Drug Therapy for Inflammation

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Drug Therapy for Inflammation

• John D. Bowman, MS, BCPS
• McWhorter School of Pharmacy
• Samford University

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NSAIDS

• NSAIDs act to
• Decrease inflammation of tissues
• Relieve pain
• Decrease fever
• Inhibit platelet aggregation

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NSAIDS

• Aspirin is the prototype for NSAIDs
• They inhibit prostaglandin synthesis
• They decrease synthesis of CYCLO-OXYGENASE
• Cyclo-oxygenase (COX) controls production of
  prostaglandins and thromboxane by cells

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NSAIDS

• Injury causes cells to increase prostaglandin
  synthesis, which results in the clinical symptoms
  of redness (dilation of blood vessels), pain
  (sensitization of pain receptors), swelling
  (leakage of fluid from capillaries), fever
  (hypothalamus thermometer)

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NSAIDS

• Decreased thromboxane synthesis inhibits clotting
  by decreasing platelet aggregation
• Platelet activation and aggregation is the first
  step in clot formation
• The practical value of this action is the
  demonstrated benefit of daily aspirin in
  preventing heart attacks

6
NSAIDS

• There are several COX enzyme types
• Of importance, COX-1 is a normal constituent of
  many cells and is important for maintaining
  homeostasis
• When COX-1 is inhibited, the parietal cells of
  the stomach do not protect the stomach from acids
  and ulcers can result
• When COX-1 is inhibited, normal blood pressure in
  kidney arterioles is not maintained, and kidney
  damage can result

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NSAIDS

• New NSAIDs have more COX-2 inhibition than COX-1
  (Celebrex, Vioxx, Bextra) but can still cause
  ulcers and kidney problems, especially in the
  elderly
• Aspirin, unlike other NSAIDs, irreversibly binds
  to platelets and increased clotting time can
  persist for days
• Other NSAIDs increase clotting time in relation
  to the drugs half life in the body

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Relief of Pain and Inflammation

• NSAIDs and acetaminophen can relieve pain
  equally, but some patients respond better to one
  drug than another
• The only injectable NSAID is ketorolac (Toradol)
  which has a risk of GI ulcers
• Aspirin should not be used in children because of
  an association with Reyes syndrome, which is
  potentially fatal

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Relief of Fever

• Aspirin, acetaminophen and NSAIDs can reduce
  fever
• Aspirin is not used in children

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Preventing Cardiovascular Disease

• Aspirin is used for primary and secondary
  prevention of heart attacks in patients with risk
  factors
• Aspirin is used for secondary prevention of
  stroke in patients with risk factors

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GI Effects

• Aspirin and NSAIDs irritate the gastric mucosa
  directly (take with meals)
• They also interfere with mucosal protection
  through prostaglandin inhibition
• COX-2 NSAIDs are somewhat safer
• Acid-reducing agents may be given

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Other Adverse Effects

• Aspirin overdose can be acute or chronic, and is
  serious
• Do not exceed maximum daily doses
• Aspirin and NSAIDs may be harmful to the kidneys
  in normal doses in older patients
• A few patients have severe hypersensitivity to
  aspirin

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Comparison of NSAIDs and Aspirin

• None has demonstrated superiority over others for
  pain relief
• However, some patients respond to one agent and
  not to another
• Generic drugs are always less expensive

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Acetaminophen

• Not an anti-inflammatory
• As good a pain reliever as NSAIDs
• High doses damage the liver

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Rheumatoid Arthritis

• An autoimmune disease
• Characterized by destruction of the synovium
• Can lead to deformities
• No cure

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Rheumatoid Arthritis

• Criteria for RA (p 227)
• Initiate treatment with aspirin or NSAIDs
• Steroids are useful during flares of disease
  activity
• Disease-modifying agents are added to NSAIDs

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Rheumatoid Arthritis

• NSAIDs are always used to initiate treatment,
  and should be given on a regular basis for most
  patients
• Refer to previous discussion about NSAID effects
  and side effects

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Rheumatoid Arthritis

• Glucocorticoids (steroids) are very effective
  anti-inflammatory agents
• Prednisone is the steroid used in RA
• They have many side effects, both short term and
  long-term
• Should be used by patients during flares
• Steroid injections into joints can be helpful but
  not more than 4/year/joint

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Rheumatoid Arthritis

• Side effects of steroids include ulcers, bone
  density loss, diabetes, psychiatric disorders,
  hypertension, etc
• They should be avoided in children due to growth
  retardation
• Patients need to know these are not the same as
  steroids that athletes abuse

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Rheumatoid Arthritis

• In the US, methotrexate is the preferred DMARD
• DMARDs slow joint destruction while NSAIDs do
  not
• Antimalarial drugs are safer than steroids or
  methotrexate but do not work for everyone
• Some DMARDs take months before effects are seen
  on RA

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Rheumatoid Arthritis

• Anti-TNF agents are the newest and most effective
  therapies
• Because of their high cost, they are not used
  initially in RA at this time
• Enbrel (etanercept) and Remicade (infliximab) are
  given by injection
• Kineret (anakinra) is an anti-IL-1 agent, also
  given by injection
• Infections can become life-threatening during
  therapy

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Osteoarthritis

• Degenerative joint disease
• Almost everyone will develop OA eventually
• Affects joints that have been traumatized before
  other joints
• Common cause of low back pain
• Usually not disfiguring

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Osteoarthritis

• Often develops in weight bearing areas (hips,
  knees)
• Osteophytes (spurs) seen on X-ray
• Start treatment with acetaminophen or NSAIDs
• Exercise of the joint is very important
• Viscosupplementation

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Osteoarthritis

• Glucosamine with chondroitin is worth a months
  trial for most patients
• Try to avoid long-term use of opiate narcotics
  such as Lortab, etc.
• Spinting, assistive devices, etc. may help
• Topical capsaicin helps some patients