ANALGESIC &

ANTI INFLAMMATORY
DRUGS

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 PAIN
 Pain is always a subjective experience
 Everyone learns the meaning of “pain” through
experiences usually related to injuries in early life
 As an unpleasant sensation it becomes an
emotional experience
 Pain is a significant stress physically, emotionally

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TYPES
 Somatic pain: caused by the activation of
pain receptors in either the cutaneous (the
body surface) or deeper tissues
(musculoskeletal tissues).
 Visceral pain: pain that is caused by
activation of pain receptors from infiltration,
compression, extension or stretching of the
thoracic, abdominal or pelvic viscera (chest,
stomach and pelvic areas).
 Neuropathic pain: caused by injury to the
nervous system either as a result of a tumor
compressing nerves or the spinal cord, or
cancer actually infiltrating into the nerves or
spinal cord.
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Various Descriptors of Pain

 Mild
 Moderate
 Severe
 Acute
 Chronic
 Malignant

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 Arthritis
 Pain
– Musculoskeletal
– Dental
– Postoperative
– Headache
– Dysmenorrhea
– Cancer
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Treatment

Non – opioid analgesics

 Salicylates , NSAID’s, Cox 2 inhibitors

Opioid analgesics – Morphine, Pethidine..

Both in combined therapy.

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Anti-Inflammatory Drugs

 Non steroidal Anti-inflammatory

Drugs
(NSAID’s)

 Steroidal agents

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 Most of the drugs used as analgesics have
the property of anti inflammatory actions
also.
 Some of these drugs have the anti-pyretic
property also.

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 PGs are derived from arachidonic acid
Cell Membrane (phospholipids)
phospholipase A2

Arachidonic acid
cyclooxygenase aspirin, indomethacin
(COX1 & COX2)
Cyclic endoperoxides (PGG2, PGH2)
prostacyclin prostaglandin thromboxane
synthetase synthetase synthetase

prostacyclin PGE2 PGF2 Thromboxane A2

PDX, PGI2
(vasodilator, (erythma (vasodilator (vasoconstriction
antiaggregating) edema uterus contractor) platelet
agregation)
pain, fever)

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NSAID’s (Nonselective COX Inhibitors)
 Salicylic acid derivatives: Aspirin,
Diflunisal etc
 Para-aminophenol derivatives:
Acetaminophen
 Indole and indene acetic acids:
Indomethacin
 Heteroaryl acetic acids: Tolmetin,
Ketorolac
 Propionic acids: Ibuprofen, Naproxen,
Ketoprofen etc
 Anthranilic acids (Fenamates):
Mefenamic acid, Meclofenamate 13
 NSAIDs
Selective COX 2 Inhibitors

 Diaryl -substituted furanones

Rofecoxib (Vioxx)
 Diaryl -substituted pyrazoles
Celecoxib (Celebrex)

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Salicylates
 Aspirin: prototype
 Aspirin uniquely inactivates COX
by irreversibly acetylating the
enzyme.

Uses
 Pain (analgesic)
 Fever (anti pyretic)
 Anti inflammatory
 Anti platelet
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 Therapeutic uses: Control of Rheumatoid
Arthritis, Gout, Osteoarthritis, Ankylosing
spondylitis and prophylaxis against platelet
aggregation. & other pains.

 Adverse effects: Gastric bleeding, Peptic ulcer,

Hypersensivity, renal toxicity and Reye’s
syndrome, tinnitus.

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Salicylates (continued)

 Diflunisal: difluorophenyl derivative of

salicylic acid.
 Diflunisal is more potent than aspirin in
analgesic & anti-inflammatory actions.
However, it is largely devoid of antipyretic
effects.
 Longer duration (half-life:8-12 hrs vs. 2.5
hrs for salicylates).
 Fewer and less intense gastrointestinal and
antiplatelet effects than does aspirin.
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Indole and Indene Acetic Acids
 Indomethacin:
 Indomethacin is a potent inhibitor of the COX.
 Indomethacin often is more effective than
aspirin in the treatment of ankylosing
spondylitis and osteoarthritis.
 It has high incidence and severity of side effects
associated with long-term administration.
• Sulindac: an indene derivative
 It must be reduced to sulfide metabolites to
become active form of NSAID.
 Sulindac has been used mainly for the
treatment of rheumatoid arthritis,
osteoarthritis, and ankylosing spondylitis.
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SE:
 GIT disturbances such as Nausea &

Vomiting, Diarrhea, Anorexia

 Frontal headache

 Dizziness

 Vertigo

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Heteroaryl Acetic Acid Derivatives

 Tolmetin:
 Tolmetin is an effective anti-
inflammatory agent that also exerts
antipyretic and analgesic effects.
 Tolmetin is approved for the
treatment of osteoarthritis,
rheumatoid arthritis and ankylosing
spondylitis.
 Tolmetin causes gastric erosions and
prolongs bleeding time.
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Ketorolac:

 Heteroaryl acetic acid derivative

 Ketorolacis a potent analgesic but only a

moderately effective anti-inflammatory drug.

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Phenyl Acetic Acid Derivatives
 Diclofenac: phenyl acetic acid derivative
 It is a COX inhibitor, and its potency is
substantially greater than that of
indomethacin.
 Diclofenac sodium (Voltaren) is approved
for the long-term symptomatic treatment
of rheumatoid arthritis, osteoarthritis,
and ankylosing spondylitis.
 It can also be used for short-term
treatment of acute musculoskeletal
injury, acute painful shoulder,
postoperative pain and Dysmenorrhea.
 Toxic effects: gastrointestinal effects are
the most common.
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Propionic Acid Derivatives
Propionic acid derivatives are used for the
symptomatic treatment of rheumatoid
arthritis, osteoarthritis, ankylosing
spondylitis and acute gouty arthritis.

