BLOOD CLOTTING ENZYMOLOGY
1 APPROVED BIOLOGICS USED FOR THERAPY AND THEIR ADVERSE EFFECTS BIOLOGICS US GUIDELINES EUROPEAN GUIDELINES BIOLOGICS AND SMALL MOLECULE DRUGS PROTEIN THERAPEUTICS SOME COMPLEXITIES OF PROTEIN THERAPEUTICS: PERCEIVED ADVANTAGES AND SOME PROBLEMS THE EVOLVING BIOLOGICS MARKET ADVERSE DRUG REACTIONS DE? NITIONS TERMINOLOGY: ADVERSE REACTIONS AND ADVERSE EVENTS CLASSI? CATION OF ADVERSE DRUG REACTIONS SYNDROMES THAT MAY BE ASSOCIATED WITH BIOLOGIC THERAPIES SUMMARY FURTHER READING 2 MONOCLONAL ANTIBODIES: INTRODUCTION MONOCLONAL ANTIBODIES FOR THERAPY EVOLUTION OF THERAPEUTIC MONOCLONAL ANTIBODIES: FROM MOUSE TO MAN TECHNOLOGICAL ADVANCES IN THE PRODUCTION OF MONOCLONAL ANTIBODIES HYBRIDOMA TECHNOLOGY AND IMMORTALIZATION OF HUMAN B CELLS PHAGE DISPLAY TRANSGENIC (KNOCKOUT) MICE MONOCLONAL ANTIBODIES FROM SINGLE HUMAN B CELLS BY GENE CLONING CONTENTS IGG ANTIBODY SUBCLASSES GLYCOSYLATION OF MONOCLONAL ANTIBODIES ANTIBODY-DEPENDENT CELL-MEDIATED AND COMPLEMENT- DEPENDENT CYTOTOXICITIES NOMENCLATURE FOR MONOCLONAL ANTIBODIES BREAKDOWN OF ANTIBODY TYPE AND APPROVED INDICATIONS FOR THE CURRENTLY APPROVED MONOCLONAL ANTIBODIES ANTIBODY-DRUG CONJUGATES FUTURE PROSPECTS OF MONOCLONAL ANTIBODY THERAPY 3 MONOCLONAL ANTIBODIES APPROVED FOR CANCER THERAPY APPROVED MONOCLONAL ANTIBODIES FOR CANCER THERAPY CATUMAXOMAB BLINATUMOMAB MONOCLONAL ANTIBODIES TARGETING CD20: RITUXIMAB, IBRITUMOMAB, OFATUMUMAB, AND OBINUTUZUMAB BRENTUXIMAB VEDOTIN ALEMTUZUMAB MONOCLONAL ANTIBODIES TARGETING EPIDERMAL GROWTH FACTOR RECEPTOR: CETUXIMAB, PANITUMUMAB, AND NECITUMUMAB BEVACIZUMAB RAMUCIRUMAB MONOCLONAL ANTIBODIES TARGETING HUMAN EPIDERMAL GROWTH FACTOR 2 (HER2): PERTUZUMAB, TRASTUZUMAB, AND ADO- TRASTUZUMAB EMTANSINE DENOSUMAB IPILIMUMAB SILTUXIMAB MONOCLONAL ANTIBODIES TARGETING PROGRAMMED CELL DEATH PROTEIN 1 (PD-1): PEMBROLIZUMAB AND NIVOLUMAB DINUTUXIMAB DARATUMUMAB ELOTUZUMAB RECENT APPROVAL: ATEZOLIZUMAB RANGE OF SIDE EFFECTS OF MONOCLONAL ANTIBODIES USED FOR CANCER THERAPY TYPES I–IV HYPERSENSITIVITIES AND CYTOPENIAS INFUSION REACTIONS AND CYTOKINE RELEASE SYNDROME PULMONARY ADVERSE EVENTS CARDIAC ADVERSE EVENTS MUCOCUTANEOUS REACTIONS TO MONOCLONAL ANTIBODIES TARGETED TO EPIDERMAL GROWTH FACTOR RECEPTOR OTHER RARE ADVERSE EVENTS FOLLOWING ANTITUMOR MONOCLONAL ANTIBODY THERAPY 4 OTHER APPROVED