2012 Toxicology

Principles of ToxicologyPrinciples of Toxicology

Endang MahatiEndang Mahati

DefinitionsDefinitions

ToxicologyToxicology

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

So what is a poison?So what is a poison?

What is a poison?What is a poison?

PoisonPoison Any substance which cause a harmful effectAny substance which cause a harmful effect when when

administered either by accident or by design to a administered either by accident or by design to a living organismliving organism

Poisoning is Poisoning is quantitative conceptquantitative concept

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

What is Toxicology?What is Toxicology?

1. Primarily a 1. Primarily a multidisciplinary multidisciplinary science that is science that is based on other sciences including:based on other sciences including:

PharmacologyPharmacologyPathologyPathology (disease/death) (disease/death)ChemistryChemistry EpidemiologyEpidemiology Hazard – potential for harmHazard – potential for harm Risk – probability of producing HarmRisk – probability of producing Harm

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

Dose Response Curve related to Dose Response Curve related to ToxicityToxicity

Dose/Time PrincipleDose/Time Principle

While While dosedose is the primary determinant of is the primary determinant of toxicity, effects of chemicals on the body toxicity, effects of chemicals on the body are also a function of the are also a function of the length of timelength of time such substances are present. such substances are present.

Blood Plasma Level ToxicityBlood Plasma Level Toxicity

More simplyMore simply

Dose makes the poisonDose makes the poison

It is the primary determinant of ToxicityIt is the primary determinant of Toxicity

23/02/201023/02/2010Mgatidjan, INTROTOXIC-10Mgatidjan, INTROTOXIC-10 99

inhalation orally intramuscularly intravenously

TOXIC SUBSTANCE

mucous membrane cells

endothelial cell

liver

endothelial cell

systemic circulating blood

site of action

effects

other tissues liver(metabolism)

kidney(excretion)

feses urine

portal vein

Toxicology in Modern TimesToxicology in Modern Times

During the last 5 decades, toxicology has During the last 5 decades, toxicology has taken on new meaningtaken on new meaning

Thalidomide tragedyThalidomide tragedy (1950’s) - phocomelias (1950’s) - phocomelias and other birth defectsand other birth defects

Silent Spring – Rachel Carson, DDTSilent Spring – Rachel Carson, DDT TV – CSI, QuincyTV – CSI, Quincy Increasing Drug AbuseIncreasing Drug Abuse Medical Malpractice suits (last 30 years)Medical Malpractice suits (last 30 years)


Amelia total

Importance of ToxicologyImportance of Toxicology 1. Important because chemicals are 1. Important because chemicals are

responsible for at least 10,000 accidental responsible for at least 10,000 accidental deaths annually. deaths annually.

ChildrenChildren under 5 years old are usually poisoned under 5 years old are usually poisoned by:by:

Plants, cosmetics, salicylates, hydrocarbons, Plants, cosmetics, salicylates, hydrocarbons, detergents and acetaminophen.detergents and acetaminophen.

AdultAdult poisoning usually involves: poisoning usually involves: Barbituates, carbon monoxide, salicylates, Barbituates, carbon monoxide, salicylates,

alcohol, narcotics and acetaminophenalcohol, narcotics and acetaminophen

2. Work place accidents associated with 2. Work place accidents associated with chemicals. chemicals.

A. Drugs (alcohol, cocaine, marijuana, etc.)A. Drugs (alcohol, cocaine, marijuana, etc.)B. Manufactured Products B. Manufactured Products

Importance of Toxicology (con’t)Importance of Toxicology (con’t)

3. Litigation3. LitigationA. ie. Drug/alcohol related accidentsA. ie. Drug/alcohol related accidents

4. Causation4. CausationA. Evidence of cause and effect based on A. Evidence of cause and effect based on exposure and dose. exposure and dose.

Toxicological TermsToxicological Terms

1. 1. LDLD5050 – dose at which 50% die – dose at which 50% die

Only animalsOnly animals

TDTD5050 – dose at which 50% have toxicity – dose at which 50% have toxicity

Measure of harmfulnessMeasure of harmfulness

2. 2. T.I.T.I. – Therapeutic Index – Therapeutic Index TDTD50 50 / ED/ ED5050

The larger the number, the safer the drugThe larger the number, the safer the drug

Measure of safetyMeasure of safety

3. 3. Acute ToxicityAcute Toxicity Single dose within 24 hrsSingle dose within 24 hrs

Defines intrinsic toxicityDefines intrinsic toxicity

Toxicological Terms (con’t)Toxicological Terms (con’t)

4. 4. Chronic ToxicityChronic Toxicity Daily exposure for up to a lifetimeDaily exposure for up to a lifetime

