Published on August 7, 2014
Antihistaminic Drug: Antihistaminic Drug 121-29-402: 121-29-402 ANTIHISTAMINE: ANTIHISTAMINE A histamine antagonist (commonly called an antihistamine ) is a pharmaceutical drug that inhibits the action of histamine by either blocking its attachment to histamine receptors, or inhibiting the enzymatic activity of histidine decarboxylase which catalyzes the transformation of histidine into histamine (atypical antihistaminics). Histamine antagonists are commonly used for the relief of allergies caused by intolerance of proteins PowerPoint Presentation: Type Location Function H 1 histamine receptor Found on: Smooth muscle E ndothelium CNS tissue Causes: vasodilation Bronchoconstriction bronchial smooth muscle contraction separation of endothelial cells (responsible for hives), and pain and itching due to insect stings; the primary receptors involved in allergic rhinitis symptoms and motion sickness; sleep regulation. PowerPoint Presentation: H 2 histamine receptor Located on parietal cells Primarily stimulate gastric acid secretion H 3 histamine receptor Found on central nervous system and to a lesser extent peripheral nervous system tissue Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine , serotonin H 4 histamine receptor Found primarily in the basophils and in the bone marrow. It is also found on thymus, small intestine, spleen, and colon. Plays a role in chemotaxis . Mechanism of action: Mechanism of action Histamine (H1)-receptors H1-receptors are found in the brain, heart, bronchi, gastrointestinal tract, vascular smooth muscles, and leukocytes. H1-receptors are membrane bound and coupled to G-proteins, specifically Gq/11, and their activation causes: increase in phospholipase A2 and D activity increases in diacylglycerol and intracellular Ca2+ increased cyclic guanosine 5′-monophosphate (cGMP) PowerPoint Presentation: Activation of H1-receptors in the brain increases wakefulness. Activation of H1-receptors in vessels causes vasodilation and an increase in permeability. Activation of H1-receptors typically stimulates nonvascular smooth muscle. 121-29-369: 121-29-369 PowerPoint Presentation: Histamine (H2)-receptors H2-receptors are membrane bound; they are found in the brain, heart, vascular smooth muscles, leukocytes, and parietal cells. The response of H2-receptors is coupled via Gαs to increased cyclic AMP (cAMP) production. Activation of H2-receptors: increases gastric acid production causes vasodilation generally relaxes smooth muscles. PowerPoint Presentation: Histamine (H3)-receptors H3-receptors are found in the central nervous system (CNS) and peripheral nervous system (PNS) at presynaptic nerve terminals. H3-receptors are membrane bound and coupled to Gi/o; their activation increases intracellular Ca2+ and decreases cAMP. PowerPoint Presentation: Histamine (H4)-receptors H4-receptors are found on hematopoietic cells and in the spleen, thymus, and colon. Stimulation of H4 receptors increases chemotaxis of mast cells and leukocytes cells toward sites of inflammation. H4 receptors are coupled to Gi/Go and thereby inhibit the production of cAMP and increase intracellular Ca2+ Histamine agonists : Histamine agonists Histamine, betazole , and impromidine. Betazole has approximately tenfold greater activity at H2-receptors than at H1-receptors. Impromidine is an investigational agent; its ratio of H2 to H1 activity is about 10,000. Methimepip is an H3-specific agonist. PowerPoint Presentation: The adverse effects of these agents can be quite severe; they include: flushing a burning sensation hypotension tachycardia bronchoconstriction. PowerPoint Presentation: Clinical Uses of Antihistamines Allergic rhinitis (common cold) Allergic conjunctivitis (pink eye) Allergic dermatological conditions Urticaria (hives) Angioedema (swelling of the skin) Puritus (atopic dermatitis, insect bites) Anaphylactic reactions (severe allergies) Nausea and vomiting (first generation H 1 -antihistamines) Sedation (first generation H 1 -antihistamines) Histamine (H1)-receptor antagonists: Histamine (H1)-receptor antagonists Competitive inhibitors. Classification: First-generation agents Second-generation agents 121-29-386: 121-29-386 First-generation