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Anti-Inflammatory Drugs

Anti-Inflammatory Drugs. Insert Inflammation Diagram. Analgesics, Anti-inflammatories and Anti-gout Agents. This group is comprised of drugs that reduce mild to moderate pain (analgesic) of a different type or quality than narcotics and by a different mechanism than the narcotic analgesics

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Anti-Inflammatory Drugs

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  1. Anti-InflammatoryDrugs

  2. Insert Inflammation Diagram

  3. Analgesics, Anti-inflammatories and Anti-gout Agents This group is comprised of drugs that reduce mild to moderate pain (analgesic) • of a different type or quality than narcotics and • by a different mechanism than the narcotic analgesics The analgesics within this group are not interchangeable for the relief of pain associated with gout, muscle ache, or muscle ischemia

  4. Nonnarcotic Analgesics Clinical Indication Prevent or interrupt mild to moderate pain associated with inflammatory conditions without altering consciousness (analgesic, antiinflammatory) Pain quality is often described as a dull ache in joint pain (osteoarthritis, gout) muscle pain (myalgia) headache (nonmigraine) Reduce elevated body temperature (fever) (antipyretic)

  5. Sensation of Pain Pain is composed of at least two elements • localized stimulation of peripheral nerves through damage or inflammation • recognition of pain within the CNS

  6. Mechanism of Action Nonnarcotic analgesics relieve pain by selectively inhibiting prostaglandin synthesis (prostaglandin synthetase) centrally (hypothalamus) and peripherally Prostaglandins stimulate peripheral nerve endings producing pain impulses that are carried to the CNS (prostaglandin G2 &H2) enhance local inflammation (prostaglandin E2) produce localized edema (E2) constrict blood vessels (local ischemia, G2 & H2)

  7. Types of NonnarcoticAnalgesics Nonnarcotic analgesics differ in their chemical class and ability to produce analgesia, antipyresis, and/or be antiinflammatory N-acetyl-p-aminophenol acetaminophen Salicylates aspirin, diflusinal Synthetic nonsteroidal antiinflammatory (NSAID) Naprosyn - Naproxen Fenoprofen - Nalfon Ibuprofen- Advil, Motrin Indomethacin - Indocin

  8. Salicylates & Aspirin • Oldest group, from willow bark, known to • reduce fever and pain • increase peripheral blood flow (vasodilation) • prophylactically inhibit clotting

  9. Pharmacological Effects Gastrointestinal Nausea due to erosion of stomach lining Decrease prostaglandin cytoprotective mucus secretion Cardiovascular Inhibit plateletaggregation & clot formation Reduce the risk of death & reinfarction following myocardial infarction

  10. Salicylates Adverse Effects • Nausea, heartburn, dyspepsia • Vomiting • Gastrointestinal bleeding • Prolong bleeding time • Hepatoxicity (elevated serum enzymes) • Hypersensitivity (in sensitive patients)- rash, laryngeal edema, asthma

  11. Nonsteroidal Antiinflammatory Drugs (NSAIDs) • reduce pain associated with inflammation • are not steroids (e.g. cortisone) • include aspirin and salicylates • are useful in the management of • headache (nonmigraine) • muscle aches and pain, • Dysmenorrhea • joint pain of osteoarthritis

  12. Nonsteroidal Antiinflammatory Drugs (NSAIDs) Inflammation is characterized by local • swelling (edema) • redness (erythema, vasodilation) • warmth • pain Intermediated by prostaglandins (G2, H2, E2, F2ά)

  13. NSAIDs Mechanism of Action Inhibit inflammation and reduce pain by blocking the synthesis of prostaglandins Stabilize cell membranes to prevent further leakage of substances (edema)

  14. NSAIDs Adverse Effects • Nausea • Gastrointestinal distress, ulceration,bleeding • Vomiting • CNS stimulation • Headache • Vertigo • Mental confusion • Hypersensitivity reactions (rash, fever) • Hepatic damage (elevated serum enzymes)

  15. NSAIDs Special Considerations Aspirin sensitive patients may develop • anaphylactic reactions • angioedema • asthma Chronic toxicity is the same as for aspirin • tinnitus • gastrointestinal bleeding • black tarry stools

