Adverse Reaction to Drugs Flashcards
most common type of adr
type a: predictable
- reaction ocurring in most normal patients given sufficient dose and duration of therapy
- related to pharmacologic action of the drug
examples of type a adrs
- overdose
- toxicity (renal failure from aminoglycosides)
- side effect: sedation from antihistamines
- secondary/indirect effect: diarrhea from antibiotics
- drug interaction: theophylline toxicity from erythromycin
t/f type b adrs are dose dependent
false, not dose dependent and pts may react to very small amounts
t/f type b adrs are unrelated to pharmacologic action of the drug
true
examples of type b adrs
intolerance, idiosyncratic reaction, drug allergy
what is intolerance
- undersirable pharmacologic effect at low and sub-therapeutic doses of the drug
- no underlying abnormalities of metabolism, excretion, or bioavailability
- ex. tinnitus with aspirin
what is an idiosyncratic reaction
- abnormal and unexpected effect
- underlying abnormalities of metabolism, excretion, or bioavailability
- ex. hemolysis with dapsone in g6pd deficiency
what is drug allergy
- ige mediated drug allergy and pseudoallergic reactions
- anaphylactoid reaction (contrast)
common manifestations of drug allergies
- cutaneous rxns!!
- maculopapular eruptions and urticaria
- systemic reaction
reactant, antigen, effector cells, and examples of type 1 ige mediated rxn
reactant: ige
antigen: soluble antigen
effector cells: mast cell activation
ex: allergic rhinitis, asthma, systemic anaphylaxis
mechanism of type 1 rxn
production of ige from mast cells + recruitment of inflammatory cells
- repeated exposure: cross linking of ige molecules -> mast cell degranulation releasing histamine
reactant, antigen, effector cells, and examples of type 2 ige mediated rxn
reactant: igg
antigen: cell-associated antigen or matrix associated antigen
effector cells: fcr+ cells
ex: hemolytic anemia, thrombocytopenia
mechanism of type 2 rxns
antigens trigger the formation of antibodies
reactant, antigen, effector cells, and examples of type 3 ige mediated rxn
reactant: igg
antigen: soluble antigen
effector cells fcr+ cells
ex: serum sickness, arthus rxn, drug fever
mechanism of type 3 rxn
deposition of antigen-antibody complexes, complement activation, recruitment of leukocytes by complement products, release of enzymes and other toxic molecules
immune reactant and effector cells of type iva
reactant: ifny, tnfa, th1
effector: macrophage activation
immune reactant and effector cells of type ivb
4 fiBe 2 = b
reactant: il-5, il-4, il-13 (th2)
effector: eosinophils
immune reactant and effector cells of type ivc
reactant: perforin/granzyme b (ctl)
effector: t cells
immune reactant and effector cells of type ivd
reactant: cxcl-8, gm-csf (t cells)
effector: neutrophils
t/f the current paradigm is that antigens must be in multivalent form to elicit a specific immune response to activate immunopathologic mechanisms
true
what is the hapten hypothesis
- haptens = chemically reactive small molecules
- these undergo stable covalent binding to larger protein or peptides (hapten-carrier complexes)
- the complexes can cause drug specific immune response
ez. penicillin
what is the pro-hapten hypothesis
- drug that is not chemically active becomes reactive after metabolism
- reactive drugs bind to proteins/peptides to become immunogenic
ex. sulfa drugs
what is the p-i concept
- pharmacologic interaction with immune receptors
- drug binds directly to t cell receptor -> interacts with mhc receptor -> immune response
when to suspect drug allergy
- symptoms of PE compatible with immune drug reaction
- definite temporal relationship
- drug is associated with immune reaction
- patient had previously received drug
- no other clear cause for presenting manifestations
- skin tests and/or lab findings are compatible with drug hypersensitivity
drug related risk factors
- nature of the drug (hapten concept, pro-hapten concept, danger concept, pharma interaction concept)
