Transcript Toxicology II

Specific Toxins
Part II
Infectious Agents
Bacterial Food
Infection/Poisoning
• Signs/Symptoms
– Nausea, vomiting
– Abdominal cramps
– Diarrhea
– History of eating same foods in same place
as others with similar symptoms
Bacterial Food
Infection/Poisoning
• Management
– Prevention
• Cook thoroughly
• Keep hot foods hot
• Keep cold foods cold
– Replace lost fluids, electrolytes
– Antiemetic agents
Botulism
• Pathophysiology
– Neurotoxin from Clostridium botulinum
– Produced in anaerobic environment at pH >4.6
– Boiling will destroy toxin
– Toxin binds to cholinergic nerve terminals;
Blocks acetylcholine release
Botulism
• Signs/Symptoms
– GI upset
– Dry mouth
– Double vision (diplopia)
– Drooping eyelids
– Slurred speech
– Descending paralysis - respiratory arrest
Botulism
• Management
– Support ABC’s
– Antitoxin
Common Cardiac Medications
Beta Blockers
• Signs/Symptoms
– Bradycardia
– Hypotension, shock
– AV blocks
– Prolonged QRS complex
– Heart failure
– Bronchospasms
Beta Blockers
• Management
– ABC’s
– Oxygen
– Bronchospasms
• Inhaled 2 agents
Beta Blockers
• Management
– Bradycardia
• Atropine 0.5 - 1.0 mg
• Glucagon 5mg every 30’
• Cardiac pacing
– Hypotension
• Glucagon 5mg every 30’
• Dopamine 5mcg/kg/min
Calcium Channel Blockers
• Signs/Symptoms
– Bradycardia
– Hypotension, shock
– AV blocks
– Heart failure
– QRS prolongation does NOT occur
Calcium Channel Blockers
• Management
– Calcium reverses decrease in contractility
– Fluid infusion increases BP
Digitalis
• Signs/Symptoms
– Central Nervous System
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Headache
Irritability
Psychosis
Yellow-green vision
– Gastrointestinal
• Anorexia
• Nausea, vomiting
Digitalis
• Signs/Symptoms
– Cardiac
• Atrial tachycardia with block
• Non-paroxysmal junctional tachycardia
• PACs, PJCs, PVCs
Tachyarrhythmias + Blocks =>Digitalis toxicity
Digitalis
• Management
– ABC’s, oxygen
– Check electrolytes, correct hypo/hyperkalemia
– Atropine: bradycardia with hypotension
– Dilantin: ectopy
– Lidocaine/magnesium sulfate: ventricular ectopy
– Digtalis immune Fab Fragments (Digibind)
Digitalis
• Precautions
– Cardioversion, pacing attempts may cause VF
– Vagal stimulation may cause bradycardia, AV
blocks
– Calcium may worsen ventricular arrhythmias
Tricyclic Antidepressants
TCAs
• Examples
– Elavil
– Tofranil
– Sinequan
– Surmontil
– Vivactil
TCAs
• Mechanism of Toxicity: Cardiovascular
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Alpha-adrenergic blockade: vasodilation
Anticholinergic effects: tachycardia, mild hypertension
Quinidine-like effects: myocardial depression
Inhibition of sodium channels: conduction defects
Metabolic or respiratory acidosis may contribute to
cardiotoxicity by inhibition of fast sodium channels
TCAs
• Mechanism of Toxicity: CNS
– Anticholinergic effects: sedation, coma
– Inhibition of NE, serotonin re-uptake: seizures
TCAs
• Three major toxic syndromes
– Anticholinergic effects
– Cardiovascular effects
– Seizures
Anticholinergic Effects
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Sedation, coma, delirium
Dilated pupils
Dry skin, mucous membranes
Tachycardia
Decreased bowel sounds
Urinary retention
Myoclonic jerking (often mistaken for seizures)
Cardiovascular Effects
• Arrhythmias, abnormal conduction, hypotension
• Prolongation of PR, QRS, QT intervals
(QRS > 0.12 is a good predictor of toxicity)
• Various degrees of AV block
• Hypotension caused by vasodilatation
• Cardiogenic shock
