BIOQUI - 28/07/2023

Introduction to Eicosanoids

Overview of Eicosanoids

• The topic of discussion is eicosanoids, which may be unfamiliar to many but are crucial in clinical settings.

• Eicosanoids are hormone-like substances that differ from traditional hormones; they have local effects and a short lifespan, typically lasting only seconds.

Characteristics of Eicosanoids

• Unlike hormones produced in specific body regions with distant effects, eicosanoids act locally and are synthesized by all cells based on tissue needs.

• The primary precursors for eicosanoid synthesis are fatty acids, particularly arachidonic acid and eicosapentaenoic acid (EPA).

Fatty Acids Involved in Eicosanoid Synthesis

Key Fatty Acids

• Arachidonic acid is a polyunsaturated fatty acid with 20 carbons and four double bonds; EPA also has 20 carbons but five double bonds.

• These fatty acids are derived from membrane phospholipids and serve as the foundation for a wide range of biologically active substances.

Functions of Eicosanoids

Clinical Relevance

• Some eicosanoids induce relaxation or contraction of smooth muscle in vascular, bronchial, or uterine tissues.

• This action is significant in allergic conditions such as rhinitis and asthma due to their influence on inflammatory processes.

Effects on Vascular Dynamics

• Certain eicosanoids can lead to vasodilation, increased vascular permeability, and edema where inflammation occurs.

• Others play roles in platelet aggregation—some promote it while others inhibit it.

Types of Eicosanoids

Major Classes

• The most clinically relevant eicosanoids include prostaglandins (PG), leukotrienes (LT), and thromboxanes.

• Additional substances like epoxyeicosatrienoic acids and lipoxins are still under research for their clinical significance.

Mechanism of Action

Synthesis Pathways

• Eicosanoid production begins with the release of arachidonic acid from membrane phospholipids via an enzyme called phospholipase A2.

Enzymatic Conversion

• Arachidonic acid can undergo various enzymatic pathways; one notable pathway involves lipoxygenases converting it into leukotrienes (LT).

Importance in Inflammation

• Leukotrienes exhibit potent inflammatory properties—reportedly up to 1000 times more effective than histamine—making them critical players in allergic diseases like asthma.

Conclusion on Allergic Responses

Understanding Allergic Reactions and Treatment

Overview of Allergic Responses

• Allergic reactions occur in response to allergens, affecting only susceptible individuals. Common allergens include pollen, household dust, and environmental pollutants.

• Continuous exposure to these allergens can lead to bronchial responses such as bronchoconstriction, edema, mucus production, and varying degrees of dyspnea.

Treatment Options for Allergies

• Leucotriene inhibitors like Montelukast are used in treatment; they block leukotriene receptors to alleviate symptoms.

• The cyclooxygenase pathway produces prostaglandins and thromboxanes that play significant roles in inflammation and other physiological processes.

Functions of Prostaglandins and Thromboxanes

• Prostaglandins have various functions including increasing gastric mucus production, reducing hydrochloric acid secretion, and influencing smooth muscle contraction in different tissues.

• Thromboxanes stimulate platelet aggregation and initiate the blood coagulation process.

Eicosanoids: Clinical Implications

Role of Eicosanoids

• Eicosanoids are involved in both pathological and physiological processes; for instance, they aid uterine contractions during childbirth.

Pharmacological Interventions

• Corticosteroids inhibit phospholipase A2 to prevent the synthesis of eicosanoid derivatives from arachidonic acid. They are crucial in clinical settings due to their potent anti-inflammatory effects.

Inhibiting Inflammatory Pathways

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• NSAIDs inhibit cyclooxygenase pathways producing prostaglandins and thromboxanes. Examples include Aspirin, Diclofenac, Ibuprofen, Meloxicam among others.

Aspirin's Unique Properties

• Aspirin serves multiple purposes: it acts as an anti-inflammatory agent, antipyretic (fever reducer), analgesic (pain reliever), and particularly as an antiplatelet agent which is vital for cardiovascular health.

Side Effects of Long-term NSAID Use

Gastrointestinal Risks

• Prolonged use of NSAIDs can lead to gastritis or peptic ulcers due to inhibition of protective gastric prostaglandins that reduce hydrochloric acid production while enhancing mucosal protection.

Current Usage Trends

Pharmacological Approaches to Managing Peptic Ulcers and Inflammatory Responses

Medications for Peptic Ulcer Prevention and Treatment

• Various medications can be used to prevent and treat side effects related to peptic ulcers, including misoprostol, a prostaglandin analog that decreases hydrochloric acid production while increasing mucus thickness.

• Ranitidine, an H2 receptor antagonist, inhibits histamine receptors that stimulate hydrochloric acid production in the stomach, thereby reducing acidity.

• Omeprazole and similar drugs inhibit proton pumps in parietal cells of the stomach, decreasing proton concentration and creating an acidic environment necessary for digestion.

Corticosteroids in Inflammatory Conditions

• Corticosteroids like prednisone and dexamethasone are utilized during COVID-19 outbreaks to mitigate cytokine storms—exaggerated immune responses leading to severe inflammation, particularly in the lungs.

• Cytokine storms can cause significant health issues by filling the lungs with fluid; corticosteroids help reduce this inflammatory response effectively.

Mechanism of Action of Corticosteroids

• The primary action of corticosteroids involves inhibiting phospholipases and downregulating genes responsible for producing inflammatory cytokines.

• While effective at reducing immune responses (making patients more susceptible to infections), corticosteroids are crucial for treating allergic reactions such as asthma or anaphylaxis.

Side Effects of Corticosteroid Use

• Long-term use of corticosteroids can lead to various side effects including increased susceptibility to infections due to immunosuppression.

• Other potential side effects include Cushing's syndrome symptoms such as edema, moon facies, muscle wasting from lipolysis, osteoporosis, hypertension, and impaired wound healing.

Prostaglandins and Their Applications

• Newer medications include prostanoids like dinoprostone which enhance uterine muscle contractions during labor or manage glaucoma by affecting iris smooth muscle contraction.

COX Enzymes: Understanding Their Role

Understanding Gastric Cells and Medications

The Role of Parietal Cells in the Stomach

• Discussion on parietal cells in the stomach, emphasizing their importance in gastric function.

• Mention of successful drug substitution aimed at reducing gastritis and peptic ulcers.

Medication Families for Gastric Issues

• Introduction to a family of medications designed to address gastric conditions.