Module 10 - Adverse Drug Reactions and Medication Errors

Question 1

what are adverse drug reactions

Answer 1

ADRs are the unintentional and undesired response from drugs
- enormous societal health problem
- 7.5% of hospital admissions in Canada (185,000 people)

Question 2

Adverse drug reactions can include what

Answer 2

1. Side effects
2. Drug toxicity
3. Allergic Reaction
4. Idiosyncratic Reaction
5. Carcinogenic Effects
6. Mutagenic Effects
7. Teratogenic Effects

Question 3

Side effects

Answer 3

• Side effects are secondary to the main therapeutic effect of the drug and are expected.
• Side effects occur at normal therapeutic doses and are often unavoidable.
• Side effects are often due to poor specificity or selectivity of the drug.

Question 4

Drug Toxicity

Answer 4

• can be considered as any severe adverse drug event
• it is often mediated by overdose where patients unintentionally or intentionally take too much medication
• these types of reactions are often extensions of the therapeutic effect
  ex: patient who takes too much insulin will experience hypoglycemia

Question 5

Allergic Reaction

Answer 5

• mediated by immune system
• allergy requires prior sensitization where a patient is exposed to the allergen
• Upon subsequent exposure to the drug an allergic reaction will occur. During allergic reactions, mast cells release chemical mediators such as histamine.
• Allergic reactions can vary from itching and rash, to life threatening anaphylaxis (bronchospasm, edema and severe hypotension).
• The intensity of allergic reactions are independent of dosage size. Therefore small doses can produce severe allergy.

~ 10% of all ADRs are related to drug allergy.

Question 6

what are the most common drug allergies?

Answer 6

penicillins, sulfonamides (antibiotics), and nonsteroidal anti-inflammatory drugs (NSAID)

Question 7

idiosyncratic Reaction

Answer 7

• These are reactions that occur rarely and unpredictably in the population.
• Recent evidence suggests that genetic polymorphisms account for the majority of idiosyncratic reactions.
• The majority of polymorphisms causing idiosyncratic reactions occur in drug metabolizing enzymes and drug transport proteins.
• It is hoped that one day, routine blood test will be able to determine people at risk for idiosyncratic reactions due to genetic polymorphisms. This already occurs in some centres for the drugs warfarin and 6-mercaptopurine which are metabolized by CYP2C9 and thiopurine methyltransferase (TPMT) respectively.

Question 8

Carcinogenic effects

Answer 8

• Carcinogenic means the ability of a drug to cause cancer.
• Relatively few drugs are carcinogenic.
• Determining whether a drug is carcinogenic is problematic because it normally takes years after the initial dose to appear.
• The drug diethylstilbestrol (DES) used to be prescribed to prevent spontaneous abortion in high-risk pregnancies. Years later it was determined that the female offspring developed vaginal or uterine cancer.

Question 9

Mutagenic Effects

Answer 9

• If a drug is mutagenic, it is able to change DNA.
• Often when a drug is mutagenic it is also carcinogenic or teratogenic.
• Sometimes drugs that are mutagenic are not carcinogenic or teratogenic. These drugs may receive approval for use from regulatory agencies if there is sufficient evidence of safety from preclinical studies.
• Drugs are tested for their potential as mutagens by the Ames test.

Question 10

what is the ames test

Answer 10

• The Ames test evaluates the ability of the test compound (i.e. a drug) to cause a mutation in specialized strains of bacteria.

Question 11

Teratogenic effects

Answer 11

• known to cause birth defects or impair fertility
• less than 1% of all birth defects are caused by drugs
• sensitivity to teratogens changes during development
• Gross malformations typically occur when exposure to a teratogen is in the 1st trimester.
• Teratogen exposure during the second and third trimesters usually disrupts function as opposed to gross anatomy.

Transfer of drugs across the placenta is thought to be greatest in the third trimester because as the placenta develops, the surface area for transfer between maternal and fetal circulation increases. In addition, the placental-fetal barrier becomes progressively thinner.