• Pulmonary edema
Seizures
• Common with TCA toxicity
• Recurrent or persistent
• Combined with diminished sweating can lead to
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Severe hyperthermia,
Rhabdomyolysis
Brain damage
Multisystem failure
DEATH
Death
• Usually occurs within hours due to :
– Ventricular fibrillation
– Intractable cardiogenic shock
– Status epilepticus with hyperthermia
TCAs
• The three C’s
– Coma
– Convulsions
– Cardiac arrhythmias
TCAs
• Overdose Evaluation
– Most have narrow therapeutic index
– Doses <10x therapeutic daily dose may
produce severe poisoning
– 10-20 mg/kg can be life threatening
– In children one tablet can cause death
TCAs
• Management of Toxicity
– ABCs
– Decontamination
(Lavage even up to 4-6 hours post ingestion
may be useful due to decreased GI motility)
– Activated charcoal
TCAs
• Management of Toxicity
– Sodium Bicarbonate (1-2 mEq/kg)
• Maintain pH of 7.45 to 7.55
• Protects cardiac membrane, corrects acidosis
– Hyperventilation to induce respiratory
alkalosis can work for short time
TCAs
• Management of Toxicity
– Pacing for bradyarrhythmias, high-degree
AV block
– Overdrive pacing for Torsades des pointes
– Do NOT use type 1a or 1c antiarrhythmic
agents for V-tach; can aggravate
cardiotoxicity
TCAs
• Management of Toxicity
– Hypotension
• Fluids
• Vasopressors
– Seizures
• Diazepam, phenobarbital.
• If these do not work, paralyze patient
Iron
Iron
• Incidence (1995 AAPCC Annual Report)
– 28,039 Exposures
– 378 moderate, major effects
– 3 deaths
Iron
• Overdose Evaluation
– How much elemental Fe could have been
ingested (mg/kg)?
• < 20mg/kg: not considered toxic, can be left at
home
• 20-60mg/kg: mild to moderate toxicity, some
treatment required
• > 60mg/kg: high toxicity; hospitalization required
Iron
Signs and Symptoms
Occur in five stages
Stage I
• 30 minutes-6 hours post ingestion
• GI irritation, due to iron’s corrosive effects
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Nausea, vomiting
Epigastric pain
GI bleeding
Drowsiness
Hypotension
Metabolic acidosis
Leukocytosis
Hyperglycemia
Stage II
• 6-24 hours post ingestion
• Sometimes absent in severely poisoned
patients
• Patient seem to improve; feels, looks
better
Stage III
• 6-48 hours post ingestion
• Metabolic, systemic derangement
– Cardiovascular collapse
– Coma
– Seizures
– Coagulopathy
– Pulmonary edema
Stage IV
• 2-7 days post ingestion
– Hepatotoxicity (jaundice)
– Coagulopathy
– Metabolic acidosis
– Renal insufficiency
Stage V
• 1-8 weeks post ingestion
• Primarily delayed GI complications
– Gastric/duodenal fibrosis
– Scarring of pylorus
– Intestinal obstruction
Iron
• Overdose Treatment
– Decontamination
• Lavage useful if done within first 60 minutes
post ingestion
• Iron does NOT bind to activated charcoal
– Whole bowel irrigation
Iron
• Overdose Treatment
– Desferal ( desferoximine )
• Chelating agent
• Binds free iron, complex is excreted renally
• “Vin rose’” urine color depending on urine pH
Isoniazid
Carbon Monoxide
• Produced by incomplete combustion
(autos, home heaters)
• Colorless, odorless, tasteless
• Binds to hemoglobin - blocks oxygen
carrying capacity
Carbon Monoxide
• Signs/Symptoms
– Headache, N/V, ringing in ears,
incontinence, seizures, coma, pulmonary
edema
– Cherry-red skin - usually a terminal event
– Suspect with a lot of “sick” patients at one
location
Organophosphates
• Pathophysiology
– Block cholinesterase.
– Cause build-up of acetylcholine in
synapses.
– Produce cholinergic crisis.
