hepatica
(Paracetamol)
2-Acetilaminofluoren N-acetoxi-AAF Legatura covalenta Cancer
AAF N-sulfat
Aflatoxin B1 Aflatoxin-2,3-epoxid Legatura covalenta Cancer hepatic