NAPLEX: Pharmacy Foundations - Drug Allergies & Adverse Drug Reactions

adverse drug reaction

unintended pharmacologic effects of a drug when administered correctly and used at recommended doses

typically dose related

type A adverse drug reactions

predictable

dose dependent + related to known pharmacologic properties of a drug

more common type of error

examples: orthostatic HoTN w doxazosin, nephrotoxicity w aminoglycosides, tachycardia w albuterol

type B adverse drug reactions

unpredictable

not related to pharmacologic action of a drug, can be influenced by patient factors (ex: genetics)

usually caused by exposure to active ingredient

further categorized as immediate (within 60 min of exposure) or delayed (days to months after exposure)

examples include: drug allergies, drug hypersensitivity reactions, idiosyncratic reactions

type B immediate reactions

onset time

within 60 min after exposure

type B delayed reactions

onset time

days to months after exposure

drug allergies

reactions that have a defined immune mechanism (ex: antibody, T cell mediated)

not typically hereditary

drug hypersensitivity reaction

resembles a drug allergy but may not be immune mediated

do not always result in contraindication to future administration

can be linked to genetics (ex: reactions that happen w HLA alleles)

idiosyncratic reactions

reactions that arise from genetic differences

ex: select medications are more likely to cause drug induced hemolytic anemia in patients w G6PD deficiency

types of drug allergies

type I reactions - immediate

IgE mediated

ranging from minor local reactions to severe systemic reactions

immediately happen within 15-30 min of drug exposure

types of drug allergies

type II reactions - delayed

antibody mediated

usually happen minutes to hours after drug exposure

ex: hemolytic anemia, thrombocytopenia

types of drug allergies

type III reactions - delayed

immune complex reactions

occur 3-10 hours after drug exposure

ex: serum sickness, DILE

types of drug allergies

type IV reactions - delayed

T cell mediated

occurring 48 hrs to weeks after exposure

ex: SJS, PPD test for TB, photosensitivity

questions to ask to assess if an adverse reaction is an intolerance or drug allergy

- what reaction occurred (mild rash, severe rash w blisters, trouble breathing)

- when did it occur? how old were you?

- can you use similar drugs in the class? (ex: if a pt has a penicillin allergy, have they used cephalexin)

- do you have any food allergies or a latex allergy

intolerance

less serious complaints (ex: nausea, constipation)

since the drug bothers the pt it should be avoided if possible

allergies

immune system response and range from mild (pruritis) to severe (anaphylaxis)

can be present in different ways (ex: can range from facial swelling, bronchoconstriction and/or drop in BP to weakness, fever, severe rash)

true or false

stomach upset is not a patient allergy

true

it should be categorized as an intolerance

drugs associated with photosensitivity

- amiodarone

- diuretics (thiazide, loop)

- methotrexate

- oral and topical retinoids

- quinolones

- st john's wort

- sulfa drugs

- tacrolimus

- tetracyclines

- voriconazole

- antihistamines (1st gen)

- chloroquine

- coal tar

- fluorouracil

- griseofulvin

- NSAIDs

- quinidine

- tigecycline

thrombotic thrombocytopenia purpura (TTP)

also known as drug induced thrombotic microangiopathy (DITMA)

blood disorder where clots form throughout the body > clotting process consumes platelets > bleeding under skin > formation of purpura (bruises) and petechiae (dots) under skin

can be fatal + should be treated immediately with plasma exchange

drugs that can cause TTP

oral P2Y12 inhibitors (clopidogrel)

sulfamethoxazole

hematoma

collection of blood under skin d/t trauma to a blood vessel > blood leaks into surrounding tissue

drugs that cause hematoma

- heparin

- LMWH

- other anticoags / phytonadione (vitamin K)

what do pt w severe drug or food allergies need to wear

medical ID bracelet to alert emergency responders

what can be used to counteract swelling and rash in allergic reaction

antihistamines

what can be used to reduce swelling in allergic reactions

systemic steroids

NSAIDs

what can be used to reverse bronchoconstriction in allergic reactions

epinephrine

opioid non IgE mediated release of histamine

how to reduce / avoid

premedicate w an antihistamine such as diphenhydramine

vancomycin histamine release

how to reduce / avoid

occurs when infused too rapidly

avoid by slowing down infusion rate

steven johnson syndrome (SJS)

epidermal detachment and skin loss that is equivalent to 3rd degree burns

usually happens 1-3 weeks after drug exposure

presents as severe mucosal erosions, high body temp, major fluid loss, organ damage (eyes, liver, kidney, lungs)

