Pharmacology: Adverse Drug Reactions (Chapter 59)

Front 1

Why is it important to carefully monitor drug reactions outside of clinical studies?

Back 1

Because something they do not become apparent until they are used by a large population over a long period of time.

Front 2

Give an example of a classic adverse drug reaction: name the drug, what it was used for, what adversity it caused and what happened as a result.

Back 2

Thalidomide
Used to treat women with morning sickness in the 1970s
Caused birth defects called micromelia
Stricter drug legislation and testing was enforced

Front 3

What is ADE?

Back 3

Adverse Drug Event
It can result when a patient develops unintended symptoms from a drug therapy

Front 4

What is ADR?

Back 4

Adverse Drug Reaction
It is an unintended or noxious reaction produced from taking a drug as part of a drug therapy at usual therapeutic doses
Does NOT include drug overdose, abuse or therapeutic errors

Front 5

How does a doctor manage a patient that shows ADR?

Back 5

1. Diagnose the reaction
2. Do a differential diagnosis of the reaction
3. Check drug history
4. Determine how probable it is that the drug caused the reaction

Front 6

What are the four levels of severity of an ADR?

Back 6

1. Mild: Does not really require hospitalization, therapy
2. Moderate: Does not require discontinuation of the drug, but does require some adjustment to the dose/therapy
3. Severe: Requires discontinuation of the drug, and treatment of the adverse symptoms
4. Lethal: Can result in death of the patient

Front 7

How are ADRs classified?

Back 7

Dose-related and not dose-related
But you can always find a dose at which a person does not have an ADR

Front 8

What is a dose-related ADR?

Back 8

A dose-related ADR is where the dosage of a particular drug produces an adverse drug reaction in a patient. These are the most frequent causes of ADR.

It can be remedied by adjusting the dose of the drug and its frequency based on the patient's needs and tolerance. For example, for someone who has renal or hepatic disease, you can decrease the drug dose so that there is no toxic build-up.

These are predictable and can be prevented.

Front 9

What is a non dose-related ADR?

Back 9

Where the ADR is not caused by the actual dose of the drug, but rather, by some other variable such as pharmacogenetic or an acquired allergy.

These ADRs are only manifested after the person has taken the drug, and cannot be prevented/predicted.

Front 10

For a dose-related and non dose-related ADR, be able to distinguish the following:

1) Nature of abnormality (quantitative or qualitative)
2) Incidence (high or low)
3) If ADR is predictable (Yes or No)
4) In presence of liver or kidney disfunction (toxicity or no)
5) Prevention (adjust dose / avoid drug)
6) Treatment (adjust dose / discontinue drug)
7) Mortality (low / high)

Back 10

See page 805
Table 59-1

Front 11

Penicillin is an example of a dose-related or non dose-related ADR?

Back 11

Non dose related
People can have allergies to penicillin (it has no active metabolites), but can become slowly desensitized to it

Front 12

What is the hapten hypothesis?

Back 12

It is a hypothesis that helps explain why non dose-related ADRs occur. While not substantiated, it states that an active metabolite of a drug binds to a protein, which makes the body identify it as foreign. The immune system responds by attacking the protein, initiating an allergic response.

It is also believed that these 'foreign' proteins can cause cell damage.

Front 13

What are the four types of non dose-related allergies that can be developed?

Back 13

1) Anaphylactic: immediate hypersensitivity
2) Cytotoxic: A drug binds to a protein, which acts as an antigen to an antibody. Cell is destroyed/kill.
3) Immune-complex mediated: The antigen-antibody complex binds to a tissue, and causes tissue damage.
4) Cell-mediated: Direct interaction of drug and lymphocyte

Front 14

What is drug monitoring?

Back 14

It is the systematic observation, collection and recording of ADRs caused by a drug.

Front 15

Names the ways that information on ADRs is collected?

Back 15

1) Spontaneous reporting to national drug centres
2) Cohort studies (a specific population or specific drug)
3) Case studies (comparing a control to a variable group)

Front 16

Are ADRs common in hospitalized patients as well as in-patients?

Back 16

Yes.
They can account for anywhere between 10 to upto 20% of patients

Front 17

What factors contribute to ADR?

Back 17

- Age (Older and newborns likely to get ADR. Older people because they have more diseases and take more drugs so adverse drug interaction, because they have slower kidney and hepatic elimination and because they are more sensitive to drugs. Newborns because they haven't developed the enzymes for drug processing)

- Sex: Women more susceptible to ADRs compared to men

- Disease state of a patient

- If they have a history of other ADRs

- If they are taking other drugs (Drug interactions)