Transcript Document

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
The analgesics within this group are not
interchangeable for the relief of pain associated
with 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
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)
Types of Nonnarcotic Analgesics
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
Salicylates & Aspirin
Oldest group, from willow bark, known to
• reduce fever and pain
• increase peripheral blood flow
(vasodilation)
•prophylactically inhibit clotting
Pharmacological Effects
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
Salicylates Adverse Effects
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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
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Nausea
Gastrointestinal distress, ulceration,bleeding
Vomiting
CNS stimulation
Headache
Vertigo
Mental confusion
Hypersensitivity reactions (rash, fever)
Hepatic damage (elevated serum enzymes)
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
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 by
children 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 Drugs
Clinical 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 Drugs
Drugs 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 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
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
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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