to treat: stop offending agent ASAP + replace fluids electrolytes + perform wound care + give pain meds

what medication is CI in TEN

systemic steroids

true or false

if a pt has a history of SJS/TEN it is appropriate to retrial the medication

false

a history of SJS/TEN to a medication is a CI to receiving it again

toxic epidermal necrolysis

epidermal detachment and skin loss that is equivalent to 3rd degree burns

usually happens 1-3 weeks after drug exposure

presents as severe mucosal erosions, high body temp, major fluid loss, organ damage (eyes, liver, kidney, lungs)

to treat: stop offending agent ASAP + replace fluids electrolytes + perform wound care + give pain meds

drug reaction with eosinophilia and systemic symptoms (DRESS)

variety of skin eruptions accompanied by systemic symptoms such as fever, hepatic dysfunction, renal dysfunction, lymphadenopathy but rarely involves mucosal surfaces

to treat: stop offending drug

NOTE: sx may continue to worsen for a period fo time after the drug has been discontinued

severe cutaneous adverse reactions (SCARs) that can be caused by drugs

- SJS

- TEN

- DRESS

when does anaphylaxis onset

usually within 1 hr of drug exposure

usually after initial exposure and subsequent immune response

drugs most associated w severe cutaneous adverse reactions

- allopurinol

- amoxicillin

- ampicillin

- carbamazepine

- ethosuximide

- lamotrigine

- nevirapine

- phenytoin

- sulfamethoxazole

- sulfasalazine

- vancomycin

- amiodarone

- etravirine

- fosphenytoin

- isoniazid

- macrolides

- minocycline

- olanzapine

- oxcarbazepine

- phenobarbital

- piroxicam

- quinine

- quinolones

- rifampin

- terbinafine

sx of anaphylaxis

- urticaria (hives)

- swelling of mouth + throat

- difficulty breathing

- wheezing sounds

- severe GI sx (repetitive vomiting, severe abdominal cramping)

- HoTN

anaphylaxis treatment

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

pt with a history of anaphylaxis should carry what

- single use epinephrine auto-injector (epipen) 1 mg/mL

- emergency contact info

- diphenhydramine tablets (25 mg x2); only take if no tongue/lip swelling

symjepi specific counseling instructions

- pull off cap, hold syringe with fingers (avoid needle)

- inject in the middle of the outer thigh, hold needle firmly in place for 2 seconds, then massage area for 10 seconds

- after injection slide safe guard over needle

auvi-q specific counseling instructions

pull off outer case then follow voice instructions to administer

hold needle firmly in place in thigh for 5 seconds

epipen counseling instuctoins

- remove from carrying case and pull off blue safety release

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

- to inject jab orange end in the middle of outer thigh at 90 degree angle

- hold needle firmly in place while counting to 3

- remove needle and massage area for 10 seconds

- after injection orange tip will extend to cover the needle; if needle visible do not reuse

epinephrine auto injector counseling notes

- it is normal to see liquid remaining in the device after injecting

- call for emergency help bc additional care might be needed

- a 2nd dose in opposite leg may be given if needed prior to medical help arriving

- refrigeration is not required

- all products can be injected through clothing

- check device periodically to make sure device is not expired

common drugs associated w allergic reactions

- beta lactams

- sulfa drugs

- opioids

- heparin

- biologics

- aspirin/NSAIDs

- radio contrast media

- peanuts and soy

- eggs

true or false

anyone who is allergic to 1 penicillin is presumed to be allergic to others in the class + should avoid the entire class

true

avoid entire class unless evaluated by a healthcare provider

exception to beta lactam allergy avoidance rule

acute otitis media (AOM)

recommend a 2nd or 3rd generation cephalosporin in pt w a non severe penicillin allergy

what is considered an alternative for beta lactams in pt w penicillin allergies

aztreonam

true or false

if a beta lactam causes a delayed onset mild rash this is a CI to receiving the drug / drugs from similar classes again

false

mild rash is NOT a CI to receiving the drug / drugs of related classes again

drugs that should be avoided in sulfa reactions

- sulfamethoxazole (in bactrim)

- solfasalazine

- sulfadiazine

non arylamine sulfonamides

- thiazide/loop diuretics (except ethacrynic acid)

