Principles of Toxicology

Clinical Case 1Seorang anak laki2, umur 7 tahun dibawa ke IGD karena muntah-muntah dan penurunan kesadaran. 30 menit sebelumnya baik-baik saja, lalu ditemukan tidak berespon di kamar mandiBau tidak spesifik dan menyengatPx fisik: pinpoint pupil (diameter 2 mm), hipersalivasi, lakrimasi. Masih berespon dengan nyeri, bicara ngelantur, GCS 9.HR 117, RR 38, BP 112/58, t 36.8C, SatO2 96%Paru: Wheezing bilateral; Abdomen: no tendernessExtremitas: hangat-dingin, capillaery refill

Clinical Case 2Seorang wanita, umur 31 tahun dibawa ke IGD karena ditemukan tidak sadar oleh suami. 1 jam sebelumnya baik-baik saja, hanya mengeluh migren-nya kambuh lagi dan tampak minum obat yang dia tidak tahu.HR 136, RR 21, TDS 82 mmHg, SatO2 100% NRMJantung: BJ I-II normal, bising -, Gallop Lain dbnECG: Takikardia dengan kompleks QRS lebar, VT

Clinical Case 2: ECGECG: Takikardia dengan kompleks QRS lebar

Clinical Case 2: ECGTerapi: Sodium bikarbonat, hiperventilasi

DefinitionsToxicology

Complex subdivision which deals with toxic substances: detection, properties, effects and regulation of toxic substances, including poisons.

So what is a poison?

DefinitionsToxic refers to the condition of a substance and the degree to which it can cause damage to you or any other organism or system. Toxic can refer to biological organisms and non-biological substancesPoisonous describes substances that will disturb organisms, usually in a harmful way. Poison implies a high level of toxicity, though any substance is technically poisonous if taken in a large enough dose. Poison always refers to biological organisms.

What is a poison?PoisonAny substance which cause a harmful effect when administered either by accident or by design to a living organism

Poisoning is quantitative concept

Any chemical at some specific dose and time is harmless, while the same chemical at other doses and time is toxic

What is Toxicology?1. Primarily a multidisciplinary science that is based on other sciences including:PharmacologyPathology (disease/death)Chemistry Epidemiology Hazard potential for harmRisk probability of producing Harm

2. Applied ScienceEnhancement of the quality of lifeProtection of EnvironmentTo learn about life processes (i.e uncoupling agents)

Dose Response Curve related to Toxicity

Dose/Time PrincipleWhile dose is the primary determinant of toxicity, effects of chemicals on the body are also a function of the length of time such substances are present.

Blood Plasma Level Toxicity

More simplyDose makes the poison

It is the primary determinant of Toxicity

Toxicology in Modern TimesDuring the last 5 decades, toxicology has taken on new meaning

Thalidomide tragedy (1950s) - phocomelias and other birth defectsSilent Spring Rachel Carson, DDTTV CSI, QuincyIncreasing Drug AbuseMedical Malpractice suits (last 30 years)

Importance of Toxicology1. Important because chemicals are responsible for at least 10,000 accidental deaths annually. Children under 5 years old are usually poisoned by:Plants, cosmetics, salicylates, hydrocarbons, detergents and acetaminophen. Adult poisoning usually involves:Barbituates, carbon monoxide, salicylates, alcohol, narcotics and acetaminophen

2. Work place accidents associated with chemicals. A. Drugs (alcohol, cocaine, marijuana, etc.)B. Manufactured Products

Importance of Toxicology (cont)

3. LitigationA. ie. Drug/alcohol related accidents

4. CausationA. Evidence of cause and effect based on exposure and dose.

Toxicological Terms1. LD50 dose at which 50% die Only animals TD50 dose at which 50% have toxicity Measure of harmfulness

2. T.I. Therapeutic Index TD50 / ED50 The larger the number, the safer the drug Measure of safety

3. Acute Toxicity Single dose within 24 hrs Defines intrinsic toxicity

Toxicological Terms (cont)4. Chronic Toxicity Daily exposure for up to a lifetime

5. TLV Threshold Limit Value

Concentration below which there is no expected untoward effect over a period of 8hrs/day 5 days/week

NOEL no observable effect level

ADI allowable daily intake

ADI = (NOEL) / x

x is some safety factor (i.e., 100)

