Journal Prsentation
EPIDEMIOLOGY AND CLASSIFICATION OF
ADVERSE DRUG REACTIONS
Noxious, unintended, and undesired effect of a
Definition drug that occurs at doses used for prevention,
diagnosis, or treatment
Hospitalization 15.1% ADRs in hospitalizations,and 6.7% serious
Outpatients 25% of patients ADRs, 13% serious
Predictable (type A) and unpredictable (type B)
Hipersensitivity reactions
IgE antibodies (type I), cytotoxic reactions (type
The Gell and Coombs II), immune complex reactions (type III), and
system of hypersensitivity delayed-type hypersensitivity reactions (type IV)
CLINICAL MANIFESTATIONS OF
IMMUNOLOGICALLY MEDIATED ADRS
EVALUATION: HISTORY TAKING
What is the name of the medication?
How long ago did the reaction occur?
Which systems (eg, cutaneous, respiratory, and gastrointestinal) were involved in the
reaction, and what were the characteristics?
When during the course did the reaction occur?
Why was the medication prescribed?
Was the patient taking concurrent medications at the time of the reaction?
What was the therapeutic management required secondary to the reaction?
Had the patient taken the same or a cross-reacting medication before the reaction?
Has the patient been exposed to the same or similar medication since the reaction?
Has the patient experienced symptoms similar to the reaction in the absence of drug
treatment?
Does the patient have an underlying condition that favors reactions to
certain medications?
DIFFERENTIAL DIAGNOSIS IN
DRUG ALLERGY
Morbilliform eruption = viral exanthem
Multiple drug allergies = underlying chronic
disease
Occurs in underlying chronic urticaria or
anxiety disorders but can also occur
asthma, vocal cord dysfunction, idiopathic
anaphylaxis, or rarely even mastocytosis
LABORATORIES IN DRUG ALLERGY
Eosinophilia is often, not always
Drug induced vasculitis (eg, antinuclear cytoplasmic antibody) and drug-induced lupus
erythematosus (DILE)
Suspect anaphylaxis serum mature tryptase (also known as b-tryptase) Detecting systemic mast
cell mediator release 24-hour urine collections metabolites of histamine or prostaglandin D2.
Haptenation of the b-lactam ring of penicillin to a protein (eg, penicilloyl-polylysine [PPL])
Specific IgE in vitro assays (eg, RASTs, ImmunoCAP, and Immulite) drug allergens to
solid-phase matrices
The basophil activation test expression of CD63 or CD203C drug allergies to b-lactam
antibiotics, NSAIDs, and muscle relaxants
Drug patch testing maculopapular exanthems, acute generalized exanthematous
pustulosis, and fixed drug eruptions,
no absolute histologic criteria
INDUCTION OF DRUG TOLERANCE AND GRADED
CHALLENGE PROCEDURES
MANAGEMENT OF COMMON ALLERGIC
REACTIONS TO SPECIFIC AGENTS
b-Lactam antibiotics: Penicillins
The most prevalent medication allergy
More likely to be treated with more expensive and broad-spectrum antibiotics
development and spread of multiple drug-resistant bacteria and leads to higher health
care costs.
These 2 compounds the minor antigenic determinants,and relevant
allergenic determinants
The negative predictive value of penicillin skin testing is very high
Resensitization after oral treatment with penicillin is rare in both pediatric and
adult patients, including after repeated courses.
Without penicillin skin testing, the approach to patients with a history of
penicillin allergy is based on the reaction history and likelihood of needing
treatment with penicillins.
b-Lactam antibiotics:
Penicillin/cephalosporin cross-reactivity
B-Lactam antibiotics: Penicillin/cephalosporin cross-reactivity
A history of penicillin allergy denied treatment with cephalosporins.
About 90% of patients have negative penicillin skin test responses and can safely
receive cephalosporins (as well as other b-lactams when penicillin skin testing is not
available, cephalosporins might be given through a full-dose or graded challenge,
Allergic cross
Avoid cephalosporins with identical R-group side chains (cefadroxil, cefprozil, and
cefatrizine)
b-Lactam antibiotics :
Penicillin/carbapenem crossreactivity
Analogous cephalosporins X penicilin
Negative penicillin skin test responses can receive
carbapenems safely
Patients with positive penicillin skin test responses
should receive carbapenems through graded challenge
Without penicillin skin testing, carbapenems can be
administered through challenge
Sulfonamides
Beside penicillins, sulfonamide antibiotics are the second
most common cause of drug-induced allergic reactions.
The N4 aromatic amine development of delayed reactions
to sulfonamide antibiotics
The N1 substituted ring IgE-mediated reactions.
No increased risk of reactions to nonantibiotic sulfonamides
in patients with a history of allergy to sulfonamide antibiotics
Cause delayed cutaneous SJS and TEN HIV have a
maculopapular/morbilliform greatly increased risk of
eruptions, and IgE-mediated cutaneous reactions from
reaction sulfonamide antibiotics
Not uncommon for HIV-
positive patients with a TMP-SMX drug of choice
history of reacting to for a number of
sulfonamides to require HIVassociated infections
treatment with the antibiotic
Local anesthetics
IgE-mediated reactions to local anesthetics are
extremely rare
There is cross-reactivity among the benzoate esters
(which do not cross-react with amides) type I
reaction
Skin prick testing is first performed with the undiluted anesthetic if
negative after 20 minutes, an intradermal test is performed with 0.04 mL of
1:100 dilution of local anesthetic. If the response is negative after 20
minutes, a 1.0-mL subcutaneous injection of saline as a placebo is
administered. If there is no reaction after 20 minutes, 1.0 mL of local
anesthetic is administered, and the patient is observed for 20 minutes.
