Questions and Answers
Which eicosanoid agonists have been demonstrated to reduce both morbidity and mortality in patients with elevated pulmonary pressures?
Specific eicosanoid agonists recommended for the treatment of pulmonary hypertension.
What precursor is primarily involved in the biosynthesis of eicosanoids?
What are the major families of eicosanoids?
Prostaglandins, thromboxanes, leukotrienes, and epoxyeicosatrienoic acids.
What do the isoforms COX-1 and COX-2 produce?
Signup and view all the answers
What is the rate limiting step in eicosanoid synthesis?
Signup and view all the answers
Leukotrienes are produced mainly in red blood cells.
Signup and view all the answers
Which eicosanoid is primarily involved in vasoconstriction?
Signup and view all the answers
What are the therapeutic uses of eicosanoids?
Signup and view all the answers
What is one major function of prostaglandins?
Signup and view all the answers
The main pathways of eicosanoid biosynthesis include cyclooxygenase (COX), lipoxygenase (LO), and __________.
Signup and view all the answers
What is the effect of PGE2 on gastric acid secretion?
Signup and view all the answers
What do NSAIDs primarily inhibit?
Signup and view all the answers
Aspirin selectively inhibits COX-2 without affecting COX-1.
Signup and view all the answers
What is the role of arachidonic acid in NSAID action?
Signup and view all the answers
What side effect can NSAIDs cause?
Signup and view all the answers
What is the primary benefit of low dose aspirin therapy?
Signup and view all the answers
Which COX enzyme is primarily expressed at sites of inflammation?
Signup and view all the answers
Name one example of a COX-2 inhibitor that has been withdrawn from the market.
Signup and view all the answers
COX-2 inhibitors have been developed to minimize GI toxicity.
Signup and view all the answers
Match the following terms with their descriptions:
Signup and view all the answers
PG analogues are used clinically to mimic endogenous ______.
Signup and view all the answers
Study Notes
Eicosanoids Overview
- Eicosanoids are endogenous fatty acid autacoids derived from arachidonic acid, a 20-carbon fatty acid.
- Short half-lives (10 seconds to 5 minutes) limit their functions to local actions.
- They bind to G-protein coupled receptors, generally increasing cellular cAMP levels.
Major Families of Eicosanoids
- Prostaglandins
- Thromboxanes
- Leukotrienes
- Epoxyeicosatrienoic acids
Roles of Eicosanoids
- Inflammation and fever regulation
- Blood pressure modulation
- Blood clotting mechanisms
- Immune system response
- Control of reproductive processes and tissue growth
- Sleep/wake cycle regulation
Biosynthesis of Eicosanoids
- Produced on-demand from phospholipid membranes via phospholipase A2 activation.
- Arachidonic acid release is the rate-limiting step in eicosanoid synthesis, inhibited by glucocorticoids.
- Key pathways include Cyclooxygenase (COX) and Lipoxygenase (LO).
Cyclooxygenase (COX) Pathway
- COX enzymes convert arachidonic acid to prostaglandin H2 (PGH2), which is then converted to various prostaglandins, thromboxane A2 (TXA2), and prostacyclin (PGI2).
- COX-1 is constitutively expressed; COX-2 is induced during inflammation.
Functions of Prostaglandins
- Cardiovascular: PGI2 dilates blood vessels; TXA2 causes vasoconstriction.
- Renal: Enhance urine formation and regulate renin release.
- Nervous: Induces fever and sensitizes pain.
- Gastrointestinal: Decrease gastric acid secretion and promote mucus production.
- Reproductive: Induce labor and increase uterine contractions.
Therapeutic Uses of Eicosanoids
- Abortion: Induction using PGE2 and PGF2α.
- Labor Induction: Carboprost and dinoprostone infusions.
- Maintenance of Ductus Arteriosus: PGE1 for pre-surgical conditions.
- Peptic Ulcers: Misoprostol to reduce ulceration risk.
- Erectile Dysfunction: Alprostadil injections for improved blood flow.
Adverse Effects of Eicosanoids
- Local pain and irritation
- Gastrointestinal disturbances: nausea, cramping, diarrhea
- Bronchospasm
NSAIDs and COX Inhibition
- Aspirin inhibits both COX-1 and COX-2, reducing pain and inflammation but poses gastrointestinal risks.
- Other NSAIDs (e.g., ibuprofen) compete with arachidonic acid for COX binding.
COX-2 Selective Inhibitors
- Developed to minimize gastrointestinal side effects while targeting inflammation.
- Examples include celecoxib and etoricoxib, with some withdrawn due to safety concerns.
Leukotrienes and Their Functions
- Mediators of inflammation and bronchoconstriction, particularly in asthma.
- LTB4 facilitates leukocyte activation and attraction.
Lipoxins and Their Role
- Derived from leukocyte action; they have anti-inflammatory properties and help resolve inflammation.
Epoxygenase Pathway
- Involves cytochrome P450 enzymes, creating epoxyeicosatrienoic acids, which modulate vascular tone.
Key Mechanisms of Action
- Eicosanoids mediate processes such as inflammation, pain response, fever induction, smooth muscle contraction/relaxation, and mucosal protection.
Recent Developments in Eicosanoid Therapy
- Research focuses on better anti-inflammatory drugs that selectively inhibit eicosanoid pathways to minimize side effects while maximizing therapeutic impact.### Eicosanoid Biosynthesis
- Initiated by phospholipase A2 activation, leading to arachidonic acid (AA) release from membrane phospholipids.
- AA is converted through cyclooxygenase (COX) and lipoxygenase (LO) pathways into eicosanoids: prostaglandins, thromboxane, and leukotrienes.
- Eicosanoid production significantly increases during inflammatory responses.
- COX and LO pathways are highly relevant in clinical settings.
COX Pathways and Pharmacology
- COX pathway is the primary target for non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used to manage pain, fever, and inflammation.
- Discovery of the two COX isozymes in 1991: COX-1 and COX-2.
- COX-2 is mainly expressed at inflammation sites and is responsible for producing pro-inflammatory eicosanoids.
COX-2 Selective Inhibitors (COXIBs)
- Developed to minimize gastrointestinal (GI) toxicity associated with traditional NSAIDs.
- COX-2 selective inhibitors have shown adverse cardiovascular effects, leading to the market withdrawal of drugs like rofecoxib and valdecoxib.
- Selective COX-2 inhibition without affecting COX-1 can disrupt the balance between prostacyclin and thromboxane, increasing thrombotic risk.
- This imbalance helps explain the cardiovascular risks associated with COX-2 selective inhibitors.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
This quiz explores the pharmacology of eicosanoids, focusing on their roles in health, disease, and therapeutic applications. Through a case study approach, students will analyze symptoms and therapeutic implications related to eicosanoid mechanisms. Enhance your understanding of pharmacological principles that underlie clinical presentations and treatments.