Toxicological Terms (cont)6. STEL Short term exposure level 4x a day, with the average being equal to the TLV

7. ALD Average Lethal DoseEstimated from accidental deaths in humans

8. ToxiconToxic principle of a given chemical entityTylenol quinone imineCCl4 free radicals

9. Primary Determinant of ToxicologyDose, Dose and Dose

Selective vs. Nonselective ToxicityNonselectiveNearly all chemical are nonselective in their actionsFew chemicals are sufficiently selective to harm certain cells

SelectiveOne mans poison is another mans pill. What may be harmful to one specimen may be relatively harmless to another. Garden spray

II. Management of a PoisoningImmediate measures are called for in every case of poisoning regardless of cause.

1. Support Vital Functions

2. ID drug poisoning as the problem

3. Reduce the amount of drug in the body

Support vital life functions (ABCs)Airway endotracheal tube if needed, watch for fluid accumulation in airway (i.e.. Aspiration of vomit)

Breathing Supplemental Oxygen, bag valve mask (BVM) and respirator.

Circulation Monitor ECG, watch for arrhythmias, cardiac arrest and shock

Vasogenic Shock faulty vasomotor tone, increase capillary permeability.

Cardiogenic Shock inadequate cardiac output can be due to cardiac dilation (barbituate, Ca channel blocker)

General Treatment of a Comatose PatientThere are several general antidotes that are used in the treatment of comatose patients upon presentation at the hospital.

What are they?

Supportive Drug TherapyTreat all patients who come into the hospital in a coma with glucose, insulin and naloxone.

Use drugs to treat emergent conditions, ie:Seizures anticonvulsants (valium)Cardiac Dysrhythmias anti-arrhythmias (lidocaine, digoxin)Severe Agitation anxiolytics (benzo)

How to ID the poison?

ID the poison1. Patient history

2. Laboratory testing

3. Comparison of drugs or chemicals with known toxicology standards.

Identification of the Poison (Sample Types)Urine - 1st choice easier to detect presence of the drug due to the accumulation of drug in the urine.

Blood/Serum 2nd choice get exact serum levels to better identify the health effects of the drug (coma/stimulant panels)

Gastric Contents 3rd choice less helpful, but can tell if you should perform a gastric lavage.

Identify Poison (Tests)Urine testsImmunoassay (EMIT, ELISA) semiquantitative tests usually with automated instrumentation. Can detect cannabinoids, amphetamines, cocaine, barbs etc.

Thin Layer Chromatography (TLC) ToxiLab, 4 stage solvents, qualitative test

Urine/Blood testsHigh Performance Liquid Chromatography (HPLC), gas chromatography and Gas Chromatography/Mass Spectroscopy (GCMS) are quantitative tests that can detect many compounds. Coma and Stimulant panels

Can be done in 2 hours

Removal of the Drug (Emesis)Utilize syrup of Ipecac to Induce emesis to remove unabsorbed drug.

Emesis inducersMechanicalApomorphineSyrup of ipecacContraindications?

Contraindications of EmesisEmesis is contraindicated in cases of:Petroleum hydrocarbon solvent chemical pneumonitisCaustic acid or alkali agent (rupture)Seizing PatientComatose Patient

Removal of the Drug (Gastric Lavage)Gastric Lavage washing of the stomach. (early tx.)

A tube is inserted through the nose or mouth, down the esophagus, and into the stomach. Sometimes a topical anesthetic may be applied to minimize irritation and gagging as the tube is being placed.

Stomach contents can be removed using suction immediately or after irrigating w/ fluids through the tube.

Activated Charcoal/CatharticsActivated Charcoal (AC)Used to bind compounds and to prevent absorption in the GI tracts. (many drugs)Contraindicated with caustic agents and petroleum distillates due to the lack of absorption of these agents by the charcoal and risk of vomiting associated with the charcoal

Order of use of charcoal and ipecac

CatharticsPromotes rapid passage of poison through the GI tractCounteracts the constipative effects of ACI.E. sorbitol, Mg Citrate, Mg Sulfate

Removal of the Drug (Other)Alteration of pH of urine to enhance excretion of the drug, useful for salicylates, chlorpropamide, etc (tx)

Diuresis often used in conjunction with urine pH alteration

Dilution with water useful in the treatment of skin or eye exposure to harmful agents. ( no neutralizers)