Organophosphates
• Signs and Symptoms
– Salivation
– Lacrimation
– Urination
– Defecation
– Gl Cramping
– Emesis
– Pin-point pupils
– Bradycardia
– Bronchospasms
– Muscle twitching
– Weakness
– Ventilatory failure
Organophosphates
• Management
– 100% oxygen, assist ventilations
– IV tko
– Monitor ECG
– Atropine 1mg IV, 2mg IM. Repeat until
atropinized
– Pulmonary edema is non-cardiogenic in
origin; avoid lasix, morphine
Drug Abuse
Self administration of drug or
drugs in manner not in accord with
accepted medical or social
patterns
Drug Abuse
• Psychological Dependency
(Habituation)
– Drug necessary to maintain user’s sense of
well-being
• Physical Dependency
– Physical symptoms if intake reduced
Drug Abuse
• Compulsive Drug Use
– Preoccupation with obtaining drug
– Rituals of preparing, using drug as
important as drug effects
• Tolerance
– Increasing doses needed to obtain drug
effect
Drug Abuse
• Addiction
– Includes
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Psychological dependence
Physical dependence
Compulsive use
Tolerance
– Plus, complete absorption with obtaining,
using drug to exclusion of all else
Drug Abuse
• Suspect drug-related problem in patients
with:
– Altered LOC
– Bizarre behavior
– Seizures
Drug Abuse
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Ask EVERY patient about recreational drugs.
Be non-judgmental.
Keep drug box/cabinet secured.
Use discretion.
If held up, give them what they want!
Narcotics
• Opium
• Opium derivatives
• Synthetic opium substitutes
Narcotics
• Examples
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Opium
Morphine
Heroin
Codeine
Dilaudid
– Oxycodone
(Percodan)
– Meperidine (Demerol)
– Propoxyphene
(Darvon)
– Talwin
– Fentanyl
Narcotics
• Effects
– Analgesia
– CNS depression
• Euphoria
• Drowsiness
• Apathy
– Antidiarrheal action
– Antitussitive action
Narcotics
• Overdose
– Mild to Moderate
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Lethargy
Pinpoint pupils
Bradycardia
Hypotension
Decreased
bowel sounds
• Flaccid muscles
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Respiratory depression
Coma
Aspiration
Seizures with certain
compounds
(meperidine,
propoxyphene,
tramadol)
Narcotics
• Overdose
– Management
• Support oxygenation/ventilation
• Vascular access
• D50W 50cc
• Narcan 0.4 to 2.0 mg
–Improve respirations
–Do NOT awaken completely
–Restrain before giving
Narcotics
• Associated Dangers
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Skin abscesses
Phlebitis
Sepsis
Hepatitis
HIV
Endocarditis
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Adulterant toxicity
“Cotton fever”
Malnutrition
Tetanus
Malaria
Narcotics
• Withdrawal
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Insomnia
Restlessness
Irritability
Anorexia
Tremors
Back, extremity pain
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Watery eyes
Yawning
Rhinorrhea
Sneezing
Diarrhea
Diaphoresis
Resembles Severe Influenza
Narcotics
• Withdrawal
– Lasts 7 to 10 days
– NOT life threatening
Sedative-Hypnotic Drugs
Categories
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Barbiturates
Benzodiazepine
Barbiturate-like non-barbiturates
Chloral hydrate
Mechanism of Action
• Most overdoses of sedative-hypnotics
are from benzodiazepines, barbiturates
• Both enhance effects of gammaaminobutyric acid (GABA)
• GABA enhancement results in downregulation of CNS activity
Sedative-Hypnotics
• Use more then a week leads to
tolerance to effects on sleep patterns
• Withdrawal after long term results in
“rebound” increase in frequency of
occurrence, duration of REM sleep.
• In high doses, sedative-hypnotics
depress CNS to point of Stage III or
general anesthesia
Sedative-Hypnotics
• Tolerance
– Happens with all sedative-hypnotics
– Appears very quickly even during shortterm use.
