ADRs and Toxicity Flashcards
ADRs: Type A Reaction**
Dose-dependent to the known pharmacologic properties of the drug, most common
-Ex. orthostatic hypotension w/ doxazosin, nephrotoxocity w/ aminogylcosides, tachycardia w/ albuterol
ADRs: Type B Reaction**
NOT dose-dependent and unrelated to pharmacologic actions of drug and can be influenced by patient-specific factors
-Can occur with active or inactive ingredient
-Categorized further as immediate (within 60 minutes of exposure) or delayed (occurring days-months after exposure)
-Ex. drug allergies (typically NOT hereditary), hypersensitivity rxns, idiosyncratic rxns (from genetic differences such as G6PD deficiency)
Drug Allergies: Type I**
Immediate - within 15-30 minutes of drug exposure
-IgE mediated, ranging from minor local to severe systemic (ex. urticaria, bronchospasms, angioedema, anaphylaxis)
Drug Allergies: Type II**
Delayed - minutes to hours after drug exposure
-Antibody-mediated, usually occurring 5-8 days after exposure
-Ex. hemolytic anemia, thrombocytopenia
Drug Allergies: Type III**
Delayed - occur 3-10 hours after drug exposure
-Immune-complex reactions, occurring >/=1 week after exposure
-Ex. serum sickness
Drug Allergies: Type IV**
Delayed - occur 48 hours to weeks after drug exposure
-T cell-mediated
-Ex. SJS
Allergy vs. Intolerance: How to determine**
Gather Information:
1. What reaction occurred (ex. mild rash, severe rash w/ blisters, trouble breathing)?
2. When did it occur? About how old were you?
3. Can you use a similar drug in the class?
4. Do you have any food allergies or latex allergies?
Confusions with allergies:
-Stomach upset or nausea in absence of other hypersenstivity symptoms often incorrectly reported as allergy
-Non-immune drug hypersensitivity rxns: vancomycin when infused too rapidly can release histamine, opioids can cause non IgE-mediated release of histamine causing itching and hives
General Allergy Management**
Antihistamines: itching, swelling, and rash
NSAIDs, steroids: can sometimes be used for swelling
Epinephrine: to reverse bronchoconstriction
Drugs that cause photosensitivity (Type IV Hypersensitivity): limit sun exposure and recommend sunscreen**
Anti-microbials: quinolones, tetracyclines, voriconazole
Sulfa drugs
Others: amiodarone, diuretics (thiazide and loop), methotrexate, PO and topical retinoids, St. John’s Wort, tacrolimus
Define the following skin reactions: papule, macules, purpura, petechiae, ecchymosis, hematoma**
Papule: raised spots
Macule: flat spots
Purpura: red/purple skin spots (lesions) due to bleeding underneath skin which includes small and large spots
Petechiae: pinpoint in size (<3mm)
Ecchymosis: large bruised area (>5mm)
Hematoma: collection of blood under skin due to trauma to blood vessel, resulting in blood leaking into surrounding tissue (drugs that can cause: heparin, LMWH< other anticoagulants, phytonadione = vitamin K if given mistakenly as IM)
Define thrombotic thrombocytopenic purpura (TTP). What drugs can cause TTP?
“Drug-induced thrombotic microangiopathy” (DITMA) which is a blood disorder that clots form throughout the body and can consume PLTs, leading to bruising under the skin and formatoin of purpura (burises) and petechiae (dots) on skin
Drugs that can cause: oral P2Y12 inhibitors (ex. clopidogrel), sulfamethoxazole
Severe Cutaneous Adverse Reactions (SCARs):
-Types
-General Management
Types:
-Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): involve epidermal detachmentand skin loss generally occurring over 1-3 weeks after drug exposure which can result in severe mucosal erosions, a high body temperature, major fluid loss, and organ damage
-Drug reaction with eosinophilia and systemic symptoms (DRESS): includes a variety of skin eruptions accompanied by systemic rxns (fever, hepatic dysfunction, renal dysfunction, lymphadenopathy), but rarely involves mucosal surface
General TX:
-SJS/TEN: D/C offending agent ASAP, replace fluids and electrolytes, wound care, and administer pain medications; systemic steroids controveral in SJS and CI in TEN
-DRESS: D/C offending agent
Drugs associated with Severe Cutaneous Adverse Reactions (SCARS)**
Allopurinol, amoxicillin, ampicillin, carbamazepine, ethosuximide, lamotrigine, nevirapine, phenytoin, sulfamethoxazole, sulfasalazine, vancomycin
Anaphylaxis:
