Toksikologi dan Terapi

Intoksikasi Akut
Hidayatul Kurniawati
 INTRODUCTION
Toxicology

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The science deal with toxic substances and its effects on the body

Toxic substance

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substance (chemical) may cause damage on biological system though may cause disorders or health problems
SCOPE
TOXICOLOGY
study of toxic toxic substance may cause damage of
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substance biological system

at which a substance ables to cause damage or

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study of the level unables to cause damage of biological system

study of safety of
substance
TOXIC SUBSTANCE
• substance may cause damage of biological system
• the ability to cause damage  toxicity parameter of toxicity 
LD50
• quantity / dose to cause death of 50% of exposure animals
• how does it enter the body
• how frequent and the length of exposure
TOXICOKINETICS
TOXICATION – DETOXICATION

biotransformation process(es) lead to toxic

●

Toxication metabolite(s) formation which are electrophiles,

free radicals, nucleophiles, redox active reactants.

biotransformation process that eliminates

Detoxication
●

the ultimate toxicant to prevent its toxicity.

TOXICOKINETICS
Toxic substance  toxic effects

• enter an organism
• are distributed throughout the organism
• reach cell or organ target  elicite effects
• are eliminated from an organism
 TOXICOKINETICS
Delivery from site of exposure to target cell

●
physicochemical properties of toxic substance,
●
the way (route) of exposure,
●
the length of some exposure.

Delivery from the body (elimination)

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biotransformation process (mostly liver)
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excretion process (mostly kidney) function
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deposition process (hair, nail stc.)
TOXICODYNAMICS
• How does toxic subtance interact with target molecules.
• How does toxic subtance exert their toxic effects at the molecular
level
• What are the biological responses (as the consequences)
• How does the organism deal with the insult
Organs Potentially suffering
from toxicity
• liver as a gate of toxic substances potentially having damage

• - blood flow :
* portal vein (80%)  including absorbed substances from stomach
and gut.
* liver artery (20%) bring oxygen.
KIDNEY
• renal blood flow 12,5 L per 100 minutes
• urin production 100 mL per 100 minutes

excessive water reabsorption (dramatic increase of filtrate xenobiotic

concentration)
Special toxicity
teratogenesis

carcinogenesis

mutagenesis
TERATOGENIC properties (+)
• aminopterine or amethopterine (folic acid antagonist) : hidrosephalus,
without fingers, etc.
• diethylstilbestrol : cancer of vagina, urogenital tract anomalia.
• phenitoin : heart anomalia, hypoplasia of nail
• thalidomide : focomilea (shorten of limb)
• warfarin : hypoplasia of nose, shorten of finger
• vitamin D : aorta stenosis, mental retardation
 TERATOGENICITY

Time of exposure

●
embryogenesis (pregnant mother in early term of pregnancy)

Amount of exposure (dose)

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different dose  different effect
Dose and time of exposure
(thalidomide)
• 50 mg on 26th days after conception  malforming embryo
• 50 mg on 10th days after conception  no malformation
• 1 mg taken any time during pregnancy  no malformation
• dose and time of exposure are determinant factors
MUTAGENICITY
• Gen mutation
• Changes of genetic code in the DNA
• It is not because of gen (DNA) recombination
• May affect somatic cells or sex chromosome
MUTAGENESIS
• material genetic – mutagen interaction
• chronic process
• damage of genetic material (gen-DNA)
• changes of genetic material

