Lecture 20 - Allergic Rxns and Anaphylaxis

type A adverse drug rxns

80-90% of all ADRs that are predictable from the known pharmacologic properties of the drug are are non-immunologic; can include normal environmental exposures

examples of type A adverse drug rxns

• diarrhea from antibiotics

• GI upset from long-term NSAID use

• poison ivy

type B adverse drug rxns / allergic rxns

10-15% of ADRs that are mediated by immunologic mechanisms; signs/symptoms not expected based on pharmacologic properties

3 subtypes of type B adverse drug rxns / allergic rxns

1. hypersensitivity rxns

2. idiosyncratic rxns (due to genetic deficiencies)

3. immunologic drug rxns (actual drug allergy)

type I immunologic drug rxn mechsnism

IgE-mediated activation of mast cells and basophils that release vasoactive substances (ex: histamine)

type I immunologic drug rxn onset

within 1hr of exposure

type I immunologic drug rxn clinical features

• anaphylaxis!!

• angioedema

• bronchospasm

• urticaria (hives)

type II immunologic drug rxn mechanism

cell-associated antigen or hapten binds to antibody, leading to cell injury / tissue death

type II immunologic drug rxn onset

>72h to weeks

type II immunologic drug rxn clinical features

• hemolytic anemia

• thrombocytopenia

• neutropenia

type III immunologic drug rxn mechanism

damage caused by formation or deposition of antigen-antibody complexes in vessels or tissue

type III immunologic drug rxn onset

>72h to weeks

type III immunologic drug rxn clinical features

• serum sickness

• arthus rxn

type IV immunologic drug rxn mechanism

t-cell mediated

drug hypersensitivity rxn (pseudo-alergic) rxn

reactions that mimic type B idiosyncratic ADRs but are likely not mediated by an immune response

drug hypersensitivity rxn (pseudo-alergic) rxn examples

• flushing after vancomycin infusions

• aspirin-induced asthma

• itching with opiates

anaphylaxis

acyte, life-threatening allergic rxn involving multiple organ systems usually beginning <1h after exposure

common anaphylaxis symptoms

• difficulty breathing / closing of airways

• rash / swelling

• increased vascular permeability leading to low BP and shock

cross-reactivity rxn

allergic reaction to an agent or its metabolite that is structurally similar, but not identical, to a known allergen

cross-reactivity rxn example

penicillins and cephalexin

patient interviewing questions for allergic rxns

• have you ever had an “allergic” reaction to a medication?

• what other foods/medications were you taking at the time

• have you ever received the drug without experiencing a reaction?

• what was the dose/route of administration?

• can you describe the adverse reaction? (how long after taking med, how long did it last, was med discontinued, any permanent damage, any treatment)

• (if antibiotics) ask what type of infection was being treated

• any risk factors for allergic rxns (liver/kidney disease, HIV)

criteria for anaphylaxis (1 of 3)

1. acute onset of a rxn that involves the skin/mucosal tissue and the respiratory tract and/or a decrease in BP

2. rapid onset of a rxn after exposure to a likely allergen that involves 2 organ systems

3. decrease in BP alone after exposure to known allergen

bi-phasic rxn

two-phase allergic response where symptoms resolve after the first reaction, only to return hours later (typically 1-72 hours) without further exposure to the trigger, and the second phase can be as severe or worse than the first, necessitating prolonged medical observation

management of type II-IV allergic rxns

stop offending agent and provide supportive care

management of MILD type I allergic rxns

1. stop/remove offending agent if possible

2. H1-blocking antihistamine (diphenhydramine)

3. potential corticosteroid and H2-blocking antihistamine

anaphylaxis management goals

1. maintain airway and breathing

2. manage vascular tone and intravascular volume losses (prevent shock)

3. stop mast cell degranulation

immediate anaphylaxis treatment

• oxygen —> keep O2 to core organs

• epinephrine —> b1 = HR, b2 = bronchodilation

• establish IV access at hospital or in transit to initiate maintenance rate of normal saline (NS) —> maintain BP

additional anaphylaxis interventions

• diphenhydramine (IV or IM) —> treat cutaneous and histamine rxns

• IV corticosteroids —> limit recurrence of biphasic rxns

• IV H2 blocker —> helps GI symptoms with diphenhydramine

epipen dosing / weights

adults and children over 30kg —> 0.3mg epinephrine

epipen jr. dosing / weights

children 15-30kg —> 0.15mg epinephrine

what to use if patient has no response to epinephrine due to use of beta blocker

injectable glucagon

epipen administration saying

“blue towards the sky, orange to the thigh”

epipen wait times

hold pen in thigh for 3 sec, massage area for 10 sec

do we use epipen before or after calling 911

before