Non-Steroidal Anti-inflammatory Drugs PDF Fall 2024

# Non-Steroidal Anti-inflamatory Drugs By Dr. Nermein Fawzy El Sayed Lecturer of pharmacology and toxicology ## NSAIDs - Are cyclo-oxygenase inhibitors, preventing the synthesis of prostaglandins - These drugs have: - Analgesic effect = relieve pain - Antipyretic action = lower elevated...

# Non-Steroidal Anti-inflamatory Drugs By Dr. Nermein Fawzy El Sayed Lecturer of pharmacology and toxicology ## NSAIDs - Are cyclo-oxygenase inhibitors, preventing the synthesis of prostaglandins - These drugs have: - Analgesic effect = relieve pain - Antipyretic action = lower elevated body temperature to normal - Anti-inflammatory role = reduces inflammation or swelling - As well as antiplatelet action for some of them = decrease platelet aggregation and inhibit thrombus formation ## Synthesis of Prostaglandins A schematic diagram showing: - Phospholipase A2 - Arachidonic acid - 5-LOX - COX - COX-1 - COX-2 - Thromboxane prostaglandins - Prostaglandins - Leukotrienes ## Role of Cyclo-oxygenases A table comparing COX-1 and COX-2 showing: - Arachidonic acid breakdown - Functions - GIT: cytoprotective, ↓HCI secretion, ↑Mucus production - Kidney: cytoprotective vasodilation - Platelet: (TXA2) enhance platelet aggregation - Macrophages: inflammatory mediators - Kidney: cytoprotective vasodilation - ↑Na and fluid excretion ## Effect of NSAIDs A schematic diagram showing: - Arachidonic acid breakdown via COX-1 & COX-2. - NSAIDs action on both COX-1 & COX-2. - Function of PGE2 and TXA2. ## Advantage of NSAIDs - Anti-inflammatory effects (the main clinical indication) - Macrophages: inflammatory mediators - Platelet: (TXA2) enhance platelet aggregation - Antiplatelet effect (clinical significance for Aspirin only. Why?) - Why Apirin is the best antiplatelet NSAID? ## Dose Dependent Therapeutic Effects Of Aspirin A graph showing the therapeutic effects of Aspirin increasing with the daily dosage, the following effects are shown: - Antithrombotic - Antipyretic, Analgesic - Anti-inflammatory ## Side-Effects of COX-1 Inhibitors - ***On GIT:*** - Suppress gastro-protective Prostaglandins - Increase gastric acid secretions - Suppress gastric mucosa - Therefore increase the risk for peptic ulcer and haemorrhage - ***The main side effect*** - ***How to decrease harmful side effect of NSAIDs on GIT??*** - Give PPIs such as Esomeprazole - Give prostaglandin agonists such as Misoprostol - ***On the Kidney:*** - Inhibition of cytoprotective prostaglandins induces renal vasoconstriction - Increase fluid and Na retention - Increase blood pressure ## Effect of Selective COX-2 inhibitors - ***Comparative table for COX-1 & COX-2:*** - ***COX-1:*** - GIT: cytoprotective ↓HCI secretion, ↑Mucus production - Kidney: cytoprotective vasodilation - Platelet: (TXA2): enhance platelet aggregation - Disadvantages: ↑ Platelet aggregation and Vasoconstriction, ↑ Renal dysfunction - ***COX-2:*** - Macrophages: inflammatory mediators - Kidney: cytoprotective vasodilation - ↑Na and fluid excretion - Advantages: Anti-inflammatory effect, Less GIT side effects - Therefore they are better choice for patients with peptic ulcer ## Side effect of COX-2 inhibitors - Enhance platelet aggregation + Vasoconstriction → cardiovascular and cerebral stroke side effects - Causes in vasodilator PGs →↓ renal perfusion →renal disease ## COX-2-selective (Coxibs) - Reduced gastrointestinal toxicity - Increased cardiovascular occlusive event - ***Diagram showing:*** - COX-1 & COX-2 action on platelets and endothelium - Effect of COX-1 & COX-2 on vessel wall - Effect of prostaglandins on platelets ## Cardiovascular complications are the most serious - Inhibition of vasodilatory effect of PGI2 and unopposed activity of TXA2 - Increase the risk of Ischemic Heart Diseases ## Side effect of NSAIDs - ***Comparative table showing effect of NSAIDs on COX-1 & COX-2:*** - Selective COX-1 Inhibitors - PGE2 - PG12 - TXA2 - Non-selective Cox Inhibitors - PGE2 - PG12 - Selective cox-2 Inhibitors - PG12 - TXA2 ## NSAID Side Effects: - ***Diagram showing:*** - Arachidonic acid breakdown via Cox-1 & COX-2 - ***GI mucosa (COX-1):*** - PGE2: - gastric protection - ↑mucus secretion - ↑ bicarbonate - ↑ mucosal blood flow - COX-1 inhibition - peptic ulcers - GI bleeding - ***Kidney (COX-1 & 2):*** - PGE2 & PGI2: - afferent arteriolar vasodilation (↑GFR) - Na & water excretion - COX inhibition - Na & water retention - hypertension - hemodynamic acute kidney injury - irreversibly inhibits platelet COX-1 - ***Cardiovascular (COX-1 & 2):*** - PGI2 & TXA2: - Vascular (COX-2: PGI2): vasodilation, inhibit platelet aggregation - Platelet (COX-1: TXA2) platelet aggregation, vasoconstriction - COX-2 > COX-1 inhibition: - Stroke - Myocardial infarction ## Keep in mind that...... - NSAIDs are contraindicated during pregnancy (except low dose aspirin can be used during pre-eclampsia)? - Becauses they : - ↑bleeding tendency. - Cause premature closure of the fetal ductus arteriosus. - Prolongs the duration of labour. - Aspirin + viral infection (varicella, influenza)in children = Reye's syndrome; a rare form of hepatic encephalopathy seen in children - Aspirin also causes severe GIT ulcers, salicylism (N,V, Tinitus, and hyperventillation) and ↑ bleeding tencency - Bleeding from high doses of Aspirin is managed by Vitamin K - Patients with peptic ulcer are adviced to avoid taking COX-1 inhibitors and better replace it with selective COX-2 - Non-selective COX inhibitors →→↑ bronchoconstriction in asthmatic patients - Cox-2 inhibitors are contraindicated in patients with heart diseases ## Acetaminophen - Acting centraly on COX-3 - Paracetamol is an Analgesic-antipyretics with poor/no anti-inflammatory action - Causes hepatotoxicity at high doses due to accumulation of NAPQI (metabolite)→ treated with Acetylcysteine ## Thank You A drawing of several blocks which spell "THANK YOU" each block is shown with a happy face drawn on it.