section name header

Introduction

  1. Dystonia, dyskinesia, and rigidity
    1. Assessment. Examples of drugs and toxins causing abnormal movements or rigidity are listed in Table I-15.
      1. Dystonic reactions are common with therapeutic or toxic doses of many antipsychotic agents and with some antiemetics. The mechanism triggering these reactions is thought to be related to central dopamine blockade. Dystonias usually consist of forced, involuntary, and often painful muscle contractions resulting in neck rotation (torticollis), tongue protrusion, jaw extension, or trismus. Other extrapyramidal or parkinsonian movement disorders (eg, pill rolling, bradykinesia, and masked facies) may also be seen. Akathisia is a sensation of inner restlessness.
      2. In contrast, dyskinesias are usually rapid, repetitive body movements that may involve small, localized muscle groups (eg, tongue darting, focal myoclonus) or may consist of generalized hyperkinetic activity. The cause is not dopamine blockade but, more commonly, increased central dopamine activity or blockade of central cholinergic effects.
      3. Rigidity may also be seen with a number of toxins and may be caused by CNS effects or spinal cord stimulation. Neuroleptic malignant syndrome and serotonin syndrome are characterized by rigidity, hyperthermia, metabolic acidosis, and an altered mental status. Rigidity seen with malignant hyperthermia is caused by a defect at the muscle cell level and may not reverse with neuromuscular blockade.
    2. Complications. Sustained muscular rigidity or hyperactivity may result in rhabdomyolysis, hyperthermia, ventilatory failure (Breathing), or metabolic acidosis.
    3. Differential diagnosis. Rule out the following:
      1. Catatonic rigidity caused by functional thought disorder.
      2. Tetanus.
      3. Cerebrovascular accident.
      4. Postanoxic encephalopathy.
      5. Idiopathic parkinsonism.
    4. Treatment
      1. Maintain the airway and assist ventilation if necessary (Airway). Administer supplemental oxygen.
      2. Check the rectal or tympanic temperature and treat hyperthermia rapidly if the temperature is above 40°C (102.2°F).
      3. Dystonia. Administer an anticholinergic agent such as diphenhydramine, 0.5-1 mg/kg IM or IV, or benztropine, 1-4 mg IM, in adults. Follow this treatment with oral therapy for 2-3 days.
      4. Dyskinesia. Do not treat with anticholinergic agents. Instead, administer a sedative such as diazepam, 0.1-0.2 mg/kg IV, or lorazepam, 0.05-0.1 mg/kg IV or IM, or midazolam, 0.05-0.1 mg/kg IV or 0.1-0.2 mg/kg IM (Benzodiazepines (Diazepam, Lorazepam, and Midazolam)).
      5. Rigidity. Do not treat with anticholinergic agents. Instead, administer a sedative (see Item 4 directly above) or provide specific pharmacologic therapy as follows:
        1. Dantrolene for malignant hyperthermia.
        2. Consider bromocriptine for neuroleptic malignant syndrome.
        3. Benzodiazepines or Latrodectus antivenom (Antivenom, Latrodectus Mactans (Black Widow Spider)) for a black widow spider bite (Spiders).
  2. Rhabdomyolysis
    1. Assessment. Muscle cell necrosis is a common complication of poisoning. Examples of drugs and toxins that cause rhabdomyolysis are listed in Table I-16.
      1. Causes of rhabdomyolysis include prolonged immobilization on a hard surface, excessive seizures or muscular hyperactivity, hyperthermia, hypoxia, and direct cytotoxic effects of the drug or toxin (eg, carbon monoxide, colchicine, hemlock, Tricholoma and Russula mushrooms, and some snake venoms).
      2. The diagnosis is made by finding Hematest-positive urine with few or no intact red blood cells or an elevated serum creatine kinase (CK) level. Serum aminotransferase levels are usually elevated, AST more than ALT.
    2. Complications. Myoglobin released by damaged muscle cells may precipitate in the kidneys, causing acute tubular necrosis and renal failure. This is more likely when the serum CK level exceeds several thousand IU/L and if the patient is dehydrated. With severe rhabdomyolysis, hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia may also occur.
    3. Differential diagnosis. Hemolysis leading to hemoglobinuria may also produce Hematest-positive urine.
    4. Treatment
      1. Early and aggressive fluid resuscitation is the primary focus of therapy.
      2. The use of mannitol (0.5 mg/kg IV) and/or sodium bicarbonate is controversial, with insufficient evidence of definitive benefit.
      3. Provide intensive supportive care, including hemodialysis if needed, for acute renal failure. Kidney function is usually regained in 2-3 weeks.
  3. Anaphylactic and anaphylactoid reactions
    1. Assessment. Examples of drugs and toxins that cause anaphylactic or anaphylactoid reactions are listed in Table I-17. These reactions are characterized by bronchospasm and increased vascular permeability that may lead to laryngeal edema, skin rash, and hypotension.
      1. Anaphylaxis occurs when a patient with antigen-specific immunoglobulin E (IgE) bound to the surface of mast cells and basophils is exposed to the antigen, triggering the release of histamine and various other vasoactive compounds.
      2. Anaphylactoid reactions are also caused by release of active compounds from mast cells but do not involve prior sensitization or mediation through IgE.
    2. Complications. Severe anaphylactic or anaphylactoid reactions can result in laryngeal obstruction, respiratory arrest, hypotension, and death.
    3. Differential diagnosis. Rule out the following:
      1. Bronchospasm or laryngeal edema from irritant gas exposure.
      2. Nonallergic pharmacologic effects of the drug or toxin.
      3. Vasovagal syncope or hyperventilation.
      4. Congenital or hereditary angioedema syndromes.
      5. Foreign-body airway obstruction.
    4. Treatment
      1. Maintain the airway and assist ventilation if necessary (Airway). Endotracheal intubation or surgical airway (cricothyrotomy) may be needed if laryngeal swelling is severe. Administer supplemental oxygen.
      2. Treat hypotension with IV crystalloid fluids (eg, normal saline) and place the patient in a supine position.
      3. Administer epinephrine as follows:
        1. For mild-to-moderate reactions, administer 0.3-0.5 mg IM (children: 0.01 mg/kg to a maximum of 0.5 mg). The thigh is the preferred site of injection, resulting in higher and more rapid maximum plasma concentrations compared with deltoid injection.
        2. For severe reactions, administer a 0.05- to 0.1-mg IV bolus every 5 minutes, or give an infusion starting at a rate of 1-4 mcg/min and titrating upward as needed.
      4. H1 and H2 receptor antagonists may also be helpful. Administer diphenhydramine, 0.5-1 mg/kg IV over 1 minute, followed by oral therapy for 2-3 days.
      5. Administer corticosteroids (hydrocortisone, 200-300 mg IV, or methylprednisolone, 40-80 mg IV) followed by oral steroids (dexamethasone or prednisone/prednisolone) for 3-5 days.
      6. Bronchodilator therapy (nebulized beta2 agonists or anticholinergics) may help bronchospasm.
TABLE I-15. SELECTED DRUGS AND TOXINS CAUSING DYSTONIAS, DYSKINESIAS, AND RIGIDITYa

