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Adverse Drug Reactions - Part I

Course Number: 536

Overdose - Clinical Manifestations

Generally, with overdose, the effects of drugs are exaggerated, ADRs become more pronounced, and other unexpected reactions may be observed. Large overdoses of some medications may cause only minimal ADRs; yet, with other medications even smaller overdoses may cause severe toxicity, to include death. A single dose of some medications can be lethal to a young child. Although clinical manifestations of drug overdose vary, the signs and symptoms in Box B are suggestive of medication-induced toxicity in general.

Box B. General Signs and Symptoms of Drug Overdose.

  • Patient’s skin may be hot and dry; or cool and sweaty
  • Patient may complain of nausea, vomiting, abdominal pain, and diarrhea
  • Patient may be sleepy, confused, or in a coma (cannot be aroused)
  • Breathing may be rapid or slow; deep or shallow
  • Blood pressure and pulse rate may be increased or decreased; in some cases the pulse may be absent (e.g., not palpable); body temperature may be elevated
  • Organs specific toxicity: for example, chest pain may suggest damage to the heart or lungs

The U.S. is in the midst of an opioid overdose epidemic. From 1999 to 2020, more than 263,000 people died in the United States from overdoses involving prescription opioids.17 During the same period, overdose deaths involving prescription opioids increased almost five-fold. In 2020, there were 91,799 drug overdose deaths in the United States, of which 68,630 (74.8%) were caused attributed to opioids.17 An opioid overdose can reliably be identified by the presence of three clinical signs and symptoms referred to as the “opioid overdose triad”: (1) pinpoint pupils (miosis), (2) unconsciousness, and (3) respiratory depression (less than 12 breaths/min).18

Combining opioid analgesics with alcohol and other central nervous system (CNS) depressants increases the risk of respiratory depression and death. Indeed, opioids, alcohol, and sedatives are often present in fatal drug overdoses. Risk factors for overdose with prescribed opioid analgesics include middle age; history of substance abuse, including prescription and illicit drugs and alcohol; comorbid mental and medical disorders; high opioid dose (particularly with added benzodiazepines); methadone use; benzodiazepine coprescribing; antidepressant coprescribing; and unemployment.19 A history of substance abuse, high prescribed dosage, male gender, older age, mental health conditions, concurrent prescriptions of other CNS depressants (e.g., benzodiazepines), and lower socioeconomic status.