Adverse drug reactions Flashcards
Adverse reaction
Harmful or seriously effects occurring at doses intended for therapeutic effect and which call for reduction of dose or withdrawal of the drug and/or forecast hazard from future administration
Type A vs B Reactions
- Type A reactions : 85-90% of all adverse drug reactions, can affect any individual, given sufficient dose and exposure, and are predictable from the known pharmacologic properties of a drug
- Type B or allergic drug reaction/hypersensitivity reaction: results from a specific immunologic response to a medication, 10-15% and occurs in a susceptible subgroup of patients, have signs and symptoms that are different from the pharmacologic actions of the drug, and usually cannot be predicted
______: implies a direct action of the drug, often at high dose.
Toxicity
Relative vs. types of special cases of toxicity
- Relative toxicity: an ordinary dose that may be toxic due to an underlying abnormality in the patient e.g. kidney disease
- Mutagenicity, carcinogenicity and teratogenicity are special cases of toxicity.
_____: a low threshold to the normal pharmacological action of a drug
Intolerance
______: an inherent qualitative abnormal reaction to a drug, usually due to a genetic abnormality e.g., porphyria-heme synthesis dysfunction.
Idiosyncrasy
______ : reactions which result in objectively
reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal subjects
Hypersensitivity
______: personal or familial tendency to develop IgE antibodies in response to low doses of allergens, and to develop typical symptoms e.g. asthma, rhinoconjuctivitis and eczema/dermatitis or tendency to develop allergies
Atopy
______: a hypersensitivity reaction initiated by immunological mechanisms
Allergy
______: a severe, life-threatening, generalized or systemic hypersensitivity reaction (subset of allergy)
Anaphylaxis
Adverse reactions cause ____% of consultations in general practice
2-3
Adverse reactions cause ___% of admissions to ICUs
3
Overall incidence in hospital in-patients due to adverse reactions is ____%
10-20
Adverse reactions cause prolonged hospital stay in ≈___% of patients in acute medical units
10
Deaths caused by ADR annually
100,000
Drug-induced Skin Reactions
– Maculopapular eruptions
– Urticarial rashes and angioneurotic edema
– Fixed drug eruptions
– Photosensitivity, phototoxicity and photoallergy
– Vasculitis
– Hyperpigmentation
– Drug-induced systemic lupus erythematosus
– Anticoagulant-induced skin necrosis
– Severe skin reactions
Drug-induced Pulmonary Reactions
- Bronchospasm -can precipitate asthma
- Drug-induced cough ACE-inhibitors
- Pulmonary edema
Blood Dyscrasias (reactions)
Thrombocytopenia
Granulocytopenia
Aplastic anemia
Hemolysis
Chronic organ toxicities that can occur due to ADRs
Eye: corneal opacities
Liver: cirrhosis
Kidney: nephropathy
Uterus: endometrial cancer
ADR’s effects in pregnancy
- Teratogens: in first trimester- alcohol, isotretinoin
- ↓ fetal bone and tooth development
- Ototoxicity
- Drugs given just prior to labor
vasoconstrictor-s↓fetal blood supply fetal distress - Drugs given during labour: diazepam- hypotonia in neonate and ↓ suckling
______ is the most common drug allergy
Penicillin
T/F Complaints of: nausea, vomiting, diarrhea,
headaches, general malaise, dizziness are examples of true allergic reactions
False - they are side effects of medication
- Not mediated by the immune response
- Not a contraindication to re-treatment with the
offending agent
- Mitigation: decrease rate of absorption, try food
or snack with oral medications
What are Pseudoallergic reactions?
- Direct stimulation of mast cells resulting in release of histamine (flushing) - Opiates, vancomycin (infuse-rate dependent)
- Non-immunologic activation of the complement cascade (Radiocontrast media)
- Change in metabolism or production of inflammatory mediators (ACE inhibitors, aspirin, NSAIDS)
Characteristics of true allergic reactions
- Mediated by immune response
- lnvolve lgE, or lgM and/or lgG antibodies, or T-cells
- Lead to mast cell degranulation and histamine release
- Present as hives, itching, angioedema, dyspnea, wheezing, anaphylaxis, severe hypotension
- May recur within or across drug classes due to ability of similar structural components between drugs to elicit similar antigenic responses (penicillins and cephalosporins)
- Contraindications to re-treatment with the offending agent and/or treatment with other similar drugs
Type 1 Allergic reactions
- Hypersensitivity Reactions/Anaphylactic
lgE-mediated - Responsible for urticaria, angioedema, hypotension,anaphylaxis
- AKA Antibody-mediated anaphylactic reactions
- AKA lmmediate hypersensitivity reactions
- Usually occur minutes to 2 hrs after second exposure
- Most common type of hypersensitivity caused by
sulfonamide antibiotics
Type 2 allergic reactions
Type ll Hypersensitivity Reactions/Cytotoxic
- Possess cytolytic and cytotoxic activity
- lgG and lgM - mediated
- Occur 7-21 days after drug initiation
- Result in hemolytic anemia, thrombocytopenia,
neutropenia
Type 3 allergic reactions
Type lll Hypersensitivity Reactions/lmmune Complex Reactions
- lgG and lgM-mediated
- Antibody-antigen complexes cause damage to entire organs
- Skin, joints, and kidneys are most commonly affected
- Occur in 5-21 days after drug initiation
- Result in vasculitis, maculopapular rash,
glomerulonephritis, or erythema multiforme
Type 4 allergic reactions
Type lV Hypersensitivity Reactions/Delayed
- AKA cell-mediated hypersensitivity
- Mediated by cytokines released by sensitized T-cells
- Result in activation of immune cascade leading to tissue damage
- Occur 48 - 72 hrs after exposure
- Examples: contact dermatitis, Stevens-Johnson syndrome
Stevens-Johnson syndrome is an example of a type ___ allergic reaction
4
T/F Always weigh the benefits of a particular medication against the risk of a serious reaction
T
_____ lnvolves giving a patient very small amount of drug and repeating administration with increasing larger amounts
Desensitization
Why is reporting allergic reactions important?
- Required for manufacturers to document and report ADRs to the FDA
- Prescribers and other healthcare professional can
voluntarily report
What to report with ADRs/Allergic reactions
observed or suspected events with human medical products, including serious drug side effects, product use errors, product quality problems, and therapeutic failures for:
