Drugs and Allergies Flashcards
Immunologically mediated reactions account for ________ of all adverse drug reactions
6-10%
What is a macule?
- flat area of altered colour under 1 cm
What is a patch?
- a large macule over 1 cm
What is a papule?
- elevated solid lesion under 1 cm
What is a nodule?
- elevated solid lesion over 1 cm
What is a plaque?
- elevated flat topped, irregular border over 1 cm
What is a vesicle?
- clear fluid filles blisters under 0.5 cm
What is a bulla?
- large fluid filled blisters over 0.5 cm
What is a pustule?
- a vesicle filled with purulent exudate
What is a wheal?
- an accumulation of dermal fluid
What is an immediate allergic reaction that lasts only 0-1 hours?
- type 1 (severe)
- can possibly be non-immunologic
What is an accelerate allergic reaction that lasts only 2-72 hours?
- may be any type
What is a late allergic reaction that lasts over 72 hours?
- may be any type, but it is rarely type 1
What is red man’s syndrome?
- when you infuse vancomycin too quickly, almost everyone will get the same beefy red rash that looks the same as an allergy
- this is because of the release of histamine from the mast cells in the body
- this happens when there is too fast of an infusion
What other drug will cause red man’s syndrome?
- morphine does the same
If you tolerate the drug for 3 days, and then you have the rash after, then you will not have an _____ type reaction
anaphylaxis
Anaphylaxis is also known as a _____ allergic reaction
type 1
What type of allergic reaction is a cytotoxic type reaction?
- type 2
An immune complex or serum sickness reaction is also known as what kind of allergic reaction?
- type 3
A cutaneous eruption (T cell mediated) is also known as a _____ reaction
type 4
What is the MOA of a type 1 allergic reaction?
- initial exposure to antigen results in a specific IgE antibody production
- preexposure after a period of several weeks is then required
- the drug (and carrier protein) reacts with IgE antibody on the surface of mast cells and basophils resulting in a mediator release
What are the typical symptoms of a type 1 allergic reaction?
- urticaria, laryngeal edema, bronchospasm, and anaphylaxis
Thrombocytopenia can be from _____
heparin
What is the MOA of a type 2 allergic reaction?
- IgG or IgM antibody mediated (hemolytic anemia, thrombocytopenia, granulocytopenia)
- eg. beta lactam hemolytic anemia from high and sustained drug concentrations, usually after 7 days
What are the 3 types of type 2 allergic reactions?
- happen cell reaction
- immune complex reaction
- autoimmune reaction
What is the MOA of a type 3 allergic reaction?
- serum sickness hypersensitivity reaction
- IgG or IgM antibody mediated - form circulating complexed with antigen. Fix complement and then lodge into tissues
- typically these occur 5-21 days after exposure
- cefaclor»_space; amoxicillin
- same as type 2 immune complex reactions (but non-hematologic)
What is a type 3 allergic reaction characterized by?
- fever
- arthralgia
- skin rash
- lymphadenopathy
Type 3 allergic reactions typically appear ____ days after administration of an allergen?
- 5-21 days
What kind of immune cells does type 4 reactions typically involve?
- involve the activation of T cells and may involve several other cell lines as well, such as macrophages, eosinophils or neutrophils
Type 4 reactions are not mediated by ______
antibodies
How many type 4 subtypes are there?
- there are 4
What is a type 4a allergic reaction?
- activation of macrophages with secretion of large amounts of interferon gamma, TNF- alpha, and interleukin-18. Some forms of contact dermatitis are an example
What is a type 4b allergic reaction?
- secretion of cytokines IL-4, IL-3 and IL-5, which promote B cell production go IgE and IgG4, macrophage, mast cell, and eosinophil responses
- involved in the bronchi of patients with allergic asthma
- certain types of morbilliform or maculopapular rashes are type 4b mediated
- DRESS is also an example of type 4b reaction
What is a type 4c allergic reaction?
T cells inducing apoptosis in resident cells of inflamed tissue, such as hepatocytes or keratinocytes
- important in the pathogenesis of several types of drug induced delayed type hypersensitivity reactions, such as some forms of contact dermaitis, maculopapular reactions, bollous drug eruptions, drug induced hepatitis, erythema multiform, SJS, and toxic epidermal necrolysis
What is a type 4d allergic reaction?
- type 4d reactions involve T cell mediated sterile neutrophilic inflammation. Acute generalized exanthematous pustulosis is an example of this type of skin reaction
What are the 3 types of type 4c allergic reactions?
- erythema multiforme
- Steven’s Johnson Syndrome
- Toxic epidermal necrolysis (TEN)
Describe the characteristics of erythema multiforme?
- begins with an eruption of erythematous, raised patches of the skin
- the centre of the lesion eventually clears and forms a characteristic target appearance within 24-48 hours
- target lesions are limited in numbers
- lesions appear on 1 mucosal surface and on the hands and feet
- pruritic and sudden onset
- usually distributed symmetrically over the body
- usually associated with herpes virus
- looks for the vesicles of herpes
- much less commonly due to drugs (<20% of cases)
- prognosis is usually benign
Vesicles are suggestive of a ____ infection
herpes
SJS is similar to erythema multiforme but the lesions break out at _______ sites
multiple (2 or more mucosal surfaces)
- but less than 10% of body surface area is involved
- may not see the target lesions in some SJS reactions however
Where will SJS most likely be seen?
- lining of the mouth, throat, genital region and eyes
What is the typical onset of SJS syndrome?
-4 days to 3 weeks
Is SJS also systemic in its presentation?
- yes it is, a fever is also usually present
- can be fatal
SJS is usually ____ induced
drug
What drug classes is SJS usually caused by?
- sulfonamides, beta lactams, NSAIDs and anticonvulsants
SJS cannot cause ______
desensitization
With over 10% of BSA, the outbreak should be considered a _______ syndrome
TENS
What is the BSA of a typical TENS presentation?
over 30% of BSA
What is the BSA of a mixed TENS/SJS syndrome?
- 10-30% BSA involvement
Even though the typical onset of TENS/SJS is 4 days to 3 weeks, it is a possibility up to ______ after
8 weeks
What can be done to trick the body to think that it is not allergic?
- you can give 1/10000 dilution of a drug, and then give 1/1000 dilution of a drug, and then give 1/100 dilution, etc
With serum sickness, ______ surfaces are never affected
mucosal
Describe TENs infections
- systemic skin disorder characterized by the top layer of skin peeling off in sheets
- begins with a painful red area that spreads quickly (days)
- affected skin has a scalded appearance, blisters may then develop
- discomfort, chills and fever are common
- spreads to the mucous membranes of the eyes, mouth and genitals
- patient should be treated as a burn patient
- can be fatal
What drug is TENS infections typically caused by?
- sulfonamides, beta lactams, NSAIDS, anticonvulsants
TENS/SJS infections are more common in what subset of patients?
- in those with an HIV infection and possibly those with lupus
What type of reaction is a DRESS reaction?
type 4b
What does DRESS stand for?
- drug rash
- eosinophils
- systemic symptoms
(also known as drug induced
Describe DRESS syndrome
- severe systemic disorder
- onset is typically 4 days to 3 weeks
- may initially appear as a simple morbilliform rash
- facial edema and erythmea are the hallmarks of DRESS
- rash may become purpuric, especially on the lower legs
- mucous membranes are NOT involved like EM, SIS or TEN
- 10% mortality
- often associated with anticonvulsants (phenobarb, phenytoin), allopurinol, NSAIDs, sulphonamides, dapsone and thiazides
Many drugs can release _____, which would give the appearance of anaphylaxis (wheezing, rash, hypotension). Is this a true anaphylactic reaction?
histamine
- no, this is not a true anaphylactic reaction
What enzyme is only detectable after anaphylaxis?
mast cell tryptase is the only enzyme that is present after anaphylaxis
Serum tryptase levels should be drawn between ______ after the reaction in order to make a definitive diagnosis
1-4 hours
What kind of penicillin reaction is a type 1 reaction?
- the most serious kind
- it is classically an erythematous, maculopapular rash
- appears later on in the treatment course
- rashes with ampicillin/amoxicillin occur with the greatest frequency
A maculopapular or mobilliform rash to penicillin is not ____ mediated. What is it then?
IgE
- it is either type 4b or 4c mediated - this makes it less serious
What does a maculopapular rash look like?
- elevation and redness all over the skin
Describe a urticaria type reaction to penicillin?
- occurred within 1 hour after drug administration
- is IgE mediated
- is an immediate type reaction
- more serious (is life threatening)
- never give the offending agent again
What does penicillin skin testing test for?
- tests for IgE antibodies
- assesses the allergic reaction to major metabolite determinants and is the most common antibody formation
- characterized accelerated reactions (2-72 hours)
- parent compound or secondary metabolite (minor) determinant (penicillin or penicillate) and is the least frequent antibody formation
- characterizes immediate reactions (under 2 hours) - is a more serious reaction
Penicillin skin testing has a high ______ predictive value
negative
over 98% with a history of penicillin allergy, but negative skin test can safely receive penicillin
Can anaphylaxis ever occur in a person with a negative penicillin skin test?
NO
What drugs can interfere with the interpretation of the skin test? What ones will not?
- antihistamines can mask the effect of a penicillin skin test
- corticosteroids will not mask the effects of the test
What drugs can interfere with the interpretation of the skin test? What ones will not?
- antihistamines can mask the effect of a penicillin skin test
- corticosteroids will not mask the effects of the test
Penicillin skin testing has absolutely no predictive value in non-IgE mediated reactions. What does this mean?
- it has no effect in predicting SJS, TEN’s, DRESS syndrome, maculopapular eruptions, contact dermatitis, cytopenias, serum sickness
Describe the cross reactivity of penicillins with cephalosporins
- the incidence of clinically relevant cross reactivity between penicillins and cephalosporins is very small
- however, cephalosporins should be used only as last resort if there are no other alternatives
Describe the characteristics of a sulphonamide rash?
- common use of allergic drug reactions
- typically it is a delayed type reaction
- fever, followed by a morbilliform eruption
- may be due to the production of hydroxyl amine reactive metabolites
- some may progress to SJS or TEN’s
Incidence of sulfonamide reactions are most common in those with what kind of conditions?
HIV infection
