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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:
TOXICOLOGIE
OCUPATIONALA LEGALA TOXICOLOGIE TOXICOLOGIE MEDIULUI VETERINARA CLINICA
TOXICOLOGIE GENETICA
IN CENTRE
DE
INTOXICATI
SAU
URGENTA
COMPUSI UZUAL IMPLICATI IMPLICATI ALCOOL ETILIC DIAZEPAM 31 MORFINICE 36 ASPIRINA FENCICLIDINA MARIJUANA AMITRIPTILINA FENOBARBITAL 32 HIDANTOINE 34 HIPNOTICE 34 AMFETAMINE NEUROLEPTICE DETERGENTI SOLVENTI
47 40 42 19
53 27 24 46
Children
Mi 263 89 26 19 15 1 6 10 7 6 21 463 Mo 58 6 3 4 3 3 3 80 S 15 6 1 2 2 26 F 1 1
Total
2586 (69.9 %) 359 (9.1%) 301 (7.7%) 256 (6.6%) 95 (2.4%) 60 (1.5%) 68 (1.7%) 51 (1.3%) 36 (0.9%) 17 (0.4%) 8 (0.2%) 89 (2.3%) 3926 (100%)
FEMEI
15-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 TOTAL 15-20 21-30 31-40 41-50
BARBATI
51-60 61-70 71-80 81-90 TOTAL
TOTAL GENERAL
POLIMEDICAMENTOASE BENZODIAZEPINE BARBITURICE ALCOOL ETILIC ALCOOL+MEDICAMENTE NEUROLEPTICE TUBERCULOSTATICE ANTIDEPRESIVE MONOXID DE CARBON ETILENGLICOL CIUPERCI COF METANOL OPIACEE SDR. INTRERUPERE SOLVENTI COROZIVE / CAUSTICE ANTICONVULSIVANTE ANXIOLITICE BETA-BLOCANTE BLOCANTE DE CALCIU PARACETAMOL METALE DIVERSE NEPRECIZATE
239 83 89 31 47 10 3 22 44 0 26 39 0 12 5 10 6 14 64 1 1 0 0 100 23
220 37 63 33 61 6 3 30 50 2 25 50 1 6 2 14 4 8 45 1 4 O 0 131 17
124 31 28 20 22 12 0 15 36 2 12 18 1 1 1 7 3 6 16 1 2 O 0 101 7
81 20 10 11 9 5 1 5 31 1 14 15 0 2 0 4 2 0 11 1 4 O 0 99 3
51 20 12 5 4 0 0 2 28 4 4 10 0 1 0 3 0 2 3 0 0 O 0 109 8
18 9 9 0 0 0 0 1 17 0 0 2 0 0 0 3 0 2 1 0 0 O 0 16 3
1327 398 478 177 230 61 14 131 322 14 124 203 3 119 61 64 26 73 360 7 14 3 1 816 136
91 39 22 109 23 7 2 5 49 3 10 19 1 127 70 13 0 8 21 1 3 0 2 30 14
110 25 23 151 84 7 3 11 57 8 24 55 5 28 20 27 3 12 10 1 4 0 0 73 20
79 26 27 145 71 3 1 9 45 12 17 52 4 5 6 27 1 13 13 3 0 0 0 92 14
29 11 8 88 28 6 0 6 37 8 11 35 1 1 6 19 10 2 7 0 6 0 0 100 6
12 9 1 38 11 0 0 0 25 8 9 19 1 1 4 10 0 0 4 0 3 0 0 76 5
15 4 5 14 5 0 0 3 19 4 2 11 0 0 0 3 1 1 0 0 0 0 0 71 4
1 3 0 2 2 0 0 0 7 0 0 1 0 0 0 4 0 0 0 0 0 0 0 16 0
555 171 165 650 319 39 14 46 296 48 95 238 13 371 261 137 20 57 103 6 18 1 2 552 99
1882 569 643 827 549 100 28 177 618 62 219 441 16 490 322 201 46 130 463 13 22 4 3 1368 235
CAUSE DISTRIBUTION OF ICU CAUSE DISTRIBUTION OF ICU HOSPITALIZED POISENED PATIENTS HOSPITALIZED POISENED PATIENTS
OTHE CAUS S R E B ARB ITURATE S P OLIDRUGS E THILICS ANTIDE RE IVE P S S NE UROLE TICS P UNDE RMINATE TE D B NZ E ODIAZE INE P S 0 5 0 10 0 10 5 20 0 20 5 30 0 30 5
W OMEN MEN
STATISTICS - 1995
Total Patients: 5 627
Hospitalisation 60%
Refuse hospitalsation 40 %
Hospitalized: 3 357
Interna l Medicin e 70%
2 357 Patients
Drug Intoxications 81%
Me n 4% 6
Women 65%
70 PATIENTS DIED
Survive 93%
DRUG INTOXICATION
