Download ANTI-INFLAMMATORY DRUGS Inflammation is the complex

ANTI-INFLAMMATORY DRUGS
Inflammation is the complex Pathophysiological response of vascularized tissue to injury.
The injury may result from various stimuli including infectious agents, thermal, physical or
chemical damage, ischemia, antigen-antibody interactions and other biologic processes. After
tissue injury, the process of tissue healing includes three distinct phases: an inflammatory phase,
a repair phase, and a remodeling phase. The desired outcome of the inflammatory response is
isolation and elimination of the injurious agent to prepare for the repair of tissue damage at the
site of injury and restoration of function. Finally, new tissue formed during the repair phase (eg,
scar tissue) may be remodeled over several months.
Pathophysiology of inflammation: Initially, The inflammation phase consists of 3 sub phases:
acute, sub acute and chronic or proliferative. The acute phase is characterized by the five classic
clinical signs: heat, redness, swelling, pain, and loss of function and typically it lasts 1–3 days.
The sub acute phase corresponds to a cleaning phase required before the repair phase and may
last from 3–4 days to ~1 month. If the sub acute phase is not resolved within ~1 month, then
inflammation is said to become chronic and can last for several months. Tissue can degenerate
and, in the loco motor system, chronic inflammation may lead to tearing and rupture.
Treatment:
Aspirin and other salicylic acid derivatives: Aspirin is the prototype of NSAIDs and in 1939 it
was officially approved by the FDA. It is the most commonly used and is the drug to which all
other anti-inflammatory agents are compared.
Mechanism of action: Aspirin is a weak organic acid, the antipyretic and anti-inflammatory
effects of salicylates are primarily due to the blockade of prostaglandin synthesis at the
thermoregulatory centers in the hypothalamus and at peripheral target sites. Furthermore, by
decreasing prostaglandin synthesis, salicylate also prevents the sensitization of pain receptors to
both mechanical and chemical stimuli. Aspirin may also depress pain stimuli at sub cortical sites
(i.e. thalamus and hypothalamus).
Therapeutic uses: Anti-inflammatory, analgesic, and antipyretic. The salicylic acid derivatives
are used in the treatment of rheumatic fever, gout, osteoarthritis, and RA. Commonly treated
conditions requiring analgesia include arthralgia, headache and myalgia.
Pharmacokinetics: The un-ionized salicylates are passively absorbed from the stomach and the
small intestine after oral administration, rectal absorption of the salicylates is slow and
unreliable, but it is a useful route for administration to vomiting children.
Adverse effects: Nausea, vomiting, respiratory depression, urticaria, bronchoconstriction, or
angioedema. Reye's syndrome.
Acetic acid derivatives: The derivatives of acetic acids include sulindac, indomethacin, and
etodolac. All have anti-inflammatory, analgesic, and antipyretic activity. They act by reversibly
inhibiting cyclooxygenase. Although the drug is less potent than indomethacin, it is useful in the
treatment of ankylosing spondylitis, RA, osteoarthritis, and acute gout.
Adverse reactions: GI problems.
Propionic acid derivatives: Ibuprofen was the first agent in this class to become available. It
has been joined by fenoprofen, flurbiprofen, ketoprofen, naproxen and oxaprozin. All these drugs
possess anti-inflammatory, analgesic, and antipyretic activity; additionally, they can also alter the
platelet function and prolong bleeding time. These drugs are reversible inhibitors of the
cyclooxygenase and thus inhibit the synthesis of prostaglandins but not of leukotrienes. All are
well absorbed orally and are almost bound totally to the serum albumin. They undergo hepatic
metabolism and are excreted by the kidney.
Adverse effects: Headache, dizziness, tinnitus and GI disorders have been reported.
Fenamates: Mefenamic acid and meclofenamate have anti-inflammatory effect other no
advantages over NSAIDs.
Adverse effects: diarrhea, and they are associated with inflammation of the bowel, hemolytic
anemia have been reported.
Heteroaryl acetic acids: Diclofenac and tolmetin
are approved for long-term use in the
treatment of osteoarthritis, RA, and ankylosing spondylitis. Diclofenac is more potent than
indomethacin or naproxen. An ophthalmic preparation is also available. Diclofenac accumulates
in synovial fluid, and the primary route of excretion for the drug and its metabolites is the
kidney. Tolmetin is an effective anti-inflammatory, antipyretic, and analgesic agent with a halflife of 5 hours. It is 99 percent bound to plasma proteins, and metabolites can be found in the
urine. Ketorolac is a potent analgesic but has moderate anti-inflammatory effects. It is available
for oral administration, for intramuscular use in the treatment of postoperative pain, and for
topical use for allergic conjunctivitis. Ketorolac undergoes hepatic metabolism, and the drug and
its metabolites are eliminated via the urine.
Oxicam derivatives: Piroxicam and meloxicam are used to treat ankylosing spondylitis, RA,
and osteoarthritis. Meloxicam inhibits both COX-1 and COX-2, with preferential binding for
COX-2, and at low to moderate doses shows less GI irritation than piroxicam. However, at high
doses, meloxicam is a nonselective NSAID, inhibiting both COX-1 and COX-2.
Nabumetone: Nabumetone is indicated for the treatment of RA and osteoarthritis and is
associated with a low incidence of adverse effects. Nabumetone metabolized by the liver to the
active metabolite, which displays the anti-inflammatory, antipyretic, and analgesic activity.
Celecoxib: Celecoxib is significantly more selective for inhibition of COX-2 than of COX-1. In
fact, at concentrations achieved in vivo, celecoxib does not block COX-1. Celecoxib is approved
for treatment of RA, osteoarthritis, and pain.
Adverse effects: Headache, diarrhea, dyspepsia and abdominal pain are the most common
adverse effects. Celecoxib is contraindicated in patients who are allergic to sulfonamides
Acetaminophen: Acetaminophen inhibits prostaglandin synthesis in the CNS. This explains its
antipyretic and analgesic properties. Acetaminophen has less effect on cyclooxygenase in
peripheral tissues, which accounts for its weak anti-inflammatory activity.