Demulcents soothes mucous membranes and coats the stomach, i.e. milk of magnesia

Hemodialysis blood transverses a semipermeable membrane that is bathed in dialysis solution or dialysate. Drugs or toxins diffuse across this membrane. (protein binding)

B. Antidotal Treatments (1. Complexation)A. Heavy MetalsChelators (BAL, EDTA) complexes with the metals making them inert

B. Heparin Protamine (base) binds to acidic heparin to terminate its action and is excreted by glomerular filtration.

C. Toxins- Botulinum Toxin ALD- < 0.5mcg LD50=10ng/kgMost potent poison known, rapidly absorbed and prevents ACH release from nerve terminalsTx: ABCs, lavage, emesis, charcoal,Trivalent anti-toxinMortality of 70% to 10% with treatment

Complexation (cont)D. OrganophosphatesPralidoxime is a nucleophillic reagent that ties up the organophosphates and permits its excretion.

E. CyanideBinds to cytochrome oxidase, LD50= 2mg/kg Causes death in 1 to 15 minutes at high doses. Chelator is made in the body, methemoglobin (Fe3+)

Give Amyl Nitrites and Na Nitrite with O2 and whole blood to convert hemoglobin to methemoglobin (LD50 increases 5 fold) .

PatofisiologiOP menghambat asetilkolinesterase (AChE) yang menghidrolisa asetilkolin. Inhibisi AChE oleh OP mengakibatkan akumulasi asetilkolin stimulasi yang berlebihan pada reseptor asetilkolin di sinaps sistem saraf otonom, sistem saraf pusat, dan neuromuscular junction. Gambar.2. Mekanisme keracunan organofosfatSumber : Department of environmental and occupational health sciences. 2007

Gambaran Klinis

Gambaran klinis dari keracunan OP terdiri dari 3 fase :

Worthley LIG. Clinical Toxicology: Part II. Diagnosis and management of uncommon poisonings. Critical Care and Resuscitation.2002;4:216-230Goel A, Aggarwal P. Pesticide poisoning. Natl Med J India. 2007;20:182-91

Sindrom kolinergik akutSumber : Lau CL, Chung KL, Kam CW. Hong Kong Journal of Emergency Medicine. 2003

Efek MuskarinikEfek NikotinikEfek SSPMiosisFasikulasi ototPenurunan kesadaranDiaphoresis/berkeringatParalisisKejangBronchorrhea/BronchospasmeKelemahan ototDepresi pernafasanBradikardiHipertensiAtaksia, disartriaSalivasiTakikardiGejala EkstrapiramidalHipotensiLetargiLakrimasiDiare/Diuresis berlebihMuntah

Penegakkan DiagnosaKeracunan organofosfat dapat didiagnosa dengan adanya 2 dari gejala berikut :1. Riwayat terpapar organofosfat2. Manifestasi dari gejala muskarinik atau nikotinik.3. Timbulnya efek antikolinergik setelah pemberian atropine. Keraguan terhadap keracunan organofosfat pemberian atropine chalange :1 mg atropine dosis 0,01-0,02 mg/kg. Tidak terdapat gejala antikolinergik keracunan asetilkolinesterase inhibitor4. Konfirmasi hasil laboratorium : pengukuran AChE di sel darah merah, atau pseudo AChE di plasma darah. Koirala DP, Rao KS, Malla KK, Malla T. A study of clinical features, management and outcome of organophosphate and carbamate poisoning in children. J. Nepal Paediatr.Soc. 2013;33(2):85-90

Antidotal Treatments (cont)2. Enhancement of metabolic conversion to a safer formExample: Cyanide Poisoning and thiosulfate treatment (LD50 increases 3 fold)

CN- SCNRhodaneseSulfurTreatment: Give Thiosulfate (Sulfur source)

Antidotal Treatments (cont)3. Inhibition of metabolic conversion to toxic forms.

A. Ethylene glycol / Methanol ethanol administration prevents Alcohol dehydrogenase (ADH) from converting these substances into toxic forms. (Km Mechanism of Toxicity)

4. Accelerating rate of excretion Compete with reabsorption (Renal Tubules). I.e. For Sr2+ or Ra2+ radiation give Ca2+; For Br1- poisoning give Cl1- to aid in excretion.

