Non-steroidal anti-inflammatory drugs

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Non-steroidal anti-inflammatory drugs
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ANTI-INFLAMMATORY DRUGS

• A class of drugs that lower inflammation and that
  includes NSAIDs and DMARDs.

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Others
Salicylates
Propionic acid Derivatives
Oxicams
Aryl acetic Acid derivatives
Indole derivatives
Fenamates
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Pharmacokinetic
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MECHANISM OF ACTION OF NSAIDS

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ASPIRIN is IRREVERSIBLE INHIBITOR TO COX ENZYMES
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NON- SLECTIVE -NON -STEROIDAL ANTI-INFLAMMATORY
DRUGS

• Are group of drugs that share in common the
  capacity to induce
• Analgesic effect.
• Antipyretic effect.
• Anti-inflammatory effect.
• Antiplatelet effect

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Mechanism Of Action
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Mechanism Of Action ( continue)
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ANALGESIC

• Drug that relieve pain.

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ANTIPYRETIC

• Drug that lower the elevated body temperature to
  normal.

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• Effect on GIT
• Inhibition of PGI2 PGE2 PGF2 resulting in
  gastric upset up to gastric ulceration bleeding

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• Kidney
• Inhibit PGE2 PGI2 resulting in salt
  water retention , edema , hyperkalemia
  interstitial nephritis

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• Respiratory system
• With aspirin
• High dose act directly on respiratory center
  causing hyperventilation respiratory alkalosis
• Toxic doses causing central respiratory
  paralysis respiratory acidosis

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THERAPEUTIC USES SHARED BY NS-NSAIDs
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• Fever.
• Analgesic (Type of pain?)
• Headache, Migraine,
• Dental pain
• Common cold.

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• Rheumatic / Rheumatoid arthritis
• Dysmenorrhea
• Muscular pain

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ADVERSE EFFECTS

• GIT upsets ( nausea, vomiting)
• GIT bleeding ulceration
• Bleeding
• Hypersensitivity reaction
• Inhibition of uterine
• contraction
• Salt water retention

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Clinical uses

• Acute rheumatic fever
• Reducing the risk of myocardial infarction
• Prevention of pre-eclampsia

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Adverse Effects Related to (A)Therapeutic Doses
Of Aspirin

• Gastric irritation
• Hypersensitivity
• ( aspirin asthma)
• Acute Gouty arthritis
• Reye's syndrome

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(B) TO high doses prolonged use of aspirin

• Salicylism ( ringing of ears (tinnitus), vertiog)
• Hyperthermia
• Gastric ulceration bleeding
• Metabolic acidosis

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side effects Related to High doses
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Contraindications

• Peptic ulcer
• Pregnancy
• Hemophilic patients
• Patients taking anticoagulants
• Children with viral infections
• Gout ( small doses )

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PARACETAMOL

• A commonly used analgesic antipyretic instead of
  aspirin in cases of

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• Peptic or gastric ulcers.
• Bleeding tendency.
• Allergy to aspirin.
• Viral infections in children .
• Pregnancy.

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Adverse Effects

• Mainly on liver due to its active metabolites
• Therapeutic doses elevate liver enzymes
• High doses cause liver kidney necrosis
• Treatment toxicity of paracetamol
• N- acetylcysteine to neutralize the toxic
  metabolites

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Propionic acid derivatives

• IBUPROFEN

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Clinical uses

• Therapeutic uses shared by NS- NSAIDs
• Acute gouty arthritis
• Patent ductus arteriosus
• More potent as an anti-inflammatory than aspirin

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Preparations of Ibuprofen

• Oral preparations.
• Topical cream for osteoarthritis.
• A liquid gel for rapid relief of postsurgical
  dental pain.
• Intravenous route as In patent ductus arteriosus

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Adverse effects

• Adverse effects shared by NS-NSAIDs
• (Gastric upset less frequent than
  aspirin)
• Rare hematologic effects (agranulocytosis
  aplastic anemia ).
• Ocular disturbance

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Contraindications

• Peptic ulcer
• Allergic patients to aspirin
• Kidney impairment
• Liver diseases
• Pregnancy
• Haemophilic patients
• The concomitant administration of ibuprofen
  antagonizes the irrevesible platelet inhibition
  of aspirin( limit cardioprotective effect of
  aspirin ).

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Oxicam derivatives

• Piroxicam
• Tenoxicam

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Piroxicam

• Half- Life 45 hours
• Given once daily

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Adverse effects

• Less frequent gastric upset (20) .
• Dizziness
• Tinnitus
• Headache
• Allergy

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Acetic acid derivatives

• Diclofenac

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Preparations of Diclofenac

• Diclofenac with misoprostol decreases upper
  gastrointestinal ulceration ,but result in
  diarrhea.
• Diclofenac with omeprazole to prevent recurrent
  bleeding.
• .1 opthalmic preparation for postoperative
  opthalmic inflammation.
• A topical gel 3 for solar keratosis.
• Rectal suppository

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• Oral mouth wash.
• Intramuscular preparations.

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Clinical uses

• Clinical uses shared by Ns-NSAIDs
• Acute gouty arthritis
• Locally to prevent or treat post opthalmic
  inflammation
• A topical gel for solar keratosis

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Adverse effects

• Adverse effects shared by NS-NSAIDs

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Selective COX-2 inhibitors

• General advantages
• Potent anti-inflammatory
• Antipyretic analgesic
• Lower incidence of gastric upset
• No effect on platelet aggregation ( COX-1)

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General adverse effects

• Renal toxicity
• Dyspepsia heartburn
• Allergy
• Cardiovascular ( do not offer the
  cardioprotective effects of non-selective group).

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Clinical uses

• Postoperative patients undergoing bone repair
• Acute gouty arthritis
• Acute musculoskeletal pain
• Ankylosing spondylitis

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Celecoxib

• Half-life 11 hours ( Given twicw daily)
• Food decrease its absorption
• Highly bound to plasma proteins
• Metabolized in liver to inactive metabolites

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Meloxicam

• Relatively selective Cox2 inhibitors.
• Safer than piroxicam.

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Pharmacokinetics

• Given orally ,rectally, I.M.,I.V.
• Metabolized in liver to inactive metabolites.
• Excreted in urine 50 and in feces 50.
• Half-life 20 hours.
• Given once daily.

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Clinical uses

• Shared by selective COX-2 inhibitors

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Adverse effects

• Shared by selective COX-2 inhibitors

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Drug interactions

• Cholestyramine increases the clearance of the
  drug .

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Nabumetone

• Relatively selective COX-2 inhibitor
• Well absorbed orally.
• Metabolized in liver to active metabolites.
• Half-life 26 hours.
• Taken once daily.

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Clinical uses

• Shared by selective COX-2 inhibitors

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Adverse effects

• Shared by selective COX-2 inhibitors
• Headache
• Tinnitus
• Photosensitivity

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