allergies, edema

drug hypersensitivity reactions

resemble allergy, may or may not produce immune response

examples: urticaria (hives), pruritus (itching), flushing

immune-mediated reactions 

drug allergy, hypersensitivity reaction to a drug that produces immune response

examples: anaphylaxis, SJS, thrombocytopenia

type 1 hypersensitivity reaction

anaphylaxis — IgE

requires sensitization (cannot happen with first dose)

IgE binds to allergen → mast cells release histamine and leukotrienes

type 1 hypersen symptoms

anaphylaxis, edema, hives, asthma/ bronchospasm

type 2 hypersensitivity reaction

autoimmune — IgG or IgM

drug binds blood cell, triggers antibodies (igg/igm) → when antibodies bind complex → cytolytic reaction

type 2 hypersen symptoms

hemolytic anemia, thrombocytopenia, agranulocytosis

type 3 hypersensitivity reaction

serum sickness — IgG or IgM

drug binds antibodies → inflam reaction

type 4 hypersensitivity reaction

delayed - T cell

antigen causes T cell inflam response

type 4 hypersen symptoms

eczema, DRESS, SJS/TEN, exanthematous pustulosis

most common drugs causing type 1 hypersens rxn

penicillins, sulfonamides, NSAIDs, opiates, cephalosporins, macrolides, fluoroquinolones

anaphylaxis pathophysiology

histamine → (vasodilation) low bp, (increased vascular permeability) swelling, increased hr

leukotrienes, PGD2, platelet-activating factor → bronchoconstriction

tumor necrosis factor → neutrophils

anaphylaxis criteria

1. acute onset of skin-mucosal involvement + respiratory compromise, low bp, or collapse

2. (2+ after exposure to likely allergen) skin-mucosal involvement, respiratory compromise, low bp, collapse, GI symptoms

3. low bp after exposure to known allergen

anaphylaxis causes

drugs, venom (bee sting), nuts, shellfish, milk, soybeans, wheat

anaphylaxis signs and symptoms

skin – angioedema, urticaria, flushing, pruritus

resp – airway angioedema, dyspnea, wheezing

cardiovascular – hypotension

GI – naus/vom/diarr

anaphylaxis management

1. activate emergency response system

2. epinephrine

3. recumbent position, legs elevated

4. oxygen, fluids, antihistamines, corticosteroids, beta agonist inhaler

epinephrine dose

• 0.01 mg/kg

• adult max = 0.5 mg IM

• ped max = 0.3 mg IM

epinephrine effect

rapidly increases bp (vascular resistance), cardiac output

reverses bronchoconstriction, edema

stabilizes mast cells

anaphylaxis adjunct

H1 blocker – diphenhydramine iv

H2 blocker — famotidine iv

glucocorticoid — methylpred iv

cephalosporins with pnc cross reactivity

cefaclor, cephalexin, cefoxitin

other abx pnc cross reactivity

carbapenems have low incidence of cross reactivity with penicillin

aztreonam has no cross reactivity but significant resistance 

sulfonamides

bactrim, thiazide and loop diureitcs, sulfonylureas, CA inhib

no evidence of cross reactivity between abx and non-abx sulfas

most common sensitivity reactions to aspirin

• asthma

• rhinorrhea (runny nose)

• urticaria (hives)

• angioedema

desensitization/induction of drug tolerance

• temporary drug tolerance when no alternatives exist

• incremental exposure to prevent allergic reaction

• reactions responsive to desensitization → flushing, itching, hives, edema, sneezing, SOB, wheezing, abdominal pain, naus/vom, hypotension

• example: pcn G for neurosyphilis

angioedema

subcutaneous or submucosal swelling, usually accompanied by hives

angioedema presentation

swelling of face, lips, mouth, throat, larynx, uvula, extremities, genitals, bowel wall

symptoms = hives, flushing, itching, bronchospasm, abdom pain, vom

angioedema causes

mast cell (IgE, direct release, arachidonic acid)

bradykinin (overproduction, inhib of degrad, hereditary)

mast cell angioedema

• IgE – caused by pcn

• direct mast cell release – caused by opiates, succinylcholine, radiocontrast

• altered arachidonic acid metabolism (increased leukotrienes) – caused by asp and NSAIDs

bradykinin angioedema

overproduction of bradykinin or inhibition of bradykinin degradation

NO hives or itching; does NOT response to epi, antihistamines or glucocorticoids

associated with GI mucosa and bowel edema

drug induced bradykinin angioedema

ACEi — block bradykinin breakdown

DPP4i — increase substance P → edema

^ treatment = d/c agent and supportive care

hereditary angioedema

increased bradykinin (low C4, impaired C1 inhib levels/function)

• general treatment = C1 inhib or kallikrein inhib

HAE prophylaxis

cinryze, haegarda, lanadelumab (kal inh)

HAE attack treatment

berinert, ruconest, ecallantide (kal inh), ictatibant (bk ant)