Question 12

CNS (central nervous system)

Answer 12

highly sensitive until week 32 of pregnancy

Question 13

Category A pregnancy risks

Answer 13

• Well controlled human studies have failed to show risk to the fetus during the 1st trimester
• No evidence of harm later in pregnancy

Question 14

Category B pregnancy risks

Answer 14

• Animal reproduction studies have failed to show harm to the fetus and there are no well controlled studies in pregnant women, OR
• Animal studies have shown an adverse effects but well controlled studies in pregnant women fail to show any harm

Question 15

Category C pregnancy risks

Answer 15

• Animal studies have shown harm to the fetus but there are no well-controlled studies in pregnant women
• Potential benefits of the drug outweigh the potential risk

Question 16

Category D pregnancy risks

Answer 16

• Clear evidence of risk to the fetus from studies in humans
• Potential benefits of the drug outweigh the potential risk

Question 17

Category X pregnancy risks

Answer 17

• Studies in animals and humans clearly demonstrate risk to the fetus
• Risks of using the drug clearly outweigh the benefits
• These drugs should never be used in pregnant women

Question 18

organ-specific toxicity

Answer 18

• Organ specific toxicity can occur to the kidney, lung, heart, liver, muscle and inner ear amongst others.
• The most common and important organ specific toxicity is observed in the liver and heart.

Question 19

Hepatotoxicity

Answer 19

All patients taking hepatotoxic drugs should be educated to look for signs of liver toxicity which include: jaundice (yellow skin), dark urine, light-coloured stool, nausea and vomiting.
- liver function tests should be performed by measuring blood levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
- Drugs known to be hepatotoxic should be used with caution in patients at high risk for hepatic disease (alcoholics), patients with hepatic disease, and patients taking other medications with known hepatotoxicity.

Question 20

Why is hepatotoxicity the most common reason for a drug to be removed from the market

Answer 20

the liver is the primary site of drug metabolism. Some drugs are metabolized to toxic metabolites which can then cause liver injury.

Question 21

what are AST and ALT

Answer 21

are liver enzymes that normally have a low concentration in the blood. When the liver is damaged, blood concentration of these enzymes increases.

Question 22

QT Interval Prolongation

Answer 22

• The electrocardiogram (ECG or EKG) shows the electrical activity of the heart. An ECG is obtained by placing electrodes on the skin and measuring the electrical activity that occurs with each heartbeat.
• More than 100 drugs are known to prolong the QT interval and many have been removed from the market.
• Drugs that prolong the QT interval should be used with caution in patients predisposed to arrhythmias such as the elderly, and patients who have bradycardia (slowed heart beat), heart failure, low potassium or congenital QT prolongation.
• Women are at higher risk than men because their normal QT interval is longer

Question 23

P-wave

Answer 23

normal atrial depolarization.

Question 24

QRS complex

Answer 24

rapid depolarization of the left and right ventricles

Question 25

T-wave

Answer 25

repolarization of the ventricles.

Question 26

U-wave

Answer 26

not always seen on ECG

Question 27

QT Interval

Answer 27

Represents the time required for the ventricles to repolarize. A prolongation of the QT interval is a major risk factor for the development of torsades de pointes, a life threatening form of ventricular arrhythmia.

Question 28

Drug Withdrawal

Answer 28

Some medications must be withdrawn slowly to prevent adverse reactions

Question 29

Opiate withdrawal

Answer 29

-consequences = anorexia, irritability, nausea, vomiting, weakness, muscle spasm

Question 30

Benzodiazepines

Answer 30

for anxiety withdrawal consequences = anxiety, insomnia, sweating, tremours, panic delirium, paranoia, convulsions

Question 31

beta blockers

Answer 31

use = hypertension/heart rate decrease consequences = rebound hypertension, chest pain, myocardial infarction, arrhythmia

Question 32

Medication errors

Answer 32

- Medication errors are the most common cause of adverse drug reactions. - If a medication error is caused by a health care professional it is called an iatrogenic error.

Question 33

Iatrogenic error

Answer 33

health care professional medication error

Question 34

5 main categories of medication errors

Answer 34

1. prescribing 2. dispensing 3. administration 4. patient education 5. patient

Question 35

prescribing med error

Answer 35

Health care professional prescribes the wrong drug, wrong dose or wrong route.

Question 36

Dispensing med error

Answer 36

The prescription is correct but the pharmacist dispenses the wrong drug

Question 37

Administration med error

Answer 37

The health care professional administers the incorrect dose and/or drug. Note, a patient can also make this error

Question 38

Patient education med error

Answer 38

Illiteracy or language barriers may cause the patient not to comprehend the instructions. The health care professional (doctor, nurse and pharmacist) must work together to ensure all patients understand information about drugs.

Question 39

Patient med error

Answer 39

The patient understands the instructions but doesn’t follow them (i.e. misses doses, takes more medication than prescribed).

Question 40

Drug naming

Answer 40

- Confusion over drug names represents ~ 15% of all medication errors.

Question 41

Abbreviations

Answer 41

- Abbreviations can be dangerous sources of errors