  16. Chronic Salicylate Toxicity Salicylism is a constellation of symptoms that occur in some patients with the chronic use of large doses of aspirin and other salicylates • Nausea • Vomiting • Headache • Tinnitus (ringing in the ears) • Hyperglycemia • Delirium

  17. Acute Salicylate Poisoning Accidental ingestion of a large dose by children or attempted suicide may produce » Depression of respiratory centers • Respiratory acidosis • CNS depression • Sweating • Dehydration, electrolyte imbalance • Hypotension & vasodilation • Coma • Death

  18. Acetaminophen • Weak prostaglandin synthetase inhibitor • Useful for reducing fever and headache (nonmigraine) • Should not substitute for antiinflammatory drugs • Does not affect platelet aggregation/clotting • May be used as an aspirin substitute in aspirin-sensitive patients

  19. Acetaminophen Adverse Effects Acute toxicity • Nausea • Vomiting • Hepatoxicity (elevated serum enzymes) • Acidosis • Respiratory depression

  20. Special Caution Aspirin and acetaminophen in children and teenagers who have active viral infections (flu or chicken pox) may result in Reye’s syndrome, potentially life-threatening

  21. Insert Gout Diagram

  22. Antigout DrugsClinical Indication Treatment of gout, a special inflammatory condition in which uric acid deposits in the joint fluid of the toes, knees, or kidneys because uric acid is • overproduced or • not efficiently excreted Phagocytes digest the uric acid and set up a cycle of localized inflammation

  23. Antigout Drugs Drugs in this class include Acute treatment • Colchicine • Aspirin, naproxenProphylaxis • Allopurinol blocks uric acid production • Probenecid for uric acid excretion • Sulfinpyrazone for uric acid excretion

  24. Drug Interactions NSAIDs are highly bound to albumen and will displace other drugs from these binding sites causing increased concentration of active drugs in the blood such as • Oral anticoagulants, e.g., warfarin • Antibiotics, Anticonvulsants, Methotrexate Increased risk of hepatotoxicity when given with alcohol, barbiturates, anticonvulsants, rifampin

  25. Immunomodulating Agents • Immunosuppressive drugs decrease the activity of the immune system and are useful in severe allergic and inflammatory conditions, and in the prevention of organ rejection following transplantation • Immunostimulant drugs activate the immune system and increase the ability of the body to resist infection and the growth of abnormal cancer cells

  26. Insert Immune Diagram

  27. Immune Cells • Macrophages initiate the immune response • Helper T-cells activate other T- and B-cells • Killer T-cells attack and kill infectious organisms • B-cells produce antibodies • Suppressor cells inhibit the immune system • Memory cells retain immunogenic information and provide long-term immunity

  28. Immunosuppressant Drugs

  29. Corticosteroid Drugs • Derivatives of adrenocorticosteroid hormones produced by the adrenal cortex • Used to suppress the immune system in severe allergy, inflammation, and prevent rejection following organ transplantation • Prednisone and prednisolone are two widely used corticosteroid drugs • Corticosteroids are often used in combination with other immunosuppressant drugs

  30. Cytotoxic Immunosuppressant Drugs • Azathioprine inhibits the synthesis of immune cell DNA and is mainly used to prevent organ transplant rejection • Cyclophosphamide is an alkylating drug used in immune-based diseases to decrease antibody production by B-cells • Mycophenolate inhibits T- and B-cell activity and is used to prevent renal organ transplant rejection

  31. Noncytotoxic Immunosuppressant Drugs • Cyclosporine inhibits the function of interleukin-2 and is widely used to prevent organ rejection following transplantation • Tacrolimus is similar to cyclosporine in action and clinical usage • Leflunomide inhibits the synthesis of DNA in T- and B-cells and is indicated for the treatment of rheumatoid arthritis

  32. Immunosuppressive Monoclonal Antibodies • Muromonab-CD3 binds to and inhibits the action of T-cells involved in organ transplant rejection • Daclizumab binds to and blocks the interleukin-2 receptor; it is used to prevent renal allograft rejection • Infliximab inhibits TNF-alpha which is an inflammatory factor active in Crohn’s disease

  33. Immunostimulant Drugs • Alpha-, Beta-, and Gamma-interferon are antiviral factors normally produced by activated immune cells, they are used as drugs to activate the immune system in certain viral infections and cancers • Interleukin-2 is an immune factor normally produced by lymphocytes, it is used as a drug to activate the immune system in certain cancers

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