• chromosome aberation
Diagnosis of acute intocication
Physical – clinical examination
• - skin pale, chery red, cyanotics, dry, wet
• - eye – pupil  miosis, mydriasis, dry, unisochoric
• - mouth  dry, hypersalivation, asymetrics
• - heart  tachycardia, bradycardia, arrhythmia
• - lung  normal, hyperventilation
• - abdomen  hypoactivity, methalic sound
• - pulse  rythmic, weak, normal, tachy– or bradycardia
• - blood pressure  high BP, low BP
Diagnosis of acute intoxication
Laboratory examination
the rest toxin or the rest of
suspect suspect
substance material

washing vomiting
THERAPY OF ACUTE
INTOXICATION
•Supportive / nonspecific measurements
•Specific measurements
– inhibits further absorption of toxic substances  emesis,
gastric lavage, adsorben, laxants
– increase elimination process  forced diuresis, dialysis,
hemoperfusion, acidify or alkalinize of urine
– inhibit or antagonize of toxic effects  antidote
First aid
assessmen ●
(airway – breathing, brain, circulation,
disability)
t of ABCD ●
cardiopulmonary resuscitation

prevent the ●
keep the victim away from source of poison
progression of ●
decontamination (wash the area of body
contact, emesis, gastric lavage, laxant)
intoxication
Supportive measurements
• Life saving  maintenance vital function (heart and lung)
• Remove mucus (from airway)
• Use appropriate suction pump (if necessary)
• Give O2
• Artificial respiration (respirator)
• Corticosteroids
Emesis
• An oral intoxication
• Consciousness
• Less than 1 – 4 hrs.
• The ingested thing was not a corrosive  material or distillated petroleum
oil
• Physical stimulation  (stimulate uvula or pharynx wall)
• Pharmacological stimulation :
* apomorphine subcutaneous injection.
* ipecac (7 g in 100 ml syrup : 30 ml in 100 ml distilled water in adult).
Gastric lavage
• Oral intoxication, not corrosive material ingestion
• Consciousness – unconsciousness :
* is not shock, delirium or convulsive patients
• 4 hours or less
• Procedure (using a gastric tube)  give 150 - 300 ml saline or water
or KMnO4, 37C few minutes  aspirated using a syringe. Do again
5 - 10 times the last aspirate leave 30 - 50 g activated charcoal in the
stomach
Adsorbent
• Inhibit gastrointestinal absorption  (by form a physicochemical
bound with toxin)
• Orally
* activated charcoal
* resin (cholestyramine)
* evaporated milk (weak adsorbent)
* kaolin
Forced diuresis
• Requirement : good heart and kidney function
• Drink water  coconut
• Intravenous ringer / ringer dextrose :
* drops according to the needs.
* monitor the urine production.
* monitor the side effect occurred.
Forced diuresis

• Harmful and side effect  lung and cerebral edema

• Contraindication :
* shock
* cardiac or / renal insufficiency
* edema, suspect cerebral edema, convulsion.
Dialysis
• Indication : life-threatening poisoning (caused by ethanol, methanol,
ethylene glycol, isopropanol)
- substance with small volume distribution
- substance with small molecule weight
- substance water soluble
- nonprotein binding (blood and tissue)
Antidotes : Substance used to
counteract the effects of poison

Neutralizing the toxic substance (poison)  (antigen-antibody reaction, chelation, chemical binding)

Antagonize the poison physiological effects  activation of the opposing nerve system, competitiveness in
metabolism or receptors
Chemical Antidotes

