Professional Documents
Culture Documents
Introductiv
Introductiv
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
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
81%
PATIENTS HOSPITALIZED IN
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
NON-DRUG
Detergents
Aniline
Mushrooms
Men
Insecticides
OPC
Methanol
Women
Solvents
CO
Ethilenglicol
Burns (acids)
Burns (bases)
80
60
40
20
140
120
100
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% 8%
2% 2% 2% 2% 2% 2% 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
CATEGORIA DL50
DL50
▪▪ SUPERTOXICE
SUPERTOXICE 55 mg/kg
mg/kg sausau <<
▪▪ EXTREM
EXTREM DE
DE TOXICE
TOXICE 55 –– 50
50 mg/kg
mg/kg
▪▪ FOARTE
FOARTE TOXICE
TOXICE 50
50 –– 500
500 mg/kg
mg/kg
▪▪ MODERAT
MODERAT TOXICE
TOXICE 0.5
0.5 –– 55 g/kg
g/kg
▪▪ CU
CU TOXICITATE
TOXICITATE REDUSA
REDUSA 55 –– 15
15 g/kg
g/kg
▪▪ PRACTIC
PRACTIC NETOXICE
NETOXICE >> 15
15 g/kg
g/kg
ENDOBIOTICE
METABOLISM
XENOBIOTICE
DETOXIFIEREA
ECHILIBRU FRAGIL PLURIFACTORIAL
BIOACTIVAREA
CITOTOXICITATE
CARCINOGENEZA
METABOLIZAREA
METABOLIZAREA XENOBIOTICELOR
XENOBIOTICELOR DE
DE
CATRE
CATRE FLORA
FLORA INTESTINALA
INTESTINALA
•• HIDROLIZA
HIDROLIZA
•• GLUCURONIZI
GLUCURONIZI
•• GLICOZIZI
GLICOZIZI
•• SULFAMATI
SULFAMATI –– CICLAMAT
CICLAMAT
•• AMIDE
AMIDE –– METOTREXAT
METOTREXAT
•• ESTERI – ACETILDIGOXINA
ESTERI – ACETILDIGOXINA
•• NITRATI
NITRATI –– PENTAERITR.
PENTAERITR. TETRANITRAT
TETRANITRAT
•• DEHIDROXILARE
DEHIDROXILARE
•• DECARBOXILARE
DECARBOXILARE AMINOACIZI
AMINOACIZI
•• DEAMINARE
DEAMINARE AMINOACIZI
AMINOACIZI
•• DEHIDROGENARE
DEHIDROGENARE COLESTEROL,
COLESTEROL, ACIZI
ACIZI BILIARI
BILIARI
•• DEHALOGENARE
DEHALOGENARE DDT
DDT
•• REDUCERE
REDUCERE
•• GRUPARE
GRUPARE NITRO
NITRO ACID
ACID P-NITROBENZOIC
P-NITROBENZOIC
•• LEGATURI
LEGATURI DUBLE
DUBLE ACIZI
ACIZI GRASI
GRASI NESATURATI
NESATURATI
•• ALDEHIDE
ALDEHIDE BENZALDEHIDE
BENZALDEHIDE
•• ALCOOLI
ALCOOLI ALCOOLI
ALCOOLI BEZILICI
BEZILICI
•• ALTE
ALTE REACTII
REACTII
•• FORMARE
FORMARE NITROZAMINE
NITROZAMINE DIMETILNITROZAMINA
DIMETILNITROZAMINA
•• AROMATIZAREA
AROMATIZAREA ACID
ACID CHINIC
CHINIC
•• ACETILAREA
ACETILAREA HISTAMINA
HISTAMINA
•• ESTERIFICAREA
ESTERIFICAREA ACID
ACID GALIC
GALIC
METABOLIZAREA
METABOLIZAREA XENOBIOTICELOR
XENOBIOTICELOR
REACTII
REACTII FAZA
FAZA II
OXIDAREA
OXIDAREA HIDROLIZA
•• MONOOXIGENAZE
MONOOXIGENAZE (P450)
(P450) • HIDROLIZA
HIDROLIZA ESTERILOR
ESTERILOR
•• XANTINOXIDAZE
XANTINOXIDAZE • CARBOXILESTERAZE
CARBOXILESTERAZE
•• PEROXIDAZE
PEROXIDAZE • AMIDAZE
AMIDAZE
•• AMINOXIDAZE
AMINOXIDAZE
•• MAO
MAO
•• DIOXIGENAZE
DIOXIGENAZE
REDUCEREA
• MONOOXIGENAZE
MONOOXIGENAZE (P450)
(P450)
• CETOREDUCTAZE
CETOREDUCTAZE
• GLUTATIONPEROXIDAZE
GLUTATIONPEROXIDAZE
• EPOXIDHIDROLAZE
EPOXIDHIDROLAZE
• SOD
SOD
REACTII
REACTII FAZA
FAZA II
II
•• GLUCURONILTRANSFERAZA
GLUCURONILTRANSFERAZA (GLUCURONIDAREA)
(GLUCURONIDAREA)
•• SULFOTRANSFERAZA
SULFOTRANSFERAZA (SULFOCONJUGAREA)
(SULFOCONJUGAREA)
•• GLUTATION
GLUTATION S-TRANSFERAZA
S-TRANSFERAZA (GLUTATION
(GLUTATION -- CONJUGAREA)
CONJUGAREA)
•• TIOLTRANSFERAZA
TIOLTRANSFERAZA
•• METILTRANSFERAZA
METILTRANSFERAZA (METILAREA)
(METILAREA)
•• N-ACETILTRANSFERAZA
N-ACETILTRANSFERAZA (ACETILAREA)
(ACETILAREA)
•• SULFTRANSFERAZA
SULFTRANSFERAZA (RODANAZA)
(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
Alil formiat Acroleina Legatura covalenta Necroza hepatica
Alilizopropil acetamida Epoxid Necunoscut Distructie citocrom P450
Porfirie
Amigdalina Mandelonitril Formare de cianura Hipoxie citotoxica
(flora intestinala)
Benzen Benzen epoxid Legatura covalenta Depresie maduva
hematopetica
Brombenzen Brombenzen Legatura covalenta Necroza hepatica, renala,
bronsiolara
Tetraclorura de carbon Radical liber Legatura covalenta, Necroza hepatica,
triclormetan peroxidarea lipidelor Cancer hepatic
Alchilnitrosamine Alfa-hidroxilare Alchilare Cancer hepatic
carciogene
Coloranti amino Derivati N-hidroxi Legatura covalenta Cancer hepatic
carciogeni
Compusi bioactivi
(modificat dupa Frank Lu, 1991)
Compusul initial Metabolit toxic Mecanismul toxicitatii Consecinte organo-functionale
Hidrocarburi policiclice Epoxizi in diverse Legatura covalenta Cancer, citotoxicitate
carciogene organe
Cloroform Fosgen Legatura covalenta Necroza hepatica, renala