Buxton: Rashes Flashcards
What are the more common cutaneous drug reactions?
cumulative toxicity
overdose
photosensitivity
drug-drug interactions
when the immune response to a drug results in an increased or exaggerated response
hypersensitivity
Drugs and their metabolites act as (blank) making some proteins immunogenic inducing either a cell-mediated or humoral response.
haptens
A drug substance that is capable of reacting with a specific antibody but cannot induce the formation of antibodies unless bound to a carrier protein or other molecule.
Also called incomplete antigen, partial antigen.
haptens
(blank) reactions are caused by the formation of drug/antigen-specific IgE that cross-links with receptors on mast cells and basophils leading to immediate release of chemical mediators, including histamine and leukotrienes.
Type 1
Clinical features of Type 1 hypersensitivity reactions?
pruritus urticaria angio-oedema bronchoconstriction anaphylaxis
Drugs most commonly responsible for type 1 hypersensitivity reactions?
aspirin
opioids
penicillins
These reactions are based on IgG or IgM-mediated mechanisms.
These involve binding of antibody to cells with subsequent binding of complement and cell rupture.
Type II hypersensitivity
Clinical features of type II sensitivity reactions?
blood cell dyscrasias
ex: haemolytic anemia and thrombocytopenia
These reactions are mediated by intravascular immune complexes that arise when drug antigen and antibodies, usually of IgG or IgM class, are both present in the circulation, with the antigen present in excess.
Slow removal of immune complexes by phagocytes leads to their deposition in the skin and the microcirculation of the kidneys, joints and gastrointestinal system
Type III hypersensitivity
Examples of type III hypersensitivity reactions
serum sickness
vasculitis
These reactions are mediated by T cells causing ‘delayed’ hypersensitivity reactions
Type 4 hypersensitivity
Examples of type 4 hypersensitivity reactions
contact dermatitis
delayed skin tests to TB
The clinical manifestations of drug hypersensitivity depend on various factors, including…
the chemical or structural features of the drug
the genetic background of the affected individual
the specificity and function of the drug-induced immune response
the classic drugs acting as haptens, but are reported to cause type 1 IgE mediated (immediate-type) hypersensitivity reactions as well as non-IgE mediated reactions, including morbilliform eruptions, erythema multiforme and Stevens–Johnson syndrome.
Penicillins
There is a high incidence of hypersensitivity reactions in patients with altered immune status, for example due to viral infections (Epstein–Barr virus or HIV). Give an example.
increased risk of trimethoprim/sulfamethoxazole hypersensitivity in HIV patients
T/F: Many drug reactions cannot be distinguished from naturally occurring eruptions.
True, misdiagnosis is very common
What are some examples of diagnostic uncertainty when it comes to rashes
A morbilliform rash may be due to viral infection or an antibiotics, and may limit the use of a particular medication
Patients may be taking multiple medications, making it difficult to establish which is responsible
If a patient is taking two drugs, one of the drugs might be more likely to cause the particular type of cutaneous eruption than the other
How can timing be used to determine what drug is responsible for causing a skin reaction?
in general, the onset occurs soon after the introduction of the causative drug
**When examining a list of medicines taken by a patient with a rash, new drugs taken within the previous month are the most likely cause.
What are two exceptions to the timing rule?
hypersensitivity reactions to penicillins can occur several weeks after the drug has been discontinued
gold can cause late reactions, too
Drugs suspected of causing skin reactions should usually be (blank) and not used again in that patient, although the risk–benefit potential needs to be considered before discontinuing any necessary medicines.
withdrawn
What are these?
mucous membrane involvement blisters or skin detachment high fever angio-edema or tongue swelling facial edema skin necrosis lymphadenopathy dyspnoea.
signs suggestive of a severe reaction
In most cases drug eruptions are (blank), resolving gradually after the causative drug is withdrawn.
Knowledge of the (blank) of the implicated drugs can be important; for medications with long (blank), the time to resolution may be several weeks or more.
reversible; half-lives; half-lives
What are these?
Acetaminophen Allopurinol Antimicrobials: cephalosporins, penicillins, chloramphenicol, erythromycin, gentamicin, amphotericin, antituberculous drugs, nalidixic acid, nitrofurantoin, sulfonamides Antifungals (allylamine type: Terbinafine) Barbiturates Captopril Carbamazepine Furosemide Gold salts Lithium Phenothiazines Phenylbutazone Phenytoin Thiazides
Drugs commonly causing exanthematous reactions
This drug usually is well tolerated at recommended therapeutic doses.
Rash and other allergic reactions occur occasionally. The rash usually is erythematous or urticarial, but sometimes it is more serious and may be accompanied by drug fever and mucosal lesions. Patients who show hypersensitivity reactions to the salicylates only rarely exhibit sensitivity
Acetaminophen
The use of (blank) has been associated anecdotally with neutropenia, thrombocytopenia, pancytopenia, hemolytic anemia, and methemoglobinemia.
Kidney damage has been reported, and liver damage is a prominent feature of overdose.
acetaminophen
What causes a fixed drug eruption? How does a fixed drug eruption present? What might the patient complain of? Where does the eruption occur?
drugs or chemicals alone;
erythematous round or oval lesion of a reddish, dusky purple or brown color, sometimes with blisters; initially, one lesion appears but many others may follow; pt may complain or itching or burning; can occur on any part of the skin or mucous membranes (hands, feet, tongue, penis, perianal areas)
