AUTOCOIDS: HISTAMINE, ANTIHISTAMINES, 5-HT/SEROTONIN, AND PROSTAGLANDINS: A TEACHER’S COMPREHENSIVE GUIDE
Welcome, future pharmacologists and healthcare professionals!
The word autocoids is derived from the Greek words ‘autos’ (self) and ‘akos’ (healing element). Autocoids are chemical signals produced by different cells of the body. They act locally at the site where they are synthesised and released (e.g., at the site of inflammation within the inflammatory pockets), hence are called local hormones. Autocoids are chemical substances that are produced within the cells and are released in response to different stimuli to cause various physiological actions.
As a pharmacology educator with years of experience teaching autocoid pharmacology, I have observed that students often find this topic challenging due to the complex physiological roles of these mediators. Let me tell you: Understanding autocoids is essential for managing allergic reactions, inflammation, gastric acid disorders, and many other conditions.
In this comprehensive guide, I will walk you through the major autocoids—histamine, antihistamines, 5-HT/serotonin, and prostaglandins. By the end of this article, you will have a thorough understanding of these essential pharmacological agents. Let us begin!
Dpharmguru’s exam insights:
Autocoids are frequently tested in pharmacology exams. Remember: Histamine is released from mast cells and causes vasodilation, increased permeability, and gastric acid secretion. H₁ antagonists treat allergies; H₂ antagonists treat peptic ulcers. 5-HT (serotonin) regulates mood, appetite, and GI motility. Prostaglandins are derived from arachidonic acid and have diverse actions—vasodilation, bronchoconstriction, platelet aggregation. These are classic exam questions!
HISTAMINE
Histamines are nitrogen-containing organic compounds belonging to the group of amines. Histamines are produced in almost all cells during a local immune response.
Physiological Role of Histamine
1. Nervous System
Histamine is a potent stimulator of sensory nerves. Release in epidermis results in itching; release in dermis results in pain (mediated via H₁ receptors).
2. Cardiovascular System
- Blood Vessels: Vasodilatation (H₁ and H₂ receptors)—decrease in blood pressure
- Increased Capillary Permeability: H₁ receptor stimulation causes endothelial cell contraction and separation—oedema (urticaria)
- Lewis’s Triple Response:
- Red spot: Localised vasodilation
- Flare: Bright red flush surrounding the red spot (axon reflex)
- Wheal: Swelling at the injection site (fluid and protein exudation)
- Histamine Shock: Intense fall in BP due to vasodilation, increased permeability, decreased venous return and cardiac output
- Heart: Increased contractility via H₂ receptors
3. Histamine and Allergic Reaction
Antigen interacts with IgE antibody on mast cell surface → stored histamine released → immediate hypersensitivity reaction (smooth muscle relaxation and vasodilatation).
4. Histamine and Gastric Acid Secretion
Histamine is a potent stimulator of gastric acid secretion (H₂ receptors on gastric parietal cells). H₂ receptor antagonists are used in peptic ulcer treatment.
5. Action on Smooth Muscles
H₁ receptors → smooth muscle contraction (bronchoconstriction in asthma). H₂ receptors → smooth muscle relaxation.
