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Anti-inflammatory drugs. By Dr Soha AlSayed Lecture of Pharmacology Faculty of Medicine Suez Canal University. Classifications of anti-inflammatory drugs. Steroids: Drugs which contain steroid nucleus They are glucocorticoids or mineralocorticoids

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anti inflammatory drugs
Anti-inflammatory drugs

By

Dr Soha AlSayed

Lecture of Pharmacology

Faculty of Medicine

Suez Canal University

classifications of anti inflammatory drugs
Classifications of anti-inflammatory drugs
  • Steroids:
    • Drugs which contain steroid nucleus
    • They are glucocorticoids or mineralocorticoids
    • Glucocorticoids have significant anti-inflammatory effect

2. Non-steroids anti-inflammatory drugs (NSAIDs) characterized by:

        • Lower high body temperature (Antipyretic)
        • Relieve pain (Analgesic)
        • Some have anti-inflammatory effect
slide3

Non steroidal anti-inflammatory drugs

Types of COX enzyme:

1. COX-1 (constitutive) especially in stomach  decrease HCl (prevent PU) & Kidney vasodilatation

2. COX-2 (inducible) by infection

  • Infection ►toxins ► IL-1&TNF ► COX-II ►▲ PG ► Inflammation ►

A. CNS:

a. hypothalamus ► elevates Heat regulatory centre► Fever

b. Thalamus► pain

2. Periphery:

a. Sensitize Nociceptors to histamine, Bradykinin & 5-HT ► pain

b. Potentiates effect of histamine & bradykinin

        • VD Redness, Hotness, capillary permeability
slide5

Non steroidal anti-inflammatory drugs

Types of NSAIDS:

1. Non-selective COX inhibitors (COX 1,2,3)

2. Selective COX-2 inhibitors (Celecoxib, Rofecoxib)

3. COX-3 inhibitors : paracetamol (not anti-inflammatory). Why?

Mechanism of action of NSAIDS

They inhibit cyclo-oxygenase enzyme ►▼Prostaglandins ► ▼Fever, pain, Inflammation.

1. Antipyretic action: decrease set point of heat regulatory centre in hypothalamus, increase sweating

slide6

The anti-inflammatory actions of NSAIDS

  • Due to reduction of PGE2 and PGI2 that participate in the inflammatory process
  • Stabilize lysosomes
  • Inhibit granulocyte adherence to damaged vasculature
  • Inhibit migration of macrophages to the inflammatory sites
  • Inhibit Kinin-Kallikrein system
slide7

Shared Adverse effects of NSAIDS

  • GIT side effects: Dyspepsia, Gastric ulceration
  • Disturbances of renal function: (Analgesic abuse nephropathy) due to decreased vasodilatory PGs
  • Hypersensitivity: e.g. aspirin induced asthma
  • Bleeding tendency
  • Displacing other drugs from plasma proteins
  • Salt and water retention and hyperkalemia
  • May prolong pregnancy and spontaneous labor
slide9

Aspirin=Acetyl salicylic acid

Pharmacokinetics:

  • Administration: Effective orally & pareneterally
  • Absorption: Absorbed from stomach & Upper intestine. Why?
  • Distribution: Bound to PP (50-80%).
  • Metabolism: mainly by conjugation to glycine & glucoronic acid.
  • Excretion: unchanged and conjugated form by kidney. How can you increase excretion?
  • In low concentration first order kinetics?
  • In high concentration zero order kinetics?
slide10

Pharmacological actions of Aspirin

1. CNS:

A. Analgesic action: central and peripheral

B. Antipyretic Action: ▼PGE

2. Anti-inflammatory actions:

3. Respiration and Acid/Base balance:

  • Ordinary doses; little effect
  • large dose ►▲RR►R alkalosis.
  • V. high L doses► Resp. depression ► Resp. acidosis.

4. Renal effects:▲ Na, water retention

slide11

Pharmacological actions of aspirin

5. Uric acid:

A. Small dose: Retention of UA

B. Large dose: Excretion of UA 

6. Blood:

A. Small dose (75-150 mg/day): ▼platelet aggregation and▲ bleeding time

B. In patients with G-6-PD defiiency ►hemolytic anemia (idiosncrasy).

7. GIT:

Epigastric distress, nausea, vomiting, ulceration, bleeding.

slide12

Indications of Aspirin

  • Fever: (Not preferred in children. Why?)
  • Analgesic: Mild to moderate pain. headache, arthritis, myalgia, common cold ( 0.5-2 gm/day)
  • Acute Rheumatic fever: Symptomatic treatment only, 10 gm /day
  • Rheumatoid arthritis: 8 gm/day
  • Antithrombotic: 75-150 mg/day
  • Gout?: > 5gm /day
slide13

Side effects & contraindicationsof Aspirin

  • GIT: What?
  • Idiosyncrasy:
  • Hypoprothrombinemia, bleeding tendency
  • Chronic use: Salicylism: Headache, mental confusion, drowsiness, vertigo, ringing in ears (Tinnitus), sweating, thirst, nausea, vomiting

5. Hepatic: Severe hepatic injury and encephalopathy in Reye’s syndrome (in children with viral infection especially influenza, Chicken pox)

6. Bronchospasm 7. Allergy

slide14

Acute Salicylate poisoning

Acute salicylate poisoning:

Hallucination, restlessness, tremors, convulsions, vomiting, dehydration, hypotension, hyperglycemia, hyperpyrexia

  • Treament of acute salicylate poisoning;
      • Gastric lavage with sod. Bicarbonates. Why?
      • Correction of hyperpyrexia (cold fomentation, ethyl alcohol evaporation
      • Correction of dehydration , acid/base balance
      • Alkalinization of urine with NaHCO3. Why?
      • Hemodialysis: Symptomatic treatment
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