 Ibuprofen:
 Naproxen:
The half-life of naproxen in plasma is
about 14 hrs.
 Ketoprofen:
 Oxaprozin: It is unique among propionic
acid derivatives because it can be
administered once daily.
 Fenoprofen
 Flurbiprofen
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Enolic Acid (Oxicams)
 Piroxicam( Feldene)
In recommended doses, Piroxicam
appears to be equivalent of aspirin,
indomethacin, or naproxen for the long-
term treatment of rheumatoid arthritis
and osteoarthritis. It may be tolerated
better than aspirin and indomethacin.

 Meloxicam (Mobic)
Recently, it was approved by the FDA
for use in treating osteoarthritis (7.5 mg
once daily).

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 Nabumetone (Relafen)
It has indicated substantial efficacy in the
treatment of rheumatoid arthritis and
osteoarthritis. The drug also appears to be
effective in the short-term treatment of soft
tissue injuries.

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FENAMATES
 Mefenamic acid & Meclofenamate
 Same actions as rest other NSAID’s

SE:
 Same as others +

 Diarrhea,

 Anemia are reported.

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Selective COX-2 inhibitors
 Diaryl substituted furanones
Rofecoxib (vioxx): It has been
approved for the treatment of
osteoarthritis, acute pain in adults , and
Dysmenorrhea. The recommended
starting dose for osteoarthritis is 12.5
mg once daily.
Diaryl substituted pyrazoles
Celecoxib (celebrex): It has been
approved for the treatment of
osteoarthritis and rheumatoid arthritis.
The recommended dose for treatment
osteoarthritis is 200 mg per day as a
single dose or as two 100-mg doses.
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Others

Acetaminophen
 Inhibits mainly PG in CNS – antipyretic,
 Weak anti inflammatory,
 No anti platelet actions

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Acetaminophen
 Good for pt’s with aspirin SE.
 Analgesic and antipyretic in viral
infections in children
 Form sulfated metabolites in liver.
 If high some portion forms N acetyl
benzoquinoneimine., a highly reactive
product with sulfhydryl groups.

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SE:
 Not much with normal doses,

 High doses –N acetyl benzoquinoneimine

reacts with sulfhydryl groups of hepatic

proteins.
 Can lead to hepatic necrosis and also renal

tubular necrosis.
 Anti dote – N - acetylcysteine

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Miscellaneous agents for
rheumatoid arthritis
These drugs are relatively toxic, and
they are reserved for patients with
progressive disease, refractory
cases or patients unable to tolerate
standard medications.
 Gold compounds:

Aurothioglucose, gold sodium

thiomalate, and auranofin
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 Gold compounds: Aurothioglucose,
Gold sodium thiomalate, and auranofin
 Mechanisms: Gold compounds inhibit
maturation and function of mononuclear
phagocytes and of T cells, thereby
suppressing immune responsiveness.
 This retards the progression of bone and
articular destruction
 Toxicity: Lesions of the mucous
membranes include stomatitis, pharyngitis
etc. Severe blood dyscrasias also may
occur.

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Miscellaneous agents for rheumatoid
arthritis (continued)
 Immunosuppressive agents, : Cyclosporine
Azathioprine, Methotrexate
Of the cytotoxic immunosuppressant, only
Azathioprine and low oral doses of
methotrexate have been approved for
treatment of RA.
 Penicillamine: orally effective alternatives to
gold in the treatment of patients with early,
mild, and nonerosive disease.
Toxicities: various cutaneous lesions, blood
dyscrasias etc.
 Antimalarial agents: Hydroxychloroquine
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Gouty arthritis
An acute attack of gout occurs as a
result of an inflammatory reaction to
crystals of sodium urate that are
deposited in the joint tissue.
The inflammatory response involves:
 Local infiltration of granulocytes,
which phagocytize the urate crystals.
 Enhanced lactate production in
synovial tissues and leukocytes.

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 Clinical manifestation of gout
 Acute gouty arthritis
- Deposition of sodium urate
mucopolysaccharide in the synovial fluid
that activates Hageman factor and initiates
the chain of events leading to bradykinin
formation.
- Neutrophils actively phagocytize urate
crystals, leading to release of lysosomal
enzymes and increased lactic acid
production.

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 Tophaceous deposit: sodium urate
deposits in and around joints in cartilage,
bone, bursa and subcutaneous tissue.
 Uric acid nephrolithiasis: formation of
urate stone
 Gouty kidney: nephropathy

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Drugs used in the treatment of gout
 Colchicine: it is largely effective only
against gouty arthritis.
- Colchicine interferes with the
function of the mitotic spindles and
causes depolymerization and
disappearance of fibrillar
microtubules in granulocytes and
other motile cells.
- Colchicine inhibits the migration of
granulocytes into the inflamed area
and a decreased metabolic and
phagocytic activity of granulocytes.
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 - Side effects: nausea, vomiting, diarrhea,
and abdominal pain.
- Toxic effects: hemorrhagic gastroenteritis,
extensive vascular damage,
nephrotoxicity, and muscular depression.

 Allopurinol: its metabolite, alloxanthine, is

an inhibitor of xanthine oxidase, which is
required to synthesize uric acid.

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Drugs used in the treatment of gout
(continued)
Uricosuric drugs: These drugs, at higher
doses, block tubular reabsorption of urate,
thus increasing urinary excretion of uric acid
and lowering serum urate concentration.
 Probenecid:
- Liberal fluid intake should be
maintained throughout therapy.
- The uricosuric action of Probenecid is
blunted by administration of
salicylates
- It can block the renal excretion of
penicillin effectively.
 Sulfinpyrazone
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