Immune Drugs PDF

Immune System Drugs Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Immunosuppressants Inhibit immune response Uses Prevention of organ rejection Treatment of autoimmune diseases Toxicity Increased risk of infection Increased ris...

Immune System Drugs Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Immunosuppressants Inhibit immune response Uses Prevention of organ rejection Treatment of autoimmune diseases Toxicity Increased risk of infection Increased risk of neoplasms 2 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Calcineurin Inhibitors Principal use: Prevention of organ rejection in transplant recipients Cyclosporine, tacrolimus, pimecrolimus: Most effective immunosuppressants available Differ in structure, but share the same mechanism Inhibition of calcineurin suppresses production of interleukin (IL-2) IL-2 needed for T-cell proliferation Cyclosporine was developed first and is used more than tacrolimus 3 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Cyclosporine [Sandimmune] Mechanism Suppresses the production of IL-2, interferon gamma, and other cytokines Therapeutic uses Drug of choice for organ rejection (kidney, liver, and heart) of an allogenic transplant Some autoimmune diseases Pharmacokinetics 4 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Cyclosporine [Sandimmune] Adverse effects Nephrotoxicity Infection Hepatotoxicity Lymphoma Hypertension Tremor Hirsutism Leukopenia, gingival hyperplasia, gynecomastia, sinusitis, hyperkalemia Anaphylactic reactions 5 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Cyclosporine [Sandimmune] Drug and food interactions Drugs that can decrease cyclosporine levels Drugs that can increase cyclosporine levels Nephrotoxic drugs Grapefruit juice Repaglinide 6 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Cyclooxygenase Inhibitors Uses Suppress inflammation Relieve pain Reduce fever Adverse effects Gastric ulceration Bleeding Renal impairment 7 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Mast Cell Degranulation Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Cyclooxygenase Inhibitors Mechanism of action Inhibit cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostanoids (prostaglandins and related compounds) Inhibition of COX-1 (“good COX”) Gastric ulceration Bleeding Renal impairment 9 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Cyclooxygenase Inhibitors Inhibition of COX-1: Beneficial effects Protection against myocardial infarction (MI) and stroke Inhibition of COX-2 (“bad COX”): Largely beneficial effects: Suppression of inflammation Alleviation of pain and reduction of fever Protection against colorectal cancer 10 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Classification of Cyclooxygenase Inhibitors Drugs with antiinflammatory properties Nonsteroidal antiinflammatory drugs (NSAIDs) Aspirin, celecoxib, ibuprofen, and naproxen Drugs without antiinflammatory properties Acetaminophen 11 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. First-Generation NSAIDs Inhibit COX-1 and COX-2 Used to treat inflammatory disorders (rheumatoid arthritis, osteoarthritis, bursitis) Alleviate mild to moderate pain Suppress fever Relieve dysmenorrhea Suppress inflammation but pose risk of serious harm 12 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Aspirin Nonselective inhibitor of cyclooxygenase Therapeutic uses Analgesic, antipyretic, antiinflammatory Suppression of platelet aggregation Protects in thrombotic disorders Dysmenorrhea Cancer prevention Prevention of Alzheimer’s disease 13 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Aspirin Adverse effects Gastrointestinal (GI) effects Bleeding Renal impairment Salicylism: Tinnitus (ringing in the ears), sweating, headache, and dizziness Reye’s syndrome Pregnancy Anemia, postpartum hemorrhage; may prolong labor Hypersensitivity reaction 14 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Aspirin Drug interactions Anticoagulants: Warfarin and heparin Glucocorticoids Alcohol Ibuprofen ACE inhibitors and ARBs Acute poisoning Immediate threats to life: Respiratory depression, hyperthermia, dehydration, and acidosis. Treatment is largely supportive. 