1. 1 Anti-inflammatory drugs By Dr Soha AlSayed Lecture of Pharmacology Faculty of Medicine Suez Canal University

2. 2 Classifications of anti-inflammatory drugs 1.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: 1. Lower high body temperature (Antipyretic) 2. Relieve pain (Analgesic) 3. Some have anti-inflammatory effect

3. 3 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 Non steroidal anti-inflammatory drugs

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5. 5 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 Non steroidal anti-inflammatory drugs

6. 6 1.Due to reduction of PGE2 and PGI2 that participate in the inflammatory process 2.Stabilize lysosomes 3.Inhibit granulocyte adherence to damaged vasculature 4.Inhibit migration of macrophages to the inflammatory sites 5.Inhibit Kinin-Kallikrein system The anti-inflammatory actions of NSAIDS

7. 7 1.GIT side effects: Dyspepsia, Gastric ulceration 2.Disturbances of renal function: (Analgesic abuse nephropathy) due to decreased vasodilatory PGs 3.Hypersensitivity: e.g. aspirin induced asthma 4.Bleeding tendency 5.Displacing other drugs from plasma proteins 6.Salt and water retention and hyperkalemia 7.May prolong pregnancy and spontaneous labor Shared Adverse effects of NSAIDS

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9. 9 Pharmacokinetics : 1.Administration: Effective orally & pareneterally 2.Absorption: Absorbed from stomach & Upper intestine. Why? 3.Distribution: Bound to PP (50-80%). 4.Metabolism 4.Metabolism: mainly by conjugation to glycine & glucoronic acid. 5.Excretion: 5.Excretion: unchanged and conjugated form by kidney. How can you increase excretion? 6.In low concentration first order kinetics? zero order kinetics? 7.In high concentration zero order kinetics? Aspirin=Acetyl salicylic acid

10. 10 1. CNS: A. Analgesic action: central and peripheral B. Antipyretic Action: ▼PGE 2. Anti-inflammatory actions: 3. Respiration and Acid/Base balance: a)Ordinary doses; little effect b)large dose ►▲RR►R alkalosis. c)V. high L doses► Resp. depression ► Resp. acidosis. 4. Renal effects: ▲ Na, water retention Pharmacological actions of Aspirin

11. 11 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. Pharmacological actions of aspirin

12. 12 1. Fever: (Not preferred in children. Why?) 2.Analgesic: Mild to moderate pain. headache, arthritis, myalgia, common cold ( 0.5-2 gm/day) 3.Acute Rheumatic fever: Symptomatic treatment only, 10 gm /day 4.Rheumatoid arthritis: 8 gm/day 5.Antithrombotic: 75-150 mg/day 6.Gout?: > 5gm /day Indications of Aspirin

13. 13 1.GIT: What? 2.Idiosyncrasy: 3.Hypoprothrombinemia, bleeding tendency 4.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 Side effects & contraindicationsof Aspirin

14. 14 Acute salicylate poisoning: Hallucination, restlessness, tremors, convulsions, vomiting, dehydration, hypotension, hyperglycemia, hyperpyrexia 1.Treament of acute salicylate poisoning; 1. Gastric lavage with sod. Bicarbonates. Why? 2. Correction of hyperpyrexia (cold fomentation, ethyl alcohol evaporation 3. Correction of dehydration, acid/base balance 4. Alkalinization of urine with NaHCO3. Why? 5.Hemodialysis: Symptomatic treatment Acute Salicylate poisoning