ANTIHISTAMINES
Types of Histamine Receptor Antagonists
- H₁ Antagonists: Classical antihistamines—used in allergic disorders
- H₂ Antagonists: Cimetidine, Ranitidine, Famotidine—reduce gastric HCl secretion—used in peptic ulcer
- H₃ Antagonists: Thioperamide—regulates histamine release in CNS
- H₄ Antagonists: Mianserin—involved in immune responses, inflammation, allergic reactions
H₁ Antagonists
Classification
- First Generation (Cross BBB—cause drowsiness):
- Ethanolamines: Diphenhydramine, Dimenhydrinate
- Ethylenediamines: Pyrilamine, Tripelennamine
- Alkylamines: Chlorpheniramine, Brompheniramine
- Piperazines: Cyclizine, Meclizine
- Piperidines: Cyproheptadine
- Phenothiazines: Promethazine
- Tricyclic Dibenzoxepins: Doxepin
- Second Generation (Do not cross BBB—less drowsiness):
- Alkylamines: Acrivastine
- Piperazines: Cetirizine
- Phthalazinones: Azelastine
- Piperidines: Terfenadine, Astemizole, Loratadine, Fexofenadine
Physiological Role of H₁ Antagonists
- Histamine Antagonism: Block capillary dilatation, decreased BP, urticaria, itching, smooth muscle contraction
- Anti-allergic: Control urticaria, itching, angioedema
- CNS: Sedative effect (first generation)
- Anticholinergic: Reduce lacrimal and nasal secretions (dry mouth)
- Antiemetic and Antitussive: Prevent motion sickness, morning sickness
- Local Anaesthetic: Some possess local anaesthetic effects
Clinical Uses of H₁ Antagonists
- Allergic disorders (urticaria, dermatitis, pruritus, hay fever, allergic rhinitis)
- Pre-anaesthetic medication (promethazine)
- Sedative, hypnotic, anxiolytic
- Parkinsonism
- Vertigo (cinnarizine)
- Motion sickness (ethanolamines, piperazines, phenothiazines)
Adverse Effects of H₁ Antagonists
- CNS: Sedation, lack of concentration, fatigue, tendency to fall asleep
- Anti-muscarinic: Dryness of mouth and nose, blurred vision
- CVS: Hypotension, palpitations
- Teratogenic: Avoid cyclizine and meclizine in pregnancy
- Overdose: Central excitation, tremors, convulsions, flushing, hypotension, respiratory and cardiovascular failure
H₂ Antagonists
Examples: Cimetidine, Ranitidine, Famotidine, Nizatidine
Physiological Role: Block pepsin and gastric acid secretions induced by histamine, gastrin, and cholinergic effect. Promote peptic ulcer healing.
Clinical Uses: Gastric hyperacidity, gastric ulcers, Zollinger-Ellison syndrome, reflux esophagitis, stress ulcers.
Adverse Effects: Cimetidine causes gynaecomastia, impotency, drug interactions. Others may cause headache, dizziness, constipation, nausea, arthralgia, vomiting.
H₃ and H₄ Antagonists
H₃ Antagonists: Thioperamide, Clobenpropit—used potentially in neuropsychiatry (cognition impairment). Improve attention and learning wakefulness without sedative effect.
H₄ Antagonists: Found in haemopoietic cells (mast cells, basophils, eosinophils)—involved in inflammation (chemotaxis). Useful in allergic rhinitis, asthma, rheumatoid arthritis.
5-HT/SEROTONIN
5-Hydroxytryptamine (5-HT) or serotonin is a monoamine neurotransmitter. Tryptophan found in the GIT, platelets, and CNS acts as the precursor of 5-HT.
Physiological Role of 5-HT
1. Cardiovascular Actions
- Vessels: Initially vasoconstriction (5-HT₂ receptors), later vasodilation
- Heart: Positive chronotropic action (5-HT₄ receptors); positive inotropic effect
- Blood Pressure: Complex action—may cause hypotension or hypertension
2. Action on Smooth Muscles
- Digestive Effects: Elevates intestinal motility (5-HT₄ and 5-HT₃ receptors); induces emesis (5-HT₃ receptors)
- Bronchial Effect: Causes bronchial constriction
- Uterus Effect: Induces uterine contraction
3. CNS Effects
5-HT regulates sleep, mood (antidepressant action), temperature, and appetite (appetite suppressant effect).
4. Other Actions
- Carcinoid Syndrome: Metastatic tumours of enterochromaffin cells in GIT secrete serotonin—characterised by diarrhoea, flushes, dyspnoea, cardiac valve damage
- Migraine: Vasoconstriction (prodromal phase) followed by vasodilation (painful phase)
- Myocardial Ischemia: 5-HT released from platelets causes vasoconstriction
5-HT Agonists
- Triptans: Sumatriptan, Rizatriptan, Zolmitriptan—used in acute migraine attacks. Adverse effects: coronary artery spasm, transient myocardial ischemia, tingling, paraesthesia, dizziness, nausea.