– Discontinuation will bring receptor
response back to normal after drug has
been metabolized
– Withdrawal symptoms may take up to a
week to see in some patients
Chloral hydrate
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“Micky Finn” when mixed with alcohol
Rapidly absorbed, acts quickly
Drowsiness, sleep
Alcohol, chloral hydrate compete for
metabolism by same enzyme
• Prolonged action for both when mixed
• Not commonly abused
Barbiturates
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Introduced in 1903
Replaced older sedative-hypnotics
Quickly became major health problem
In 1950’s-60’s barbiturates were
implicated in overdoses; were
responsible for majority of drug-related
suicides
Barbiturates
• Short-acting
– Amytal
– Pentathiol
• Intermediate-acting
– Nembutal
– Seconal
– Tuinal
• Long-acting
– Phenobarbital
Barbiturates
• Initial overdose presentation
– Slurred speech
– Ataxia
– Lethargy
– Nystagmus
– Headache
– Confusion
Barbiturates
• As overdose progresses
– Depth of coma increases
• Patient anesthetized with loss of neurologic
function
• EEG may mimic brain death
– Respiratory depression occurs
– Peripheral vasodilation occurs
• Hypotension, shock
• Hypothermia
– Blisters (bullae) form on skin
Barbiturates
• Early deaths
– Respiratory arrest
– Cardiovascular collapse
• Delayed deaths
– Acute renal failure
– Pneumonia
– Pulmonary edema
– Cerebral edema
Barbiturates
• Overdose management
– Secure airway
– Support oxygenation/ventilation
– IV with LR or NS
– Prevent heat loss secondary to
vasodilation
– Bicarbonate to alkalinize urine (long-acting
only)
Barbiturates
• Withdrawal signs/symptoms
– Apprehensiveness
– Anxiety
– Tremulousness
– Diarrhea
– Nausea
– Vomiting
– Seizures
Barbiturate-like, nonbarbiturates
• Examples
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Doriden (glutethimide)
Quaalude (methaqualone)
Placidyl (ethchlorvynol)
Noludar
• Overdose produces sudden, prolonged
apnea
• Highly addictive
• Withdrawal resembles barbiturate withdrawal
• Only Placidyl, Doriden remain available in
U.S.
Placidyl (ethchlorvynol)
• “Pickles”, “jelly beans”, “Mr. Green Jeans”
• Produces vinyl-like odor on breath
• Concentrates in CNS, slow hepatic
metabolism
• Half-life >100 hrs
• Prolonged deep coma (100 to 300 hrs),
hypothermia, respiratory depression,
hypotension, bradycardia
• EEG is flatline
• Keep patient on life support for a few days;
they wake up, are ok
Doriden (gluthethimide)
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Abused in combination with codeine
“sets”, “hits”, “loads”, “fours and doors”
Prolonged coma (average 48 hours)
Hypotension, shock common
Anticholinergic signs: dilated pupils,
tachycardia, dry mouth, ileus, urinary
retention, hyperthermia
Benzodiazepines
• Developed due to overdoses, deaths
related to barbiturates, barbiturate-like
non-barbiturates
• Relatively few deaths
• In 1993, prescription rate for
barbiturates dropped to one-sixth that of
benzos
Benzodiazepines
• Examples
– Valium (diazepam)
– Ativan (lorazepam)
– Versed (midazolam)
– Librium (chlorodiazepoxide)
– Tranxene (chlorazepate dipotassium)
– Dalmane (flurazepam)
– Halcion (triaxolam)
– Restoril (temazepam)
Benzodiazepines
• Adverse Effects
– Weakness
– Headache
– Blurred vision
– Vertigo
– Nausea
– Diarrhea
– Chest pain
Benzodiazepines
• Overdoses
– Relatively safe taken by themselves, even in
overdose
– Can be lethal with other CNS depressants
especially alcohol
– Look like other CNS depressant overdoses
– Antidote is Romazicon ( flumazenil )
• Only recommended in known, controlled
situations
• Can lead to seizures that cannot be controlled
Benzodiazepines
• Produce withdrawal syndrome similar to