5. Competition for Essential receptorsA. Carbon MonoxideCO is found in cigarette smoke (5%) and auto exhaust (9%). Not in natural gas itself. Commonly used as a means of suicide; over 5000 fatalities a year from CO poisoning.

Carboxyhemoglobin is found in very small amounts in non-smokers ~2.5% of the bodys hemoglobin and 7-10% for smoker

TLV 35ppm STEL 200ppm (15min) ALD - 0.1%

CO has a 210x greater affinity for Hb than O2 does

Carbon Monoxide PoisoningTreatment: Artificial Respiration with pure O2 to promote displacement of CO

Carboxyhemoblobin ConcentrationSymptoms0-10%None20-30%Slight headache, exertional dyspnea30-40%Throbbing headache, fatigue, dizziness, SOB40-60%Severe headache, weakness, dizziness, confusion, dimness of vision (some have a cherry red appearance)>60%Convulsions, coma, Respiratory collapse leading to death

Competition for Essential receptors (cont)B. Turbocurare/pancuroniumCause a competition between the poison and Ach at the skeletal muscle endplate. Treatment: Cholinesterase Inhibitors (i.e. Neostigmine and physostigmine) Administration of ACH alone ineffective

C. CoumarinAnticoagulant that interferes with synthesis of coagulation factors II, VII, IX and X. Treatment: Vitamin K

D. OpiatesCompetition at opiate receptors with antagonists like naloxone and naltrexone.

6. Repair or Bypass effect of poisonA. Nitrites/sulfa drugsConverts hemoglobin into methemoglobin, which reduces the ability of the blood to carry O2. Methylene blue causes a direct reduction of methhemoglobin back to hemoglobin.

B. DigitalisToxic effects include GI disturbances, neurologic, disorders and cardiac arrhythmias. Give antidote of DigibindC. 5-Fluorouracil and 5-fluodeoxyuridineAntitumor agents used to decrease DNA synthesis. Thymidine is a specific and effective antidote.

7. Blockade of receptors responsible for Toxic EffectsThe toxic action and the therapeutic action are mediate by different receptors.

A. AnticholinesterasesFound in pesticides and chemical warfare agents. increases level of acetylcholine resulting in Cholinomimetic effectsAtropine blocks muscarinic receptors to block the effect of the ACHe inhibitors. (anticholinesterases)

Toxicology

ToxidromesToxidromes are clinical syndromes that are essential for the successful recognition of poisoning patterns sindroma toksik.

The most important toxidromes, clinically, are:

Sympathomimetics Sedative Hypnotics Opiates AnticholinergicsCholinergics Tricyclics (TCAs)Salicylates

Sympathomimetic Toxidrome

CNSAgitation, hallucinations, paranoiaRespiration--PupilsMydriasisOtherSeizure, hypertension, tremor, hyperreflexia, hyperthermiaDrugsCocaine, amphetamines, PCP

Sedative/Hypnotic Toxidrome

CNSComaRespirationDecreasedPupilsMydriasisOtherHypothermia, decrease reflexes, hypotensionDrugsAlcohol, barbiturates, benzodiazepines

Opioid/Opiate

CNSComaRespirationDepressionPupilsPinpointOtherHypothermia, hypotension, triad, histamine releaseDrugsOpiates, morphine, codeine, propoxyphene, oxycodone, hydrocodone

Anticholinergic Toxidrome

CNSAgitationRespiration---PupilsMydriasisOtherFever, dry skin, flushing, urinary retention (ACS) [Hot, dry, mad, red, blind]DrugsAnticholinergics, antidepressants

Cholinergic Toxidrome

CNSComa (not quaternary)Respiration---PupilsPPPOtherFasciculation, incontinence, salivation, wheezing, lacrimation, bradycardia (SLUDE)DrugsOrganophosphates, carbamates, nicotine

Tricyclic Antidepressant Toxidrome

CNSComa agitationRespiration----PupilsMydriasisOtherArrythmias, convulsions, hypotension, mycoclonus, hyperthermiasDrugsTCAs, amipramine, imipramine, desipramine

Salicylate Toxidrome

CNSVariable up or downRespirationCan increase or normalPupils-----OtherDiaphoresis, tinnitis, agitation, alkalosis (early), acidosis (late), feverDrugsASA, aspirin, (salicylates)

