Toxicological Considerations in Uncommon Overdoses

Introduction:

Toxicity following a drug overdose manifests as abdominal pain, vomiting, tremor, altered mental status, seizures, cardiac dysrhythmias, and respiratory depression. These symptoms should be carefully looked into as they can lead to the diagnosis, especially in cases when the toxicity is of unknown origin. Timely and effective management of the condition can lead to better prognosis and good treatment outcomes. The majority of drug overdose cases can be diagnosed rapidly by carrying out a careful physical examination and laboratory investigations. Once the patient has been stabilized with supportive care, the physician has to take measures to minimize the bioavailability of toxin that is yet to be absorbed and make use of an antidote to reverse the toxic effects of the drug.

What Are the Toxicological Signs and Symptoms of Various Uncommon Drug Overdoses?

A. Bradycardia:

• Propranolol (beta-blockers), opiates, Propoxyphene, and Physostigmine.

• Anticholinesterase drugs.

• Antiarrhythmics.

• Clonidine.

• Calcium channel blockers.

• Ethanol and other alcohols.

• Digoxin, Digitalis.

B. Tachycardia:

• Free-base or other forms of cocaine.

• Anticholinergics, antihistamines, antipsychotics, and amphetamines.

• Alcohol withdrawal.

• Sympathomimetics like cocaine, caffeine, and amphetamines,

• Strychnine.

• Theophylline, TCAs (tricyclic antidepressants), and thyroid hormones.

C. Hypothermia:

• Carbon monoxide.

• Opioids.

• Oral hypoglycemics.

• Insulin.

• Liquor.

• Sedative-hypnotics.

D. Hypotension:

• Clonidine and calcium channel blockers.

• Rodenticides.

• Antidepressants.

• Aminophylline and antihypertensives.

• Sedative-hypnotics.

• Opiates.

E . Hyperthermia:

• Nicotine.

• Antihistamines and alcohol withdrawal.

• Salicylates, sympathomimetics, and serotonin syndrome.

• Anticholinergics, antidepressants, and antipsychotics.

F. Hypertension:

• Cocaine.

• Thyroid supplements.

• Sympathomimetics.

• Caffeine.

• Anticholinergics and amphetamines.

• Nicotine.

G. Coma:

• Ethanol, Ethylene glycol, and Ethchlorvynol.

• Tricyclic antidepressants.

• Antidepressants, anticonvulsants, antipsychotics, and antihistamines.

• Rohypnol, Risperidone.

• Isoniazid, and Insulin.

• Clonidine.

H. Seizures:

• Organophosphates, oral hypoglycemics.

• Tricyclic antidepressants, Isoniazid, and Insulin.

• Sympathomimetics, Strychnine, and salicylates.

• Amphetamines and anticholinergics.

• Methylxanthines like Theophylline and Methanol.

• Propranolol.

• Benzodiazepine withdrawal and Bupropion.

• Ethanol withdrawal and Ethylene glycol.

• Lidocaine, and Lindane .

I. Pupil Size (Miosis):

• Cholinergic, Clonidine, and carbamates.

• Opiates and organophosphates.

• Phenothiazines, and Pilocarpine,

• Sedative-hypnotics.

J. Pupil Size (Mydriasis):

• Sympathomimetics.

• Anticholinergics withdrawal.

K. Skin Changes:

1. Diaphoretic Skin:

• Sympathomimetics.

• Organophosphates.

• Acetylsalicylic acid and other salicylates.

• Phencyclidine.

2. Dry Skin:

• Antihistamines and anticholinergics.

3. Bullae:

• Barbiturates and other sedative-hypnotics.

4. Flushed Appearance:

• Anticholinergics, and Niacin.

• Boric acid.

5. Cyanosis:

• Ergotamine.

• Nitrates and nitrites.

• Aniline dyes.

• Phenazopyridine.

• Dapsone.

How Is the Toxicity Caused by Drug Overdose Diagnosed?

1. Prehospital Care:

• Apart from basic stabilization measures, the emergency medical system (EMS) providers need to take certain measures in case of an overdosed patient, especially when the transport time to the nearest hospital is short.

• Serum glucose levels need to be checked in a patient with altered mental status, and intravenous dextrose should be administered as soon as possible.

• Naloxone in limited quantities is given in case of opioid toxicity or if the patient is suffering from hypoxia and airway compromise.

• Benzodiazepines are preferred in toxin-induced seizures.

• For the toxicity caused by sodium channel blocking agent (cardiac) overdose, and in cases of widened QRS complex, intravenous sodium bicarbonate is administered.

2. History Taking:

• A careful history should be elicited as it can unravel important information such as the type of toxic drug, the timing of exposure, and the dosage and route of administration (ingestion, intravenous, inhalation) that can be obtained, which determines the prognosis.

• It is also important to get information regarding the cause of drug toxicity (accidental, suicide attempt, euphoria, therapeutic misadventure), and any history of psychiatric illness or previous suicide attempts should be noted.

• A clinician should have an insight regarding signs and symptoms of certain toxins like protracted coughing with hydrocarbon ingestions, hematemesis with iron ingestions, seizures with Isoniazid overdose, and loss of consciousness with carbon monoxide.

