Adverse Drug reactions Flashcards
Reasons children and infants are at high risk of adrs
medication dosages must be tailored to their specific weight or body mass index. Inattention to weigh based dosing may cause harm. The very young may have immature organ function which further complicates dosing and increases the risk for ADRS.
Reasons elderly are at high risk for ADRS
they take more medication and take them more often.
decreased renal and hepatic function results in decreased metabolism and clearance causing medications to accumulate and cause toxicity.
increased risk of hospitalization with adr
polypharm should be minimized unless necessary
Types of ADRS
Type 1 immunoglobulin E-mediated, immediate type sensitivity. Angio edema, anaphylaxis
Type 2 antibody-dependent cytotoxicity (heparin-induced thrombocytopenia.
Type 3 Immune complex hypersensitivity( Arthus reaction to tetanus vaccine.
Type 4 cell-mediated or delayed hypersensitivity (drug rash, eosinophilia, and systemic syndrome (
dress)
Type 1 - immune-medicated reactions (immunoglobulin E-mediated, immediate-type hypersensitivity
provoked by re-exposure to an antigen.
Can be local or systemic
involves skin, bronchopulmonary system, nasopharyngeal tract, eyes, gi tract.
caused by inducing the release of mediators(histamine, leukotrienes, prostaglandins) from mast cells, basophil, and recruited inflammatory cells after antigen exposure which activates IgE
Type 1 symptoms
Most cases are mild
Can be mild-severe
conjunctivitis, rhinitis, bronchospasm, urticaria, atopic dermatitis.
Life threatening- Angio edema, anaphylactic shock.
symptoms may occur immediately, or delayed for several hours.
Acute anaphylaxis possible medication reactions
antibiotics (pcn, cephalosporin, sulfonamides)
neuromuscular blockers (suxamethonium, alcuronium, vecuronium, pancuronium, atracurium)
some chemotherapy(carboplatin, oxaliplatin)
monoclonal antibodies (cetuximab, rituximab)
treatment of type 1
usually involves administration of epi, antihistamines, and corticosteroids.
Type 2 hypersensitivity reactions
antibody-dependent cytotoxicity
may affect a variety of organs and tissues
in the bloodstream, and on the surface of cells, antibodies unite with antigens or haptens and induce destruction of cells and tissues through activation of the complement system or through removal by macrophages.
Drug induced immune thrombocytopenia
Type 2 reaction
caused by medications, but can also be caused by foods or herbal products.
associated with formation of drug-dependent antibodies that bind to glycoprotein and cause an antibody-platelet reaction resulting in thrombocytopenia
medications that may cause type two reactions
abciximab, argatroban, beta-lactam antibiotics, carbamazepine, eptifibatide, linezolid, phenytoin, quinine, quinidine, sulfonamide, rifampin, ranitidine, tirofiban, trimethoprim-sulfamethoxazole, valproi acid, and vancomycin.
DITP and heparin
heparin binds to platelet factor 4 proteins resulting in the formation of an antigenic complex where IgG antibodies bine to the platelets. The anti-body coated platelets are viewed by the body as foreign and the body destroys the platelets via complement activation, causing thrombocytopenia.
hemolytic anemia
type 2 occurs when a drug binds to antigens on the surface of red blood cells, resulting in complement activation and cell lysis. cephalosporins (cefotetan, ceftriaxone) pcn or pcn derivatives nsaids quinidine, quinin trimethoprim-sulfamethoxazole
Neutropenia
occurs when antibodies unite with antigens on the surface of neutrophils. reaction within minutes to hours clozapine antithyroid methimazole, carbimazole sulfasalazine clomipramine trimethoprim-sulfamethoxazole angiotensin converting enzyme (ACE) inhibitors H2 receptor antagonists
treatment of type 2
anti-inflammatory and immunosuppressive agents.
Type 3 hypersensitivity reactions
immune complex hypersensitivity
occurs when aggregates of antigens and IgG and IgM antibodies create insoluble immune complexes in vessels or the blood that may be deposited in tissues.
type 3 kinds of reactions
takes a week or more to occur
serum sickness
drug fever
vasculitis
Arthus reaction
local vasculitis reaction that causes severe pain, swelling, edema, induration, hemorrhage, possible necrosis.
can occur after a tetanus/diphtheria toxoid (Td) vaccination.
elevated risk when person receives vaccination more frequently than every 10 years.
Arthus reaction results from deposition of immune complexes and complement activation. Patients who experience the reaction recommended not to have Td done more frequently than every 10 years
Type 3 medications that cause the reaction
Td vaccine streptokinase monoclonal antibodies (rituximab, infliximab, alemtuzumab, omalizumab, natalizumab) rabies vaccine antivenom antitoxins
How are type 3 reactions treated
antihistamines and anti-inflammatory agents (nsaids, corticosteroids).
Type 4 hypersensitivity
Cell-mediated or delayed type hypersensitivity
not antibody mediated reaction
cell-mediated response that results in activation and proliferation of T cells.
result of autoimmune and infectious diseases or contact dermatitis.
occurs within 2-3 days but can take weeks
rechallenge reaction may occur within 24 hours
type 4 reactions
contact dermatitis morbilliform or maculopapular eruptions Stevens-Johnson syndrome toxic epidermal necrolysis Drug-induced hypersensitivity syndrome (DIHS severe or DRESS) reaction causing rash/fever eosinophilia organ failure.
