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Inflammation Block Session Objectives

Immunopharmacology (Beckman)

1. Define the three general principles of immunosuppression.
2. List seven immunosuppressants and, for each, describe the mechanism of action, clinical uses and toxicities.
3. Describe the mechanisms of action, clinical uses, and toxicities of antibodies used as immunosuppressants.
4. Describe the different types of allergic reactions to drugs.

DrugList:
Immunosuppressants: prednisone, cyclosporine, tacrolimus, sirolimus(rapamycin), azathioprine, cyclosphosphamide, mycophenolate mofetil
Antimetabolites: methotrexate
Immunomodulatory: thalidomide
Antibody Reagents: antilymphocyte globulin, antithymocyte globulin, Rho(D)immune globulin, muromonab-CD3, infliximab, daclizumab, etanercept
Natural Adjuvants: Aldesleukin, Interferon-α-2a, interferon-β-1a, Interferon-γ-1b

Antihistamines & Histamine (Mondal)

1. Explain how histamine is formed and describe the locations of its synthesis, storage and catabolism.
2. Explain the difference between H1 and H2 receptors.
3. Describe the "triple response of Lewis" and the mechanism(s) underlying each response.
4. Describe the physiologic/pathophysiologic functions of histamine in: a) the cardiovascular system; b) the pulmonary system; c) non-vascular smooth muscle; d) sensory nerve endings; e) gastric glands.
5. Explain the applications of H1 antihistamines in allergy, common cold, local anesthetics, motion sickness, migraine headache, and as antiemetics.
6. Describe the applications of H2 antihistamines in duodenal ulcers, gastric ulcers, reflux esophagitis & as antacids.
7. Describe the pharmacokinetic properties, and side effects of H1 and H2 antagonists.

Drug List:
H1 antagonists: bromopheniramine, chlorpheniramine, diphenydramine, fexofenadine, loratidine, hydroxyzine.
H2 blockers: cimetidine, famotidine, nizatidine, ranitidine.
Antidegranulating drugs: cromolyn sodium, nedocromil sodium.
Histamine, betazole.

Eicosanoids (McNamara)

1. Explain what eicosanoids are, which are the key enzymes in the overall eiccosanoid pathway, what drugs affect each enzyme and the rate-limiting step.
2. Explain the termination of action of eicosanoids.
3. Explain what COX1 and COX2 are; explain their physiologic and pathophysiologic significance.
4. Explain what lipoxygenase products are & how they are formed.
5. Describe the role of eicosanoids in: a) inflammation, b) pain & c) fever.
6. Explain the meaning of “aspirin trials” and the theory supporting these trails.
7. Describe the lipoxygenase pathway of arachidonic acid metabolism & explain how the biologic actions of these products differ from each other.
8. Explain what PAF is.
9. Explain what roles are played by PAF.
10. Describe the role of omega-3 (fish oil) and omega-6 polyunsaturated fatty acids (arachidonic acid) in the formation of lipid mediators.
    

Drug list:
Selective COX 2 Inhibitors: celecoxib (Celebrex ®), rofecoxib (Vioxx ®)**
Nonselective COX inhibitor: aspirin
Leukotriene Inhibitors: montelukast, zafirlukast, zileuton

**Vioxx is not commercially available. It is mentioned for historical context only.

Clinical Pharmacology I: NSAIDs, Acetaminophen, Steroids (McNamara)

1. Describe the common pharmacological effects of NSAIDs.
2. List the common adverse effects of NSAIDs.
3. Explain the special properties of aspirin.
4. Explain the basis for aspirin resistance & aspirin allergy.
5. Describe the dose-dependent mechanisms for, & symptoms of, aspirin toxicity.
6. Explain the basis for COX-2 inhibitor toxicity.
7. Explain the therapeutic use of prostaglandins and prostaglandin analogs.
8. Explain the use of lipoxygenase inhibitors and leukotriene antagonists in the treatment of asthma.
9. Explain the mechanism of action of acetaminophen and describe the symptoms of acetaminophen toxicity & its treatment.
   

Drug List:
Selective Cox-2 Inhibitor (NSAID): celecoxib (Celebrex ®)
Nonselective Cox Inhibitors (NSAIDs): aspirin, ibuprofen, naproxen, nabumetone & diclofenac.
Analgesic & Antipyretic: acetaminophen [Rx: N-acetylcysteine]
Glucocorticoids: beclomethasone, dexamethasone

Clinical Pharmacology II: NSAIDs, DMARDs, Rx Arthritis & Gout (McNamara)

1. Explain the difference in the mechanism of action of steroids vs. NSAIDs.
2. Explain the mechanism of action of Disease Modifying Drugs.
3. Explain the synthesis & excretion of uric acid.
4. Explain the etiology of acute gouty arthritis & acute gouty flare-up.
5. Explain the rationale for the treatment of acute gouty arthritis & acute gouty flare-up.
6. Explain the relationship between Reye’s syndrome & aspirin.

Drug List:
Disease-Modifying Antirheumatic Drugs (DMARDs): gold salts, azathioprine, chloroquine, penicillamine,
  methotrexate, sulfasalazine
TNF-alpha blocking Anitbodies: adalimunab, infliximab, etanercept;
Rx of Gout: colchicine, allopurinol, probenecid, sulfinpyrazone, pegloticase.

Glucocorticoids & Pharmacology of the Adrenal Cortex - JiTT Session (Beckman)

1. Describe the physiologic regulation of the hypothalamic-pituitary adrenal axis.
2. List the natural and synthetic adrenocortical steroids, their actions, and adverse effects.
3. Describe the clinical use of glucocorticoids in asthma, Addison’s disease, Cushing’s syndrome.
4. Explain the major clinical indications of agents that affect the glucocorticoid pathway.
5. Explain the adverse effects of drugs that affect the glucocorticoid pathway.
6. Explain the adverse effects of drugs that affect the  mineralocorticoid pathway.
7. Explain what can happen if chronic treatment with glucocorticoids is abruptly ceased. 

Drug List:
prednisone, hydrocortisone, dexamethasone, triamcinolone, fludrocortisone, methylprednisone, mifepristone (RU-486), metyrapone