Chapter 5 Flashcards
how many serious adverse drug reactions are reported annually
660,000 that result in ED visits, hospital admissions and 120,000 reported deaths.
total cost associated with ADR
3.5 billion to 126 billion per year
ADR
any undesirable or unintented effect after administration of a medical product, whter or not the effect is considered related to amedical product.
Two basic types of ADRs
phamacological and idiosyncratic
phamacological reaction
predictable baed on the drug’s MOA and is typically dose realted
Idosyncratic reaction sare
unpredictable and may more lkely to result in moretality
which type of reaction is more common
pharmacological
Example of a pharmacological reaction
hypotention from a beta blocker, diarrhea from the fat-blocking drog orlistat, and insomnia from the stimulat methylphenidate. Seondary effects are included such as weight gain from atypical antipsycotics.
Idiosyncratic reactions are
unpredictable, often serious and may result in death.
Idiosyncratic reactions are mediated
mediated by the immune syste, receptor abnormaliteis, dug-durg-intractions, abnormailites in metabolisy, pharmaceutical variations or unmasking of abnormal biogical sytms.
Hapten hypothesis
describes how drugs may cause an immune-mediated hypersensitivety reaction. The hypotheis suggests taht drugs are haptens, which are low-molecular weight chemcicals that can become antigenic when they covalently bind to a carrier molecule, usually a protein. Through this mechanism, individual patterns of metabolism may generat reactive metabolites that act as haptens to elicit an immune medicate reaction. Penicillin is an example of a haptin with low molecular weight that is able to bind to a protein and result in type I sensivity reaction.
Medicatoins that rae not haptens may also eliciit an immune-medicate raction through a different mechanism called the
pharmacologic interaction with immune receptors
an example of a phmacologic interaction with immune receptors
licocain, sulfamethoxazole, mepivacaine, celecoxib, carbamazepine, lamotrigine, and ciprofloxacin are chemcically inert drugs, unable to covalently bind to protins, howevier if amedication or its metabolite is able to bind covalently to a protein, it can form hapten-carrier complex and resutl in an immune response.
These hapten carrier complexes that restul in immune mediate reactions are called
type I, II, III, or IV
Type one are provoked by
exposure to an antigen
type one reaction is an
acute hypersensitivety reaction that may be local or systemic involving the skin, or bronchpulmonary system, nasopharngeal tract, eyes and GI tract
Typ one is caused by inducing the release of
mediators (histimine, leukotrienes and prosagrandins from mast cells, basophils, and recruited inflammatory cells after antigen exposure which then activates IGE.
Type one reactions vary from mild to severe and can come one
within minutes or have delayed onset where it takes severl hours to present symptoms. can be life threatenting.
Type one basics and examples
immunoglobulin E mediated, immediate type hpersensitivty. Eample angioedema and anaphylaxis
Type two basics and examples
antibody-dependent cytotoxicity, example heparin-induced thrombocytopenia
type three basics and examples
immune complex hypersensitivity, example arthus reaction to tetanus vaccine
type four basics and examples
cell mediated or delayed hypersensitivty, example, drug rash eosinophilia, and systemic syndrome (DRESS)
Type two hypersensitivy reactions may affect a variety of organs and tissues. In the bloodstreat
and on the surface of cells, antibodies unite with antigens or hapttens and induse destrcution of cells and tissues throguh activatio nof complent systems or through removal by macrophages.
hapetns
a small molecule which, when combined with a larger carrier such as a protein, can elicit the production of antibodies which bind specifically to it (in the free or combined state).
Immune mediated thrmboocytopenia also called
drug-induced immune thrombocytopenia (DITP) is generally cuaed by medications, but foods or herble products
thrombocytopenia
a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood.
Most DITP reactions are assoicated with the formation of
drug dependent antibodies that bind to glycoprotein and cause an antibody-platelet reaction resulting in thrombocytopenia.
examples of medications presenting a risk of DITY include
abciximab, argatroban, bata-lactam antibiotics, carbamazepine, eptifibatide, linezolid, phenytoin,
DITP can also occur when heparin binds to
platelet factor 4 proetins resulting in the formation of antigenic complex where IgG antibodies bond to the pltelet. Teh atnibody-coated platelets are viewed by the body as foreign and the body destroys the platelets visa complement activation, causing thromboycytopenia.
Hemolytic anemai accurs when
a drug binds to antigens on the surface of red blood cells resulting in complement activation and cell lysis. Examples of medications that cause hemolytic anemia include cephalosporins, penicillin, NSAIDs,
Neutropenia or agranulocytosis
can occur when antibodyies unite with antigens on the surface of neutrophils. the reaction time is minutes to hours
Examples of durts that can cause neutropenia.
clozapine, anithyroid medications, sulfasalazone, clompipramine, trimethoprism sulfatheoxazole, angiotensin-converting enzyme inhibitors and H2 receptor antagoints.
treatment for drugs that cuase neutropenia
anti-inflamatory drugs
Type III hyperseitivty reactions occur
when aggregates of antigens IgG and IgM antibodies create insoluble immune complexes in vessesl or the blood that may be deposited in tissues (joints, kidnes)
The type three reaction generally takes
a week or more to occur and may present as serum sickness, drug fever, or vasculitis.
The arthus reaction is a
locla vasculitis reaction that causes severe pain, swelling, edema, induration, hemorrhage, and possibly necrosis which can occur after tenanus/diptheria toxoid vaccination (type three)
The risk of arthrus reaction from TD vaccine is elevated when a patient receives
vaccinatin more frequently than every 10 eyears.
It is recomended that patients who have expereinced an arthus reaction after vaccination with tetanus toxoid do
not receive TD more frequently than every 10 years even if the vaccine is part of ap rotocol for wound managment
Type iV
are unlike others because they are not an ntibody-mediated reaction, but rather cell-mediated response that results in activation an dporliferation of T cells.
Typ four hypersesitivty reaction are the result of atuoimmune and infectoius disease or contact dermatitis. These reactions generally occur witthin
2 to three days, but may take days or weeks to occur
The type four reaction may be in the form of
contact dermatitis, morbillifom or maculopapular euptious, sevents jhonsome syndrome, toxic epidermal necrolysis, or drug inducsed hyperseitivty sindrom.
DIHS is a
severe reaction that not only causes rash but also is frequetly associated with fever, esoinophilia, and organ failure.
DIHS is also known as
DRESS, drug rash eosinophilia, and systemic symptoms.
Examples of drugs that cuase DRESS
abacavir, allopurinol, carbamazepine, dapsone, minocycline, nevirapine, and phenobarbital.
treatment for DRESS
corticosteroids and other immunosupressive gents
adverse drug reactions have also been categorized as types
a through f
Type A reactions are equivalent to
pharacological reactions and account of r85% to 90 % of ADRs, are dose dependent, and are not predeicable
Adverse reactions have been further stratified by letters
C through F, reactions that result from chronic medication use
Type D reactions
are delayed
Type F reactions result from
treament failures
