Adverse Drug Reactions

Question 1

What is an adverse drug reaction (ADR)?

Answer 1

any undesirable or unintended effect following administration of a medical product, whether or not the effect is considered related to the medical product

Question 2

When do ADRs usually resolve if not severe?

Answer 2

• when the drug is discontinued
• when the dose is reduced
• ADRs can diminish as the body adjusts to the drug

Question 3

How should ADRs be categorized since they manifest in many forms?

Answer 3

It is helpful to categorize the reactions based on:

• type
• onset
• severity

Question 4

What are two basic types of ADRs?

Answer 4

• pharmacological

- idiosyncratic

Question 5

What is a pharmacological ADR?

Answer 5

• often predictable
• based on the drug’s mechanism of action
• typically dose-related

Question 6

What is an idiosyncratic ADR?

Answer 6

• unpredictable

- may be more likely to result in mortality

Question 7

What are idiosyncratic reactions mediated by?

Answer 7

• immune system
• receptor abnormalities
• drug–drug interactions
• abnormalities in drug metabolism
• pharmaceutical variations
• unmasking of an abnormal biological system

Question 8

What is the most common way idiosyncratic reactions are mediated?

Answer 8

By the immune system when a drug molecule is recognized as a foreign substance

Question 9

What are haptens?

Answer 9

• low-molecular-weight chemicals that can become antigenic when they covalently bind to a carrier molecule, which is usually a protein
• reacts specifically with an antibody but is incapable of stimulating antibody production except in combination with an associated protein molecule

Question 10

What is an antigenic?

Answer 10

A substance that stimulates the production of an antibody when introduced into the body

Question 11

What type of reaction does Penicillin, a hapten, produce?

Answer 11

Binds to a protein and results in a Type I hypersensitivity (anaphylaxis) reaction

Question 12

What are the categories of immune-mediated hypersensitivity reactions?

Answer 12

• Type I
• Type II
• Type III
• Type IV

Question 13

What is a Type I immune-mediated ADR? Give an example.

Answer 13

• IgE-mediated, immediate-type hypersensitivity

- Example: angioedema and anaphylaxis

Question 14

What is a Type II immune-mediated ADR? Give an example.

Answer 14

• Antibody-dependent cytotoxicity

- Example: heparin-induced thrombocytopenia

Question 15

What is a Type III immune-mediated ADR? Give an example.

Answer 15

• Immune complex hypersensitivity

- Example: Arthus reaction to tetanus vaccine

Question 16

What is a Type IV immune-mediated ADR? Give an example.

Answer 16

• Cell-mediated or delayed hypersensivity

- Example: Drug Rash, Eosinophilia and Systemic Syndrome

Question 17

How do medications that are not haptens able to elicit an immune-mediated reaction?

Answer 17

• through a different mechanism called the “pharmacologic interaction with immune receptors”
• there are chemically inert drugs, unable to covalently bind to proteins
• these medications are able to “fit” into major histocompatibility complex (a set of surface molecules) and the T-cell receptor sandwich

Question 18

What is the definition on covalent?

Answer 18

relating to or denoting chemical bonds formed by the sharing of electrons between atoms

Question 19

What are Type I immune-mediated reactions (IgE-mediated, immediate-type hypersensitivity) are provoked by?

Answer 19

• provoked by reexposure to an antigen.

- an acute hypersensitivity reaction that may be local or systemic

Question 20

What does a Type I cell-mediated response involve?

Answer 20

Involves the:

• skin
• bronchopulmonary system
• nasopharnyx tract
• eyes
• gastrointestinal tract

Question 21

What causes Type I cell-mediated responses?

Answer 21

It is caused by inducing the release of mediators (i.e., histamine, leukotrienes, and prostaglandins) from mast cells, basophils, and recruited inflammatory cells following antigen exposure, which then activates IgE.

Question 22

How are Type I reactions managed?

Answer 22

Administration of:

• epinephrine
• antihistamines
• corticosteroids

Question 23

What do Type II cell-mediated reactions affect?

Answer 23

In the bloodstream and on the surface of cells, antibodies unite with antigens or haptens and induce destruction of cells and tissues through activation of the complement system or through removal by macrophages.