Drug allergies and ADR

Question 1

(ADR) Adverse Drug Reaction:

Answer 1

is a term that encompasses all UNINTENDED PHARMACOLOGIC EFFECTS of a drug when it is administered correctly and used at recommended doses.

Effects from a drug when it is administered CORRECTLY.
ADR are typically DOSE-RELATED; the ADR severity increases with higher doses/reduced renal clearance.

Question 2

Medication Error:

Answer 2

can include overdose and administration mistakes.

Something WRONG occurred, such as giving a medication dose to the WRONG person.

Question 3

Urticaria (hives):

Answer 3

a rash with red/pinkish raised patches. the patches have varied shapes and sizes.

Question 4

Pruritus (itching):

Answer 4

any rash or reaction that causes itching can be referred to as pruritis.

Question 5

Erythema:

Answer 5

redness on the skin from superficial (near the surface) capillaries, often due to inflammation with pruritis. When pressed down, the red skin will blanch (whiten) temporarily because the blood flow is blocked. erythematous refers to an area on the skin, such as a patch, with erythema.

Question 6

Angioedema:

Answer 6

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

Question 7

Morbilliform:

Answer 7

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

Question 8

(ADR) Adverse Drug Reactions:

are categorized into 2 types:

1)

2)

Answer 8

1) (Type A) predictable

2) (Type B) unpredictable

Question 9

(Type A) predictable

Answer 9

• Dose-dependent
• predictable based on the drug’s pharmacology, pharmacologic actions
• can occur in anyone
• ranges from mild to severe
• ## most common, account for 80% of ADRs

ex. orthostatic hypotension with doxazosin, because of this risk, the dose of the medication should be slowly titrated.

Question 10

(Type B) unpredictable

Answer 10

• NOT dose -dependent
• idiosyncratic: NOT predictable from drug’s pharmacology
• can be influenced by patient specific factors
  Type B reactions include:

Drug allergies

Pseudoallergic reactions

Idiosyncratic reactions

ex. SJS

Question 11

Type I Reactions:

Answer 11

IgE-mediated and immediate, within 60 minutes of drug exposure, ranging from minor local reactions to severe systemic reactions.

ex. urticaria, bronchospasm, angioedema, anaphylaxis,

Question 12

Type II Reactions:

Answer 12

Antibody-mediated, occurring several days (usually 5-8 days) after drug exposure.

ex. hemolytic anemia, thrombocytopenia

Question 13

Type III Reactions:

Answer 13

Immune Complex reactions, occurring > greater than or equal to 1 week after drug exposure.

ex. drug induced lupus erythematosus

Question 14

Type IV Reactions:

Answer 14

Cell-mediated or delayed hypersensitivity reactions, occurring anytime from 48 hours to several weeks after drug exposure.

ex. Stevens-Johnson syndrome

Question 15

Type I Reactions:
- occur right after drug has been taken, immediate (within 15-30 minutes of drug exposure).
- so, if taken orally, may take a little longer because drug has to get digested and be exposed to blood
- IgE-mediated allergic reaction
- severity ranges from minor inconvenience to death
- mostly due to Histamine release from basophils
- urticaria (hives), angioedema

Type II Reactions:
- minutes to hours after drug exposure
-ex. hemolytic anemia, thrombocytopenia (platelet count down a lot)

Type III Reactions:
- they occur 3-10 hours after drug exposure
-ex. drug-induced lupus and serum sickness

Type IV Reactions: “Delayed hypersensitivity reactions”
- they can take anywhere from 48 hours to several weeks after drug exposure.
- PPD skin test for tuberculosis, which peaks at 48-72 hours

Answer 15

• a lot are injectables

histamine comes from 2 types of cells:
- basophils
- mast cells

Question 16

Boxed Warnings:
- the strictest warning.
- a boxed warning indicates a risk of death or permanent disability from a drug.

Question 17

Contraindications:
- indicate that the drug CANNOT be used in that patient.
- The risk will outweigh any possible benefit.