15 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. First-Generation NSAIDs Ibuprofen [Advil, Motrin] Inhibits cyclooxygenase and has antiinflammatory, analgesic, and antipyretic actions Indications: Fever, mild to moderate pain, arthritis Generally well tolerated Low incidence of adverse effects SAFETY ALERT: All first-generation NSAIDs are associated with an increased risk of GI bleeding that can lead to hospitalization or death 16 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Acetaminophen [Tylenol] Therapeutic uses Analgesic, antipyretic Does not have any antiinflammatory or antirheumatic actions Not associated with Reye’s syndrome Action Inhibits prostaglandin synthesis in central nervous system 17 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Acetaminophen [Tylenol] Adverse effects Very few at normal doses Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and toxic epidermal necrolysis (TEN) Hepatotoxicity With overdose or in patients with liver failure Overdose: Hepatic necrosis Signs and symptoms of hepatic failure, coma, death Early symptoms: Nausea and vomiting, diarrhea, sweating, abdominal pain Treatment for overdose: Acetylcysteine (Mucomyst) 18 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Acetaminophen [Tylenol] Drug interactions Alcohol Warfarin Vaccines 19 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoid physiology Effects during stress Physiologic stress (for example, surgery, infection, trauma, hypovolemia): Adrenal glands secrete large quantities of glucocorticoids and epinephrine Result: Hormones help maintain blood pressure and blood glucose levels Insufficient release of glucocorticoids: Hypotension and hypoglycemia occur Very severe stress: Glucocorticoid insufficiency can result in circulatory failure and death 20 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoid Drugs Also known as corticosteroids and nearly identical to steroids produced by the adrenal cortex Physiologic effects (low doses) Modulation of glucose metabolism in adrenocortical insufficiency Pharmacologic effects (high doses) Suppression of inflammation 21 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoid Drugs Adverse effects Elevates blood glucose Promotes storage of glucose in the form of glycogen Reduces muscle mass Decreases the protein matrix of bone Causes thinning of the skin Lipolysis Redistribution of fat: “Potbelly,” “moon face,” and “buffalo hump” 22 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoids in Nonendocrine Disorders Glucocorticoid physiology Effects on water and electrolytes Can exert actions like those of aldosterone Can act on the kidney to promote retention of sodium and water while increasing urinary excretion of potassium Net result is hypernatremia, hypokalemia, and edema Most glucocorticoids used as drugs have very low mineralocorticoid activity 23 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Pharmacology of Glucocorticoids Anti-inflammatory and immunosuppressant effects Major clinical applications of the glucocorticoids stem from their ability to suppress immune responses and inflammation Therapeutic uses in autoimmune disorders Rheumatoid arthritis Systemic lupus erythematosus Inflammatory bowel disease 24 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Pharmacology of Glucocorticoids Therapeutic uses in nonendocrine disorders (Cont.) Allergic conditions Asthma Dermatologic disorders Neoplasms Suppression of allograft rejection Prevention of respiratory distress syndrome in preterm infants 25 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Pharmacology of Glucocorticoids Adverse effects Adrenal insufficiency with prolonged administration Osteoporosis with prolonged systemic therapy Infection Glucose intolerance: Hyperglycemia and glycosuria Myopathy: Proximal muscles of the arms and legs are affected most 26 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Pharmacology of Glucocorticoids Adverse effects (Cont.) Peptic ulcer disease: Inhibit prostaglandin synthesis, augment secretion of gastric acid and pepsin, inhibit production of cytoprotective mucus, and reduce gastric mucosal blood flow 27 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Pharmacology of Glucocorticoids Drug interactions Interactions related to potassium loss Nonsteroidal anti-inflammatory drugs Insulin and oral hypoglycemics Vaccines 28 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Pharmacology of Glucocorticoids Contraindications and precautions Patients with systemic fungal infections Those receiving live virus vaccines Use with caution in pediatric patients and in pregnancy/breast- feeding 29 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoid Routes of Administration Oral, parenteral (IV, IM, subQ), and topical Individual glucocorticoids differ in three ways: Biologic half-life Mineralocorticoid potency Glucocorticoid potency 30 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoid Drugs Hydrocortisone Prednisone Dexamethasone 31 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved. Glucocorticoid Dosage Determined empirically (trial and error) No immediate threat: Start low and slow Immediate threat: Start high; decrease as possible Long-time use: Smallest effective amount Increased in times of stress Gradual weaning Administer before 0900 32 Copyright © 2016, 2013, 2010 by Saunders, an imprint of Elsevier Inc. All rights reserved.