UWORLD Chapter 76: Drug Allergies & Adverse Drug Reactions

What is an adverse drug reaction?

all unintended pharmacologic effects of a drug when it is administered correctly and used at recommended doses (typically these are dose related)

What is a medication error?

Something wrong occurred (giving medication dose to the wrong person)

What is urticaria (hives)?

A rash with red/pinkish raised patches

(Varied shapes and size)

What is pruritis (itching)?

any rash or reaction that causes itching

What is erythema?

Redness on the skin from superficial (near the surface) capillaries, often due to inflammation with pruritus. When pressed down, the red skin will blanch (whiten) temporarily because the blood flow is blocked.

What is morbilliform?

Macular or maculopapular rash (or both) with 1-10 mm lesions and healthy skin between lesions

What is angioedema?

Swelling caused by edema in the deeper dermal, cutaneous, and submucosal tissue

What are Type A ADRs? Give examples

dose dependent, related to the known pharmacologic properties of the drug, can occur in any patient and can range from mild to severe. Most common type. Example is nephrotoxicity with aminoglycosides.

What are Type B ADRs?

Not dose dependency and are unrelated to the pharmacologic actions of the drug and can be influenced by patient specific factors. Categorized as immediate (occurring within 60 minutes after exposure) or delayed (occurring days to months after exposure)

What are drug allergies?

patient's immune system identifies a drug as a dangerous, foreign substance to be neutralized or destroyed

What are hypersensitivity reactions?

resemble drug allergies but may or may not be immune related. examples are histamine release with vancomycin, and genetic linkages

What are idiosyncratic reactions?

usually genetic, an example is select medications are more likely to cause drug induced hemolytic anemia in patients with G6PD deficiency

What is the definition, timing and examples of type 1 reactions?

- IgE-mediated, ranging from minor local reactions to severe systemic reactions

- Timing: Immediate

- Examples: urticaria, bronchospasm, angioedema, anaphylaxis

What is the definition, timing and examples of type 2 reactions?

- Antibody mediated

- Timing: usually occurring 5-8 days after exposure

- Examples: hemolytic anemia, thrombocytopenia

What is the definition, timing and examples of type 3 reactions?

- Immune complex reactions

- Timing: occurring 1 week or more after exposure

- Examples: serum sickness

What is the definition, timing and examples of type 4 reactions?

- T cell mediated

- Timing: occurring 48 hours to weeks after exposure

- Examples: Steven's-Johnson syndrome

What are intolerances?

less serious complaints, such as nausea or constipation. Since the drug bothers the patient, it should be avoided, if possible.

How do you determine whether a reaction is a drug allergy or drug intolerance?

pharmacists must ask the right questions to determine whether an adverse reaction is either of these types of reactions

What is GI upset in the absence of other hypersensitivity symptoms?

not an allergy, categorized as an intolerance

What is a counseling point to tell patients that use drugs that cause photosensitivity?

use broad spectrum sunscreen that blocks both UVA and UVB radiation

What are key drugs that cause photosensitivity?

- Amiodarone

- Diuretics (thiazides and loops)

- Methotrexate

- Oral and topical retinoids

- Quinolones

- St. John's wort

- Sulfa drugs

- Tacrolimus

- Tetracyclines

- Voriconazole

What is thrombotic thrombocytopenia purpura?

Blood disorder that results in blood clots forming in small vessels throughout the body, resulting in consumption of platelets and red blood cells due to their breakdown. Leads to bruises and dots on the skin.

What drugs cause TTP?

clopidogrel and sulfamethoxazole

What are papules?

raised lesions

What are macules?

flat, reddened lesions

What are purpura?

Red/purple skin spots (lesions) due to bleeding underneath the skin. includes small and large spots.

What are petechiae?

pin-point red or purple spots caused by small hemorrhages

What are ecchymosis?

large subcutaneous hematoma (>1-2 cm)

What is a hematoma?

a collection of blood under the skin due to trauma (injury) to a blood vessel, resulting in blood leaking into the surrounding tissue.

What can a reaction without breathing difficulty sometimes be treated with?

by stopping the offending agent

What are agents that can treat allergic reactions?

antihistamines, systemic steroids, NSAIDs can decrease swelling, epinephrine is used to reverse bronchoconstriction

What type of nondrug mediated reaction can opioids cause?

non-IgE mediated release of histamine from mast cells in the skin, causing itching and hives

What is vancomycin infusion reaction and how is it mitigated?

Direct release of histamine from cutaneous mast cells, causing flushing, hives, and sometimes hypotension when drug is infused too fast. Slow down infusion to mitigate

What do mutations in HLA alleles increase the chance of? Name an example of this.

delayed type hypersensitivity syndromes

example is patients positive for HLA-B*5701 being at increased risk of abacavir hypersensitivity

What are examples of severe cutaneous reactions?

Stevens-Johnson Syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms

What are SJS and TENS and how do you mitigate them?

- involve epidermal detachment and skin loss equivalent to third degree burns

- stop the offending agent, perform wound care, drugs with a history of SJS and TENS reactions are not contraindicated in that patient

When are systemic steroids contraindicated vs usable in severe skin reactions?

contraindicated with TENS, may be used for SJS

What are drugs most associated with severe cutaneous adverse reactions?