3. Physical Examination:

• In an emergency setting, stabilizing the patient is given priority, which is then followed by a detailed physical examination.

• Once the patient is stable, a more detailed physical examination can be attempted, which reveals certain additional signs about a specific poison.

• One has to be aware of the complications that might occur in case of toxic drug overdoses like aspiration pneumonia, rhabdomyolysis, and anoxic brain injury, and steps should be taken to manage the same effectively.

• The toxin ingested can be determined by careful assessment of toxic vital signs presented clinically.

• Patients with altered mental status should undergo a thorough neurologic evaluation.

• Skin examination should be done and is usually assessed for changes in the color and temperature, and changes like dryness or diaphoresis should be checked.

• The skin examination should involve the evaluation of pharmaceutical patches, such as opioids like Fentanyl.

• In cases of drug abuse, there is a possibility of the presence of patches in unusual locations, such as the vagina and scrotum.

• Some poisons produce odors characteristic enough to arrive at a diagnosis, such as oil of wintergreen in case of Methyl salicylate poisoning, garlic odor in organophosphates, insecticides, arsenic poisoning, and noxious rotten-egg smell in sulfur dioxide, and hydrogen sulfide poisoning.

4. Laboratory Tests:

• Many readily available and simple laboratory tests aid in providing an apt diagnosis in case of drug toxicity in symptomatic patients, which include measurement of electrolytes, blood urea nitrogen, creatinine, serum glucose, bicarbonate levels, and arterial blood gasses.

• A pregnancy test is beneficial in female patients of child-bearing age as the attempts may be suicidal or cause abortions.

• Calcium oxalate crystals can be found in Ethylene glycol poisoning.

• An orange to red-orange color is diagnostic of Phenazopyridine, Rifampin, and Deferoxamine toxicity.

• Similarly, pink color with Ampicillin or Cephalosporins, brown color with Chloroquine, and greenish-blue color urine with copper sulfate or methylene blue poisoning can be detected.

5. Radiological Imaging:

• A plain abdominal radiograph (KUB) is an important diagnostic tool as it detects radiopaque pills, drug-filled packets, or other toxic substances.

• The KUB is also very useful in determining heavy metal objects in the gastrointestinal tract and can also be used to evaluate gastrointestinal decontamination, such as whole bowel irrigation.

• Chest films detect occasional pneumothorax or pneumomediastinum, characteristic of patients abusing cocaine or other sympathomimetic agents.

How Is the Toxicity Caused by Drug Overdose Managed?

• The management of a toxic drug overdose first involves basic supportive therapy to stabilize the patient.

• Once the patient is stabilized, other treatment modalities can be initiated.

• When the patient presents with unconsciousness or coma, a ‘‘coma cocktail’’ is initiated. It refers to the empiric administration of certain medications or delivery of drugs in such patients to reverse the effects. The most commonly used drugs are Dextrose, Naloxone, and Thiamine.

• Hypoglycemia is rapidly corrected with a dextrose bolus.

• In cases of opioid poisoning, an intravenous Naloxone infusion is given as it is an opioid antagonist.

• Flumazenil, a benzodiazepine antagonist, is given in case of benzodiazepine toxicity to reverse the coma effect.

• Physostigmine is given in severe cases of anticholinergic drug poisoning.

• Gastric lavage is considered if a patient has ingested a toxic dosage of the drug and presents within an hour of ingestion of the drug.

• Activated charcoal has become the preferred method of decontamination for most drug toxicities and is effective when administered soon after the ingestion of the toxic drug.

• Activated charcoal with 25 percent of the concentration is therapeutically used.

• The appropriate dosage of activated charcoal is given as a 10:1 ratio of activated charcoal to the toxic drug ingested.

• Patients with hemodynamic stability and normal bowel function and anatomy can undergo whole bowel irrigation (WBI).

• WBI involves using a large volume of a Polyethylene glycol solution to clear the gastrointestinal tract by mechanical action without interfering with the fluid or electrolyte balance.

• WBI is indicated in heavy metal and lithium toxicity and to remove the substances that are not adsorbed by charcoal, drug-filled packets, and other potentially toxic foreign bodies.

• Whole bowel irrigation is performed by placing a nasogastric tube and administering a Polyethylene glycol solution of 1 to 2 L/hour and 25 to 50 mL/kg/hour in pediatric patients and should be continued until the rectal effluent is clear.

• Antidotal therapy should be used carefully and judiciously and considered only in known toxic drug poisoning.

• Except for Naloxone, antidotal therapy use is limited in patients with unknown toxic drug poisoning.

• Most poisoned patients can have an uneventful recovery if timely and optimum routine supportive care is given.

Conclusion:

Managing a patient with a toxic overdose of an unknown drug is quite challenging. Hence, a detailed history and thorough physical examination consisting of identifying the toxic vital signs and symptoms aid in appropriate diagnosis and treatment planning. Consulting a regional poison center or clinical toxicologist soon after the toxic drug exposure can have positive outcomes in terms of the management and post-hospital recovery in such patients.