Answer 17

e. a Hx of VTE is a contraindication to raloxifene (Evista )

raloxifene (Evista) is a selective estrogen receptor modulator (SERM): used to reduce the of hormone receptor-positive breast cancer in women with a higher than average risk of disease.

Question 18

Warnings and Precautions:
- include serious reactions that can result in death, hospitalization, medical intervention, disability or teratogenicity.
- may or may not change a prescribing decision

Question 19

Adverse Reactions:
- refer to undesirable, uncomfortable or dangerous effects from a drug (e.g. arthralgia from raloxifene).
- the risk-benefit assessment is patient specific

Question 20

(REMS) Risk Evaluation and Mitigation Strategies:
- are developed by the manufacturer and approved by the FDA to ensure the benefits of a drug outweigh the risk.
- REMS programs can include a medication guide or patient package insert, communication plan, ELEMENTS TO ASSURE SAFE USE (ETASU) or an implementation system.

Answer 20

ex. the REMS for a drug could require prescribers or pharmacies to have a special certification to prescribe or dispense the drug, enroll patients in a registry so that ADRs can be tracked, or evaluate lab tests before dispensing.

ex.
clozapine REMS
isotretinoin iPLEDGE program
REMS to reduce misuse of long-acting opioids.

Question 21

Medication Guides:
- are FDA approved patient handouts that detail a drug’s important adverse events in non-technical language.
-** are considered drug’s labeling
- if a medication has a MedGuide, it should be dispensed with the original prescription AND with each refill.

Answer 21

• There are required MedGuides for many individual drugs and, in some cases, entire classes of medications
• “think about what is the major toxicity that this drug/drug class has that the FDA is requiring the patient to have a MedGuide to learn about the drug”
  (e.g.
  anticonvulsants- suicide risk
  antidepressants- suicidal ideation
  long-acting opioids-
  NSAIDs- cardiovascular effects, GI bleeding
  ADHD stimulants- heart related problems

Question 22

Medication Guides:

**The Medguides must be given to the patient:
- EVERY TIME the drug is dispensed to the patient in the outpatient setting- including with refills.

PLUS:

• the first time the drug is being dispensed to a healthcare provider for administration to a patient in an outpatient setting
• when the patient or patient’s caregiver requests it
• if the drug is subject to a Risk evaluation and Mitigation Strategy (REMS) that requires a MedGuide.

Question 23

Naranjo scale: Assessing whether a drug caused an Adverse Drug Reaction (ADR).

Answer 23

• a validated causality assessment scale
• helps determine the likelihood that a drug caused an adverse reaction.
• is based on the questionnaire.

Score > greater or equal to 9 = definite ADR

Score 5-8 = probable ADR

Score 1-4 = possible ADR

Score 0 = doubtful ADR

Question 24

Characterizing an Adverse Drug Reaction:

Pharmacists MUST Ask the Right Questions: Most patients are NOT registered pharmacists.

What reaction occurred? (e.g. mild rash, severe rash with blisters, trouble breathing)

When did it occur? About hold old, were you?

Can you use similar drugs in the class?
For example, for a penicillin allergy, ask if cephalexin has been used.

Do you have any food allergies or latex allergies?

Question 25

(ADR) Adverse Drug Reaction Reporting: [FAERS] FDAs Adverse Event Reporting System = FDA's MedWatch program [VAERS] Vaccine Event Reporting System - vaccines are reported

Answer 25

- side effects, adverse effects and allergies should be reported.

Question 26

(ADR) Adverse Drug Reaction Reporting: Phase IV Post-Marketing-

Answer 26

- the FDA can require Phase IV trials (post-marketing safety surveillance programs) for approved drugs and biologics, to collect and analyze reports and better understand a drug's safety profile in a real-world setting. - Post- marketing reports ALSO help identify side effects that occur less frequently. If a drug causes a reaction in 1 out of every 3000 people, the problem may not be apparent in a smaller clinical trial. For this reason, community-based ADR reporting is critical.

