Anti-InflammatoryDrugs

Insert Inflammation Diagram

Analgesics, Anti-inflammatories and Anti-gout Agents

This group is comprised of drugs that reducemild 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 associatedwith gout, muscle ache, or muscle ischemia

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)

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

Nonnarcotic analgesics relieve pain byselectively 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)

Mechanism of Action

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

Types of Nonnarcotic Analgesics

Salicylates & Aspirin

Oldest group, from willow bark, known to

• reduce fever and pain

• increase peripheral blood flow (vasodilation)

•prophylactically inhibit clotting

Gastrointestinal • Nausea due to erosion of stomach lining• Decrease prostaglandin cytoprotective mucus secretion

Cardiovascular• Inhibit platelet aggregation & clot formation• Reduce the risk of death & reinfarction following myocardial infarction

Pharmacological Effects

Salicylates Adverse Effects• Nausea, heartburn, dyspepsia

• Vomiting

• Gastrointestinal bleeding

• Prolong bleeding time

• Hepatoxicity (elevated serum enzymes)

• Hypersensitivity (in sensitive patients)- rash, laryngeal edema, asthma

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

o headache (nonmigraine)

o muscle aches and pain,

o Dysmenorrhea

o joint pain of osteoarthritis

Nonsteroidal Antiinflammatory Drugs (NSAIDs)

Inflammation is characterized by local

• swelling (edema)

• redness (erythema, vasodilation)

• warmth

• pain

Intermediated by prostaglandins (G2, H2, E2, F2ά)

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)

NSAIDs Adverse Effects• Nausea

• Gastrointestinal distress, ulceration,bleeding

• Vomiting

• CNS stimulation

• Headache

• Vertigo

• Mental confusion

• Hypersensitivity reactions (rash, fever)

• Hepatic damage (elevated serum enzymes)

NSAIDs Special ConsiderationsAspirin sensitive patients may develop• anaphylactic reactions• angioedema• asthma

Chronic toxicity is the same as for aspirin• tinnitus• gastrointestinal bleeding• black tarry stools

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

Acute Salicylate Poisoning

Accidental ingestion of a large dose bychildren or attempted suicide may produce

» Depression of respiratory centers» Respiratory acidosis» CNS depression» Sweating» Dehydration, electrolyte imbalance» Hypotension & vasodilation» Coma» Death

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

Acetaminophen Adverse Effects

Acute toxicity

• Nausea

• Vomiting

• Hepatoxicity (elevated serum enzymes)

• Acidosis

• Respiratory depression

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

Insert Gout Diagram

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

Antigout DrugsDrugs in this class include

Acute treatment• Colchicine • Aspirin, naproxen

Prophylaxis• Allopurinol blocks uric acid production• Probenecid for uric acid excretion• Sulfinpyrazone for uric acid excretion

Drug InteractionsNSAIDs are highly bound to albumen and will displace other drugs from these binding sitescausing increased concentration of active drugs in

the blood such as – Oral anticoagulants, e.g., warfarin– Antibiotics, Anticonvulsants, Methotrexate

Increased risk of hepatotoxicity when given withalcohol, barbiturates, anticonvulsants, rifampin

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

Insert Immune Diagram

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

Immunosuppressant Drugs

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

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

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

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

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