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

Theophylline

Theophylline

• Actions– Relaxes bronchial smooth muscle– Stimulates respiration– Stimulates cardiovascular constriction– Stimulates gastric acid secretion– Augments cardiac inotrophy– Relax uterine smooth muscle– Diuresis (Stronger than caffeine but shorter

duration)

Theophylline

• Narrow therapeutic index

• Leading cause of drug induced seizures– Seizures can occur with levels slightly over

20 mcg/ml.

• Common causes of toxicity– Large single dose– Accidental accumulation secondary to

inadvertent overmedication.

Theophylline

• Mild Toxicity (20-40 mcg/ml)– Gastrointestinal discomfort, vomiting, diarrhea

• Most common sign of toxicity • 60-100% of patients experience vomiting

– Restlessness, irritability

Theophylline

• Moderate Toxicity (40 - 100mcg/ml)

– Wakefulness– Mild Sinus Tachycardia– Tachydysrhythmias– Increased Blood Pressure– Decreased blood pressure

– Hyperthermia– Albuminuria– Dehydration– Hematemesis– Manic behavior– Hallucinations

Theophylline

– Dysrhythmias– VF threshold reduction– Seizures

• Mechanism unknown• Indicate poor outcome• May lead to rhabdomyolysis,

renal failure, permanent neurologic sequelae

• On EEG seizure is continuous

• Severe Toxicity (>100mcg/ml)

– Dehydration– Metabolic

abnormalities– Hyperthermia– Coma– DEATH

Theophylline

• Management– ABCs

• Provide O2

• Intubate, if necessary• Support vital signs• Control seizures, arrhythmias

Theophylline

• Management– Decontamination

• Lavage, activated charcoal• Due to possible rapid onset of seizures, emesis NOT

recommended.• Whole bowel irrigation may be necessary if

Theophylline levels continue to rise secondary to sustained release preparations.

• Endoscopic removal of bezoar may be necessary if levels continue to rise, patient’s condition deteriorates

Theophylline

• Management– Sinus tachycardia

• Rarely requires treatment

– Supraventricular tachycardia • Verapamil• Cardiospecific beta blockers

– Ventricular ectopy• Lidocaine

Theophylline

• Management– Hypotension

• Correct SVT, if present• Fluids• Dopamine• Norepinephrine

– Seizures• Valium• Phenytoin• Phenobarbitol• General anesthesia

for status seizures

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

Isoniazid

• Drug of Choice for – Tuberculosis treatment– Tuberculosis prophylaxis

• Used in prevention of opportunistic Infections in HIV infected patients

Isoniazid

• Mechanisms of Toxicity: Acute– Neurological

• Competes with pyridoxal 5-phosphate (vitamin B6) for enzyme glutamic acid decarboxylase

• Results in decreased GABA levels

• Causes seizures

– Hepatic• Inhibits hepatic conversion of lactate to pyruvate

• Produces lactic acidosis.

Isoniazid

• Mechanisms of Toxicity: Chronic– Peripheral neuritis (thought to be related to

competition with pyridoxine)– Systemic Lupus Erythematosus – Hepatic Injury

Isoniazid

• Toxic Doses– Acute Ingestion: As little as 1.5 gms– Chronic Use: 10-20% incidence of hepatic

toxicity when dose is 10mg/kg/day

Isoniazid

• Acute Overdose– Slurred Speech– Ataxia– Coma– Seizures (within 30 - 60 minutes)– Profound anion gap metabolic acidosis

Isoniazid

• Management– ABCs– Treat coma, seizures, metabolic acidosis

accordingly.

– Pyridoxine ( vitamin B6 )• One gram for each gram of isoniazid ingested• If amount unknown give at least 5gm IV• If amount on hand is insufficient, give what is

available and then give diazepam

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

Anhydrous Ammonia

• Signs/Symptoms– Acute pulmonary edema– Laryngeal edema– Ventricular arrhythmias/hypotension– Ocular necrosis - blindness– Partial and full thickness skin burns

Anhydrous Ammonia• Management

– SCBA/Protective equipment required!– Delay entry until equipment available

– Wash patient with large amounts of H2O

– ABC’s, O2, assist ventilations

– Intubate/suction lower airway PRN– Assist ventilation/consider PEEP– Irrigate eyes– Admit/observe for delayed effects