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Anti-inflammatory Drugs:- PPT / PDF

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
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  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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