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

• 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– 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

• 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

– 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

– 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

• 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

• 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– 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

• Lethargy

• Pinpoint pupils

• Bradycardia

• Hypotension

• Decreased bowel sounds

• Flaccid muscles

– Severe• 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– Skin abscesses– Phlebitis– Sepsis– Hepatitis– HIV– Endocarditis

– Adulterant toxicity– “Cotton fever”– Malnutrition– Tetanus– Malaria

Narcotics• Withdrawal

– Insomnia– Restlessness– Irritability– Anorexia– Tremors– Back, extremity pain

– Watery eyes– Yawning– Rhinorrhea– Sneezing– Diarrhea– Diaphoresis

Resembles Severe Influenza

Narcotics

• Withdrawal– Lasts 7 to 10 days– NOT life threatening

Sedative-Hypnotic Drugs

Categories

• Barbiturates

• Benzodiazepine

• Barbiturate-like non-barbiturates

• Chloral hydrate

Mechanism of Action

• Most overdoses of sedative-hypnotics are from benzodiazepines, barbiturates

• Both enhance effects of gamma-aminobutyric acid (GABA)

• GABA enhancement results in down-regulation 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 short-term

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

• “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

• 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, non-barbiturates

• Examples– 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)

• 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 non-benzos

• 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

• Hyperthermia• Muscular rigidity• Altered LOC• Tachycardia, hypotension

Neuroleptics

• Neuroleptic malignant syndrome– Management

• 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

• LSD (acid)• Morning-glory

seeds• Psilocybin• DMT

– Amphetamine-like hallucinogens

• Peyote• Mescaline• DOM• MDA• 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– Paranoia, fearfulness, combativeness– Anxiety, excitement– Nausea, vomiting– Tachycardia, tachypnea– Tearfulness– Bizarre Reasoning

Hallucinogens

• Moderate Intoxication– Tachycardia– Mydriasis– Diaphoresis– Short attention span– Tremor– Hypertension– Hyperreflexia– Fever

Hallucinogens

• Life-threatening toxicity (rare)– 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– 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