- degree of exposure (dose, duration, frequency)
- route of administration
- cross sensitization
host related risk factors
- age, gender
- genetic factors
- atopy (for latex and radiocontrast)
- hla-b 1502: carbamazepine
- hla-b 5801: allopurinol
- hla-b 5701: abacavir
- concurrent medical illness
- previous drug reaction
- multiple allergy syndrome
immediate type of symptoms
onset: 1-2 hrs
type: ige mediated (silent sensitization)
sx: urticaria, angioedema, bronchospasm, anaphylaxis
delayed type of symptoms
onset: >6 hours to weeks
type: t cell or igg mediated
sx: exanthems (bullous, maculopapular, acute generalize exenthematous pustulosis)
danger s/sx in delayed type reaction
- extensive, confluent infiltrated exanthema
- bullae, pustules
- (+) nikolsky’s sign: the very thin top layer of skin will shear off, leaving skin pink and moist, and usually very tender
- erythroderma
- painful skin
- mucosal affection
- facial edema
- lymphadenopathy
- constitutional symptoms
read figure 10
immediate rxn laboratory tests
- serum tryptase (6 hours)
- serum histamine (elevated, 1 hour)
- skin prick and intradermal tests (ige rxns)
delayed rxn laboratory tests
- cbc
- liver function tests
- serum creatinine
- urine microscopy and dipstick
- crp
more common epilepsy drug that causes hypersensitivity rxn
phenytoin
- anticonvulsant hypersensitivity syndrome
- drug reaction with eosinophilia and systemic symptoms
antibiotic agents that cause hypersensitivity
- beta lactams
- haptens
- cross reaction with penicillins and cephalosporins
- cause maculopapular exanthema > urticaria > anaphylaxis > sjs
mechanisms of radiocontrast media hypersensitivtiy
anaphylactoid: direct mast cell activation, complement activation, not ige-mediated
delayed type IV reactions
risk factors for rcm hypersensitivity
- female
- asthma
- cvd
- prior rxn to rcm
t/f neuromuscular blocking agents can cause hypersensitivity reactions
true
what is widal or samter’s triad
underlying asthma, sinusitis, or nasal polyposis
read other nsaid phenotypes!
diagnosis for nsaid hypersensitivity reactions
- inhalational lysine aspirin challenge
- oral aspirin drug provocation test
- search for alternative by dpt
miscellaneous syndromes for hypersensitivity
read
manifestation of erythema multiforme
target lesions:
- erythematous central papule that may blister
- edematous middle ring
- erythematous outer ring
early treatment can prevent progression to sjs
manifestation of sjs and ten
- blisters and mucosal or epidermal detachment resulting from full thickness epidermal necrosis
spectrum of nikolsky’s sign or epidermal detachment
- <10% total body = sjs
- 10-30% = sjs-ten
- > 30% = ten
treatment for sjs and ten
sjs: steroids
ten: fluid and electrolyte management, nutritional support, infection control, pain management, ivig
what is drug fever
- caused by release of pyrogens from phagocytes following engulfment of igg complexes and stimulation of t cells
- 7-10 days after therapy
- variable fever pattern
- no more fever after 48 hrs of stopping drug
what is dress
- maculopapular eruption mimicking exanthematous drug rash, but may progress to exfoliative erythroderma
- multiorgan failure
- mortality rate of 10%
what is red man syndrome
- infusion related reaction to vancomycin
treatment for adrs
- identify and stop suspected drugs
- antihistamines, im epinephrine, systemic corticosteroids, high dose ivig
- emollients and skin care, hydration and prevention of superinfection
indications for inpatient care
- angioedema, anaphylaxis
- severe skin reactions (bullous drug eruption, em/sjs/ten)
- systemic symptoms
- possibly >1 drug
indications for outpatient care
- urticaria/maculopapular rash
- fixed drug eruption
- drug allergy without systemic symptoms
when to refer to allergist
- uncertain whether reaction was drug allergy
- uncertain which drug (reevaluation and testing)
- desensitization, hepatitis