5. 5. TLVTLV – Threshold Limit Value – Threshold Limit Value

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

NOELNOEL – no observable effect level – no observable effect level

ADIADI – allowable daily intake – allowable daily intake

ADI = (NOEL) / xADI = (NOEL) / x

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

Toxicological Terms (con’t)Toxicological Terms (con’t)

6. 6. STELSTEL – Short term exposure level – Short term exposure level 4x a day, with the average being equal to the TLV4x a day, with the average being equal to the TLV

7.7. ALD ALD – Average Lethal Dose – Average Lethal DoseEstimated from accidental deaths in humansEstimated from accidental deaths in humans

8. 8. ToxiconToxiconToxic principle of a given chemical entityToxic principle of a given chemical entity

Tylenol – quinone imineTylenol – quinone imine CClCCl44 – free radicals – free radicals

9. Primary Determinant of Toxicology9. Primary Determinant of ToxicologyDose, Dose and DoseDose, Dose and Dose

Selective vs. Nonselective ToxicitySelective vs. Nonselective Toxicity

NonselectiveNonselectiveNearly all chemical are nonselective in their Nearly all chemical are nonselective in their actionsactionsFew chemicals are sufficiently selective to harm Few chemicals are sufficiently selective to harm certain cellscertain cells

SelectiveSelectiveOne man’s poison is another man’s pill. One man’s poison is another man’s pill. What may be harmful to one specimen may be What may be harmful to one specimen may be relatively harmless to another. relatively harmless to another. Garden spray Garden spray

II. Management of a PoisoningII. Management of a Poisoning

Immediate measures are called for in Immediate measures are called for in every case of poisoning regardless of every case of poisoning regardless of cause. cause.

1. Support Vital Functions1. Support Vital Functions

2. ID drug poisoning as the problem2. ID drug poisoning as the problem

3. Reduce the amount of drug in the body 3. Reduce the amount of drug in the body

Support vital life functions (ABC’s)Support vital life functions (ABC’s)

AAirwayirway – endotracheal tube if needed, watch for fluid – endotracheal tube if needed, watch for fluid accumulation in airway (i.e.. Aspiration of vomit)accumulation in airway (i.e.. Aspiration of vomit)

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

CCirculationirculation – Monitor ECG, watch for arrhythmias, cardiac – Monitor ECG, watch for arrhythmias, cardiac arrest and shockarrest and shock

Vasogenic ShockVasogenic Shock – faulty vasomotor tone, increase capillary – faulty vasomotor tone, increase capillary permeability. permeability.

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

General Treatment of a General Treatment of a Comatose PatientComatose Patient

There are several general antidotes that There are several general antidotes that are used in the treatment of comatose are used in the treatment of comatose patients upon presentation at the hospital. patients upon presentation at the hospital.

What are they?What are they?

Supportive Drug TherapySupportive Drug Therapy

Treat all patients who come into the Treat all patients who come into the hospital in a coma with hospital in a coma with glucose, insulin glucose, insulin and naloxoneand naloxone. .

Use drugs to treat emergent conditions, ie:Use drugs to treat emergent conditions, ie:SeizuresSeizures – anticonvulsants (valium) – anticonvulsants (valium)

Cardiac DysrhythmiasCardiac Dysrhythmias – anti-arrhythmias (lidocaine, – anti-arrhythmias (lidocaine, digoxin)digoxin)

Severe AgitationSevere Agitation – anxiolytics (benzo) – anxiolytics (benzo)

How to ID the poison?How to ID the poison?

IDID the poison the poison

1. Patient history1. Patient history

2. Laboratory testing2. Laboratory testing

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

Identification of the Poison Identification of the Poison ((Sample TypesSample Types))

UrineUrine - 1 - 1stst choice – easier to detect presence of choice – easier to detect presence of the drug due to the accumulation of drug in the the drug due to the accumulation of drug in the urine. urine.

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

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

Identify Poison (Identify Poison (TestsTests))Urine testsUrine tests

Immunoassay (Immunoassay (EMITEMIT, ELISA) – semiquantitative tests , ELISA) – semiquantitative tests usually with automated instrumentation. Can detect usually with automated instrumentation. Can detect cannabinoids, amphetamines, cocaine, barbs etc. cannabinoids, amphetamines, cocaine, barbs etc.

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

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

Can be done in 2 hoursCan be done in 2 hours

Removal of the Drug (Removal of the Drug (EmesisEmesis))

Utilize syrup of Ipecac to Induce Utilize syrup of Ipecac to Induce emesis to remove unabsorbed emesis to remove unabsorbed drug. drug.

