Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)

F. Dzinjalamala, BSc., BSc (Hons), MSc, PhD

Lecturer in Pharmacology and Medicinal Chemistry

Department of Pharmacy College of Medicine University of Malawi

Lesson objectives
Describe the effects of aspirin on prostaglandin synthesis List common toxic effects of aspirin and related NSAIDs Contrast the actions of aspirin and the newer NSAIDS List NSAID contraindications and to be watched out for co-morbidities

NSAIDS
Most common analgesic worldwide Millions (>300) use NSAIDS worldwide Millions (100) prescriptions for NSAIDS per year Prescription verus OTC NSAIDS in Malawi?

NSAIDS Properties
Can reduce inflammation Can relieve mild to moderate pain (produce analgesia) Have the ability to reduce elevated body temperature associated with fever (exhibit antipyretic activity) Have ability to decrease blood clotting by inhibiting platelet aggregation (anticoagulation activity) Called NSAIDS to contrast them from corticosteroids used to treat inflamation
NOTE:An old class of medications: been in use several decades.

Indications for NSAIDS

These drugs are used to treat a wide variety of conditions:
allergic reactions, auto-immune disorders, rejection episodes in patients with transplants, pneumonia, asthma, Stevens-Johnson Syndrome, joint inflammation, pain, swelling, etc.

Advantages for NSAID Use

When used for chronic pain management, produce:
No euphoria No withdrawal/dysphoria No tolerance development

NSAID Chemical classes

NSAID classes and recommended doses

NSAID Chemical classes contd

Mechanism of action of NSAIDS

Inhibit COX-dependent prostaglandin synthesis

TWO MAJOR COX ISOENZYMES

COX-2 is induced in inflammation

COX-1 is expressed constitutively (constantly) in most tissues

Why is inhibition of prostaglandin synthesis important?

Mediators of inflammation are : prostaglandins histamine thromboxanes leukotrienes Prostaglandins mediate: Pain Inflamation Thrombus formation Dysmenorrhea Fever

NSAIDs: What Are the Risks? Prescription & OTC

GI Tract Ulcers, perforations, bleeding, obstruction/ strictures, enteropathy Kidney Sodium and fluid retention Hyperkalemia Acute renal failure Hypertension Platelet Inhibition of aggregation leading to increased potential for bleeding

Mechanisms of NSAID/ Aspirin-induced AspirinMucosal Injury

Alterations in gastric mucosal barrier Prostaglandin synthesis Mucus and bicarbonate secretion Submucosal blood flow Mucosal ATP Cell turnover Platelet function (irreversible)

Side effects from NSAID Treatment

New class of NSAIDS

Discussion in passing: students to take notes

Side effects from NSAID Treatment

ACETAMINOPHEN
Has analgesic and antipyretic effects Has low upper GI tract irritation Reyes syndrome has not been associated High doses lead to liver damage Has no anti-inflammatory effect Has no anti-clotting/coagulant effect

Summary
Prescribed/OTC NSAIDs are associated with GI risks GI Risks of OTC NSAIDs include upper and lower GI bleeding Risks are related to NSAID dose and or chronic therapy. Much of GI risks associated with OTC NSAIDs is related to aspirin, even at low-dose. lowLowLow-dose aspirin combined with NSAID increases risks 2-4 fold. EntericEnteric-coated and buffered aspirin do not reduce risk. Hepatotoxicity with OTC NSAIDs and Low-Dose LowAspirin is rare. Newer NSAIDS carry with them CV risks whilest they exhibit fewer GI effects

Recommended Readings
Rang and Dale Pharmacology, 6th ed and above Basic and Clinical Pharmacology
10th ed and above Betrum and Katzung