Drug Allergies Flashcards
Risk factors
- chemical structure
- Molecular weight
- route of administration
- Dose, duration of therapy, repeated exposure to drug
Immunogenic compoud
Hapten/carrier
molecular mass required for immunogenicity
greater than 10,000 daltons
binding between Hapten and carrier
covalent
what must occur for drug to form a hapten/carrier conjugate
be chemically reactive
what if the drug is not intrinsically reactive, how can it be activated?
- Biotransformation
- Photoactivation
what does complete antigen mean?
macromolecular drugs that do not require binding to invoke an immune response
Gell and Coombs classification
I. Anaphylactic - IgE mediated (
Fatal anaphylaxis
Asphyxia due to laryngeal edema or cardiovascular collapse
Serum sickness
syndrome due to soluble circulating immune complexes (Ag excess)
Presents with fever, malaise, lymphadenopathy
Morbilliform skin eruptions
onset is a week - 2 wks post exposure
Serum sickness
- cephalosporins (ceflacor)
- antivenin (equine serum)
may be due to release of factors or direct pharmacologic effects on tissues (eg w/ chemo)
High variable temperature pattern (spiking)
prompt resolution after removal of causative drug
Drug fever
Amphotericin B
Antimicrobials
Rigors, fever, and hypotension after use of TCN, Doxy, Pen G for treatment of spirochetal and bacterial infections, Louse Borne relapsing fever or Tick borne refractory fever
Jarisch-Herxheimer Reaction
JHR happens due to
sudden release of bacterial components from injured and or killed bacteria
Drug induced SLE
- drug characteristics?
- Sex distribution?
- Which drugs?
- When does it typically resolve?
- Hydrazine/Amino group linked to an aromatic ring
- Equal
- HIPP: Hydralazine, Isoniazid, procainamide, phenytoin (also quinidine and penicillamine)
- 3-6 mos
Onset - several mo after beginning drug
Fever, malaise, rash, Arthralgias, myalgias, mucosal ulcers, pulmonary involvement
Systemic Lupus erythematosus
Fever, rash, eosinophilia
proteinuria, hematuria, eosinophiluria
Interstitial Nephritis
- Anti staphylococal PCN
- Cephalosporins
- Sulfonamides
- Cimetidine
Mechanisms for Interstitial nephritis
- Humoral: Ab to a drug - basement membrane complex
- Cell mediated
Eosinophilia, fever, rash, granulomas on biopsy
- eliminated kidney as the problem
which drugs caused the problem?
Hepatic Hypersensitivity reaction/ toxic hepatitis
- Erythromycin
- PCN
How does Hepatic Hypersensitivity reaction/ toxic hepatitis induce autoimmune reaction
- drug acts as a hapten
- may not be inherently toxic to the liver
Palpable purpuric lesions
in lower extrimities
Vasculitis
Vasculitis is characterized by
inflammation and necrosis of blood vessels
Dermatologic reactions - Mild vs Sever. which is common?
Mild is most common
Mild:
- Pruritis
- Maculopapular rash
- Urticaria/Angioedema
- Fixed drug reactions
- Phototoxic
Severe:
- Toxic epidermal necrolysis (TENs)
- Stevens-Johnson Syndrome (SJS)
Symmetrical, flat red rash - small confluent bumps
itchy
Begins in back/extremities
Not seen on palms and soles
Maculopapular/Morbilliform Rash
early/late onset depends on sensitization
PCN, antibiotics, anticonvulsants
Pruritic, edematous wheals with surrounding erythema
Dermatographism
Urticaria/Angioedema
Angioedema is found specifically found
what type of drug typically causes this issue
facial (esp mouth) and periorbital
ACE inhibitors
What causes urticaria
Histamine release from mast cells in dermis causing blood plasma to leak out of small BV
Common agents that cause Urticaria/Angioedema
Antibiotics, NSAIDs, Anticonvulsants (eg: phenytoin)
Dark red or violet lesion that is single or multiple edematous that reappears in the same location if drug is reinitiated
Fixed Drug eruptions
Common agents that cause fixed drug eruptions
Antibiotics: PCN, TCN, Cipro, Bactrim
NSAIDs, Quinidine, Sulfonamides
Immediately post treatment after short exposure to sunlight
Phototoxicity
Activated by long wavelength sunlight
- urticarial, eczematous papulovesicular, or exudative eruptions
Hapten formed with UV light + drug
Photoallergy
Common Agents that cause phototox/allergy
TCN Carbamazepine Griseofulvin Coal Tar derivatives OCs
Topical treatment of preexisting dermatosis causes a new rash to develop. The rash becomes erythematous, indurated, and vesicular
Eczematous Contact Dermatitis
Concentric (target) lesions that look like “bulls eye”
Erythema multiforme
Severe variant of erythema multiforme
Stevens Johnson Syndrome
Mucosal and conjunctival edema
High fever, myalgias, arthralgias with conjunctival scarring that can lead to blindness
Stevens Johnson syndrome
Common agents that cause stevens johnson
Sulfas
Anticonvulsants
NSAIDs
Erythematous rash that progresses to large flaccid bullae
epidermis sloughs and exposes raw dermis - equivalent to 2nd degree burn
Toxic Epidermal Necrolysis
Steven Johnsons that covers more than 30% of the body
Most dermatologic rxns are due to
Antibiotics
Anticonvulsants
NSAIDs
scale used for management of ADR
Naranjo Scale
Drug induced autoimmunity
- SLE
- Hemolytic anemia
- Renal interstitial nephritis
- Hepatic hypersensitivity
Pulmonary reactions
- rhinitis/asthma
- Acute infiltrate/chronic fibrotic pulmonary rxn (Nitrofurantoin)
Aplastic anemia is usually seen with
chloramphenicol