1. Severe, life-threatening allergic reaction that usually happens within ________ of drug exposure.
- S/Sx of anaphylaxis
- Treatment
- 1 hour
- Generalized uticaria (hives), swelling of mouth and throat, difficulty breathing or wheezing sounds, severe GI symptoms (ex. repetitive vomiting, severe abdominal cramping), and/or hypotension (dizziness, lightheadedness, loss of consciousness)
- -Call 911
-Typical TX: epinephrine injection + diphenhydramine + steroids +/- IV fluids
-DO NOT give any medications under head or in mouth to avoid airway obstruction
-Hx of anaphylaxis: carry a single-use epinephrine auto-injector (EpiPen, EpiPen Jr, Auvi-Q) –> generally available as 1mg/mL (previously labeled as 1:1000) in doses of 0.3mg (adults) and 0.15mg (pediatrics); emergency kit should consist of contact information, diphenhydramine tablets (25mg x2) if NO tongue/lip swelling
Epinephrine Counseling
ALL auto-injectors:
-Normal to see liquid remaining in device after injecting
-Call for emergency help because additional care may be needed
-A second dose in opposite leg may be give if needed prior to arrival of medical help
-Refrigeration NOT required
-All products can be injected through clothing
-Check the device periodically to make sure the medication is clear and NOT expired
-Tell family, caregivers, and others where pen is kept and how to use
EpiPen Administration:
-Remove from the carrying case and pull off blue safety release.
-Keep thumb, fingers, and hand away from orange (needle) end of device
-To inject, jab the orange end into the middle of outer thigh at a 90 degree angle
-Hold the needle firmly in place while counting to three
-Remove the needle and massage the area for ten seconds
-After injection, the orange tip will extend to cover the needle (if visible, should NOT be reused)
Symjepi: Pull off the cap, holding the syringe with the fingers. Inject in the middle of outer thigh, hold needle firmly in place for two seconds, then massage area for 10 seconds. After injection, slide the safety guard out over the needle.
Auvi-Q: Pull off the outer case, then follow the voice instructions to administer. Hold the needle firmly in place on the thigh for five seconds.
While cross-reactivity between cephalosporins and carbapenems to penicillins, on the NAPLEX, beta-lactams should be avoided. A notable exception is in ____________ where __________ can be used in a non-severe pencillin allergy.**
Acute otitis media; 2nd or 3rd gen cephalosporin
_________ is an antibiotic considered safe in penicillin allergy.**
Aztreonam
How to determine a true penicillin allergy.**
For immediate-type reactions (ex. anaphylaxis), a skin test can assess risk:
-Pts with negative result should be given an PO drug “challenge” dose before full dose TX
-Pts with positive result should avoid use of drug
-Should NOT be performed if hx of severe cutaneous rxns (SJS/TEN)
-Many cephalosporins can be safely tolerated in pts w/ mild PCN allergy
When would desensitization of a pencillin allergy be considered? Is densensitization a cure for the allergy?**
Penicillin is the ONLY acceptable treatment in pregnant or non-adherent pts with syphilis. If skin test positive, temporarily desensitize and admnister PCN.
-Densensitization: NOT a cure, only temporarily allows pt to receive medication, if dose missed, drug-free period allows immune system to re-sensitize
Drugs commonly associated with allergic rxns
- Beta-lactams**
- Sulfa drugs - most common in sulfamethoxazole (in Bactrim), other drugs should be avoided including sulfasalazine and sulfadiazine
-Package labeling for “non-arylamine” sulfonamides (ex. thiazide direutics, loop diuretics except ethacrynic acid, sulfonylureas, acetazolamide, zonisamide, celecoxib, cidofovir, darunavir, foasmprenavir, tipranavir) contain warnings/CIs for sulfa allergy (in-practice, low risk, but watch on NAPLEX)
-Sulfite or sulfate allergies do NOT cross-reaction with sulfonamides - Opioids - common hypersensitivity rxn with histamine release, but true allergy uncommon
- Heparin - watch for heparin-induced thrombocytopenia (HIT)
- Biologics - hypersensitivity rxns (ex. rituximab)
- ASA/NSAIDs - hypersensitivity rxns (most common: respiratory such as asthma or rhinorrhea and urticaria/angioedema)
- Radiocontrast media - immediate and delayed hypersensitivity rxns
________ and _______ foods are in the same family and can have cross-reactivity.**
Soy and Peanut
________, ________, and ______ are drugs CI in soy allergy.**
Clevidipine, propofol, Prometrium
_________, _________, and __________ are CI in egg allergy.**
Clevidipine, propofol, yellow fever vaccine
What are vaccine considerations with egg allergies?**
Even in severe egg allergy, can receive any inactivated flu vaccine
-Egg-free options: Flublok, Flucelvax
-In severe reaction to influenza vaccine, should NOT receive further doses of ANY influenza vaccine
CI in egg allergy: Yellow Fever