barbiturate withdrawal
Benzodiazepine-like nonbenzos
• BuSpar (buspirone)
– Used for generalized anxiety disorder
– Less sedating than diazepam
– Less potentiation by other CNS
depressants
• Ambien, Stilnox (zolpidem)
– Used for short-term insomnia treatment
– Toxic effects similar to benzos
Neuroleptics
• Antipsychotics, major tranquilizers
• Used in treatment of schizophrenia,
other psychoses
• Examples
– Haldol
– Mellaril
– Thorazine
– Stellazine
– Compazine
Neuroleptics
• Extrapyramidal muscle contractions
(dystonias)
– Bizarre, acute, involuntary movements,
spasms of skeletal muscles
– Reversible with Benadryl
Neuroleptics
• Acute Overdose Presentation
– CNS depression
– Hypotension
– Anticholinergic symptoms: flushing, dry
mouth, hyperthermia, tachycardia, urinary
retention
– Ventricular arrhythmias, including Torsades
– Seizures
Neuroleptics
• Acute Overdose Management
– ABCs
– Fluid, vasopressors for hypotension
– Lidocaine, phenytoin for ventricular
arrhythmia
– Magnesium, isoproterenol for Torsades
– Benzodiazepines, phenobarbital for
seizures
Neuroleptics
• Neuroleptic malignant syndrome
– Life-threatening reaction
– Signs, symptoms
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Hyperthermia
Muscular rigidity
Altered LOC
Tachycardia, hypotension
Neuroleptics
• Neuroleptic malignant syndrome
– Management
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ABCs
Oxygen
Assist ventilation, as needed
Benzodiazepines
Rapid cooling
Volume for hypotension
Stimulants
• Examples
– Cocaine
– Amphetamines
• Benzedrine (bennies)
• Dexedrine (dexies, copilots)
• Methamphetamine (ice, black beauties)
– Ephedrine
– Caffeine
– Ritalin
Stimulants
• Produce
– euphoria
– hyperactivity
– alertness
– sense of enhanced energy
– anorexia
Stimulants
• Overdose signs/symptoms
– Euphoria, restlessness, agitation, anxiety
– Paranoia, irritability, delirium, psychosis
– Muscle tremors, rigidity
– Seizures, coma
– Nausea, vomiting, chills, sweating,
headache
– Elevated body temperature
– Tachycardia, hypertension
– Ventricular arrhythmias
Stimulants
• Overdose complications
– Hyperthermia, heat stroke
– Hypertensive crisis
– CVA
– Acute MI
– Intestinal infarctions
– Rhabdomyolysis
– Acute renal failure
Stimulants
• Chronic effects
– Weight loss
– Cardiomyopathy
– Paranoia
– Psychosis
– Stereotypic behavior: picking at skin
(“cocaine bugs”)
Stimulants
• Overdose management
– Oxygen, monitor, IV
– Activated charcoal for decontamination in
first hour
– Valium for sedation
– Hypertension control
• Nipride
• Phentolamine
• Avoid beta-blockers, including labetolol (Why?)
– Body temperature reduction
Stimulants
• Withdrawal
– Drowsiness
– Profound depression (“cocaine blues”)
– Increased appetite
– Abdominal cramps, diarrhea, nausea
– Headache
Hallucinogens
• Examples
– Indole hallucinogens – Amphetamine-like
hallucinogens
• LSD (acid)
• Peyote
• Morning-glory
• Mescaline
seeds
• DOM
• Psilocybin
• MDA
• DMT
• MDMA (ecstasy)
Hallucinogens
• Produce altered/enhanced sensation
• Effects highly variable depending on
patient
• Increased dose does not intensify effect
• Toxic overdose virtually impossible
Hallucinogens
• Some patients may experience “bad
trips”
• Depends on surroundings, emotional
state
• Signs and symptoms
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Paranoia, fearfulness, combativeness
Anxiety, excitement
Nausea, vomiting
Tachycardia, tachypnea
Tearfulness
Bizarre Reasoning
Hallucinogens
• Moderate Intoxication
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Tachycardia
Mydriasis
Diaphoresis
Short attention span
Tremor
Hypertension
Hyperreflexia
Fever
Hallucinogens
• Life-threatening toxicity (rare)