THERAPEUTIC MONOCLONAL ANTIBODIES MONOCLONAL ANTIBODIES TARGETED TO HUMAN TUMOR NECROSIS FACTOR: ADALIMUMAB, CERTOLIZUMAB PEGOL, IN? IXIMAB, AND GOLIMUMAB BOXED WARNINGS AND PRECAUTIONS FOR ADALIMUMAB, CERTOLIZUMAB PEGOL, IN? IXIMAB, AND GOLIMUMAB ADALIMUMAB CERTOLIZUMAB PEGOL IN? IXIMAB GOLIMUMAB ABCIXIMAB INTEGRIN RECOGNITION BY ABCIXIMAB INDICATIONS, WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS IMMUNOGENICITY OF ABCIXIMAB BASILIXIMAB THE IL-2 RECEPTOR AND MECHANISM OF ACTION OF BASILIXIMAB BASILIXIMAB INDICATIONS, WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS IMMUNOGENICITY OF BASILIXIMAB BELIMUMAB BLYS AND BELIMUMAB BELIMUMAB WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS IMMUNOGENICITY OF BELIMUMAB APRIL, LUPUS, AND ATACICEPT CANAKINUMAB CAPS AND THE MECHANISM OF ACTION OF CANAKINUMAB CAPS DISEASES AND APPROVED INDICATIONS FOR CANAKINUMAB WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS FOR CANAKINUMAB ECULIZUMAB APPROVED INDICATIONS PAROXYSMAL NOCTURNAL HEMOGLOBINURIA, ATYPICAL HEMOLYTIC UREMIC SYNDROME, AND MECHANISM OF ACTION OF ECULIZUMAB WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS IMMUNOGENICITY OF ECULIZUMAB MONOCLONAL ANTIBODY INTEGRIN INHIBITORS: NATALIZUMAB AND VEDOLIZUMAB NATALIZUMAB VEDOLIZUMAB OMALIZUMAB MECHANISM OF ACTION OF OMALIZUMAB SAFETY OF OMALIZUMAB PALIVISUMAB RANIBIZUMAB RAXIBACUMAB ANTHRAX AND BACKGROUND TO THE DEVELOPMENT OF RAXIBACUMAB MECHANISM OF ACTION OF RAXIBACUMAB INDICATIONS AND USAGE OF RAXIBACUMAB SAFETY OF RAXIBACUMAB SECUKINUMAB MECHANISM OF ACTION OF SECUKINUMAB APPROVED INDICATIONS AND SAFETY OF SECUKINUMAB TOCILIZUMAB IL-6 AND MECHANISM OF ACTION OF TOCILIZUMAB APPROVED INDICATIONS AND SAFETY OF TOCILIZUMAB USTEKINUMAB IL-12 AND IL-23 AND IMMUNE-MEDIATED DISEASES MECHANISM OF ACTION OF USTEKINUMAB INDICATIONS AND SAFETY OF USTEKINUMAB PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) INHIBITORS: ALIROCUMAB AND EVOLOCUMAB ALIROCUMAB: INDICATIONS AND SAFETY EVOLOCUMAB: INDICATIONS AND SAFETY IDARUCIZUMAB MECHANISM OF ACTION OF IDARUCIZUMAB INDICATIONS AND SAFETY OF IDARUCIZUMAB MEPOLIZUMAB MECHANISM OF ACTION OF MEPOLIZUMAB INDICATIONS AND SAFETY OF MEPOLIZUMAB RECENT APPROVALS: OBILTOXAXIMAB, IKEXIZUMAB, RESLIZUMAB 5 CYTOKINES INTRODUCTION GENERAL CHARACTERISTICS CLASSI? CATION OF CYTOKINES ADVERSE