Autacoids—locally acting biochemical mediators—play essential roles in inflammation, allergy, smooth muscle function, vascular regulation, and pain perception. Understanding these naturally occurring substances and the drugs that influence them is crucial for modern therapeutics. Unit 3 examines the pharmacology of autacoids such as histamine, serotonin, prostaglandins, and kinins, along with major drug classes used to treat inflammation, gout, and rheumatic disorders. This article provides a comprehensive and updated overview in a clear, news-style educational format.
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Introduction to Autacoids and Their Classification
What Are Autacoids?
Autacoids are endogenous substances produced by cells to exert local, short-acting physiological effects. Unlike hormones, they are not circulated systematically in high concentrations but act near their site of synthesis. Their roles include regulating inflammation, smooth muscle tone, vascular permeability, and neurotransmission.
Classification of Autacoids
Autacoids are broadly classified into:
Biogenic amines (Histamine, Serotonin)
Eicosanoids (Prostaglandins, Thromboxanes, Leukotrienes)
Peptides (Bradykinin, Substance P, Angiotensin)
Other related mediators involved in inflammatory and immunological responses
Their wide physiological influence makes them essential targets for various therapeutic agents.
Histamine, Serotonin (5-HT), and Their Antagonists
Histamine: Physiological Roles and Implications
Histamine is stored mainly in mast cells and is released during allergic reactions. It causes vasodilation, increased vascular permeability, bronchoconstriction, and gastric acid secretion. Excess histamine release leads to conditions such as allergic rhinitis, urticaria, and anaphylaxis.
Antihistamines
Drugs targeting histamine receptors include H1 antagonists (e.g., chlorpheniramine, cetirizine) used to treat allergies, and H2 antagonists (e.g., ranitidine, famotidine) used for peptic ulcer therapy.
Modern H1 antihistamines offer effective symptom relief with fewer sedative effects, making them preferred for long-term allergy management.
Serotonin (5-HT) and Its Antagonists
Serotonin regulates mood, appetite, sleep, and platelet aggregation. It also affects gastrointestinal motility and vascular smooth muscle.
Serotonin antagonists such as ondansetron are widely used as antiemetics, while 5-HT blockers like cyproheptadine help manage migraine and allergic reactions. Understanding serotonin’s multifaceted role supports the development of targeted therapies for neurological, gastrointestinal, and vascular disorders.
Prostaglandins, Thromboxanes, and Leukotrienes: Powerful Eicosanoid Mediators
Role of Prostaglandins
Prostaglandins modulate inflammation, fever, pain, labor induction, and gastric protection. Their widespread physiological roles make them therapeutic targets in obstetrics, ophthalmology, and pain management.
Synthetic analogs such as misoprostol and dinoprostone have significant clinical applications, ranging from gastric ulcer prevention to labor induction.
Thromboxanes
Thromboxanes are potent mediators of platelet aggregation and vasoconstriction, playing critical roles in hemostasis and thrombosis. Antiplatelet drugs like aspirin inhibit thromboxane synthesis, reducing the risk of heart attack and stroke.
Leukotrienes
Leukotrienes contribute to bronchoconstriction, mucus secretion, and inflammatory cell recruitment. They are central to asthma and allergic disorders.
Drugs such as montelukast and zafirlukast, which block leukotriene receptors, provide effective long-term asthma control and help reduce the frequency of exacerbations.
Angiotensin, Bradykinin, and Substance P: The Regulatory Peptides
Angiotensin
Angiotensin II is a powerful vasoconstrictor that increases blood pressure and stimulates aldosterone secretion. Drugs that modulate this peptide—ACE inhibitors, ARBs, and renin inhibitors—are fundamental in managing hypertension, heart failure, and diabetic nephropathy.
Bradykinin
Bradykinin promotes vasodilation, pain sensation, and increased vascular permeability. While beneficial in certain physiological processes, excessive activity can contribute to inflammation and angioedema. ACE inhibitors increase bradykinin levels, which partly explains their cough-related side effects.
Substance P
Substance P transmits pain signals and induces inflammatory responses. Drugs targeting Substance P receptors are being explored for treating chronic pain, migraine, and neuroinflammatory disorders.
Non-Steroidal Anti-Inflammatory Agents (NSAIDs): Cornerstones of Pain and Inflammation Management
Mechanism and Applications
NSAIDs reduce pain, fever, and inflammation by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin synthesis.
Traditional NSAIDs like ibuprofen and diclofenac inhibit both COX-1 and COX-2, while selective COX-2 inhibitors such as celecoxib minimize gastrointestinal side effects.
Clinical Importance
NSAIDs are widely used for arthritis, musculoskeletal pain, dysmenorrhea, and postoperative inflammation. Their therapeutic value lies in balancing efficacy with risks such as gastric irritation and renal impairment.
Anti-Gout Drugs: Managing Uric Acid Imbalance
Pharmacological Strategy
Gout results from elevated uric acid levels leading to joint inflammation. Treatment involves reducing uric acid production or enhancing its elimination.
Major Drug Classes
Allopurinol and febuxostat lower uric acid synthesis by inhibiting xanthine oxidase. Probenecid increases uric acid excretion, while colchicine reduces inflammatory responses during acute gout attacks.
Together, these agents help prevent painful flares and reduce the progression of chronic gouty arthritis.
Antirheumatic Drugs: Controlling Autoimmune Joint Disorders
Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
Antirheumatic drugs slow disease progression in rheumatoid arthritis and other autoimmune joint diseases. Methotrexate, sulfasalazine, and hydroxychloroquine remain cornerstone therapies.
Biological Agents
Modern biologics—such as TNF-α inhibitors (etanercept, infliximab) and IL-6 inhibitors—offer targeted suppression of inflammatory pathways. These drugs dramatically improve quality of life for patients who do not respond to conventional treatments.