Analgesics (Part 2) PDF

Analgesics Dr. Nesreen El-Gayar  Outlines Analgesics. Non-opioids: ✓ NSAIDs. ✓ Paracetamol.  Analgesics Non Opioids Opioids NSAIDs Morphine Paracetamol Synthetic opioids Non-Opioid Analgesics NSAIDs Paracetamol...

Analgesics Dr. Nesreen El-Gayar  Outlines Analgesics. Non-opioids: ✓ NSAIDs. ✓ Paracetamol.  Analgesics Non Opioids Opioids NSAIDs Morphine Paracetamol Synthetic opioids Non-Opioid Analgesics NSAIDs Paracetamol Used in mild to moderate pain Advantages over opioid analgesics: No dependence. No respiratory depression  NSAIDs Selective Non-selective NSAID NSAID (COX-2 I)  Selective Arachidonic acid COX2 I COX 1 COX 2 (Constitutive) Non-selective (Inducible) NSAID Prostaglandins Prostaglandins Inhibition of COX-2 → Anti- inflammatory effect Pain &Fever Inhibition of COX-1 → G. ulcer & Inhibition of COX-2VD→ Nephropathy Nephropathy, Stroke &ISHD  Non-selective NSAID Irreversible Reversible COX I COX I  Aspirin High-Dose (4-8 g/d) Anti-inflammatory Intermediate dose (325 mg tab) 1-2 tab/4 h Analgesic Antipyretic Low-Dose (75-150 mg/d) Prophylactic ↓↓Alzheimer ↓↓Cancer Anti-platelet colon  Adverse Effects of nonselective NSAIDs 1. GIT upset (most common) → G ulcer & bleeding Reduced by misoprostol or omeprazole. 2. Nephropathy (irreversible) 3. Hypersensitivity reactions  ↑ spasmogenic LTs Asthma 4.  Bleeding tendency Antiplatelet effect. & Displace warfarin from PPBs (stop aspirin 1 week before surgery) 5. Hepatotoxicity  Membrane Phospholipids PLA2 Arachidonic acid NSAID COX LOX Cyclic Leukotriens endoperoxides Prostaglandins TXA2 Aspirin-induced asthma  Adverse Effects Specific to Aspirin 1. Hypoprothrombinemia: bleeding risk 2. Hyperuricemia (low dose) 3. Reye’s syndrome (CI in children < 12 years). 4. Chronic toxicity (salicylism) 5. Acute toxicity  Indomethacin Strong anti-inflammatory But, Serious adverse effects → Limit its use: 1. Rheumatoid & gouty arthritis. 2. Postoperative pain. 3. Patent ductus arteriosus Adverse Effects 1. As other NSAIDs (see before). 2. CNS: dizziness, confusion, ataxia (cerebral VD). 3. Aplastic anemia. (Bone marrow depression) Drug interactions of NSAIDs 1.↓ Effects mediated by PG production: ACEIs , B-blockers & diuretics 2. Displace Warfarin from PPBs 3. ↑ Risk of G. Ulcer with Glucocorticoids Selective COX-2 Inhibitors Celecoxib  Selective Arachidonic acid COX2 I COX 1 COX 2 (Constitutive) (Inducible) Prostaglandins Prostaglandins Inhibition of COX-2 → Anti- inflammatory effect Inhibition of COX-2 → Nephropathy, Stroke &ISHD VD  Selective COX-2 Inhibitors Celecoxib Uses 1. Anti-inflammatory (↓risk of G. ulcer). 2.  Progression of Alzheimer disease. ↓↓Alzheimer 3.  Risk of colorectal cancer ↓↓Cancer colon  Selective COX-2 Inhibitors Celecoxib Adverse Effects of COX-2 Inhibitors 1. Nephrotoxicity 2. Stroke & Myocardial infarction Stroke 3. Skin rash with celecoxib (Like sulfa). MI  Paracetamol Weak Anti- Analgesic Antipyretic inflammatory 500 mg 2-3 times daily  Paracetamol ✓ It is preferred to aspirin in: 1. Allergy to aspirin. 2. Peptic ulcer (no GIT disturbances). 3. Gout (aspirin small dose → hyperuricemia). 4. Viral infections in children (to avoid Reye’s syndrome with aspirin). 5. Bleeding disorders (does not affect platelet function).  Paracetamol (Well tolerated) Adverse effects 1.Nephropathy (High doses for long periods). 2. Paracetamol hepatotoxicity (in toxic doses [150 mg/kg] Treatment 1- Acetylcysteine (orally or IV) or 2- Methionine (orally)