Inflammation Block Session Objectives
- Define the three general principles of immunosuppression.
- List seven immunosuppressants and, for each, describe the mechanism of action, clinical uses and toxicities.
- Describe the mechanisms of action, clinical uses, and toxicities of antibodies used as immunosuppressants.
- Describe the different types of allergic reactions to drugs.
Immunosuppressants: prednisone, cyclosporine, tacrolimus, sirolimus(rapamycin), azathioprine, cyclosphosphamide, mycophenolate mofetil
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)
- Explain how histamine is formed and describe the locations of its synthesis, storage and catabolism.
- Explain the difference between H1 and H2 receptors.
- Describe the "triple response of Lewis" and the mechanism(s) underlying each response.
- 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.
- Explain the applications of H1 antihistamines in allergy, common cold, local anesthetics, motion sickness, migraine headache, and as antiemetics.
- Describe the applications of H2 antihistamines in duodenal ulcers, gastric ulcers, reflux esophagitis & as antacids.
- Describe the pharmacokinetic properties, and side effects of H1 and H2 antagonists.
H1 antagonists: bromopheniramine, chlorpheniramine, diphenydramine, fexofenadine, loratidine, hydroxyzine.
H2 blockers: cimetidine, famotidine, nizatidine, ranitidine.
Antidegranulating drugs: cromolyn sodium, nedocromil sodium.
- Explain what eicosanoids are, which are the key enzymes in the overall eiccosanoid pathway, what drugs affect each enzyme and the rate-limiting step.
- Explain the termination of action of eicosanoids.
- Explain what COX1 and COX2 are; explain their physiologic and pathophysiologic significance.
- Explain what lipoxygenase products are & how they are formed.
- Describe the role of eicosanoids in: a) inflammation, b) pain & c) fever.
- Explain the meaning of “aspirin trials” and the theory supporting these trails.
- Describe the lipoxygenase pathway of arachidonic acid metabolism & explain how the biologic actions of these products differ from each other.
- Explain what PAF is.
- Explain what roles are played by PAF.
- Describe the role of omega-3 (fish oil) and omega-6 polyunsaturated fatty acids (arachidonic acid) in the formation of lipid mediators.
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)
- Describe the common pharmacological effects of NSAIDs.
- List the common adverse effects of NSAIDs.
- Explain the special properties of aspirin.
- Explain the basis for aspirin resistance & aspirin allergy.
- Describe the dose-dependent mechanisms for, & symptoms of, aspirin toxicity.
- Explain the basis for COX-2 inhibitor toxicity.
- Explain the therapeutic use of prostaglandins and prostaglandin analogs.
- Explain the use of lipoxygenase inhibitors and leukotriene antagonists in the treatment of asthma.
- Explain the mechanism of action of acetaminophen and describe the symptoms of acetaminophen toxicity & its treatment.
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)
- Explain the difference in the mechanism of action of steroids vs. NSAIDs.
- Explain the mechanism of action of Disease Modifying Drugs.
- Explain the synthesis & excretion of uric acid.
- Explain the etiology of acute gouty arthritis & acute gouty flare-up.
- Explain the rationale for the treatment of acute gouty arthritis & acute gouty flare-up.
- Explain the relationship between Reye’s syndrome & aspirin.
Disease-Modifying Antirheumatic Drugs (DMARDs): gold salts, azathioprine, chloroquine, penicillamine,
TNF-alpha blocking Anitbodies: adalimunab, infliximab, etanercept;
Rx of Gout: colchicine, allopurinol, probenecid, sulfinpyrazone, pegloticase.
Glucocorticoids & Pharmacology of the Adrenal Cortex - JiTT Session (Beckman)
- Describe the physiologic regulation of the hypothalamic-pituitary adrenal axis.
- List the natural and synthetic adrenocortical steroids, their actions, and adverse effects.
- Describe the clinical use of glucocorticoids in asthma, Addison’s disease, Cushing’s syndrome.
- Explain the major clinical indications of agents that affect the glucocorticoid pathway.
- Explain the adverse effects of drugs that affect the glucocorticoid pathway.
- Explain the adverse effects of drugs that affect the mineralocorticoid pathway.
- Explain what can happen if chronic treatment with glucocorticoids is abruptly ceased.
prednisone, hydrocortisone, dexamethasone, triamcinolone, fludrocortisone, methylprednisone, mifepristone (RU-486), metyrapone