EFFECTS OF INDIVIDUAL APPROVED RECOMBINANT CYTOKINE ANALOGS INDIVIDUAL APPROVED CYTOKINES INTERFERON ALFA INTERFERON BETA INTERFERON GAMMA COLONY-STIMULATING FACTORS: FILGRASTIM, SARGRAMOSTIM, AND TBO-FILGRASTIM OPRELVEKIN BECAPLERMIN PALIFERMIN ALDESLEUKIN ANAKINRA EPOETINS BONE MORPHOGENETIC PROTEINS METRELEPTIN ANCESTIM CONCLUDING REMARKS 6 FUSION PROTEINS DESIRED PROPERTIES AND COMPOSITION OF CHIMERIC FUSION PROTEINS FC FUSION PROTEINS FC FUSION PROTEINS AS GLYCOPROTEINS IGG SUBCLASSES OF FC FUSION PROTEINS: INCREASING AND DECREASING EFFECTOR FUNCTION ORIGIN, NATURE, MECHANISM OF ACTION, AND USAGE OF FC FUSION PROTEINS ETANERCEPT BELATACEPT ABATACEPT RILONACEPT A? IBERCEPT ROMIPLOSTIM ALEFACEPT FACTOR VIII FC FUSION PROTEIN FACTOR IX FC FUSION PROTEIN DULAGLUTIDE ATACICEPT SAFETY OF APPROVED FC FUSION PROTEINS BELATACEPT SAFETY A? IBERCEPT SAFETY ALBUMIN FUSION PROTEINS ALBIGLUTIDE FACTOR IX ALBUMIN FUSION PROTEIN ALBUMIN FUSION PROTEINS IN LATE STAGE DEVELOPMENT ALBUMIN FUSION PROTEINS IN THE EARLY STAGE OF DEVELOPMENT DENILEUKIN DIFTITOX THE IMMUNOGENICITY OF THERAPEUTIC FUSION PROTEINS: ATTEMPTS TO HELP RECOGNIZE PATIENTS AT RISK DIAGNOSIS OF HYPERSENSITIVITIES TO FUSION PROTEINS, PREMEDICATION, AND DESENSITIZATION 7 PEPTIDE HORMONES INSULIN DIABETES MELLITUS PRODUCTION OF INSULIN STRUCTURE OF INSULIN RELEASE OF INSULIN INSULIN BINDING TO ITS RECEPTOR AND ENSUING SIGNALING DIFFERENT AVAILABLE INSULIN PREPARATIONS SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS ASSOCIATED WITH INSULIN USE GLUCAGON STRUCTURE AND MECHANISM OF ACTION OF GLUCAGON INDICATIONS AND ADVERSE EFFECTS OF GLUCAGON GLUCAGON HYPERSENSITIVITY GLUCAGON-LIKE PEPTIDE 1 GLUCAGON-LIKE PEPTIDE 2 GLUCAGON-LIKE PEPTIDE 1 AND THE INCRETIN EFFECT GLP-1 RECEPTOR AGONISTS SAFETY OF GLP-1 RECEPTOR AGONISTS IMMUNOGENICITY OF GLP-1 RECEPTOR AGONISTS DIPEPTIDYL PEPTIDASE-4 (DPP-4) INHIBITORS (GLIPTINS) PRAMLINTIDE HUMAN GROWTH HORMONE STRUCTURE AND MECHANISM OF ACTION OF GROWTH HORMONE INDICATIONS AND USAGE OF SOMATROPIN ADVERSE EVENTS TO SOMATROPIN IMMUNOGENICITY OF GROWTH HORMONE PEGVISOMANT: A GROWTH HORMONE RECEPTOR ANTAGONIST INSULIN-LIKE GROWTH FACTOR 1 STRUCTURE AND MECHANISM OF ACTION IGF-1 AND GROWTH STIMULATION MECASERMIN SOMATOSTATIN SYNTHETIC ANALOGS OF SOMATOSTATIN APPROVED INDICATIONS FOR SOMATOSTATIN ANALOGS WARNINGS