Drug Reactions Lecture Flashcards
Common drugs
Penicillin Sulfonamides Barbiturates Anticonvulsants Insulin preps Local anesthetics Iodine preps
Prevalence and characteristics
1-5% experience cutaneous drug eruptions
No correlation with the diagnosis or underlying illness
Women»_space; men
Occur with previously tolerated drugs
Overlooked or misdiagnosed
Non-immunologic in nature (due to direct toxic effect on skin tissue or direct action to release histamine from mast cells and do not involve antibodies or T cells directly
Non-immunologic in nature means?
Due to direct toxic effect on skin tissue or direct action to release histamine from mast cells
Do NOT involve antibodies or T cells directly
Immune mediated allergic reactions
Drug-protein interactions may be mediated by metabolic enzymes and are processed by langerhans cells in skin (presented to T cells which produce TH1 or TH2 response)
Type 1 Gell-Coombs Classification
Classic immediate hypersensitivity - anaphylaxis
- Antibody: IgE mediated on mast cells and basophils
- Minutes to one hour
- Life-threatening
Type II Gell- Coombs Classification
Cytotoxic antibody reaction
- Antibody: IgE or IgM interacts with complement system resulting in cell lysis
- Within several hours
- Caused by drugs, food, emotions, environment
Type III Gell- Coombs Classification
Immune complex reaction
- Ige or IgM antibodies formed against drug to form an immune complex –> inflammation
Type IV Gell Coombs Classification
Delayed hypersensitivity reaction
- Sensitized T cells –> CYTOKINES and inflammation
- Late time course
- Drug induced skin rashes, cell mediated reactions (no antibodies)
- Stop ASAP, improves rapidly
Type V Gell Coombs Classification
Autoimmune response
- Antibody is produced and binds to some receptor in the body (self-antigen binding)
Type I Drugs
Epinephrine
Diphenhydramine (H1 blocker)
Hydrocortisone
Bronchodilators, IV fluids, and H2 antagonists
- Usually antihistamine and steroids
- 15% are H2 so just a H1 blocker wouldn’t do the job
Type II or III Drugs
H1 and H2 blocker (doxepin)
Hydrocortisone
Type IV Drugs
Mild and topical agents
- Oral antihistamine or corticosteroids
Exanthem
Rash
May be maculopapular, morbilliform, erythematous
- 2-3 days after drug admin
- Treated with an antihistamine, wet dressing or systemic corticosteroids
- Disappears after drug termination (2-4 days)
- Type IV
Urticarial eruptions
Hives
Treat with H1 and H2 blockers or systemic corticosteroids
Clear in 1-2 days
Fixed drug reaction
Oval lesion
Reoccur 30 minutes to 8 hours after rechallenge
Drugs not effective
Lesion heal 7-10 days after termination
Photosensitive
Senstivity to sun
Phototoxic: within hours of exposure
Photoallergic: within 1-2 days
Discontinue drug use
Alopecia
Toxic reaction
Interferes with normal growth phases of the hair
Acneiform eruptions
Acne like lesions, usually on neck, chest or back
2-4 week onset
Uniform size and symmetrical distribution
Erythema Nodosum
Red PAINFUL nodules
Discontinue drug
Heals over 2-3 weeks after termination
Exfoliative dermatitis
Severy with erthema and abundant flaky desquamation (skin sloughs)
Loss of fluids
Treat with fluids, steroids, pain meds and antibiotics
Toxic Epidermal Necrolysis (TEN)
Life threatening Medicated by cytotoxic T cells 30% mortality Discontinue drug use, use corticosteroids, antihistamines, fluids and antibiotics Severe pain Intensity: 1-3 days >30% of body
Stevens-Johnson Syndrome
Life threatening Mediacted by cytotoxic T cells Mortality rate 5-18% Symptoms: maculopapular bullae, vesicles, hemorrhagic lesions in the mouth, lips and conjunctiva Mild pain Intensity: 7-15 days <10% of body
Macule
Circumscribed, flat lesion of any shape or size
Differing from surrounding skin due to color
Papule
Small solid elevated lesion
Plaque
A mesa-like elevated lesion occupying a relatively large area in comparison to height
Hives
Urticarial lesion
Nodule
Palpable, solid round or ellipsoidal lesion
Vesicle
Small, circumscribed, fluid-filled blister
Bullae
Large vesicle
Angioedema
Sudden appearance of edematous areas of skin, mucous membranes and occasionally viscera
Of immune or unknown origin
Morbilliform
Multi-shaped red flat rash resembling measles
Erthema
Presence of a red color
Exanthem
Rash or eruption of the skin
Urticaria
Vascular reaction of skin marked by transient slightly elevated patches that are redder or paler than surround skin –> intense itching
First generation H1 antagonists
Hydroxyzine, chlorpheniramine, diphenhydramine, cyproheptadine
- Pass the BB –> CNS sedation
- Help sleep but not good if you need to be alert
Second generation H1 Antagonists
Loratadine and cetirizine
Do not penetrate CNS, non-sedating but metabolized by 3A4 and 2D6
H2 Antagonists
Cimetidine, ranitidine, famatidine, nizatidine
- Cimetidine has many interact
Cimetidine
Many interaction
Disturb kidney function and drug metabolisms
leukotriene Receptor Antagonists
Block LT1 receptor to reduce inflammation and itching
Zafirlukast
Montelukast
Antidepressants
Tricyclic antidepressants (increase NE and dopa)
Antihistamic and anticholinergic sedating properties
Mood-elevating effects
Doxepin, topical cream
Oral or Parenteral steroids
Hydrocortisone: anaphylaxis
Methyprednisolone: more severe reactions
Prednisone: milder conditions
- Alter gene expression and direct receptor mediated effects
- Decreased response to sun, chemical, mechanical, infectious and immunological stimuli
- Decrease lots
Withdrawal of therapy adverse effects
Flare underlying disease
Acute adrenal insufficiency due to long term suppresion of hypothalamic-pituitary acis
Metabolic/organ system dysfunction
Continued use at higher levels = disorders develope
Antimetabolites
Folic acid analog used to inhibit DHFR and reduce immunocompetent cells of skin
- Avoid interaction with other folate antagonists and co-admin with aspirin or NSAIDs