- Buspirone: 5-HT₁A receptor agonist—non-benzodiazepine antianxiety drug. Adverse effects: mental confusion, muscle weakness, chest pain.
- Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine—enhance and prolong action of 5-HT; most effective antidepressants.
- Fenfluramine and Dexfenfluramine: Appetite suppressants—enhance 5-HT release in CNS. Adverse effects: lethargy, drowsiness, pyrexia, nasopharyngitis.
5-HT Antagonists
- Cyproheptadine: H₁ and 5-HT₂A blocker—used in skin allergies (pruritus, urticaria). Adverse effects: dizziness, seizures, palpitations, blurred vision.
- Ketanserin: 5-HT₂A and 5-HT₂C blocker—antagonises platelet aggregation; causes vasodilation. Adverse effects: drowsiness, fatigue, headache, dry mouth.
- Ondansetron, Granisetron, Dolasetron: 5-HT₃ receptor antagonists—prevent nausea and vomiting (cancer chemotherapy, radiation therapy).
- Clozapine: 5-HT₂A and 5-HT₂C antagonist—used to treat schizophrenia. Adverse effects: hypersalivation, tachycardia, hypotension, sedation, delirium, coma.
- Risperidone: 5-HT₂A and 5-HT₂C antagonist + D₁ receptor blocking—management of schizophrenia. Adverse effects: drowsiness, trouble with thinking, trouble with body movements.
PROSTAGLANDINS
The term prostaglandin is derived from the prostate gland (their first site of origin). They are derived from fatty acids by enzymatic reactions—each with potent and specific biological actions. Chemically, prostaglandins have 20 carbon atoms including a 5-carbon ring (cyclopentane ring), a carboxylic acid, and a 15-hydroxyl group.
Major sub-series: PG₁, PG₂, and PG₃
Physiological Role of Prostaglandins
- CVS: Vasodilatation and fall in BP (PGE₂α, PGI₂); Thromboxane A₂ causes vasoconstriction
- Platelets: Thromboxane A₂ causes platelet aggregation; PGI₂ prevents platelet aggregation
- Bronchial Muscle: PGE₂α, PGD₂, TXA₂ are bronchoconstrictors; PGE₂ is a bronchodilator
- Reproductive System: Uterine contraction (PGE₂, PGF₂α); dysmenorrhoea pain due to increased PG synthesis; facilitate sperm transport, fertilisation, labour; cause regression of corpus luteum
- GIT: Some PGs cause diarrhoea; PGE₂ decreases gastric acid secretion
- Kidneys: PGs regulate blood flow and tubular reabsorption; cause vasodilatation, increased blood flow, and diuresis
- Other Actions: Affect ANS, endocrine system, peripheral nerves; sensitise afferent nerve endings—induce pain; PGEs exert insulin-like action
Adverse Effects of Prostaglandins
- Nausea
- Vomiting
- Diarrhoea
- Flushing
- Headache
- Dizziness
- Hypotension
Dpharmguru’s exam insights:
Autocoids are frequently tested in pharmacology exams. Remember: Histamine causes vasodilation, increased permeability, and gastric acid secretion. H₁ antagonists (first generation—sedative; second generation—non-sedative) treat allergies. H₂ antagonists (Cimetidine, Ranitidine) treat peptic ulcers. 5-HT (serotonin) regulates mood, appetite, and GI motility. Triptans are 5-HT agonists used in migraine. Ondansetron is a 5-HT₃ antagonist used as an anti-emetic. Prostaglandins are derived from arachidonic acid—TXA₂ causes platelet aggregation, PGI₂ inhibits it. These are classic exam questions!
