Description
Introduction to Anti-inflammatory Drugs
• Inflamation
Normal protective response to
tissue injury
caused by
• Physical Trauma
• Noxicious Chemicals
• Microbial Agents
✓ When Inflammation process is
subside
When Healing is Complete
• Classification of anti-inflammatory drugs
• 2. The mechanisms of NSAIDs
• Cyclooxygenases: COX 1, COX 2
• Peripheral mechanisms of pain
• Pharmacodynamic Effects of NSAIDs
• antipyretic : compared with chlorpromazine
• Analgesic : compared with Opioids
• Anti-inflammatory: compared with glucocorticoid
• NSAIDs and Platelets/Endothelial Cells
• Negative or adverse effects
Gastric irritant
Decreased renal perfusion
Bleeding
• 5. Drug interactions
• Salicylates – aspirin
• Aspirin
Dose-Dependent Effects:
Low: < 300mg
blocks platelet aggregation
Intermediate: 300-2400mg/day
antipyretic and analgesic effects
High: 2400-4000mg/day
anti-inflammatory effects
• Side effects of aspirin
• NSAIDs: Classification by half-life
• Acetaminophen
• COX-2 selective anti-
inflammatory drugs
• TNF- inhibitor
Etanercept
Infliximab
Adalimumab
They are recombinant proteins that can not orally taken;
The long-term safety is not determined.
- Subject:- pharmacology 3
- Course:- B.pharm (pharmacy),
- Semester:- 5th sem , sem :- 5
Introduction to
Anti-inflammatory Drugs
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2012.10
Inflamation
Normal protective response to
tissue injury
caused by
• Physical Trauma
• Noxicious Chemicals
• Microbial Agents
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Inflamation
Body’s effort
• To inactive or destroy invading organisms
• To remove Irritants, and
• Set the stage for tissue repair
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When Inflammation process is
subside
When Healing is Complete
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Peripheral mechanisms of pain www.remixeducation.in
Classification of anti-inflammatory drugs
(1) Non-Steroid Anti-Inflammatory Drugs (NSAIDs)
(Antipyretic-Analgesic and Anti-inflammatory Drugs)
eg. aspirin, Diclofenac, Flurbiprofen, ibuprofen, indomethacin,
Ketoprofen, Meloxicam, Methyl salicylate, Naproxen, Piroxicam,
(2) COX 2 inhibitor
Celecoxib
(3) Other Analgesics
Acetaminophen
(4) Drugs use For Arthritis
Infliximab, Methotrexate, Rituximab, Chloriquine, Gold Salts,
(5) Drugs for Gout
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Allopurinol, Colchicine, Probenecid,
2. The mechanisms of NSAIDs
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2. The mechanisms of NSAIDs
Cyclooxygenases: COX 1, COX 2
- PGs, mostly by COX-1, are constitutively expressed in almost all
tissues; COX-2 appears to only be constitutively expressed in the brain,
kidney, bones, reproductive organs, and some neoplasms
- Under normal physiologic conditions, PGs play an essential homeostatic
role in cytoprotection of gastric mucosa, hemostasis, renal physiology,
gestation, and parturition
- In platelets there is only COX-1exist (converts arachidonic acid to TxA2)
- COX-1 predominant in gastric mucosa (source of cytoprotective PGs)
- The production of PGs, (inducible COX-2 activity >> COX-1) at sites
of inflammation propagate pain, fever
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2. The mechanisms of NSAIDs
NSAID inhibition of PG production alleviates
most of the pathologic effects associated with
inflammation, but it also interferes with the
physiologic role of these molecules
Consequently, long-term therapy with
nonspecific NSAIDs is frequently limited by their
adverse effects, particularly those caused by
erosion of gastric mucosal protection
—— GI bleeding
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3. Pharmacodynamic Effects of NSAIDs
Positive
Analgesic (0.3-0.6 g/day) - refers to the relief of pain by a mechanism other than
the reduction of inflammation (for example, headache);
- produce a mild degree of analgesia which is much less than the
analgesia produced by opioid analgesics such as morphine
anti-inflammatory (3-5 g/day) - these drugs are used to treat inflammatory
diseases and injuries, and with larger doses - rheumatoid disorders
antipyretic (0.3-0.6 g/day) - reduce fever; lower elevated body temperature by
their action on the hypothalamus; normal body temperature is not reduced
antiplatelet (30-100 mg/day)- inhibit platelet aggregation, prolong bleeding time;
have anticoagulant effects
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3. Pharmacodynamic Effects of NSAIDs
antipyretic : compared with chlorpromazine
NSAIDs Chlorpromazine
Effects Inhibit PGs synthesis Inhibit thermotaxic center in
and enhance hypothalamus. The body
thermolysis temperature change
according to the environment.
Clinical usage Lower the abnormal artificial hibernation,
high temperature to Hypothermic anesthesia,
normal. Used for
various fever.
Side effects GI reactions，no addiction Extrapyramidal effects
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3. Pharmacodynamic Effects of NSAIDs
Analgesic : compared with Opioids
NSAIDs Opioids
Effects Inhibit PGs and TxA2 Stimulate opioid receptors
synthesis by
inhibiting COX
Clinical usage Headache, toothache， Various pain including
neuralgia, arthronalgia,, severe pain
courbature (Lambague)
menalgia
Side effects GI reactions，no addiction Addiction
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3. Pharmacodynamic Effects of NSAIDs
Anti-inflammatory: compared with glucocorticoid
NSAIDs Glucocorticoid
Effects Inhibit PGs and TxA2 Various effects including
synthesis by inhibition of PLA2
inhibiting COX
Clinical usage Rheumatic, rheumatoid, Various inflammation
trauma
Side effects GI reactions Various side effects, such
as metabolism disturbance,
damage of defense etc.
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3. Pharmacodynamic Effects of NSAIDs www.remixeducation.in
NSAIDs and Platelets/Endothelial Cells
4. Adverse Effects associated with NSAIDs
Non-selective
Negative or adverse effects
Gastric irritant
Decreased renal perfusion
Bleeding
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5. Drug interactions
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Salicylates - aspirin
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Salicylism
Aspirin
Dose-Dependent Effects:
Low: < 300mg
blocks platelet aggregation
Intermediate: 300-2400mg/day
antipyretic and analgesic effects
High: 2400-4000mg/day
anti-inflammatory effects
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Side effects of aspirin
• Gastrointestinal symptoms
• CNS toxicity
• Allergic reaction (urticaria, angioneurotic edema, aspirin
asthma, occasionally anaphylactic shock)
• Salicylate reaction (CNS reaction)
• Renal damage
• Hematologic effects
• Metabolic acidosis stimulates medullary respiratory
center respiratory alkalosis
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4. Adverse Effects associated with NSAIDs
• Salicylism
dose > 5g/d: CNS symptoms, including mental
confusion; hyperventilation.
Rescure: i.v. NaHCO3 promote the excretion
• Hepatic damage
Overdose:
hepatic damage
Reye’s syndrome (kids)
severe hepatic damage and
encephalopathy
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NSAIDs: Classification by half-life
Plasma Elimination Half Lives
Short Half Life (< 6 hours):
more rapid effect and clearance
• Aspirin (0.25-0.33 hrs),
• Diclofenac (1.1 ± 0.2 hrs)
• Ketoprofen (1.8 ± 0.4 hrs),
• Ibuprofen (2.1 ± 0.3 hrs)
• Indomethacin (4.6 ± 0.7 hrs)
Long Half Life (> 10 hours):
slower onset of effect and slower clearance
• Naproxen (14 ± 2 hrs)
• Sulindac (14 ± 8 hrs),
• Piroxicam (57 ± 22 hrs)
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Acetaminophen
- analgesia
- antipyretic
- no significant anti-inflammatory effects
- no gastric irritation
- no platelet function interference
- half life 2 –3 h
- weak inhibitor of COX-1, -2;
- not contraindicated for asthma
- not associated with Reye’s Syndrome
- The major concern regarding the use of acetaminophen is the
potential for high doses to cause liver toxicity
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Differences between
NSAIDs and
Acetaminophen
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• indomethacin
stronger efficacy, controlling special types of
fever; severe adverse effects
• Sulindac
Its metabolite possess 500 fold PG inhibition than
itself.
Strong anti-inflammation and lower adverse
effects than indomethacin.
• Etodolac
Used as a pain killer after operation
Lower GI upset
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• Tolmetin
Moderate anti-inflammation and mild analgesic and
antipyretic effect
• ibuprofen
stronger antipyretic, analgesic and anti-
inflammatory effects; weaker GI reactions; vision
damage
• piloxicam
long-acting anti-inflammatory and analgesic agent;
long-term use induces hemorrhage and ulcers in GI
tract www.remixeducation.in
COX-2 selective anti-
inflammatory drugs
Meloxicam
stronger effect on COX-2 than COX-1
long-acting (t1/2 20 h)
weaker GI reactions
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TNF- inhibitor
Etanercept
Infliximab
Adalimumab
They are recombinant proteins that can not orally taken;
The long-term safety is not determined.
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Thank you
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