Module 10 - Adverse Drug Reactions and Medication Errors Flashcards
what are adverse drug reactions
ADRs are the unintentional and undesired response from drugs
- enormous societal health problem
- 7.5% of hospital admissions in Canada (185,000 people)
Adverse drug reactions can include what
- Side effects
- Drug toxicity
- Allergic Reaction
- Idiosyncratic Reaction
- Carcinogenic Effects
- Mutagenic Effects
- Teratogenic Effects
Side effects
- 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.
Drug Toxicity
- 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
Allergic Reaction
- 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.
what are the most common drug allergies?
penicillins, sulfonamides (antibiotics), and nonsteroidal anti-inflammatory drugs (NSAID)
idiosyncratic Reaction
- 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.
Carcinogenic effects
- 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.
Mutagenic Effects
- 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.
what is the ames test
- The Ames test evaluates the ability of the test compound (i.e. a drug) to cause a mutation in specialized strains of bacteria.
Teratogenic effects
- 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.
CNS (central nervous system)
highly sensitive until week 32 of pregnancy
Category A pregnancy risks
- Well controlled human studies have failed to show risk to the fetus during the 1st trimester
- No evidence of harm later in pregnancy
Category B pregnancy risks
- 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
Category C pregnancy risks
- 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
Category D pregnancy risks
- Clear evidence of risk to the fetus from studies in humans
- Potential benefits of the drug outweigh the potential risk