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CHaPTEr 48 Drug Hypersensitivity 661

Sulfonamide antibiotics reactions Sulfonamide antibiotics structure
Arylamine group
O O N O CH 3 O O N N CH O CH 3
S CH 3 N S 3 N SO NH
Serum sickness H N N H H N SO NH N H N N H S H 2 2 N CH 3
2
2
Immediate Rash/fever 2 Sulfamethoxazole Sulfamerazine 2 Sulfamethizole Sulfamoxole
hypersensitivity +systemic CH 3 O
Urticaria/ symptoms H N SO 2 NH N NH 2 SO NH N H N SO NH S
2
2
2
2
anaphylaxis DRESS N CH 3 CH 3 CH 3 N
Sulfamethazine Sulfisoxazole Sulfapyridine
Non-antibiotic sulfonamides structure
O Cl
Delayed Sulfonamide Furosemide O Celecoxib
maculopapular antibiotics SJS/TEN Hydrochlorothiazide HN S O Acetazolamide
rash Sulfasalazine NH 2 Sumatriptan
O Glyburide
OH
A B
FiG 48.8 Reactions to and structures of sulfonamide antibiotics (A). Structures of sulfonamide
antibiotics (B). (Adapted from Tilles, SA, Slatore, CG. Hypersensitivity reactions to non-beta-lactam
antibiotics. Clin Rev Allergy Immunol. 2003; 24: 221–8.)

ASPIRIN-TOLERANT AERD

• Platelets not adherent to leukocytes • Platelets adherent to leukocytes
• Leukocyte adhesion receptors upregulated

• Few eosinophils in tissue or blood • Increased eosinophil numbers in tissue and blood

• Few mast cells in tissue • Increased mast cell numbers in tissue

• PGE (signaling through EP ) blocks 5-LO • Less blockade of 5-LO by PGE (due to less EP )
2
2
2
2
Very little LTA produced Leukocytes LTA is produced, passed to adherent platelets
4
4
Baseline • Platelet-derived TXA downregulates LTC S Platelets • Platelet-derived TXA downregulates LTC S
4
2
4
2
Very little LTA converted to cysLTs
Some LTA converted to cysLTs by adherent platelets
4
4
Low baseline cysLT levels OUTCOME High baseline cysLT levels
• PGE level stays constant through COX-2 Leukocytes • PGE 2 production decreases in absence of COX-2
2
EP signaling keeps 5-LO inactive
PGE + less EP signaling = 5-LO is activated
Following COX-1 inhibition • TXA2 levels Platelets • TXA levels
2
2
2
Very little LTA produced
LTA is produced
4
4
2
LTC S is upregulated
LTC S is upregulated
4
4
production still low and few adherent
• LTA converted to cysLTs by eosinophils, mast cells, or
• LTA 4
4
platelets to convert it to cysLTs
cysLT levels stay constant OUTCOME adherent platelets
cysLT levels rise; respiratory reaction occurs
FiG 48.9 Summary of the pathogenesis of aspirin-exacerbated respiratory disease (AERD) at
baseline and after cyclooxygenase 1 (COX-1) inhibition. PGE 2 , prostaglandin E2; 5-LO, 5-lipoxygenase;
LTA 4 , leukotriene A4; LTC 4 S, leukotriene C4 synthase; cysLTs, cysteinyl leukotrienes; COX-2,
cyclo-oxygenase-2; TXA 2 , thromboxane A2; EP 2 , prostaglandin E2 receptor 2. (From Laidlaw TM,
Boyce JA. Pathogenesis of aspirin-exacerbated respiratory disease and reactions. Immunol Allergy
Clin North Am. 2013; 33: 195–210.)