Drugs that cause type 4
abacavir allopurinol carbamazepine dapsone minocycline nevirapine phenobarbital
treatment for type 4 reactions
corticosteroids, immunosuppressive agents.
Types A-F ADRS
A- pharmacological reactions 85-90% dose dependent, predictable
B- reactions are idiosyncratic 10-15% not dose dependent, are not predictable
C-reactions result from chronic medication
D-reactions are delayed
E- result from drug-drug interactions
F-result from treatment failures
Pharmacological ADRS
common, majority of ADRS.
reactions are exaggerated physiological response related to pharmacology of the drug (hypotension from metoprolol, diarrhea from fat-blocking drug orlistat, insomnia from stimulant methylphenidate.
Can occur based on secondary pharmacology, such as weight gain from atypical antipsychotic olanzapine, flatulence from psyllium, or myopathy from HNG_CoA reductase inhibitor simvastatin.
Management of pharmacological ADRs
withdrawing the medication or reducing the dose.
Idiosyncratic reactions
Mediated by the immune system receptor abnormalities drug-drug interactions abnormalities in drug metabolism pharmaceutical variations unmasking of abnormal biological system Most commonly reactions are mediated by the immune system when a drug molecule is recognized as a foreign substance.
Hapten hypothesis
describes how drugs may cause an immune-mediated hypersensitivity reaction. Suggests that drugs are haptens, which are low=molecular weight chemicals that can become antigenic when they covalently bind to a carrier molecule, usually a protein. Through this mechanism, individual patterns of metabolism may generate reactive metabolites that act as haptens to elicit and immune-mediated reaction.
PCN results in type 1 hypersensitivity (anaphylaxis) reaction.
MedWatch system
MedWatch is the FDA’s safety information and adverse event reporting program that provide healthcare providers with medical product information on prescription and nonprescription drugs, biologicals, medical devices, and nutritional products. Health providers have an obligation to provide data to allow the FDA to monitor medication and vaccine safety. It allows providers and consumers to report adverse events and serious problems caused by FDA-regulated products. The FDA publishes alerts in MedWatch and consumer publications. To ensure a favorable balance between benefits and risks for certain drugs or biologicals, the FDA requires manufacturers to implement a Risk Evaluation and Mitigation Strategy (REMS) REMS protocol is composed of various actions (ETASU, elements to assure safe use), including letters to prescriber, additional patient information, and required patient, prescriber, and pharmacy registration and training. REMS are required for many drugs.
Buprenorphine
Naloxone
Extended release and long-acting opioid analgesics
Liraglutide
Metoclopramide
Mifepristone
Naltrexone
Olanzapine
TestosteroneVaccine Adverse Event Reporting system
A separate program used to report adverse events related to vaccinations which also allows voluntary reporting of adverse events by providers and consumers. The FDA monitors adverse events and can respond with safety announcements, alerts, and removal of vaccines from the market.
What is the Naranjo ADR Probability scale
A framework for assessing the probability that an adverse reaction is related to the administration of a particular drug. It is based on timing, prior history and reports, rechallenge, alternative causes, dose dependency, and objective evidence, it defines the relationship between the drug and adverse reaction as definite, probable, possible, or doubtful based upon the score.
Naranjo ADR scores and meanings
Definitive greater than 8
Probably 5-8
Possible 1-4
Doubtful less than 1
Malignant hyperthermia
occurs after administration of general anesthetics. An example of a receptor abnormality (mutations encoding for abnormal RYRI or DHP receptors, which result in sustained muscle contraction from unregulated calcium from the sarcoplasmic reticulum into the intracellular space. Genetic factors can also increase the likelihood of a hapten-induced hypersensitivity.
rapid reactions
occur during or immediately after the administration of a medication. These unintended adverse reactions generally occur when medications are administered improperly and are not necessarily associated with first dose.
Vancomycin can cause red man syndrome when administered too rapidly.
Phenytoin can cause an adverse reaction known as purple glove syndrome (blood vessel irritation and inflammation) when administered peripherally.
Skin or tissue necrosis secondary to extravasation of a chemotherapeutic agents. Hand foot mouth syndrome.
first dose reactions
occur after the first dose of a medication.
orthostatic hypotension is a common reaction that occurs after the first dose of doxazosin, and does not happen with repeated doses.
Cytokine release syndrome occur after first dose of orthoclone OKT3.
Early reactions
occur early in treatment and generally resolve with continued treatment as patient develops tolerance. These reactions do not require discontinuation of the drug but may require that the patient adapt to the medication. However, not all early reactions will resolve with continued treatment. Immune hypersensitivities may occur after the first or subsequent dose and usually requires immediate discontinuation, and may require further medical treatment.
gi upset initiation of metformin and ssri
intermediate reactions
occur after repeated exposure to a medication. hyperuricemia from furosemide hemolytic anemia from ceftriaxone interstitial nephritis from pcn G contact dermatitis from neomycin
needs vigilant monitoring especially during therapy
late reactions
occur after prolonged exposure to an offending agent.
osteoporosis or thinning of the skin due to prolonged corticosteroid use.
hypogonadism after prolonged use of opioids.
It may be possible to symptomatically treat late ADRs, but most are predictable and occur after repeated exposures. Thus, it is recommended to remove the offending agent before the reactions predicted to occur to manage this type of adverse effect.
tapering the drug to reduce adrs when removing medications.
oxycodone- anxiety, insomnia, rhinorrhea, diaphoresis, tremor, vomiting, diarrhea, tachycardia. Pt’s with clonidine or propranolol may experience rebound hypertension.
