Autacoids and Mediators of Inflammation (Antihistamines) PDF

AUTACOIDS AND MEDIATORS OF INFLAMMATION (ANTIHISTAMINES) Mrs Mutoya LEARNING OBJECTIVES  At the end of the lesson, students should be able to:  Know what autacoids are and how they differ from hormones  Know the different types of histamine receptors and their physiological functions  Know th...

AUTACOIDS AND MEDIATORS OF INFLAMMATION (ANTIHISTAMINES) Mrs Mutoya LEARNING OBJECTIVES  At the end of the lesson, students should be able to:  Know what autacoids are and how they differ from hormones  Know the different types of histamine receptors and their physiological functions  Know the different classes of antihistamines and how they work  Know the different conditions in which antihistamines may be employed INTRODUCTION  AUTACOIDS  This term is derived from Greek:  autos—self, akos—healing substance or remedy.  These are diverse substances produced by a wide variety of cells in the body, having intense biological activity, but generally act locally (e.g. within inf lammatory pockets) at the site of synthesis and release.  They have also been called ‘local hormones’. However, they differ from ‘hormones’ in two important ways—hormones are produced by specif ic cells, and are transported through circulation to act on distant target tissues.  AUTACOIDS  Autacoids are involved in a number of physiological and pathological processes (especially reaction to injury and immunological insult) and even serve as transmitters or modulators in the nervous system, but their role at many sites is not precisely known.  TYPES: The important autacoids include:  Histamine,  Hydroxytryptamine (5-HT, serotonin),  Prostaglandins,  Leukotrienes, and  Kinins. HISTAMINE
Histamine, meaning ‘tissue amine’ (histos— tissue)  I t i s a b as e ami n e for me d fr om h i s ti di n e b y decarboxylase enzyme.  It is present in high concentration in lung, skin and GIT.  It is stored in mast cells and basophiles with Heparin and acidic proteins. SYNTHESIS AND DEGRADATION  HISTAMINE RECEPTORS  There are 4 receptor subtypes that mediate the actions of histamine (H1, H2, H3 and H4) and all of them are G-protein coupled  The main peripheral pathophysiological roles of histamine are: Stimulant of gastric acid secretion Mediator of type I hypersensitivity reactions such as urticarial and hay fever  ACTIONS OF HISTAMINE: Histamine acts on specific receptors namely H , H ,H H 1 2 3, 4 H receptors in; 1  Smooth muscle; cause spasm in intestine, uterus and bronchi. Blood vessels; cause vasodilatation leading to drop of blood pressure, increased capillary permeability with oedema. Sensory nerve endings; cause itching. Receptors are blocked by anti-histamines (H 1  ACTIONS OF HISTAMINE: H receptors in; 2  Stomach; increases gastric HCl secretion.  Blood vessels; cause vasodilatation and drop of blood pressure, increased capillary permeability with oedema.  Heart; cause positive inotropic and chronotropic actions.  H receptors are blocked by H blockers e.g. Cimetidine and Ranitidine. 2 2  H receptors are present in presynaptic neurons. They regulate histamine release. 3  H receptors are blocked by Burimamibe. 3  H4 receptors  Location: haematopoietic cells, spleen, thymus and colon  Actions: Increase chemotaxis of mast cells and leukocytes toward sites of inflammation  PHARMACOLOGY OF ANTIHISTAMINES H1 Receptors:  H1 receptors are primarily located in the smooth muscle, endothelium, and central nervous system.  Activation of H1 receptors mediates bronchoconstriction, vasodilation, increased vascular permeability, pruritus, and pain.  Antihistamines that selectively block H1 receptors are commonly used to treat allergic rhinitis, urticaria, and other histamine-mediated diseases.  Fi rst - ge ne rat i o n ant i hi st ami ne s, suc h as d i phe nhyd rami ne and chlorpheniramine, cross the blood-brain barrier and cause sedation, drowsiness, and other central nervous system side effects.  ANTIHISTAMINES (H1 HISTAMINE RECEPTOR ANTAGONISTS)

