Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

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FURTHER READING REFERENCE Scott DW, Miller WH 1999 Antihistamines in the management of allergic pruritus in dogs and cats. J Small Anim Pract 40: 359-364 FURTHER READING Aronson LR, Drobatz KJ, Hunter CA, Mason N 2005 Effects of CD28 blockade on subsets of naïve T cells in cats. Am J Vet Res 66: 483-492 Cohn LA 1991 The influence of corticosteroids on host defence mechanisms. J Vet Intern Med 5: 95-104 Cohn LA 1997 Glucocorticosteroids as immunosuppressive agents. Semin Vet Med Surg 12: 150-156 DeBoer DJ, Griffin CE 2001 The ACVD task force on canine atopic dermatitis (XXI): antihistamine pharmacotherapy. Vet Immunol Immunopathol 81: 323-329 Dunn J 1998 Therapy of immune-mediated disease in small animals. In Pract 20: 147-153 Hill PB, Martin RJ 1998 A review of mast cell biology. Vet Dermatol 9: 145-166 Hansson H, Bergvall K, Bondesson U et al 2004 Clinical pharmacology of clemastine in healthy dogs. Vet Dermatol 15: 152-158 Lucena R, Ginel PJ, Hernandez E, Novales M 1999 Effects of short courses of different doses of prednisone and dexamethasone on serum third component of complement (C3) levels in dogs. Vet Immunol Immunopathol 68: 187-192 Lyles KW, Jackson TW, Nesbitt T, Quarles LD 1993 Salmon calcitonin reduces vertebral bone loss in glucocorticoid-treated beagles. Am J Physiol 264: E938-E942 Miller E 1992 Immunosuppressive therapy in the treatment of immune-mediated disease. J Vet Intern Med 6: 206-213 Moore GE, Mahaffey EA, Hoenig M 1992 Hematologic and serum biochemical effects of long-term administration of anti-inflammatory doses of prednisolone in dogs. Am J Vet Res 53: 1033-1037 Nara PL, Krakowka S, Powers TE 1979 Effects of prednisolone on the development of immune responses to canine distemper virus in beagle pups. Am J Vet Res 40: 1742-1747 Olivry T, Mueller RS 2003 Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy of canine atopic dermatitis. Vet Dermatol 14: 121-146 Olivry T, Sousa CA 2001 The ACVD task force on canine atopic dermatitis (XX): glucocorticoid pharmacotherapy. Vet Immunol Immunopathol 81: 317-322 Paterson S 1994 Use of antihistamines to control pruritus in atopic dogs. J Small Anim Pract 35: 415-419 Paterson S 1995 Additive effects of EFAs in dogs with atopic dermatitis after partial response to antihistamine therapy. J Small Anim Pract 36: 389-394 Rinkardt NE, Kruth SA, Kaushik A 1999 The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs. Can J Vet Res 63: 18-24 Rohrer CR, Hill RC, Fischer A et al 1999 Gastric hemorrhage in dogs given high doses of methylprednisolone sodium succinate. Am J Vet Res 60: 977-981 Solter PF, Hoffmann WE, Chambers MD, Schaeffer DJ, Kuhlenschmidt MS 1994 Hepatic total 3-alpha-hydroxy bile-acids concentration and enzyme-activities in prednisone-treated dogs. Am J Vet Res 55: 1086-1092 Trowald-Wigh G, Hakansson L, Johannisson A, Edqvist LE 1998 The effect of prednisolone on canine neutrophil function: in vivo and in vitro studies. Acta Vet Scand 39: 201-213 Van Den Broek AHM, Stafford WL 1992 Epidermal and hepatic glucocorticoid receptors in cats and dogs. Res Vet Sci 52: 312-315 Waters CB, Adams LG, Scott Moncrieff JC et al 1997 Effects of glucocorticoid therapy on urine protein-to-creatinine ratios and renal morphology in dogs. J Vet Intern Med 11: 172-177 Watson ADJ, Nicholson A, Church DB, Pearson MRB 1996 Use of antiinflammatory and analgesic drugs in dogs and cats. Austr Vet J 74: 203-210 Wiedmyer CE, Solter PF, Hoffman WE 2002 Kinetics of mRNA expression of alkaline phosphatase isoenzymes in hepatic tissues from glucocorticoid-treated dogs. Am J Vet Res 63: 1089-1095 269
12 Immunomodulatory therapy Michael J Day INTRODUCTION In clinical veterinary medicine there are numerous situations in which it would be advantageous to either enhance the immune system (immunostimulatory therapy) or downregulate it (immunosuppressive therapy). The form of immunomodulatory therapy most commonly used in veterinary practice is immunosuppression and currently this is achieved through the use of glucocorticoids, given alone or in combination with a range of adjunct drugs. These agents cause ‘blanket immunosuppression’ of both deleterious and beneficial immune responses. Methods of inducing selective immunosuppression of a specific pathological immune response that leave general immunity intact are currently a major research focus. By contrast, immunostimulation is at present difficult to achieve in the practice situation by pharmacological means. Although some agents are advocated for their immune-stimulatory properties, there have been few studies of the effects of these drugs on immunological parameters in companion animals. This chapter will not address the application of the glucocorticoids (which are reviewed in Chapter 11) but will describe other agents with immunomodulatory capacity that are currently available to veterinary practitioners. Potential future developments in this important area will also be addressed. Relevant pathophysiology The rational use of immunomodulatory agents requires a working knowledge of the immune response. An overview of the complex interactions that make up any immune response is given in Figure 12.1. The key regulatory cell of the immune system is the CD4 + T lymphocyte, which is activated following molecular interactions with an ‘antigen-presenting cell’ that has previously processed native antigen to a form that can be recognized by the antigen-specific T-cell receptor. The activated T cell in turn induces the specific immunological effector mechanisms that deal with the antigenic insult to the host. There are several regulatory subsets of CD4 + T cells that mediate different end-effects. The Th2 CD4 + T cell induces B lymphocyte differentiation to antibodysecreting plasma cells (humoral or type 2 immunity). The Th1 CD4 + T cell activates a range of cytotoxic cell populations, which can destroy neoplastic or infected target cells, or enable phagocytes to destroy intracellular pathogens (cell-mediated or type 1 immunity). By contrast, the effector function of Th3 or Treg CD4 + T cells inhibits or ‘suppresses’ the immune response rather than amplifying it. All these regulatory functions are mediated by cytokines – soluble factors released from cells that initiate intracellular signaling pathways with resultant gene transcription in effector cells