Dystonia and/or akathisia

 Haloperidol and droperidol

 Metoclopramide

 Phenothiazines (prochlorperazine)

 Ziprasidone and other atypical antipsychotic agents

Rigidity

 Black widow spider bite

 Baclofen (both toxicity and withdrawal)

 Lithium

 Malignant hyperthermia

 Manganese

 Methaqualone

 Monoamine oxidase inhibitors

 Neuroleptic malignant syndrome

 Phencyclidine (PCP)

 Strychnine

 Tetanus

Dyskinesias

 Amphetamines

 Anticholinergic agents

 Antihistamines

 Bismuth

 Caffeine

 Carbamazepine

 Carisoprodol

 Cathinones (“bath salts”)

 Cocaine

 GHB (gamma hydroxybutyrate)

 Ketamine

 Levodopa

 Lithium

 Phencyclidine (PCP)

 Serotonin reuptake inhibitors (SSRIs)

 Tricyclic antidepressants

aReprinted by permission from the Springer Nature: Med Toxicol. 2,52-81; Physical assessment and differential diagnosis of the poisoned patient, Olson KR, et al. ©1987.

TABLE I-16. SELECTED DRUGS AND TOXINS ASSOCIATED WITH RHABDOMYOLYSIS

Excessive muscular hyperactivity, rigidity, or seizures

 Amphetamines and derivatives

 Antihistamines and anticholinergics

 Cholinesterase inhibitors (fasciculations)

 Clozapine and olanzapine

 Cocaine

 Lithium

 Monoamine oxidase inhibitors

 Phencyclidine (PCP)

 Seizures caused by a variety of agents

 Strychnine

 Tetanus

 Tricyclic antidepressants

Other or unknown mechanisms

 Carbon monoxide

 Chlorophenoxy herbicides

 Colchicine

 Ethanol

 Ethylene glycol

 Gemfibrozil

 Haff disease (unknown toxin found in

 Baltic fish, buffalo fish)

 Hemlock

 Hyperthermia (caused by a variety of agents)

 Hypokalemia

 Mushrooms (some Amanita, Russula, Tricholoma species)

 Palytoxin

 Paraphenylenediamine (hair dye)

 Prolonged immobility (eg, coma due to central nervous system depressant drug overdose)

 “Statin” cholesterol drugs (eg, cerivastatin)

 Trauma

TABLE I-17. EXAMPLES OF DRUGS AND TOXINS CAUSING ANAPHYLACTIC OR ANAPHYLACTOID REACTIONS

Anaphylactic reactions (IgE-mediated)

 Antisera (antivenins)

 Foods (nuts, fish, shellfish)

 Hymenoptera and other insect stings

 Immunotherapy allergen extracts

 Penicillins and other antibiotics

 Vaccines

Other or unclassified

 Exercise

 Familial/hereditary angioedema

 Immunological adjuvants

 Monoclonal antibody therapy

 Sulfites

 Tartrazine dye

Anaphylactoid reactions (not IgE-mediated)

 Acetylcysteine (when given IV)

 Blood products

 Iodinated contrast media

 Opioids (eg, morphine)

 Scombroid

 Tubocurarine