Emesis inducersEmesis inducers MechanicalMechanical ApomorphineApomorphine Syrup of ipecacSyrup of ipecac Contraindications? Contraindications?

Contraindications of EmesisContraindications of Emesis

Emesis is contraindicated in cases of:Emesis is contraindicated in cases of:Petroleum hydrocarbon solvent – chemical Petroleum hydrocarbon solvent – chemical pneumonitispneumonitis

Caustic acid or alkali agent (rupture)Caustic acid or alkali agent (rupture)

Seizing PatientSeizing Patient

Comatose PatientComatose Patient

Removal of the Drug Removal of the Drug ((Gastric LavageGastric Lavage))

Gastric Lavage – washing of Gastric Lavage – washing of the stomach. (the stomach. (early tx.)early tx.)

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

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

Activated CharcoalActivated Charcoal//CatharticsCathartics

Activated CharcoalActivated Charcoal (AC) (AC)Used to bind compounds and to prevent absorption in the Used to bind compounds and to prevent absorption in the GI tracts. (GI tracts. (many drugsmany drugs))

Contraindicated with caustic agents and petroleum Contraindicated with caustic agents and petroleum distillates due to the lack of absorption of these agents by distillates due to the lack of absorption of these agents by the charcoal and risk of vomiting associated with the the charcoal and risk of vomiting associated with the charcoal charcoal

Order of use of charcoal and ipecacOrder of use of charcoal and ipecac

CatharticsCatharticsPromotes rapid passage of poison through the GI tractPromotes rapid passage of poison through the GI tract

Counteracts the constipative effects of ACCounteracts the constipative effects of AC

I.E. sorbitol, Mg Citrate, I.E. sorbitol, Mg Citrate, Mg SulfateMg Sulfate

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

DiuresisDiuresis – often used in conjunction with urine pH alteration – often used in conjunction with urine pH alteration

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

DemulcentsDemulcents – soothes mucous membranes and coats the – soothes mucous membranes and coats the stomach, i.e. milk of magnesiastomach, i.e. milk of magnesia

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

B. B. Antidotal Treatments (Antidotal Treatments (1. Complexation)1. Complexation)

A. Heavy MetalsA. Heavy MetalsChelators (Chelators (BAL, EDTABAL, EDTA) complexes with the metals ) complexes with the metals making them inertmaking them inert

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

C. Toxins- C. Toxins- Botulinum Toxin ALD- < 0.5mcg LDBotulinum Toxin ALD- < 0.5mcg LD5050=10ng/kg=10ng/kg

Most potent poison known, rapidly absorbed and Most potent poison known, rapidly absorbed and prevents ACH release from nerve terminalsprevents ACH release from nerve terminalsTx: ABCs, lavage, emesis, charcoal,Trivalent anti-toxinTx: ABCs, lavage, emesis, charcoal,Trivalent anti-toxinMortality of 70% to 10% with treatmentMortality of 70% to 10% with treatment

Complexation (con’t)Complexation (con’t)D. OrganophosphatesD. Organophosphates

PralidoximePralidoxime is a nucleophillic reagent that ties up is a nucleophillic reagent that ties up the organophosphates and permits its excretion. the organophosphates and permits its excretion.

E. CyanideE. CyanideBinds to cytochrome oxidase, LDBinds to cytochrome oxidase, LD5050= 2mg/kg = 2mg/kg

Causes death in 1 to 15 minutes at high doses.Causes death in 1 to 15 minutes at high doses. Chelator is made in the body, Chelator is made in the body, methemoglobin methemoglobin (Fe(Fe3+3+))

Give Give Amyl NitritesAmyl Nitrites and and Na NitriteNa Nitrite with O with O22 and whole and whole blood to convert hemoglobin to blood to convert hemoglobin to methemoglobin methemoglobin (LD(LD50 50 increases 5 fold)increases 5 fold) . .

Antidotal Treatments (con’t)Antidotal Treatments (con’t)

2.2. Enhancement of metabolic conversion to a Enhancement of metabolic conversion to a safer formsafer form

Example: Cyanide Poisoning and thiosulfate Example: Cyanide Poisoning and thiosulfate treatment (LDtreatment (LD50 50 increases 3 fold)increases 3 fold)

CNCN- - SCNSCNRhodanese

SulfurTreatment: Give

Thiosulfate (Sulfur source)

Antidotal Treatments (con’t)Antidotal Treatments (con’t)

3. Inhibition of metabolic conversion to 3. Inhibition of metabolic conversion to toxic forms. toxic forms.

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

4. Accelerating rate of excretion4. Accelerating rate of excretion Compete with reabsorption (Compete with reabsorption (Renal TubulesRenal Tubules). ). I.e. For SrI.e. For Sr2+ 2+ or Raor Ra2+ 2+ radiation give radiation give CaCa2+2+;; For Br For Br1- 1-

poisoning give poisoning give ClCl1-1- to aid in excretion. to aid in excretion.