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Seizures
Severe hyperthermia
Hypertension, arrhythmias
Obtunded, agitated, or thrashing about
Diaphoretic, hyperreflexic
Untreated hyperthermia can lead to hypotension,
coagulopathy, rhabdomyolysis and multiple organ
failure
Hallucinogens
• Management of “bad trip”
– Rule out other causes of hallucinations
• Hypoglycemia
• Alcohol, drug withdrawal
• Infection
– Quiet, supportive environment
– Benzodiazepines, haldol for agitation,
anxiety
Phencyclidine (PCP)
• Street names
– Angel dust
– Peace Pill
– Hog
– Krystal
– Animal tranquilizer
• Used as veterinary anesthetic
Phencyclidine (PCP)
• Actions
– Dissociative anesthesia
– Generalized loss of pain perception
– Little or no depression of airway reflexes or
ventilation
– CNS-stimulant, anticholinergic, opiate, and
alpha-adrenergic effects
Phencyclidine (PCP)
• Low Doses
– Lethargy, euphoria, hallucinations
– Slurred speech
– Blank stare
– Insensitivity to pain
– Midposition to dilated pupils
– Vertical and horizontal nystagmus
– Occasionally bizarre or violent
behavior
Phencyclidine (PCP)
• High Doses
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Diaphoresis
Salivation
Hypertension
Tachycardia
Hyperthermia
• Localized dystonic
reactions
• Wide-eyed coma
• Rigidity
• Seizures
Phencyclidine (PCP)
• Treatment
– Maintain airway
– Assist ventilations, as needed
– Treat coma, seizures, hypertension,
hypothermia as needed
– Quiet environment
– Sedation if needed to control agitation
• Haldol
• Benzodiazepines
Inhalants
• Examples
– Hydrocarbons (solvents, paints, aerosols)
– Gases (freon, halon fire extinguishing
agent)
– Metallic paints (“huffing”)
Inhalants
• Effects
– Dysrhythmias including VF
– CNS depression
– Seizures
– Respiratory irritation
– Epinephrine may increase risk of
dysrhythmias
• Treatment
– Oxygen
– Treat symptomatically
“Date rape” drugs
• Flunitrazepam (Rhohypnol)
• Gamma hydroxybutyrate
Flunitrazepam (Rhohypnol)
• Street names
– Rophies
– Roofies
– R2
– Roofenol
– Roche
– Roachies
– La rocha
– Rope
– Rib
Flunitrazepam (Rhohypnol)
• Benzodiazepine
• Similar to Valium but 10x more potent
• Produced, sold legally in Europe, South
America
• Uses
– Short-term treatment of insomnia
– Sedative hypnotic
– Preanesthetic medication
Flunitrazepam (Rhohypnol)
• Effects
– Disinhibition and amnesia
– Onset within 30 minutes, peak within 2
hours, may persist 8 hours or more
– Frequently abused with alcohol or other
drugs
– Enhances high produced by heroin
Flunitrazepam (Rhohypnol)
• Adverse Effects
– Drowsiness
– Dizziness
– Confusion
– Decreased BP
– Memory impairment
– GI disturbances
– Excitability, aggressive behavior
Flunitrazepam (Rhohypnol)
• Management of overdose
– Lethal overdose very unlikely
– Oxygenate, ventilate
– Intubate if necessary to control airway
– Vascular access
– ECG
– Fluid for hypotension
– Dextrostick (rule out hypoglycemia)
– Treat trauma resulting from assault
Flunitrazepam (Rhohypnol)
• Withdrawal
– Headache
– Anxiety, tension
– Numbness, tingling
of extremities
– Restlessness,
confusion
– Loss of identity
– Hallucinations
– Delirium
– Seizures (up to a
week after cessation)
– Shock
– Cardiovascular
collapse
Flunitrazepam (Rhohypnol)
• Management of withdrawal
– Oxygen/ventilation
– Intubate if necessary
– EKG
– Vascular access
– Fluid for hypotension
– Dextrostick
– Diazepam for seizures
Gamma hydroxybutyrate
• Street names
– Cherry meth
– Liquid X
– Liquid ecstacy
• Originally developed as anesthetic
• Banned in 1991 because of side effects
• Promoted as aphrodisiac
Gamma hydroxybutyrate
(GHB)
• Effects
– Odorless, nearly tasteless
– Tremors
– Seizures
– Death