Polidrug Ba rbitura s te Be nzodia pine ze s Ne urole ptics Tricic a ide sive lic nt pre Izonia zide Anticonvulsiva e nt s Une xpla d Substa s ine nce
0 2 0 4 0 6 0 8 0 10 0 10 2 10 4 10 6 10 8 20 0
Tota l
Wo e mn
Me n
De th a
NON-DRUG INTOXICATION
Mn e
W mn o e
8 0
6 0
4 0
10 4
10 2
10 0
2 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 70 60 50 40 30 20 10 0
75
45 47
22
17 6
Number and % of Poisoning Related ED Visits by the 10 Leading Principal Diagnoses for Poisoning Related Injuries, Averaged over a 4-Year Period: US, 1993-1996 Principal Diagnosis ICD-9-CM Poisoning 95% CI % Poisoning- 95% CI
Code Related ED Visits in 1000s
200 79 52 42 39 34 31 30 24
Related ED visits
20,7 8.2 5.4 4.4 4.1 3.6 3.2 3.1 2.5
Poisoning by other and unspecified drugs and medicinal substances Poisoning by analgesic, antipyretics and antirheumatics Poisoning by psyhotrops agents Toxic effect of other gases, fumes or vapors Toxic effect of other substances, chiefly nonmedical as to source Toxic effect of carbon monoxide Neurotic disorders Certain adverse effects not elsewhere classified Depressive disorder, not elsewhere classified
18.1, 23.3 5.6, 10.8 3.9, 6.9 2.9, 5.9 2.8, 5.4 2.1, 5.1 1.8, 4.6 1.7, 4.5 1.4, 3.6
(Source: CDC/NCHS, NVSS, 1995; NHDS, 1995; NHAMCS, 1993 1996; and TESS, 1995)
13
59
14 7
The prevalence of drug addicts (overdose and withdrawal syndrome) between 19892008
13% 12% 8%
14
8%
6.70% 5%
12
4% 3% 0% 1%1% 2% 2% 2% 2% 2% 2%
4%
2.70%
4%
10
8%
6%
4%
2%
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
0%
mg/kg
DML (DOZA MINIMA LETALA OM) 0.5 g 70 ml 50 mg 100 ml 25 mg 10 ml 0.1 g 50 mg 0.8 g 30 ml ARSENIC 100 mg
Mortalitate (%)
Doza (mg/kg)
Compusul
moleculara (g/mol)
46 58.443 151.908 285.34
ETANOL CLORURA DE SODIU SULFAT FEROS MORFINA SULFAT FENOBARBITAL SULFAT DDT PICROTOXINA STRICNINA SULFAT NICOTINA d-TUBOCURARINA HEMICOLINIUM-3 TETRODOTOXIN DIOXINA TOXINA BOTULINICA
SOARECE SOARECE SOBOLAN SOBOLAN SOBOLAN SOBOLAN SOBOLAN SOBOLAN SOBOLAN SOBOLAN SOBOLAN SOBOLAN COBAI SOBOLAN
0.2173 0.068 0.0098 0.0031 0.00064 0.00028 0.0000082 0.0000059 0.0000061 0.0000008 0.0000004 0.0000003
232.235 354.49 602.583 334.41 162.26 624.765 414.538 319.27 84.07 149322.7
PREDICTIA CONSECINTELOR METABOLICE DETERMINAREA POTENTIALULUI TOXIC METABOLISM DETERMINANTA A TOXICITATII DETOXIFIERE A BIOACTIVARE A
METABOLIZAREA XENOBIOTICELOR METABOLIZAREA XENOBIOTICELOR DE CATRE FLORA INTESTINALA DE CATRE FLORA INTESTINALA
HIDROLIZA HIDROLIZA
GLUCURONIZI GLUCURONIZI GLICOZIZI GLICOZIZI SULFAMATI CICLAMAT SULFAMATI CICLAMAT AMIDE METOTREXAT AMIDE METOTREXAT ESTERI ACETILDIGOXINA ESTERI ACETILDIGOXINA NITRATI PENTAERITR. TETRANITRAT NITRATI PENTAERITR. TETRANITRAT
DEHIDROXILARE DEHIDROXILARE DECARBOXILARE DECARBOXILARE DEAMINARE DEAMINARE DEHIDROGENARE DEHIDROGENARE DEHALOGENARE DEHALOGENARE REDUCERE REDUCERE