5. Competition for Essential receptors5. Competition for Essential receptors

A. Carbon MonoxideA. Carbon MonoxideCO is found in cigarette smoke (5%) and auto CO is found in cigarette smoke (5%) and auto exhaust (9%). exhaust (9%). Not in natural gas itself. Not in natural gas itself.

Commonly used as a means of suicide; over 5000 Commonly used as a means of suicide; over 5000 fatalities a year from CO poisoning. fatalities a year from CO poisoning.

Carboxyhemoglobin is found in very small amounts Carboxyhemoglobin is found in very small amounts in non-smokers ~2.5% of the body’s hemoglobin and in non-smokers ~2.5% of the body’s hemoglobin and 7-10% for smoker7-10% for smoker

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

CO has a 210x greater affinity for Hb than OCO has a 210x greater affinity for Hb than O22 does does

Carbon Monoxide PoisoningCarbon Monoxide PoisoningCarboxyhemoblobin Carboxyhemoblobin

ConcentrationConcentrationSymptomsSymptoms

0-10%0-10% NoneNone

20-30%20-30% Slight headache, exertional dyspneaSlight headache, exertional dyspnea

30-40%30-40% Throbbing headache, fatigue, dizziness, Throbbing headache, fatigue, dizziness, SOBSOB

40-60%40-60% Severe headache, weakness, dizziness, Severe headache, weakness, dizziness, confusion, dimness of vision (some have a confusion, dimness of vision (some have a

cherry red appearancecherry red appearance))

>60%>60% Convulsions, coma, Respiratory collapse Convulsions, coma, Respiratory collapse leading to deathleading to death

Treatment: Artificial Respiration with pure O2 to promote displacement of CO

Competition for Essential receptors Competition for Essential receptors (con’t)(con’t)

B. Turbocurare/pancuroniumB. Turbocurare/pancuroniumCause a competition between the poison and Ach at the Cause a competition between the poison and Ach at the skeletal muscle endplate. skeletal muscle endplate. Treatment: Treatment: Cholinesterase Inhibitors Cholinesterase Inhibitors (i.e. Neostigmine (i.e. Neostigmine and physostigmine) and physostigmine) Administration of ACH alone ineffectiveAdministration of ACH alone ineffective

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

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

6. Repair or Bypass effect of poison6. Repair or Bypass effect of poison

A. Nitrites/sulfa drugsA. Nitrites/sulfa drugsConverts hemoglobin into methemoglobin, which reduces Converts hemoglobin into methemoglobin, which reduces the ability of the blood to carry Othe ability of the blood to carry O22. .

Methylene blueMethylene blue causes a direct reduction of causes a direct reduction of methhemoglobin back to hemoglobin. methhemoglobin back to hemoglobin.

B. DigitalisB. DigitalisToxic effects include GI disturbances, neurologic, disorders Toxic effects include GI disturbances, neurologic, disorders and cardiac arrhythmias. and cardiac arrhythmias. Give antidote of Give antidote of DigibindDigibind

C. 5-Fluorouracil and 5-fluodeoxyuridineC. 5-Fluorouracil and 5-fluodeoxyuridineAntitumor agents used to decrease DNA synthesis. Antitumor agents used to decrease DNA synthesis. ThymidineThymidine is a specific and effective antidote. is a specific and effective antidote.

7. Blockade of receptors 7. Blockade of receptors responsible for Toxic Effectsresponsible for Toxic Effects

The toxic action and the therapeutic action The toxic action and the therapeutic action are mediate by different receptors. are mediate by different receptors.

AnticholinesterasesAnticholinesterasesFound in pesticides and chemical warfare agents. Found in pesticides and chemical warfare agents.

increases level of acetylcholine resulting in increases level of acetylcholine resulting in Cholinomimetic effectsCholinomimetic effects

Atropine Atropine blocks muscarinic receptors to block the blocks muscarinic receptors to block the effect of the ACHe inhibitors. (anticholinesterases)effect of the ACHe inhibitors. (anticholinesterases)

ToxicologyToxicology

ToxidromesToxidromes

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

The most important toxidromes, clinically, The most important toxidromes, clinically, are:are:

Sympathomimetics Sympathomimetics

Sedative Hypnotics Sedative Hypnotics

Opiates Opiates

AnticholinergicsAnticholinergics

Cholinergics Cholinergics

Tricyclics (TCAs)Tricyclics (TCAs)

SalicylatesSalicylates

Sympathomimetic ToxidromeSympathomimetic Toxidrome

CNS Agitation, hallucinations, paranoiaAgitation, hallucinations, paranoia

Respiration ----

Pupils MydriasisMydriasis

Other Seizure, hypertension, tremor, Seizure, hypertension, tremor, hyperreflexia, hyperthermiahyperreflexia, hyperthermia

Drugs Cocaine, amphetamines, PCPCocaine, amphetamines, PCP

Sedative/Hypnotic ToxidromeSedative/Hypnotic Toxidrome

CNS ComaComa

Respiration DecreasedDecreased


Other Hypothermia, decrease reflexes, Hypothermia, decrease reflexes, hypotensionhypotension

Drugs Alcohol, barbiturates, Alcohol, barbiturates, benzodiazepinesbenzodiazepines

Opioid/OpiateOpioid/Opiate

CNS ComaComa

Respiration DepressionDepression

Pupils PinpointPinpoint

Other Hypothermia, hypotension, triad, Hypothermia, hypotension, triad, histamine releasehistamine release

Drugs Opiates, morphine, codeine, Opiates, morphine, codeine, propoxyphene, oxycodone, propoxyphene, oxycodone, hydrocodonehydrocodone

Anticholinergic ToxidromeAnticholinergic Toxidrome

CNS AgitationAgitation

Respiration ------


Other Fever, dry skin, flushing, urinary Fever, dry skin, flushing, urinary retention (ACS) retention (ACS) [Hot, dry, mad, red, [Hot, dry, mad, red, blind]blind]

Drugs Anticholinergics, antidepressantsAnticholinergics, antidepressants

Cholinergic ToxidromeCholinergic Toxidrome

CNS Coma (not quaternary)Coma (not quaternary)

Respiration ------

Pupils PPPPPP

Other Fasciculation, incontinence, Fasciculation, incontinence, salivation, wheezing, lacrimation, salivation, wheezing, lacrimation, bradycardia (SLUDE)bradycardia (SLUDE)

Drugs Organophosphates, carbamates, Organophosphates, carbamates, nicotinenicotine

Tricyclic Antidepressant ToxidromeTricyclic Antidepressant Toxidrome

CNS Coma agitationComa agitation

Respiration --------


Other Arrythmias, convulsions, Arrythmias, convulsions, hypotension, mycoclonus, hypotension, mycoclonus, hyperthermiashyperthermias

Drugs TCA’s, amipramine, imipramine, TCA’s, amipramine, imipramine, desipraminedesipramine

Salicylate ToxidromeSalicylate Toxidrome

CNS Variable up or downVariable up or down

Respiration Can increase or normalCan increase or normal

Pupils ----------

Other Diaphoresis, tinnitis, agitation, Diaphoresis, tinnitis, agitation, alkalosis (early), acidosis (late), alkalosis (early), acidosis (late), feverfever

Drugs ASA, aspirin, (salicylates)ASA, aspirin, (salicylates)

SourceSource Lye, liquid plumber, oven cleanerLye, liquid plumber, oven cleaner

SignsSigns Swallowing is painful and difficult, Swallowing is painful and difficult, vomitus thick and slimyvomitus thick and slimy and may and may contain blood, shock, esophageal contain blood, shock, esophageal strictures, causes progressive strictures, causes progressive damage…25% mortalitydamage…25% mortality

TreatmentTreatment ABC’s, demulcents, lots of water, ABC’s, demulcents, lots of water, analgesics, steroids, antibiotics, no analgesics, steroids, antibiotics, no lavage or emeticslavage or emetics

2. Base

Specific Poisons Frequently Specific Poisons Frequently EncounteredEncountered

Differences between acids and BasesDifferences between acids and Bases

AcidsAcids

1. Immediate pain in 1. Immediate pain in buccal cavity and buccal cavity and esophagusesophagus

2. Less often 2. Less often swallowed than basesswallowed than bases

No esophageal No esophageal perforationperforation

BasesBases

1. Primary cause of 1. Primary cause of chemical burnschemical burns

2. Rapidly penetrating 2. Rapidly penetrating liquefactive necrosis. liquefactive necrosis.

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

4. Esophageal damage 4. Esophageal damage severe including severe including perforation. perforation.

SourceSource Heroin, morphine, oxycodone, Heroin, morphine, oxycodone, hydrocodonehydrocodone

SignsSigns Bilateral miosis (Bilateral miosis (PPPPPP), CNS ), CNS depression, apnea, decrease in body depression, apnea, decrease in body temperature, heart rate and temperature, heart rate and respiratory depression/arrestrespiratory depression/arrest. .