2. BaseSpecific Poisons Frequently Encountered

SourceLye, liquid plumber, oven cleanerSignsSwallowing is painful and difficult, vomitus thick and slimy and may contain blood, shock, esophageal strictures, causes progressive damage25% mortalityTreatmentABCs, demulcents, lots of water, analgesics, steroids, antibiotics, no lavage or emetics

Differences between acids and BasesAcids

1. Immediate pain in buccal cavity and esophagus

2. Less often swallowed than bases

No esophageal perforation

Bases

1. Primary cause of chemical burns

2. Rapidly penetrating liquefactive necrosis.

3. Primary effects on esophagus and only 20% on stomach.

4. Esophageal damage severe including perforation.

3. OpiatesSpecific Poisons Frequently Encountered

SourceHeroin, morphine, oxycodone, hydrocodoneSignsBilateral miosis (PPP), CNS depression, apnea, decrease in body temperature, heart rate and respiratory depression/arrest. TreatmentABCs, Naloxone, gastric lavage and supportive care.

4. MeperidineSpecific Poisons Frequently Encountered

SourceDemerolSignsDilated pupils due to antimuscarinic effects, increase in HR, convulsions due to metabolite (nor-meperidine), respiratory depression/arrest, coma. Few fatalities with meperidine (tolerance). TreatmentABCs, Gastric lavage (if oral), diazepam for seizures and naloxone for depressive effects (not for tremors)

5. AtropineSpecific Poisons Frequently Encountered

SourceAtropine, Deadly Nightshade plantSignsDry mucous membranes, burning in throat, intense thirst, dilation of pupils, hot dry skin, hyperpyrexia, tachycardia, mania and delirium; death from respiratory failureHot, dry, mad, red and blind. TreatmentABCs, Lavage with 4% tannic acid, pilocarpine or physostigmine, aspirin (antipyretic) and alcohol sponges.

6. BarbituratesSpecific Poisons Frequently Encountered

SourceSuicide, automatism (forget you already took your dose) SignsCNS depression (progressive), drowsiness, shallow rapid respiration, CV collapse, low body temp and death due to respiratory depressionTreatmentABCs, Lavage with KmNO4, charcoal, alkaline diuresis (NaHCO3), hemodialysis (long acting barbs)

7. BenzodiazepinesSpecific Poisons Frequently Encountered

SourceDiazepam (long acting), alprazolam (short acting), triazolam (ultra short)SignsSame as barbiturates, rarely fatal unless taken with ETOH or other CNS depressant due to synergistic CNS depressionTreatmentABCs, emesis, gastric lavage, antidote: flumazenil short T1/2 may require multiple doses.

8. EthanolSpecific Poisons Frequently Encountered

SourceWhisky, wine, beer etc.SignsOdor on breath, impaired motor coordination, slurred speech, dehydration, gastritis, hypothermia, coma and death due to respiratory depressionTreatmentABCs, gastric lavage with bicarb, caffeine, hemodialysis (if >500mg%)

9. NeurolepticsSpecific Poisons Frequently Encountered

SourceMajor tranquilizers, antipsychotic agents (phenothiazines, thioxanthenes)SignsExtrapyramidal signs (EPS), hyperactive, tardive dyskinesia, CNS depression, seizures, hypotension, poikilothermiaTreatmentABCs, lavage (even hours hours later due to lower gastric motility), Treat arrhythmias as needed and diphenhydramine for EPS.

10. KeroseneSpecific Poisons Frequently Encountered

SourceIlluminating fuels, paint thinnersSignsEuphoria, burning in the chest, headache, weakness, drowsiness, convulsions, death due to respiratory arrest or ventricular fibrillationTreatmentABCs, large amounts of water, olive oil and saline cathartic, antibiotics, corticosteroids to reduce kerosene pneumonitis, no emetics or lavage.

11. ParathionSpecific Poisons Frequently Encountered

SourceOrganophosphate insecticideSignsSLUDE, fixed pin point pupils, loss of muscle coordination, muscle twitching, mental confusion, death due to respiratory arrest. TreatmentABCs, atropine, pralidoxine, lavage with 5% NaHCO3, wash affected areas, avoid morphine, barbituates and phenothiazines.