GRUPARE NITRO GRUPARE NITRO LEGATURI DUBLE LEGATURI DUBLE ALDEHIDE ALDEHIDE ALCOOLI ALCOOLI FORMARE NITROZAMINE FORMARE NITROZAMINE AROMATIZAREA AROMATIZAREA ACETILAREA ACETILAREA ESTERIFICAREA ESTERIFICAREA
AMINOACIZI AMINOACIZI AMINOACIZI AMINOACIZI COLESTEROL, ACIZI BILIARI COLESTEROL, ACIZI BILIARI DDT DDT
ACID P-NITROBENZOIC ACID P-NITROBENZOIC ACIZI GRASI NESATURATI ACIZI GRASI NESATURATI BENZALDEHIDE BENZALDEHIDE ALCOOLI BEZILICI ALCOOLI BEZILICI DIMETILNITROZAMINA DIMETILNITROZAMINA ACID CHINIC ACID CHINIC HISTAMINA HISTAMINA ACID GALIC ACID GALIC
HIDROLIZA
MONOOXIGENAZE (P450) MONOOXIGENAZE (P450) XANTINOXIDAZE XANTINOXIDAZE PEROXIDAZE PEROXIDAZE AMINOXIDAZE AMINOXIDAZE MAO MAO DIOXIGENAZE DIOXIGENAZE
REDUCEREA
GLUCURONILTRANSFERAZA GLUCURONILTRANSFERAZA SULFOTRANSFERAZA SULFOTRANSFERAZA GLUTATION S-TRANSFERAZA GLUTATION S-TRANSFERAZA CONJUGAREA) CONJUGAREA) TIOLTRANSFERAZA TIOLTRANSFERAZA METILTRANSFERAZA METILTRANSFERAZA N-ACETILTRANSFERAZA N-ACETILTRANSFERAZA SULFTRANSFERAZA SULFTRANSFERAZA
EPOXIZI
RADICALI LIBERI
NITRITI
Aflatoxin-2,3-epoxidLegatura covalenta Cancer hepatic Acroleina Epoxid Mandelonitril (flora intestinala) Benzen epoxid Brombenzen Radical liber triclormetan Legatura covalenta Necroza hepatica Necunoscut Distructie citocrom P450 Porfirie
Formare de cianura Hipoxie citotoxica Legatura covalenta Depresie maduva hematopetica Legatura covalenta Necroza hepatica, renala, bronsiolara Legatura covalenta, Necroza hepatica, peroxidarea Cancer hepatic lipidelor
Legatura covalenta Necroza hepatica, renala Alchilare Necunoscut Complex Cancer, necroza hepatica Cancer de vezica Diferite
Inhibitie enzimatica Toxicitate generala Legatura covalenta Necroza hepatica, renala Legatura covalenta Necroza hepatica Hemoliza
Consecinte organofunctionale
Compusi nitro si Metaboliti N-hidroxi Oxidare, reducere amine aromatice ciclica methemoglobinizante Metoxifluran Naftilamina Nitriti si amine secundare si tertiare Olefine Paration Fluor anorganic N-hidroxi naftilamina Nitrosamine Epoxizi Paraoxon
Inhibitie enzimatica Insuficienta renala Legatura covalenta Cancer vezical Alchilare Cancer hepatic, pulmonar
Legatura covalenta Cancer de piele Legatura covalenta Paralizie neuromusculara, cu colinesterazele insuficienta respiratorie Sinteza letala, incorporare letala Necunoscut Citotoxicitate
Analogi baze purinice Mononucleotide, si pirimidinice nucleotizi trifosfat Alcaloizi pirolizidinici Derivati pirolitici
FARMACOCINETICA TOXOCINETICA
PARAMETRU
DOZA EFECT STEADY STATE DATE CLINICE COROBORANTE CONCENTRATIE-EFECTE
FARMACOCINETICA TOXOCINETICA
CUNOSCUTA REDUSA TERAPEUTIC UZUAL FRECVENT DA NECUNOSCUTA FOARTE MARE TOXIC NU INCOMPLETE INCOMPLETE
TETRACLORURA DE RADICALI LIBERI CARBON PEROXIDARE BROMTRICLORMETAN NICOTINA CURARIZANTE MUSCARINA STIMULARE DIRECTA BLOCARE, PARALIZIE STIMULARE INTENSA, SINDROM