This document discusses fatal medication errors and adverse drug reactions. It defines adverse drug reactions and medication errors. Several studies investigating harm from drugs and errors are summarized, including population studies, analyses of spontaneous reporting databases, and hospital admission data. Three case studies of fatal medication errors and adverse drug reactions are presented and analyzed. The cases involve drug interactions leading to overdose, an air embolism due to lack of contrast medium, and gastrointestinal bleeding from concurrent use of warfarin and diclofenac without INR monitoring.

1. Fatal Medication Errors and
Adverse Drug Reactions
Rowa’ Al Ramahi
2021

2. INTRODUCTION
• The harms from the therapeutic use of drugs
include adverse consequences from reactions
to drugs, adverse interactions between drugs,
and the harm that comes from medication
errors.

3. INTRODUCTION
• A widely accepted definition of an adverse
drug reaction (ADR) is (WHO, 1972) a
response to a drug that is noxious and
unintended and occurs at doses normally
used in man for prophylaxis, diagnosis or
therapy of disease, or for modification of
physiological function

4. • Some difficulties with this are overcome by the
following definition (Aronson and Ferner, 2005):
• an appreciably harmful or unpleasant reaction,
resulting from an intervention related to the use
of a medicinal product; adverse effects usually
predict hazard from future administration and
warrant prevention, or specific treatment, or
alteration of the dosage regimen, or withdrawal
of the product.

5. • Medication errors (i.e., errors in prescribing,
drawing up, and administering drugs) are a
particularly important cause of drug-related
harm, because they are potentially preventable.
There are several suggested definitions. We have
proposed the following:
• a medication error is a failure in the treatment
process that leads to, or has the potential to lead
to, harm to the patient (Ferner and Aronson,
1999, 2006).

6. THE HARMS FROM ERRORS AND
ADVERSE DRUG REACTIONS
• THE LITERATURE RELATING TO FATAL HARM
FROM DRUGS
• DRs and errors can cause serious harm and even
death. However, fatal adverse events are
relatively rare.
• STUDIES INVESTIGATING ADVERSE DRUG
REACTIONS
• A wide variety of study designs has been used by
researchers to determine the nature and
incidence of ADRs

7. • Meta-Analyses
• Data from Spontaneous Adverse Drug
Reaction Reporting Databases: E.g
anticonvulsants, antibiotics, antiinflammatory
drugs
• Data from Hospital Admissions
• Data from Surveillance Schemes
• Fatal Cases of Adverse Drug Reactions
• Population Studies

8. STUDIES INVESTIGATING HARM FROM
DRUGS AND MEDICATION ERRORS
• Case 1
• A 14-year-old boy who was taking fluoxetine 20mg daily and
diazepam 3mg twice daily was admitted for detoxification to a
specialist center for the treatment of drug and alcohol addiction.
The patient was prescribed 20mg of methadone and 50mg of
thioridazine, and the dose of diazepam was increased to 10mg
twice daily upon admission. At 36h after admission, the patient was
found in bed blue and not breathing. Cardio-pulmonary
resuscitation was unsuccessful. The pathologist considered the
death to be because of the inhalation of gastric contents and
asphyxia secondary to potentially toxic blood concentration of
methadone, in the presence of significant therapeutic
concentrations of diazepam and thioridazine and high therapeutic
concentrations of fluoxetine.

9. STUDIES INVESTIGATING HARM FROM
DRUGS AND MEDICATION ERRORS
• Case 1
• Comment: No analysis for drugs of abuse was taken
upon admission to the center, so the treating doctors
did not know whether the patient was actually abusing
heroin or other drugs. Methadone is an extremely
dangerous drug, which is absorbed only slowly after
oral administration, so that maximum blood
concentrations, and hence maximum respiratory
depression, can occur many hours after ingestion.
Pharmacodynamic interactions with other respiratory
sedatives, including diazepam, are to be expected.

10. • Case 2
• A 58-year-old man with a grade 1 subarachnoid
hemorrhage underwent carotid angiography. Staff
failed to recognize that no contrast medium (a clear,
colorless liquid) had been loaded into the syringe, and
therefore a bolus of air, instead of contrast, was
injected into the right carotid artery. The patient died
in spite of appropriate emergency treatment of air
embolism.
• Comment: A rare example of an ADR because of the
(unobserved) absence of drug.

11. • Case 3
• A 64-year-old man who was taking diclofenac for chronic
joint pain underwent arthroplasty of the left hip and
insertion of a spacer. During the operation, he developed
atrial fibrillation and was treated with warfarin;
postoperatively, his heart rhythm returned to normal. Six
days later he passed large amounts of melena and was
presumed to have had acute gastrointestinal bleeding.
Intravenous vitamin K was given because his international
normalized ratio (INR) was increased. (The INR is a measure
of blood clotting, a value of 1.3 or less is normal and the
therapeutic target is usually 2.5.) He had a cardiac arrest
and died in spite of resuscitation.
• Comment: This case highlights the risks of prescribing
warfarin with diclofenac, especially if the INR is not
carefully monitored.