AND PRECAUTIONS FOR SOMATOSTATIN ANALOGS ADVERSE EVENTS TO SOMATOSTATIN ANALOGS VASOPRESSIN PHYSIOLOGIC ACTIONS OF VASOPRESSIN VASOPRESSIN GENE AND HORMONE STRUCTURE VASOPRESSIN RECEPTORS SAFETY OF VASOPRESSIN THERAPY DESMOPRESSIN TERLIPRESSIN VAPTANS: VASOPRESSIN RECEPTOR ANTAGONISTS OXYTOCIN INDICATIONS OXYTOCIN STRUCTURE OXYTOCIN RECEPTORS SAFETY OF OXYTOCIN SAFETY OF CARBETOCIN SAFETY OF ATOSIBAN ADRENOCORTICOTROPIC HORMONE STRUCTURE, FUNCTION, AND INDICATIONS OF ACTH ADVERSE EVENTS TO COSYNTROPIN GONADOTROPIN-RELEASING HORMONE STRUCTURE OF GNRH GNRH NEURONS AND SECRETION GNRH RECEPTOR GNRH AGONISTS AND ANTAGONISTS SAFETY OF GNRH ANALOGS PARATHYROID HORMONE STRUCTURE AND ACTION OF HUMAN PARATHYROID HORMONE PARATHYROID HORMONE RECEPTORS AND SIGNALING SAFETY OF PARATHYROID HORMONE 8 GLYCOPROTEIN HORMONES FOLLICLE-STIMULATING HORMONE INDICATIONS AND USAGE OF FOLLICLE-STIMULATING HORMONE LUTEINIZING HORMONE INDICATIONS AND USAGE OF LUTROPIN ALFA WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS ASSOCIATED WITH LUTROPIN ALFA HUMAN CHORIONIC GONADOTROPIN INDICATIONS AND USAGE OF CHORIONIC GONADOTROPIN THYROID-STIMULATING HORMONE INDICATIONS AND USAGE OF THYROTROPIN ALFA THYROSTIMULIN 9 ENZYMES APPROVED FOR THERAPY TOWARD SUCCESSFUL ENZYME REPLACEMENT THERAPY: GAUCHER DISEASE APPROVED ENZYMES AS REPLACEMENT THERAPY FOR LYSOSOMAL STORAGE DISEASES OTHER ENZYMES APPROVED FOR THERAPY TISSUE PLASMINOGEN ACTIVATORS ASFOTASE ALFA ASPARAGINASE COLLAGENASE DORNASE ALFA GLUCARPIDASE HYALURONIDASE OCRIPLASMIN PEGADEMASE BOVINE PEGLOTICASE RASBURICASE STREPTOKINASE SAFETY OF APPROVED ENZYMES USED AS THERAPY FOR LYSOSOMAL STORAGE DISEASES AGALSIDASE BETA FOR FABRY DISEASE ALGLUCOSIDASE ALFA FOR POMPE DISEASE RECOMBINANT ENZYMES USED TO TREAT GAUCHER DISEASE: IMIGLUCERASE, TALIGLUCERASE ALFA, AND VELAGLUCERASE ALFA SEBELIPASE ALFA FOR LYSOSOMAL ACID LIPASE DE? CIENCY LARONIDASE FOR MPS I IDURSULFASE FOR MPS II ELOSULFASE ALFA FOR MPS IVA GALSULFASE FOR MPS VI ADVERSE EVENTS CAUSED BY OTHER APPROVED ENZYMES L-ASPARAGINASE ANTIBODY RESPONSES TO ENZYMES OTHER THERAPIES FOR LYSOSOMAL STORAGE DISEASES STEM CELL TRANSPLANTATION SUBSTRATE REDUCTION THERAPY CHAPERONES GENE THERAPY LIVING WITH ENZYME REPLACEMENT THERAPY 10 BLOOD COAGULATION PLATELET ACTIVATION AND VON WILLEBRAND FACTOR THE KALLIKREIN-KININ SYSTEM AND