Radiocontrast media
Occur in about 1% to 3% of patients who receive ionic radiocontrast media (RCM) and less
than 0.5% of patients who receive nonionic agents.
Risk factors female sex, asthma, and a history of a previous anaphylactoid reaction to
RCM; b-blocker exposure, the presence of cardiovascular conditions, or both are associated
with greater risk for more serious anaphylactoid reactions.41
Direct effects on mast cells and basophil
Management = (1) determine whether the study is essential; (2) determine that the patient
understands the risks; (3) ensure proper hydration; (4) use a nonionic, iso-osmolar RCM,
especially in high-risk patients (asthmatic patients, patients taking b-blockers, and those with
cardiovascular disease); and (5) use a pretreatment regimen that has been documented to
be successful in preventing most reactions but is less successful in preventing recurrence of
severe
reactions.
Medications used for pretreatment mast cell stabilization 50 mg of prednisone and 1
hour before the procedure; 50 mg of diphenhydramine 1 hour before the procedure; and
either 25 mg of ephedrine or 4 mg of albuterol 1 hour before the procedure
H2 antagonists in the pretreatment regimen is controversial
Delayed reactions to RCM 1 hour and 1 week after administration T-cell mediated
Angiotensin-converting enzyme inhibitor:
Cough and angioedema
Cough and angioedema.
The cause for ACE-I–induced cough is unclear but might be related to bradykinin,
substance P resolves in
1 to 4 weeks and rarely lingers up to 3 months
To reduce coughing cromolyn, theophylline, NSAIDs, amlodipine, nifedipine,
and ferrous sulfate.
Bradykinin is a prominent mediator in both hereditary angioedema
contraindicated in patients with hereditary angioedema switched to an
angiotensin II receptor blockers
Treatment discontinuing the medication, management of the airway, and fresh
frozen plasma
Acetylsalicylic acid/NSAID reactions
Cause exacerbation of underlying respiratory disease, urticaria, angioedema, anaphylaxis,
and rarely pneumonitis and meningitis.
cross-reactivity to other NSAIDs and aspirin, whereas some reactions might be drug
specific
Aspirin-exacerbated respiratory disease (AERD) underlying chronic respiratory
diseases, such as asthma, rhinitis, sinusitis, and/or nasal polyposis.
Fundamental to the pathophysiology excessive production of cysteinyl leukotrienes,
increased numbers of inflammatory cells expressing cysteinyl leukotriene 1 receptors, and
greater airway responsiveness to cysteinyl leukotrienes.
Within minutes of ingestion of therapeutic doses of ASA or NSAIDs, patients with AERD
typically have both rhinoconjunctivitis and bronchospasm.
There is no diagnostic in vitro or skin test for AERD. on history, but when a definitive
diagnosis is required, a controlled oral provocation challenge with ASA can be performed
Management of patients with AERD involves avoidance of aspirin and NSAIDs and
aggressive medical, surgical, or both types of treatment of underlying asthma and
rhinitis/sinusitis.
HIV medications
An increased frequency of drug-induced allergic reactions, and the
reasons behind this are likely multifactorial. Drug exanthems from TMP-
SMX most common drug-induced allergic
Abacavir deserves special mention because of the successful
implementation of a pharmacogenetics approach to management This
multiorgan fever, rash, malaise/fatigue, gastrointestinal symptoms, and
respiratory symptoms. In 90% of cases, hypersensitivity reactions
occurred within the first 6 weeks after initiation of abacavir.
Genetic risk factors several HLA alleles, most notably HLA-B*5701,
were strongly associated with risk of abacavir hypersensitivity reactions
Cancer chemotherapeutic agents
Taxanes, such as paclitaxel and docetaxel anaphylactoid
reactions (non–IgE-mediated anaphylaxis), frequently with the
first administration.
Pretreatment with antihistamines and corticosteroids will
prevent reactions in greater than 90% of cases.
Platinum compounds, such as cisplatin, carboplatin, and
oxaliplatin e hypersensitivity reactions after several treatment
courses an IgE-mediated mechanism.
Cetuximab (colorectal cancer and squamous cell carcinoma of
the head and neck) anaphylactic reactions IgE antibodies
majority of anaphylactic reactions
Biologic modifiers
Proteins such as cytokines, mAbs, and fusion proteins of solubilized
receptors.
High-dose reactions high cytokine levels antibody or cell mediated. Immune
or cytokine dysregulation can result in secondary immunodeficiency, autoimmunity, or
allergic/atopic disorders.
Interferons high-dose flu-like symptoms, hypersensitivity reactions of urticaria,
autoimmune reactions (including thyroid disease and psoriasis), and nonimmunologic
effects, such as depression.
Clinical and biochemical findings fever, edema (peripheral, pulmonary, ascites, and
pleural/pericardial effusions), weight gain, hypotension, hypoalbuminemia, and
multiorgan failure.
Endothelial damage inherent biologic effects of these cytokines.
Ifliximab, Etanercept, adalimumab, intravenous gamma globulin