12. SalicylatesSpecific Poisons Frequently Encountered

SourceAspirin, percodanSignsDeep and rapid breathing, tinnitis, hallucinations, convulsions, resp. alkalosis (adult), metabolic acidosis (child), respiratory and CV collapseSerum level > 400mcg/mlTreatmentABCs, emetics, gastric lavage 5% NaHCO3, monitor pH, barbituates or benzos for seizures, hemodialysis if needed.

13. AcetaminophenSpecific Poisons Frequently Encountered

SourceTylenol, Vicodin, PercocetSignsAfter depletion of glutathione, nausea, vomiting, elevated liver enzymes (SGOT, SGPT, bilirubin), hepatic necrosis and death due to hepatic failure. TreatmentABCs, emetics, lavage, charcoal, N-acetylcysteine to restore glutathione earlier the better (grapefruit juice), monitor liver enzymes.

Acetaminophen Blood level EffectsPlasma levels of > 250mcg/ml at 3-5 hours post ingestion.

Rumack Matthew nomogram Probable toxicity

Children (9-10yrs) are less susceptible to the toxic effect of acetaminophen.

14. CocaineSpecific Poisons Frequently Encountered

SourceCoca plant, cocaine, crackSignsCNS stimulation, euphoria, cocaine bugs,halo lights, seizures, hallucinations, cardiac arrhythmias lead to cardiac arrest TreatmentABCs, charcoal, diazepam (seizures), lidocaine (arrhythmias), no dialysis or lavage.

Forms of cocaineCrack (type of free base)Baking soda, hard rock, volatile

Cocaine HCL (salt)Non-volatile, white crystalline powder

15. Phencyclidine (PCP)Specific Poisons Frequently Encountered

SourceAngel dust, Sernyl (old veterinary general anesthetic)SignsPsychosis, sensory analgesia, rotary nystagmus, hypertension, hyperactive reflexes, seizures. TreatmentLock in padded room, diazepam, antipsychotic agent (Haloperidol), cranberry juice (100x increase in excretion)

16. Tricyclic AntidepressantsSpecific Poisons Frequently Encountered

SourceAmitryptyline, imipramine, doxepinSignsAnticholinergic Syndrome (ACS) [dry mouth, mydriasis, hyperpyrexia, increase HR, decreased GI motility] hallucinations, seizures, respiratory depression, cardiac arrhythmias (quinidine-like effect)TreatmentABCs, emesis, lavage, physostigmine (till ACS stops), treat arrhythmias (phenytoin, bicarb)

17. MethaqualoneSpecific Poisons Frequently Encountered

SourceQuaalude, ludes (sedative/hypnotic)SignsDepersonalization, tongue discoloration, dizziness, nausea, hemorrhage, abstinence syndromeTreatmentABCs, emesis, lavage, hemodialysis

18. DigoxinSpecific Poisons Frequently Encountered

SourceDigitalis, digoxinSignsHeadache, nausea, vomiting, blurred vision, delirium, slowed pulse, cardiac irregularities, hypokalemia, arrhythmias, ventricular fibrillationlow TITreatmentABCs Dose adjustment, drug withdrawal, lavage, charcoal, emesis, Digibind, K+ supplement, treat arrhythmias (lidocaine, phenytoin, propranolol)

19. PhenytoinSpecific Poisons Frequently Encountered

SourceDilantinSignsNystagmus, ataxia, drowsiness, seizuresdeath is rare but is usually due to ventricular fibrillation and cardiac arrest. Toxicity >25mcg/mlTreatmentABCs, emesis (if conscious), lavage, charcoal, cathartics, discontinue phenytoin

20. TheophyllineSpecific Poisons Frequently Encountered

SourceAminophyllineSignsCNS stimulation, hyperreflexia, cardiac arrhythmia, convulsions, death is due to respiratory failure. Toxic plasma level >20mcg/ml. TreatmentABCs, discontinue drug, charcoal, emesis, fluids and anticonvulsants (diazepam) as needed.

21. Dioxin (2,3,7,8 TCDD)

SourceHerbicides, cigarette smoke, smoke from burning trash and debrisSignsChloracne (small yellow comedones) mainly on the face can last 30 years, hepatomegaly, fatigue, irritability, blurred vision, porphyria cutanea tarda (slate gray skin pigmentation), limited systemic effects, Death??TreatmentABCs, alkaline diuresis, If recent ingestion: [emesis, lavage, charcoal, cathartic], mainly supportive care

Dioxin PoisoningViktor Yushchenko: Ukraine President

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