TreatmentTreatment ABC’s, Naloxone, gastric lavage and ABC’s, Naloxone, gastric lavage and supportive care. supportive care.

3. Opiates


SourceSource DemerolDemerol

SignsSigns Dilated pupilsDilated pupils due to antimuscarinic due to antimuscarinic effects, effects, increase in HRincrease in HR, convulsions , convulsions due to metabolite (nor-meperidine), due to metabolite (nor-meperidine), respiratory depression/arrest, coma. respiratory depression/arrest, coma. Few fatalities with meperidine Few fatalities with meperidine (tolerance). (tolerance).

TreatmentTreatment ABC’s, Gastric lavage (if oral), ABC’s, Gastric lavage (if oral), diazepam for seizures and naloxone diazepam for seizures and naloxone for depressive effects (not for tremors) for depressive effects (not for tremors)

4. Meperidine


SourceSource Atropine, Deadly NightshadeAtropine, Deadly Nightshade plantplant

SignsSigns Dry mucous membranes, burning in Dry mucous membranes, burning in throat, intense thirst, dilation of pupils, throat, intense thirst, dilation of pupils, hot dry skin, hyperpyrexia, tachycardia, hot dry skin, hyperpyrexia, tachycardia, mania and delirium; death from mania and delirium; death from respiratory failurerespiratory failure

Hot, dry, mad, red and blind. Hot, dry, mad, red and blind.

TreatmentTreatment ABC’s, Lavage with 4% tannic acid, ABC’s, Lavage with 4% tannic acid, pilocarpine or physostigmine, aspirin pilocarpine or physostigmine, aspirin (antipyretic) and alcohol sponges. (antipyretic) and alcohol sponges.

5. Atropine


SourceSource Suicide, Suicide, automatismautomatism (forget you (forget you already took your dose) already took your dose)

SignsSigns CNS depression (progressive), CNS depression (progressive), drowsiness, shallow rapid respiration, drowsiness, shallow rapid respiration, CV collapse, low body temp and death CV collapse, low body temp and death due to respiratory depressiondue to respiratory depression

TreatmentTreatment ABC’s, Lavage with KmNOABC’s, Lavage with KmNO44, charcoal, , charcoal,

alkaline diuresis (NaHCOalkaline diuresis (NaHCO33), ),

hemodialysis (long acting barbs)hemodialysis (long acting barbs)

6. Barbiturates


SourceSource Diazepam (long acting), alprazolam Diazepam (long acting), alprazolam (short acting), triazolam (ultra short)(short acting), triazolam (ultra short)

SignsSigns Same as barbiturates, Same as barbiturates, rarely fatalrarely fatal unless taken with ETOH or other CNS unless taken with ETOH or other CNS depressant due to synergistic CNS depressant due to synergistic CNS depressiondepression

TreatmentTreatment ABC’s, emesis, gastric lavage, ABC’s, emesis, gastric lavage, antidote:antidote: flumazenil flumazenil short Tshort T1/21/2 may may

require multiple doses. require multiple doses.

7. Benzodiazepines


SourceSource Whisky, wine, beer etc.Whisky, wine, beer etc.

SignsSigns Odor on breath, impaired motor Odor on breath, impaired motor coordination, slurred speech, coordination, slurred speech, dehydration, gastritis, hypothermia, dehydration, gastritis, hypothermia, coma and death due to respiratory coma and death due to respiratory depressiondepression

TreatmentTreatment ABC’s, gastric lavage with bicarb, ABC’s, gastric lavage with bicarb, caffeine, hemodialysis (if >500mg%)caffeine, hemodialysis (if >500mg%)

8. Ethanol


SourceSource Major tranquilizers, antipsychotic agents Major tranquilizers, antipsychotic agents (phenothiazines, thioxanthenes)(phenothiazines, thioxanthenes)

SignsSigns Extrapyramidal signs (EPS), Extrapyramidal signs (EPS), hyperactive, hyperactive, tardive dyskinesiatardive dyskinesia, CNS , CNS depression, seizures, hypotension, depression, seizures, hypotension, poikilothermiapoikilothermia

TreatmentTreatment ABC’s, lavage (even hours hours later ABC’s, lavage (even hours hours later due to lower gastric motility), Treat due to lower gastric motility), Treat arrhythmias as needed and arrhythmias as needed and diphenhydramine for EPS. diphenhydramine for EPS.