expressing appropriate cytokine receptors. There is intrinsic interconnection between the immune and inflammatory pathways and factors such as the complement cascade provide a bridge between the systems. Immunomodulatory agents have the ability to act at different levels of these complex pathways. In some instances, a drug has a selective and specific action on one individual component (e.g. ciclosporin chiefly affects T lymphocytes) but this may have broad effects on other populations that are regulated by the target cell. By contrast, the mechanism and target of many other immunomodulatory agents are incompletely understood, despite the clinical effects observed. DRUGS WITH IMMUNOSUPPRESSIVE EFFECTS Azathioprine Clinical applications Although azathioprine is classified as a cytotoxic drug, it is used almost exclusively in small animal practice in the management of immune-mediated disease. Azathioprine has been used successfully in a large range of immune-mediated and inflammatory disorders in dogs and to a lesser extent in cats. This drug is often administered as an adjunct to immunomodulatory therapy with corticosteroids as this combination may have complementary immunological effects and concurrent azathioprine treatment usually permits lower doses of corticosteroids to be used in the maintenance phase of therapy. Disorders in which azathioprine has been used include myasthenia gravis, immune-mediated hemolytic anemia, 270
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An imprint of Elsevier Limited © E
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CONTRIBUTORS Matthias J Kleinz Depa
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Dedication To Tom, Rosalind and Jim
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CHAPTER 1 PRINCIPLES OF CLINICAL PH
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CHAPTER 2 CLINICAL PHARMACOKINETICS
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CHAPTER 3 ADVERSE DRUG REACTIONS Un
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CHAPTER 4 THE PHARMACOLOGY OF THE A
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CHAPTER 5 ANESTHETIC AGENTS However
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CHAPTER 5 ANESTHETIC AGENTS Table 5
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CHAPTER 5 ANESTHETIC AGENTS doses.
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CHAPTER 5 ANESTHETIC AGENTS Pharmac
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CHAPTER 5 ANESTHETIC AGENTS Table 5
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CHAPTER 5 ANESTHETIC AGENTS FURTHER
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CHAPTER 6 SEDATIVES ● noradrenali
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CHAPTER 6 SEDATIVES treatment, with
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CHAPTER 6 SEDATIVES Benzodiazepines
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CHAPTER 6 SEDATIVES It is not misci
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CHAPTER 6 SEDATIVES respectively. H
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CHAPTER 6 SEDATIVES Table 6.1 Sugge
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7 Behavior-modifying drugs Kersti S
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CHAPTER 7 BEHAVIOR-MODIFYING DRUGS
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8 Antibacterial drugs Jill E Maddis
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CHAPTER 8 ANTIBACTERIAL DRUGS phary
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CHAPTER 8 ANTIBACTERIAL DRUGS dose
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CHAPTER 8 ANTIBACTERIAL DRUGS RIFAM
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9 Systemic antifungal therapy Josep
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CHAPTER 9 SYSTEMIC ANTIFUNGAL THERA
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10 Antiparasitic drugs Stephen W Pa
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CHAPTER 10 ANTIPARASITIC DRUGS ●
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15 Cancer chemotherapy Jane M Dobso
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CHAPTER 15 CANCER CHEMOTHERAPY to m
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CHAPTER 16 ANTICONVULSANT DRUGS sei
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17 Drugs used in the management of
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CHAPTER 17 DRUGS USED IN THE MANAGE
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CHAPTER 19 GASTROINTESTINAL DRUGS C
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CHAPTER 19 GASTROINTESTINAL DRUGS
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CHAPTER 19 GASTROINTESTINAL DRUGS
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CHAPTER 21 DRUGS USED IN THE TREATM
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23 Drugs and reproduction Philip G
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CHAPTER 23 DRUGS AND REPRODUCTION I
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CHAPTER 23 DRUGS AND REPRODUCTION F
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CHAPTER 23 DRUGS AND REPRODUCTION C
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CHAPTER 23 DRUGS AND REPRODUCTION M
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CHAPTER 23 DRUGS AND REPRODUCTION n
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CHAPTER 23 DRUGS AND REPRODUCTION E
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24 Topical dermatological therapy R
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CHAPTER 24 TOPICAL DERMATOLOGICAL T
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CHAPTER 25 OCULAR CLINICAL PHARMACO
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Index A α-adrenergic receptors 70,
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INDEX Antiplatelet drugs 456-457 pi
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INDEX Ceftazidime 168 Ceftiofur 166
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INDEX Drug receptors 4-8 Drug-drug
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INDEX Hepatic excretion 33 Hepatic
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INDEX Metabolism dogs vs cats 47 an
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INDEX Pentazocine 319, 327 Pentobar
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INDEX Semicarbazone 230 Septic arth
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