Question 27

For this reason, community-based ADR reporting is critical. Reporting is voluntary but has important implications for safe medication use. Healthcare professionals and patients can report adverse events to the drug manufacturer who is required by law to send the report to the FDA. reporting can be done: - - If the FDA receives enough reports that a drug is linked to a particular problem, the manufacturer can be required to update the labeling (e.g. package insert) In especially risky cases, a *drug safety alert* is issued to prescribers, usually before the labeling is changed.

Answer 27

- The MedWatch form used online - reports can be made by calling the FDA directly - -

Question 28

Intolerances, Sensitivities, and Idiosyncratic reactions: ALLERGIES are due to an -

Answer 28

an immune response and can affect multiple areas (eg bronchoconstriction and serve drop in BP from taking codeine) - Facial swelling, bronchoconstriction and severe drop in BP - Weakness, fever, severe rash

Question 29

Intolerances, Sensitivities, and Idiosyncratic reactions: INTOLEANCES are -

Answer 29

less serious complaints, such as nausea or constipation. Since the drug bothers the patient, it should be avoided, IF POSSIBLE. - upset stomach or nausea

Question 30

Histamine Release: Urticaria - erythematous swelling of the skin, with pruritis (itching) Angioedema - Swelling caused by edema in the deeper dermal, cutaneous and sun-cutaneous tissue. Pruritus, hives only? Rx, OTC: diphenhydramine Rx: hydroxyzine More than that? - get the airways open with epinephrine. Reduce swelling with steroids. Give antihistamine.

Question 31

Photosensitivity Recommended SPF 30 SPF Calculation with: (TTB) Time To Burn = take the usual time the person would burn (e.g. 15 minutes) AND multiple by the (SPF) Sun Protection Factor TTB = 20 SPF x 15min = 300 [patient won't burn until out in sunlight for 300 minutes of sunlight] Reapply Sunscreen at least every 2 hours.

Question 32

Spots and Rashes: Papules- raised spots Macules- Flat spots Purpura: Red/purple skin spots (lesions) due to bleeding underneath the skin. Purpura includes small and large spots. Petechiae: small lesions < 3mm Ecchymoses: Larger lesions > 5mm Hematoma- due to trauma A collection of blood under the skin, visible or not.

Question 33

PHOTOSENSITIVITY: Sunlight + Drug -------> severe sunburn on sun-exposed areas. " one type of photosensitivity" "second type of photosensitivity" Elicits what type of hypersensitivity ? Key Drugs Commonly associated with PHOTOSENSITIVITY: - - -

Answer 33

TYPE IV HYPERSENSITIVITY (DELAYED) - [Cell-mediated OR delayed hypersensitivity reactions, occurring anytime from 48 hours to several weeks after drug exposure]. - Amiodarone - Diuretics (thiazide and loop) - Methotrexate - oral and topical retinoids - Quinolones - St. John's wort - Sulfa antibiotics - Tacrolimus - Tetracyclines - Voriconazole - NSAIDs - Antihistamines (1st generation)

Question 33

(TTP) Thrombotic Thrombocytopenic Purpura: "spots of petechiae & Ecchymoses, clotting, low platelets" A blood clotting disorder in which cots form throughout the body. The clotting process consumes platelets and leads to bleeding under the skin with purpura. TTP can be fatal and should be treated immediately with plasma exchange. Key Drugs commonly associated with TTP:

Answer 33

- Oral P2Y12 inhibitors (e.g. clopidogrel) - ticlopidine - sulfamethoxazole - acyclovir - famciclovir -quinine - valacyclovir

Question 34

Severe Skin Reactions: (SJS) Stevens-Johnson syndrome (TEN) toxic epidermal necrolysis (DRESS) Drug reaction with Eosinophilia and Systemic Symptoms *All of these can be life threatening AND require prompt treatment Safe Drugs are NOT safe for everyone- acetaminophen, ibuprofen have caused SJS/TEN Key Drugs Commonly associated with Severe Skin Reactions:

Answer 34

- allopurinol - lamotrigine -phenytoin - penicillin's - sulfamethoxazole -piroxicam (NSAID)- Do NOT dispense

Question 35

What is Contraindicated with TEN?

Answer 35

Systemic steroids