• Chelators
EDTA and CaNa2EDTA (edatamil) for Pb, Au and Cd intoxication
BAL (dimercaprol) for As, Pb, Fe, Se, and U intoxication
diferoxamine (for Fe intoxication)
penicilamine (for Cu, Hg and Zn intoxication)
• KMnO4 (oxidize the alkaloids  for alkaloids intoxication)
• Activated charcoal
Physiological antidote
• ethanol (for methanol intoxication)
• anticonvulsants (for caffeine intoxication)
• atropine (for AChE inhibitor intoxication)
• antihistamines (for histamine intoxication)
• anticonvulsants (for chlorine intoxication)
• naloxone (for morphine intoxication)
• acetylcystein (for acetaminophen intoxication)
List of recommended antidote
• activated charcoal (general adsorbent)
• antivenin polyvalent (for crotalidae snake bite)
• antivenin Lactrodectus (for black widow spider bite)
• atropine (for ACh E inhibitor intoxication)
• botulinal antitoxin (ABE trivalent)  for botulinus intoxication
• cyanide kit (amylnitrite, Na-nitrite and Na-thiosulfate)  (for
cyanide poisoning)
List of recommended antidote
• deferoxamine mesylate (for Fe intoxication)
• dextrose water solution (50%, 20%) for hypoglycemic agent
• intoxication (insulin and OAD)
• diazepam, midazolam (for seizure – occurring in intoxication)
• digoxin specific antibodies (for digoxin intoxication)
• dimercaprol – BAL (for As, Pb, Hg poisoning)
• diphenhydramine (for histamine containing food or other histamine
containing material poisoning)
List of recommended antidote
• ethanol 100% or 10% (for methanol intoxication)
• ipecac, syrup of (for emeticum – to induce emesis)
• naloxone (for opioid intoxication)
• oxygen hyperbaric (for CO and cyanide poisoning)
• phenobarbiton injection (anticonvulsant)
• phenytoin injection (anticonvulsant)
• pralidoxime (for / as AChE reactivator)
Tanda dan Gejala Keracunan Pestisida

Pestisida Golongan Organoklor (Dicofan 460 EC ;

Keltane 250 EC)
Pestisida golongan organoklor bekerja mempengaruhi sistem saraf
pusat. Tanda dan gejala keracunan pestisida organoklor dapat
berupa sakit kepala, rasa pusing, mual, muntah, diare, badan lemah,
gugup, gemetar, kejang-kejang dan kesadaran hilang.
Pestisida Golongan Organofostat (Basta 150 EC ;
Eagle 480 AS)

• Apabila masuk kedalam tubuh, baik melalui kulit, mulut dan saluran
pernafasan maupun saluran pencernaan, pestisida golongan
organofosfat akan berikatan dengan enzim dalam darah yang
berfungsi mengatur bekerjanya saraf, yaitu kholinesterase. Apabila
kholinesterase terikat, maka enzim tersebut tidak dapat
melaksanakan tugasnya sehingga saraf terus-menerus mengirimkan
perintah kepada otot-otot tertentu. Dalam keadaan demikian otot-
otot tersebut senantiasa bergerak tanpa dapat dikendalikan
• tanda dan gejala lain dari keracunan pestisida organofosfat adalah
pupil menyempit sehingga penglihatan menjadi kabur, mata berair,
mulut berbusa atau mengeluarkan banyak air liur, sakit kepala, rasa
pusing, berkeringat banyak, detak jantung yang cepat, mual, muntah,
kejang pada perut, diare, sukar bernafas, otot-otot tidak dapat
digerakkan atau lumpuh dan pingsan.
Pertolongan Pertama
• Berhenti bernafas  pernafasan buatan. Terlebih dahulu bersihkan
mulut dari air liur, lendir atau makanan yang menyumbat jalan
• Kulit  lepaskan pakaian yang terkena dan kulit dicuci dengan air
sabun.
• Mata  segera cuci dengan banyak air selama 15 menit
Pengobatan
• Segera diberikan antidotum Sulfas atropin 2 mg IV atau IM  diulang
setiap 10 – 15 menit sampai terlihat gejala keracunan atropin yang
ringan  wajah merah, kulit dan mulut kering, midriasis dan takikardi.
• Atropinisasi ringan dipertahankan selama 24 – 48 jam, karena gejala
dapat muncul kembali.
• Hari pertama  50 mg atropin, kemudian atropin dapat diberikan
oral 1 – 2 mg selang beberapa jam, tergantung kebutuhan.
Pengobatan
• Diberikan segera Pralidoksim(reaktivator enzim kolinesterase) setelah
atropin
• Dosis normal  1 gram pada orang dewasa. Jika kelemahan otot tidak
ada perbaikan, dosis dapat diulangi dalam 1 – 2 jam.
• Terapi suportif
TERIMAKASIH