ADVERSE DRUG REACTIONS

An adverse drug reactions as defined by the WHO, is any noxious, unintended , and undesired effect that occurs at normal drug doses.

Adverse reactions can range from annoying to life threatening.

Drugs can adversely affect all body systems in varying degrees of intensity. Examples of mild drug reactions include but not limited to: drowsiness, nausea, itching, and rash.
Severe reactions include things such as: depression, neutropenia, hepatocellular injury, anaphylaxis, and hemorrhage---all of which can be fatal.

Adverse events are most common in the elderly and the very young. Severe illness also increases the risk of the adverse drug reaction.

Adverse reactions could possibly be the fourth leading cause of death, exceeded only by heart disease, cancer and stroke.

DEFINITIONS

Side Effect: a nearly unavoidable secondary drug effect produced at therapeutic doses. Ex. Drowsiness from antihistamines, gastric irritation from aspirin.

Toxicity: an adverse drug reaction caused by excessive dosing.

Allergic Reaction: an immune response. For an allergic reaction to occur there must be prior sensitization of the immune system. Once the immune system has been sensitized to a drug the re-exposure to that drug can trigger an allergic response. The intensity of the reaction can range from mild itching to sever rash to anaphylaxsis.

Idiosyncratic Effect: an uncommon drug response resulting from a genetic predisposition.

Iatrogenic Disease: disease produced by a physician or a disease produced by drugs.

Physical Dependence: a state in which the body has adapted to drug exposure in such a way that an abstinence syndrome will result if the drug use is discontinued. Although we think of narcotics these are not the only thing that one can be addicted to, consider, ethanol, barbiturates, amphetamines as well. There are also medications that should not be discontinued abruptly, they should be tapered off the medications.

Carcinogenic Effect: refers to the ability of certain medications and environmental chemicals to cause cancers.
Evidence of neoplastic desease may not appear until 20 or more years after initial exposure to a cancer-causing compound.

Teratogenic Effect: can be defined as a drug-induced birth defect.

ORGAN-SPECIFIC TOXICITY

Many drugs are toxic to specific organs.

EXAMPLES:
Kidneys - amphotericin B (an antifungal drug)
Heart - doxorubicin (an anticancer drug)
Lungs - amiodarone (an antidysrhythmic drug)
Inner ear - aminoglycoside antibiotics (eg. Gentamicin)

Hepatotoxic Drugs:
In the US, drugs are the leading cause of acute liver failure, a rare condition that can rapidly prove fatal. Most cases end with a liver transplant or in death. The ability to cause severe liver damage is the most common reason for withdrawing an approved drug from the market. (There are many examples of hepatotoxic drugs listed in table 7-1)

How do drugs damage the liver? The liver is the primary site of drug metabolism. As some drugs undergo metabolism they are converted to toxic products that can injure liver cells.
Combining a hepatotoxic drug with certain other drugs may increase the risk of liver damage. A good example is the combination of acetaminophen (Tylenol) with alcohol. ACETAMINOPHEN (normal dose) TAKEN WITH JUST 2-3 DRINKS OF ALCOHOL CAN CAUSE SEVERE LIVER INJURY!
Patients taking hepatotoxic drugs should have liver function tests done on a regular basis. Starting with a baseline and then every 3 months. Labs that should be done: AST (aspartate aminotransferase, ALT (alanine aminotransferase).

Patient education on receiving hepatotoxic drugs should be done.
Signs of liver injury: Jaundice - yellow skin and eyes
Dark urine
Light-colored stools
Nausea
Vomiting
Malaise
Abdominal discomfort
Loss of appetite

QT Interval Drugs:
The term QT interval drugs refers to the ability of some medications to prolong the QT interval on the ECG. This increases the risk of serious dysrhythmias. The QT interval is a measure of he time required for the ventricles to repolarize after each contraction. When the QT interval is prolonged, patients can develop a dysrhythmia known as torsades de pointes, which can progress to potentially fatal ventricular fibrillation.
These drugs should be used with caution in patients predisposed to:
dysrhythmias
elderly
patients with bradycardia
heart failure
congenital QT prolongation
low levels of potassium or magnesium
Women are also at risk because their normal QT interval is longer than the QT interval in men.

Concurrent use of two or more QT drugs should be avoided, as should the concurrent use of a QT drug with another drug that can raise its blood level (eg. by inhibiting its metabolism)

IDENTIFYING ADVERSE DRUG REACTIONS
To help determine if a particular drug is responsible, the following questions should be asked:
• Did symptoms appear shortly after the drug was first used?
• Did symptoms abate when the drug was discontinued?
• Did symptoms reappear when the drug was reinstituted?
• Is the illness itself sufficient to explain the event?
• Are other drugs in the regimen sufficient to explain the event?

MEDICATION ERRORS

The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) defines a medication error as "any preventable event that may cause or lead to inappropriate medication use or patient harm, while the medication is in the control of the healthcare professional, patient, or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing; order communications; product labeling, packageing and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use" NOTE: BY THIS DEFINITION, MEDICATION ERRORS CAN BE MADE BY MANY PEOPLE---BEGINNING WITH WORKERS IN THE PHARMACEUTICAL INDUSTRY, FOLLOWED BY PEOPLE IN THE HEALTHCARE DELIVERY SYSTEM, AND ENDING WITH PATIENTS AND THEIR FAMILY MEMBERS.

The nurse is the last person (typically) in the sequence of medication administration, the nurse is the patient's last line of defense against mistakes--and also the last person with the opportunity to make one. Note also that the nurse is the only person whose actions are not routinely checked by anyone else. Because the nurse is the last person who can catch mistakes made by others, and because no one is there to catch mistakes made by others, and because no one is there to catch mistakes the nurse might make, the nurse bears a heavy responsibility for ensuring patient safety. Can you think of a better reason to learn all you can about drugs?