COAGULATION THE CLOTTING CASCADE FACTOR XII AND COAGULATION FACTOR VIII B-DOMAIN DELETED RECOMBINANT FACTOR VIII TUROCTOCOG ALFA SIMOCTOCOG ALFA SUSOCTOCOG ALFA CLOTTING FACTOR FUSION PROTEINS SAFETY OF APPROVED BLOOD COAGULATION PREPARATIONS INHIBITORS IN HEMOPHILIA AND BYPASS THERAPY FACTOR VIIA FACTOR VIII FULL LENGTH PREPARATIONS MOROCTOCOG ALFA: B-DOMAIN DEPLETED FACTOR VIII OTHER B-DOMAIN-DEPLETED FACTOR VIII PREPARATIONS: TUROCTOCOG ALFA, SIMOCTOCOG ALFA AND SUSOCTOCOG ALFA FACTOR IX FUSION PROTEINS FACTOR XIII A-SUBUNIT VON WILLEBRAND FACTOR/COAGULATION FACTOR VIII COMPLEX ANTIHEMOPHILIC FACTOR/VON WILLEBRAND FACTOR COMPLEX RECOMBINANT VON WILLEBRAND FACTOR FACTOR EIGHT INHIBITOR BYPASSING ACTIVITY (FEIBA), ANTI- INHIBITOR COAGULANT COMPLEX PROTHROMBIN COMPLEX CONCENTRATE FIBRINOGEN PREPARATIONS TO CONTROL BLEEDING 11 VACCINES VACCINES: DE? NITION, ATTENUATION, AND SUBUNIT, ACELLULAR, CARBOHYDRATE, CONJUGATE AND DNA VACCINES CURRENTLY APPROVED VACCINES: DESCRIPTION, INDICATIONS, WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS “ALLERGY”/ADVERSE REACTIONS TO VACCINES AND ADDED COMPONENTS ALLERGIC REACTIONS TO EGG PROTEINS IN VACCINES ALLERGIC REACTIONS TO GELATIN IN VACCINES ALUMINIUM ADJUVANTS REACTIONS TO OTHER VACCINE ADDITIVES CUTANEOUS REACTIONS TO VACCINATIONS INJECTION SITE REACTIONS CUTANEOUS HYPERSENSITIVITY REACTIONS TO VACCINES OTHER DERMATOLOGIC REACTIONS 12 BOTULINUM NEUROTOXINS BOTULINUM NEUROTOXIN SEROTYPES TOXIN STRUCTURE AND MECHANISMS OF ACTION STRUCTURE OF BOTULINUM NEUROTOXIN BONT STRUCTURE AND ABSORPTION OF BOTULINUM NEUROTOXIN COMPLEX MECHANISM OF ACTION AT THE NEUROMUSCULAR JUNCTION THERAPEUTIC APPLICATIONS OF BOTULINUM NEUROTOXIN NOMENCLATURE AND EQUIVALENCE OF DIFFERENT BOTULINUM TOXIN PREPARATIONS APPROVED INDICATIONS OF FDA REGISTERED BOTULINUM NEUROTOXIN PREPARATIONS OTHER POSSIBLE INDICATIONS FOR BOTULINUM NEUROTOXINS ADVERSE EFFECTS OF BOTULINUM NEUROTOXIN WARNINGS AND PRECAUTIONS ADVERSE EVENTS FOLLOWING THERAPEUTIC AND COSMETIC USE OF BOTULINUM NEUROTOXIN IMMUNOGENICITY AND CLINICAL RELEVANCE OF BOTULINUM NEUROTOXIN ANTI-NEUROTOXIN ANTIBODIES DETECTION AND MEASUREMENT OF NEUTRALIZING ANTIBODIES 13 BIOSIMILARS THE CONTINUING EVOLUTION OF BIOSIMILARS NAMING OF BIOSIMILARS AND PHARMACOVIGILANCE CONSIDERATIONS BIOBETTERS BIOSIMILARS IN THE IMMEDIATE FUTURE