9. Neuroleptics


SourceSource Illuminating fuels, paint thinnersIlluminating fuels, paint thinners

SignsSigns EuphoriaEuphoria, burning in the chest, , burning in the chest, headache, weakness, drowsiness, headache, weakness, drowsiness, convulsions, death due to respiratory convulsions, death due to respiratory arrest or arrest or ventricular fibrillationventricular fibrillation

TreatmentTreatment ABC’s, large amounts of water, olive ABC’s, large amounts of water, olive oil and saline cathartic, antibiotics, oil and saline cathartic, antibiotics, corticosteroids to reduce kerosene corticosteroids to reduce kerosene pneumonitis, no emetics or lavage. pneumonitis, no emetics or lavage.

10. Kerosene


SourceSource Organophosphate insecticideOrganophosphate insecticide

SignsSigns SLUDESLUDE, fixed pin point pupils, loss of , fixed pin point pupils, loss of muscle coordination, muscle twitching, muscle coordination, muscle twitching, mental confusion, death due to mental confusion, death due to respiratory arrest. respiratory arrest.

TreatmentTreatment ABC’s, atropine, pralidoxine, lavage ABC’s, atropine, pralidoxine, lavage with 5% NaHCOwith 5% NaHCO33, wash affected , wash affected

areas, avoid morphine, barbituates areas, avoid morphine, barbituates and phenothiazines. and phenothiazines.

11. Parathion


SourceSource Aspirin, percodanAspirin, percodan

SignsSigns Deep and rapid breathingDeep and rapid breathing, , tinnitistinnitis, , hallucinations, convulsions, resp. hallucinations, convulsions, resp. alkalosis (adult), metabolic acidosis alkalosis (adult), metabolic acidosis (child), respiratory and CV collapse(child), respiratory and CV collapse

Serum level > 400mcg/mlSerum level > 400mcg/ml

TreatmentTreatment ABC’s, emetics, gastric lavage 5% ABC’s, emetics, gastric lavage 5% NaHCONaHCO33, monitor pH, barbituates or , monitor pH, barbituates or

benzo’s for seizures, hemodialysis if benzo’s for seizures, hemodialysis if needed. needed.

12. Salicylates


SourceSource Tylenol, Vicodin, PercocetTylenol, Vicodin, Percocet

SignsSigns After depletion of glutathione, nausea, After depletion of glutathione, nausea, vomiting, elevated liver enzymes vomiting, elevated liver enzymes (SGOT, SGPT, bilirubin), hepatic (SGOT, SGPT, bilirubin), hepatic necrosis and death due to hepatic necrosis and death due to hepatic failure. failure.

TreatmentTreatment ABCs, emetics, lavage, charcoal, N-ABCs, emetics, lavage, charcoal, N-acetylcysteine to restore glutathione acetylcysteine to restore glutathione earlier the better (grapefruit juice), earlier the better (grapefruit juice), monitor liver enzymes. monitor liver enzymes.

13. Acetaminophen


Acetaminophen Blood level Acetaminophen Blood level EffectsEffects

Plasma levels of > 250mcg/ml at 3-5 hours Plasma levels of > 250mcg/ml at 3-5 hours post ingestion. post ingestion.

Rumack Matthew nomogram – Probable Rumack Matthew nomogram – Probable toxicitytoxicity

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

SourceSource Coca plant, cocaine, crackCoca plant, cocaine, crack

SignsSigns CNS stimulation, euphoria, “cocaine CNS stimulation, euphoria, “cocaine bugs”,halo lights, seizures, hallucinations, bugs”,halo lights, seizures, hallucinations, cardiac arrhythmias lead to cardiac cardiac arrhythmias lead to cardiac arrest arrest

TreatmentTreatment ABC’s, charcoal, diazepam (seizures), ABC’s, charcoal, diazepam (seizures), lidocaine (arrhythmias), no dialysis or lidocaine (arrhythmias), no dialysis or lavage. lavage.

14. Cocaine


Forms of cocaineForms of cocaine

Crack (type of free base)Crack (type of free base)Baking soda, hard rock, volatileBaking soda, hard rock, volatile

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

SourceSource Angel dust, Sernyl (old veterinary Angel dust, Sernyl (old veterinary general anesthetic)general anesthetic)

SignsSigns Psychosis, sensory analgesia, Psychosis, sensory analgesia, rotary rotary nystagmusnystagmus, hypertension, hyperactive , hypertension, hyperactive reflexes, seizures. reflexes, seizures.

