Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Immunologic Factors/therapeutic use , Serine Proteinase Inhibitors/therapeutic use , alpha 1-Antitrypsin/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/supply & distribution , Cardiovascular Diseases/drug therapy , Congresses as Topic , Connective Tissue Diseases/drug therapy , Crohn Disease/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Humans , Immunologic Factors/supply & distribution , Lung Diseases/drug therapy , Serine Proteinase Inhibitors/supply & distribution , Virus Diseases/drug therapy , alpha 1-Antitrypsin/supply & distribution , alpha 1-Antitrypsin Deficiency/drug therapyABSTRACT
Complex biological systems are often shaped and maintained by opposing forces. A relevant biological example is the delicate balance between proteases and their inhibitors. Serine proteases contain a serine residue in the active site of the molecule that is essential to the activity of the enzyme. Protease inhibitors limit the activity of proteases in the body. As examples, aprotinin (Trasylol), a serine protease inhibitor, and aminocaproic acid (Amicar), a lysine protease inhibitor, are used to decrease the rate of fibrinolysis and have recently been the subject of considerable controversy in the literature regarding safety and efficacy. This AANA journal course reviews 2 common examples of protease inhibitor disorders, angioedema and a form of emphysema, that are of particular anesthetic relevance.
Subject(s)
Angioedema , Pulmonary Emphysema , Serine Proteinase Inhibitors/physiology , Serpins/physiology , alpha 1-Antitrypsin Deficiency , Angioedema/etiology , Angioedema/therapy , Homeostasis/physiology , Humans , Macrophages/physiology , Neutrophils/physiology , Nurse Anesthetists/education , Protein Folding , Pulmonary Emphysema/etiology , Pulmonary Emphysema/therapy , Serine Proteinase Inhibitors/adverse effects , Serpins/adverse effects , Yin-Yang , alpha 1-Antitrypsin/supply & distribution , alpha 1-Antitrypsin/therapeutic use , alpha 1-Antitrypsin Deficiency/etiology , alpha 1-Antitrypsin Deficiency/therapyABSTRACT
PURPOSE: The purpose of this study was to investigate adverse reaction reports of pain and/or cyanosis attributed to alpha 1-proteinase inhibitor (A1PI), a plasma alpha-globulin protein used to treat A1PI deficiency. PATIENTS AND METHODS: The Food and Drug Administration's (FDA) Spontaneous Reporting System for the collection and analysis of suspected adverse reactions to drugs and biologics was searched for all reports with dates from January 1, 1988, through October 31, 1989, in which A1PI was named as the suspect biologic. A case of pain and/or cyanosis was defined and characteristics of cases were compared with all other reactions. Information about the production of A1PI and results from animal studies conducted by the manufacturer were also gathered. RESULTS: Fourteen cases of acute chest pain, back pain, and/or cyanosis among patients receiving A1PI infusions were reported to the FDA. The clinical aspects of reported cases were consistent with a rapidly acting, nonallergic mechanism and were easily distinguished from other reactions associated with A1PI. The characteristics of reported cases, the epidemic curve, and lot-specific analyses suggested a point source and strongly implicated two A1PI lots. Information about the production of A1PI and results from animal studies further implicated high-molecular-weight polysaccharides associated with sucrose stabilization of the suspect lots. CONCLUSION: These cases resemble adverse reactions attributed to complexes of protamine and heparin (a mucopolysaccharide). Similar vasoactive mechanisms are suggested. Research is needed to further define the pathophysiology associated with polysaccharide moieties.