COMPARISON: AUTACOIDS
| Autacoid | Source | Key Actions | Clinical Relevance |
|---|---|---|---|
| Histamine | Mast cells, basophils | Vasodilation, increased permeability, gastric acid secretion, bronchoconstriction | Allergies, anaphylaxis, peptic ulcer |
| 5-HT (Serotonin) | GIT, platelets, CNS | Vasoconstriction, platelet aggregation, mood regulation, GI motility, emesis | Migraine, depression, carcinoid syndrome |
| Prostaglandins | Various tissues | Vasodilation, bronchoconstriction, platelet aggregation, uterine contraction | Inflammation, pain, dysmenorrhoea, labour |
FREQUENTLY ASKED QUESTIONS (FAQs)
1. What is the difference between H₁ and H₂ antagonists?
H₁ antagonists block histamine at H₁ receptors—used in allergic disorders (urticaria, rhinitis, pruritus). H₂ antagonists block histamine at H₂ receptors on gastric parietal cells—used to reduce gastric acid secretion in peptic ulcers and GERD.
2. What is Lewis’s Triple Response?
Lewis’s Triple Response is a characteristic response to intradermal histamine injection: Red spot (local vasodilation), Flare (bright red flush due to axon reflex), and Wheal (swelling due to fluid and protein exudation).
3. What is the mechanism of action of triptans?
Triptans are 5-HT₁B/1D receptor agonists. They cause vasoconstriction of cerebral blood vessels and inhibit the release of pro-inflammatory neuropeptides, relieving migraine pain.
4. What is the mechanism of action of ondansetron?
Ondansetron is a selective 5-HT₃ receptor antagonist. It blocks serotonin receptors in the chemoreceptor trigger zone (CTZ) and gastrointestinal tract, preventing nausea and vomiting induced by chemotherapy and radiation.
5. What is the difference between first and second generation H₁ antagonists?
First generation H₁ antagonists (Diphenhydramine, Chlorpheniramine) cross the blood-brain barrier and cause significant drowsiness. Second generation H₁ antagonists (Loratadine, Fexofenadine, Cetirizine) do not readily cross the BBB and cause less drowsiness.
6. What are the actions of prostaglandins?
Prostaglandins have diverse actions: vasodilation, bronchoconstriction, platelet aggregation (TXA₂), inhibition of platelet aggregation (PGI₂), uterine contraction, gastric acid secretion inhibition, and pain sensitisation.
SUMMARY
This comprehensive guide covered the essential autocoids:
- Histamine: Released from mast cells—causes vasodilation, increased permeability, gastric acid secretion, bronchoconstriction. H₁ antagonists treat allergies; H₂ antagonists treat peptic ulcers.
- Antihistamines: H₁ (first generation—sedative; second generation—non-sedative), H₂ (Cimetidine, Ranitidine), H₃, and H₄ antagonists.
- 5-HT/Serotonin: Regulates mood, appetite, sleep, GI motility, and platelet aggregation. Triptans (5-HT agonists) treat migraine; Ondansetron (5-HT₃ antagonist) treats nausea.
- Prostaglandins: Derived from arachidonic acid—diverse actions including vasodilation, bronchoconstriction, platelet aggregation, uterine contraction, and inflammation.
As I always tell my students: “Understanding autocoids is essential for managing allergic reactions, inflammation, gastric acid disorders, migraine, and many other conditions that affect millions of patients worldwide.”
REFERENCES AND FURTHER READING
- Pharmacy Council of India (PCI). (2022). Pharmacology Syllabus. New Delhi: PCI.
- Rang, H. P., & Dale, M. M. (2021). Rang & Dale’s Pharmacology (9th ed.). Elsevier.
- Goodman, L. S., & Gilman, A. (2018). Goodman & Gilman’s The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill.
- Katzung, B. G. (2021). Basic and Clinical Pharmacology (15th ed.). McGraw-Hill.
- World Health Organization (WHO). (2022). Essential Medicines and Pharmacology. Retrieved from https://www.who.int.
Disclaimer: This article is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare professionals for medical concerns. Pharmaceutical regulations and guidelines may vary by region—always refer to your local regulatory authorities for specific requirements.
written by:
Dr. N. Sujith Kumar
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