- sulfonylureas

- acetazolamide

- zonisamide

- celecoxib

- cidofovir

- darunavir

- fosamprenavir

- tipranavir

what do allergic reactions to ASA/NSAIDs look like

respiratory (asthma, rhinorrhea)

urticaria/angioedema

pt aspirin should be avoided in

- hx of ashma

- nasal polyps

- prior respiratory reactions to NSAIDs

onset of radiocontrast media hypersensitivity reactions

can be immediate or delayed

palforzia

oral immunotherapy indicated to mitigate allergic reactions to peanuts

true or false

peanuts and soy have cross reactivity

true

they are in the same family

drugs that are CI w a soy allergy

clevidipine (cleviprex)

propofol (diprivan)

progesterone in prometrium capsules

drugs that should be avoided in pt w an egg allergy

clevidipine (cleviprex)

propofol (diprivan)

yellow fever vaccine

true or false

pt w a severe egg allergy can receive any indicated inactivated influenza vaccine

true

flublok and flucelvax are also egg free options

true or false

if a severe reaction to an influenza vaccine occurs, pt should not receive further doses of any influenza vaccine

true

goal of penicillin skin testing

identify pt who are at greatest risk of type I hypersensitivity reaction if exposed to systemic penicillin

penicillin skin test

use components of penicillin that most often cause immune response such as diagnostic agent Pre-Pen (benzylpenicilloyl polylysine injection) w dilue dilutions of penicillin G

step wise skin test (skin prick test > intradermal testing)

positive control = histamine

negative control = saline

interpreting penicillin skin test

localized reaction larger than negative control

high risk of reaction to systemic penicillin

pt should not receive penicillin

penicillin skin test

what to do if a pt has a negative skin test

try an oral drug challenge

if safe pt can safely receive penicillin

penicillin skin testing is approved for ____ reactions

IgE mediated

penicillin skin testing is contraindicated for who

severe delayed reactions (ex: SJS, TEN)

pt should not be rechallenged

desensitization

induction of drug tolerance

step wise approach where a very small dose of medication is administered then is incrementally increased at regular intervals up to target dose, allowing for temporary safe treatment

must take place in a medical setting where emergency care can be provided if reaction occurs

use if no alternative medications are available for treatment

drug desensitization

if doses are missed

drug free period allows immune system to re-sensitize to drug, serious hypersensitivity reactions can happen w subsequent doses

NEVER MISS DOSES AFTER DESENSITIZATION

after desensitization can the allergic reaction be removed from the pt's medical record

no

if a drug is required on a separate occasion does the desensitization process need to be repeated

yes

can desensitization be attempted if a drug has previously caused SJS or TEN

no

true or false

if a drug allergy is found to be disproved (by skin test, drug challenge, otherwise) allergy label should be removed from pt profile

true

naranjo scale

scale that helps determine the likelihood that a drug caused the adverse reaction

naranjo scale interpretation

>9

definite ADR

naranjo scale interpretation

5-8

probable ADR

naranjo scale interpretation

1-4

possible ADR

naranjo scale interpretation

0

doubtful ADR

where should side effects, ADR, and allergies to drugs be reported to

FDA adverse event reporting system (FAERS) aka FDA MedWatch program

where should vaccine reactions be reported to

VAERS

true or false

if the FDA receives enough report that a drug is linked to a particular problem the manufacturer can be required to update the labeling + issue a drug safety alert

true

boxed warning

indicates a risk of death or permanent disability from a drug

contraindications

a drug cannot be used in that patient

risk will outweigh any possible benefit

warnings and precuations

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

adverse reactions

undesirable, uncomfortable, or dangerous effects from a drug

risk evaluation and mitigation strategies (REMS)

programs required by FDA for some drug

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

can include a med guide or pt package insert, communication plan, elements to assure safe use in an implementation system

medication guides

FDA approved patient handouts that detail a drug's most important adverse events in non technical language

must be dispensed with the original prescription and with each refill

if post marketing safety data is required, what clinical trial stage does it occur?

stage IV

what kind of cells release histamine

basophils

mast cells

which adverse events are not reported in FAERS

investigational drugs

vaccines

how to manage photosensitivity

- stay out of the sun 10am-4pm including on cloudy days

- wear sun protective clothing

- recommend SPF 30 broad spectrum (UVA and UVB)

- apply liberally and at least q2 hrs and reapply after swimming or sweating

- keep infants out of the sun

SPF calculation

TTB (usual time the person would burn) * SPF

papules

raised spots

macules

flat spots

purpura

red / purple skin spots (lesions) d/t bleeding underneath the skin

petechiae (smaller lesions) <3 mm

ecchymoses (large lesions) > 5 mm

SJS vs TEN

SJS = rash on <10% BSA

TEN = rash on >30% BSA