- allopurinol

- amoxicillin

- ampicillin

- Carbamazepine

- ethosuximide

- lamotrigine

- nevirapine

- phenytoin

- sulfamethoxazole

- sulfasalazine

- vancomycin

What is treatment for DRESS?

stopping offending drug, although symptoms may worsen at first

What is anaphylaxis?

a severe, life threatening allergic reaction that usually happens within 1 hour of drug exposure

What are potential symptoms of anaphylaxis?

urticaria (hives), swelling of the mouth and throat, difficulty breathing or wheezing sounds, severe GI symptoms, hypotension

What are treatments for anaphylaxis?

- immediate emergency medical care, call 911

- epinephrine +/- diphenhydramine +/- steroids +/- IV fluids

What are the different names of epinephrine auto injectors and their concentration?

- EpiPen, EpiPen Jr., Auvi-Q

- 1 mg/mL or 1:1000

What strength of tablets and how many tablets of diphenhydramine should be in a patient's emergency kit?

two 25 mg tablets

What are the instructions for the EpiPen?

- Remove from carrying case and pull blue safety release

- Keep thumb, fingers, and hand away from orange (needle) end of the device

- To inject, jab the orange end into the middle of the 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 10 seconds

- After the injection, the orange tip will extend to cover the needle. If the needle is visible, it should not be reused

What are counseling points for all epinephrine auto injectors?

- It's normal to see liquid still remaining in the device after injecting

- Call for emergency help because additional care may be needed

- A second dose in the opposite leg may be given, if needed, prior to the arrival of medical help

- refrigeration is not required

- all products can be injected through clothing

- check the device periodically to make sure the medication is clear and not expired

What is the rule with penicillin allergies?

allergic to one means allergic to all others in that class. The entire class should be avoided until being evaluated by a healthcare provider.

What other classes are cross reactive to penicillins?

Cephalosporins and carbapenems

What disease state can 2nd and 3rd generation cephalosporins be given in a non-severe penicillin allergy?

acute otitis media

What drug is safe in patients with penicillin allergies?

Aztreonam (a monobactam)

What can beta lactams cause and should be treated through this reaction?

delayed onset mild rash

What are sulfa drugs?

sulfamethoxazole, sulfasalazine, sulfadiazine

What are sulfonamide drugs?

- thiazides

- loop diuretics

- sulfonylureas

- acetazolamide, zonisamide

- celecoxib

- darunavir

Do sulfite and sulfate allergies cross react with sulfonamides?

no cross reaction

What are the most common hypersensitivity reactions with NSAIDs and aspirin?

respiratory (asthma and rhinorrhea) and urticaria/angioedema

What reaction can radiocontrast dye cause?

immediate and delayed hypersensitivity reactions

What drugs have cross reactivity with a peanut or soy allergy?

clevidipine and propofol

What drugs/vaccines can a patient with a true egg allergy not have?

clevidipine, propofol, and the yellow fever vaccine

How do you handle an allergy to eggs with the flu vaccine?

Flublok and Flucelvax are egg free options; if a severe reaction to an influenza vaccine occurs, the patient should not receive further doses of any influenza vaccine

What is important with antibodies and true penicillin reactions?

antibodies can wane overtime

What is the goal of penicillin skin testing?

To identify individuals at the greatest risk of a Type I hypersensitivity reaction

What reaction is skin testing contraindicated with?

SJS or TEN

What is a situation in which desensitization may be recommended?

if a pregnant patient with syphilis has a penicillin allergy, the CDC recommends desensitization and penicillin treatment

How is desensitization performed?

step wise process that begins be administering a very small dose of the medication and incrementally increasing the dose at regular intervals up to a target dose

Where must desensitization take place?

in a medical setting where emergency care can be provided

What is delabeling?

when allergies are found to be disproven, the allergy label should be removed from the patient's profile

What is the Naranjo Scale?

Used to help determine the likelihood that a drug caused an adverse reaction. (≥ 9: definite)

Where should side effects, adverse events, and allergies be reported to?

FDA's MedWatch program, which is called the FDA Adverse Event Reporting System (FAERS)

What type of trial can the FDA require after the drug has already been approved?

Phase IV trials (post-marketing safety surveillance programs

What can happen if the FDA receives enough reports of a particular reaction occurring?

manufacturer can be required to update the labeling (package insert). In especially risky cases, a drug safety alert is issued to prescribers

What are boxed warnings?

Warnings that highlight serious or life-threatening risks associated with a medication.

What are contraindications?

indicate that the drug cannot be used in that patient. The risk will outweigh any possible benefit

What are warnings and precautions?

serious reactions that can result in death, hospitalization, medical intervention, disability or teratogenicity

What are REMS programs?

developed by the manufacturer and approved by the FDA to ensure the benefits of a drug outweigh the risks

What are the most known REMS programs?

opioids, isotretinoin

What are medication guides?

FDA-approved patient handouts created to educate patients about how to minimize harm from potentially dangerous drugs

When does a medication guide need to be dispensed?

with the original prescription and with each refill