 The Classical or First Generation Antihistamines:  Members (Preparations): - Diphenyhydramine - Chlorpheniramine (piriton) - Promethazine.  Actions:  Block the actions of Histamine on H receptors. 1  CNS; block H receptors causing sedation and hypnosis. 1  Anticholinergic (atropine-like) effects.  Therapeutic Uses:  Allergic reactions e.g. allergic rhinitis and urticaria.  Motion sickness for their anticholinergic and sedative effects.  Parkinsonism for their anticholinergic effects.  Side Effects: - Sedation and drowsiness. - Anticholinergic effects e.g. dry mouth, urine retention, constipation.  ANTI HISTAMINE (H2 BLOCKERS) H2 Receptors:  H2 receptors are primarily located in the gastric parietal cells, heart, and blood vessels.  Activation of H2 receptors mediates gastric acid secretion, increased heart rate, and vasodilation.  H2 receptor antagonists, such as ranitidine and famotidine, are commonly used to reduce gastric acid secretion in patients with peptic ulcer disease, gastroesophageal ref lux disease, and other acid- related disorders.  These drugs work by blocking the H2 receptor, which is responsible for the production of gastric acid.  H2 receptor antagonists are generally well-tolerated but may cause adverse effects such as headache, dizziness, and diarrhea.  HISTAMINE RELATED DISEASES Allergic rhinitis:  Allergic rhinitis is a type of allergic reaction that affects the nasal mucosa. It is caused by the release of histamine from mast cells and basophils in response to allergens such as pollen, dust mites, and animal dander. Hi st a mi ne bi nds t o H1 recept ors on t h e na sa l mu cosa , l ea di ng t o vasodilation, increased vascular permeability, and mucus secretion, resulting in symptoms such as nasal congestion, sneezing, itching, and rhinorrhea. 2. Urticaria:  Urticaria, also known as hives, is a skin condition characterized by the development of itchy, raised, red, or white bumps on the skin. It is caused by the release of histamine from mast cells in response to allergens, drugs, or other triggers. Histamine binds to H1 receptors on the skin, leading to vasodilation and increased vascular permeability, resulting in the formation of hives. URTICARIA AND ALLERGIC RHINITIS  HISTAMINE RELATED DISEASES Asthma:  Asthma is a chronic respiratory disease characterized by airway inf la mmation, bronchoconstriction, and increased mucus production. Histamine plays a role in the pathophysiology of asthma by causing bronchoconstriction and mucus secretion. Histamine is released from mast cells in the airways in response to various triggers such as allergens, irritants, and exercise. Histamine binds to H1 receptors on the bronchial smooth muscle, leading to bronchoconstriction, and to H2 receptors on the airway epithelial cells, leading to increased mucus production. 4. Peptic ulcer disease:  Peptic ulcer disease is a gastrointestinal disorder characterized by the formation of ulcers in the stomach or duodenum. Histamine plays a role in the pathophysiology of peptic ulcer disease by stimulating gastric acid secretion. Histamine is released from enterochromaf fin-like cells in the gastric mucosa in response to various stimuli such as food and stress. Histamine binds to H2 receptors on the gastric parietal cells, leading to the activation of the proton pump and the secretion of hydrochloric acid, which can damage the gastric mucosa and contribute to ulcer formation.  PHARMACOLOGICAL APPROACHES FOR TREATING HISTAMINE-RELATED DISEASES Antihistamines: These drugs work by blocking the H1 receptor, which is responsible for the symptoms of allergic reactions. Antihistamines are commonly used to treat allergic rhinitis, urticaria, and other allergic conditions. Examples of antihistamines include loratadine, cetirizine, and fexofenadine. 2. H2 receptor antagonists: These drugs work by blocking the H2 receptor, which is responsible for the production of gastric acid. H2 receptor antagonists are used for the treatment of peptic ulcer disease and gastroesophageal ref lu x disease (GERD). Examples of H2 receptor antagonists include ranitidine and famotidine. PHARMACOLOGICAL APPROACHES FOR TREATING HISTAMINE-RELATED DISEASES Mast cell stabilizers: These drugs work by stabilizing the mast cells and preventing the release of histamine. Mast cell stabilizers are used for the treatment of allergic rhinitis, asthma, and other allergic conditions. Examples of mast cell stabilizers include cromolyn and nedocromil. 4. Epinephrine: This drug works by stimulating the alpha and beta adrenergic receptors, which can reverse the effects of histamine in the body. Epinephrine is used for the treatment of anaphylaxis, a severe allergic reaction that can be life-threatening. PHARMACOLOGICAL APPROACHES FOR TREATING HISTAMINE-RELATED DISEASES 5. Corticosteroids: These drugs work by suppressing the immune system and reducing inf la mmation. Corticosteroids are used for the treatment of various inf la mmatory condit ions, including ast hm a, allergic rhinit is, and derm at it is. Exam ples of corticosteroids include prednisone and dexamethasone. In conclusion: The pharmacological approaches for treating histamine-related diseases include antihistamines, H2 receptor antagonists, mast cell stabilizers, epinephrine, and corticosteroids. These drugs work by different mechanisms to relieve the symptoms and treat the underlying causes of histamine-related diseases. The choice of medication depends on the specif ic condition, severity of symptoms, and individual patient factors QUIZ  Mention one f ir s t generation and one s econd generation antihistamine.  How do H2 blockers work?