TreatmentTreatment Lock in padded room, diazepam, Lock in padded room, diazepam, antipsychotic agent (Haloperidol), antipsychotic agent (Haloperidol), cranberry juice (100x increase in cranberry juice (100x increase in excretion)excretion)

15. Phencyclidine (PCP)


SourceSource Amitryptyline, imipramine, doxepinAmitryptyline, imipramine, doxepin

SignsSigns Anticholinergic Syndrome (ACS) Anticholinergic Syndrome (ACS) [dry [dry mouth, mydriasis, hyperpyrexia, increase mouth, mydriasis, hyperpyrexia, increase HR, decreased GI motility]HR, decreased GI motility] hallucinations, hallucinations, seizures, respiratory depression, cardiac seizures, respiratory depression, cardiac arrhythmias (quinidine-like effect)arrhythmias (quinidine-like effect)

TreatmentTreatment ABC’s, emesis, lavage, physostigmine ABC’s, emesis, lavage, physostigmine (till ACS stops), treat arrhythmias (till ACS stops), treat arrhythmias (phenytoin, bicarb)(phenytoin, bicarb)

16. Tricyclic Antidepressants


SourceSource Quaalude, ludes (sedative/hypnotic)Quaalude, ludes (sedative/hypnotic)

SignsSigns Depersonalization, tongue Depersonalization, tongue discoloration, dizziness, nausea, discoloration, dizziness, nausea, hemorrhage, abstinence syndromehemorrhage, abstinence syndrome

TreatmentTreatment ABC’s, emesis, lavage, hemodialysis ABC’s, emesis, lavage, hemodialysis

17. Methaqualone


SourceSource Digitalis, digoxinDigitalis, digoxin

SignsSigns Headache, nausea, vomiting, blurred Headache, nausea, vomiting, blurred vision, delirium, slowed pulse, cardiac vision, delirium, slowed pulse, cardiac irregularities, hypokalemia, irregularities, hypokalemia, arrhythmias, ventricular fibrillation…arrhythmias, ventricular fibrillation…low TIlow TI

TreatmentTreatment ABC’s Dose adjustment, drug ABC’s Dose adjustment, drug withdrawal, lavage, charcoal, emesis, withdrawal, lavage, charcoal, emesis, Digibind, KDigibind, K++ supplement, treat supplement, treat arrhythmias (lidocaine, phenytoin, arrhythmias (lidocaine, phenytoin, propranolol)propranolol)

18. DigoxinSpecific Poisons Frequently Specific Poisons Frequently

EncounteredEncountered

SourceSource DilantinDilantin

SignsSigns Nystagmus, ataxia, drowsiness, Nystagmus, ataxia, drowsiness, seizures…death is rare but is usually seizures…death is rare but is usually due to ventricular fibrillation and due to ventricular fibrillation and cardiac arrest. Toxicity >25mcg/mlcardiac arrest. Toxicity >25mcg/ml

TreatmentTreatment ABC’s, emesis (if conscious), lavage, ABC’s, emesis (if conscious), lavage, charcoal, cathartics, discontinue charcoal, cathartics, discontinue phenytoinphenytoin

19. Phenytoin


SourceSource AminophyllineAminophylline

SignsSigns CNS stimulation, hyperreflexia, CNS stimulation, hyperreflexia, cardiac arrhythmia, convulsions, death cardiac arrhythmia, convulsions, death is due to respiratory failure. Toxic is due to respiratory failure. Toxic plasma level >20mcg/ml. plasma level >20mcg/ml.

TreatmentTreatment ABC’s, discontinue drug, charcoal, ABC’s, discontinue drug, charcoal, emesis, fluids and anticonvulsants emesis, fluids and anticonvulsants (diazepam) as needed. (diazepam) as needed.

20. Theophylline


SourceSource Herbicides, cigarette smoke, smoke Herbicides, cigarette smoke, smoke from burning trash and debrisfrom burning trash and debris

SignsSigns ChloracneChloracne (small yellow comedones) (small yellow comedones) mainly on the face can last 30 years, mainly on the face can last 30 years, hepatomegaly, fatigue, irritability, hepatomegaly, fatigue, irritability, blurred vision, porphyria cutanea tarda blurred vision, porphyria cutanea tarda (slate gray skin pigmentation), (slate gray skin pigmentation), limited limited systemic effects, Death??systemic effects, Death??

TreatmentTreatment ABC’s, alkaline diuresis, If recent ABC’s, alkaline diuresis, If recent ingestion: [emesis, lavage, charcoal, ingestion: [emesis, lavage, charcoal, cathartic], mainly supportive carecathartic], mainly supportive care

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

Dioxin PoisoningDioxin Poisoning

Viktor Yushchenko: Ukraine President

2012 Toxicology

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Transcript of 2012 Toxicology