agents: First-generation agents Groups: Alkylamines Ethanolamines Ethylenediamines Piperazines Tricyclics First-generation agents : First-generation agents Alkylamines Alkylamines include Chlor pheniramine Brom pheniramine These agents produce slight sedation. PowerPoint Presentation: 2. Ethanolamines Include diphenhydramine doxylamine clemastine dimenhydrinate (combination of diphenhydramine and 8-chlorotheophylline) Ethanolamines produce marked sedation; doxylamine is marketed only as a sleeping aid. Ethanolamines also act as antiemetics. PowerPoint Presentation: 3. Ethylenediamines Include: pyrilamine and antazoline. Ethylenediamines produce moderate sedation and can cause gastrointestinal upset. PowerPoint Presentation: Piperazines include meclizine and cyclizine. Piperazines produce marked adverse gastrointestinal effects and moderate sedation. These agents have antiemetic antivertigo activities. PowerPoint Presentation: Phenothiazines include promethazine . Phenothazines produce marked sedation. These agents have antiemetic activity. Phenothiazines are also weak α-adrenoceptor antagonists. PowerPoint Presentation: Methylpiperidines include cyproheptadine. have antihistamine, anticholinergic, and antiserotonin activities. Second-generation agents: Second-generation agents Piperidines Loratadine [Claritin] Desloratadine [ Clarinex ] Poor CNS penetration: reduced sedation Little or no anticholinergic activity Desloratadine : is the active metabolite of loratadine has about 15-fold greater affinity for the H1 receptor than the parent compound PowerPoint Presentation: Fexophenadine is structurally different than the other piperidine antihistamines, sedative activity is low but dose dependent. 121-29-389: 121-29-389 Histamine (H1)-receptor antagonists: Histamine (H1)-receptor antagonists Competitive inhibitors. Classification: First-generation agents Second-generation agents Third -generation agents First-generation agents: First-generation agents Groups: Aminoalkyl ethers Ethanolamines Ethylenediamines Piperazines Phenothiazines 6. Propyl amine First-generation agents : First-generation agents Aminoalkyl ethers. It include Chlorpheniramine Diphenhydramine -These agents produce slight sedation. PowerPoint Presentation: 2. Ethanolamines Include doxylamine clemastine dimenhydrinate (combination of diphenhydramine and 8-chlorotheophylline) Ethanolamines produce marked sedation; doxylamine is marketed only as a sleeping aid. Ethanolamines also act as antiemetics. Ethanolamines: Ethanolamines Clemastine Dimenhydrinate (Dramamine) Exhibits fewer side effects than most antihistamines Widely used as an antiprurtic (stops itching) Anti-emetic (anti nausea) Also causes strong sedation PowerPoint Presentation: 3 . Ethylenediamines Include: Tripelennamine and antazoline. Ethylenediamines produce moderate sedation and can cause gastrointestinal upset. Tripelennamine PowerPoint Presentation: Piperazines include meclizine and cyclizine. Piperazines produce marked adverse gastrointestinal effects and moderate sedation. cyclizine. PowerPoint Presentation: Phenothiazines include promethazine. Phenothazines produce marked sedation. These agents have antiemetic activity. Phenothiazines are also weak α-adrenoceptor antagonists. PowerPoint Presentation: 6.Propyl amine: - include Chlorphenamine Second -generation agents: Second -generation agents Loratadine (Claritin) Terfenadine (Seldane) It is the only drug of its class available over the counter It has long lasting effects and does not cause drowsiness. http://en.wikipedia.org/wiki/Image:Loratadin.svg http://scienceblogs.com/moleculeoftheday/images/terfenadine.gif It was formerly used to treat allergic conditions Third-generation agents: Third-generation agents Deslortadine (Clarinex) Fexofenadine (Allegra) It is the active metabolite of Lortadine. It was developed as an alternative to Terfenadine Fexofenadine was proven to be more effective and safe 121-29-403: 121-29-403 Therapeutic Uses: Therapeutic Uses Treatment of allergic rhinitis and conjunctivitis. Clemastine is approved for the treatment of rhinorrhea. Many antihistamines are used to treat the common cold, based on their anticholinergic properties, but they are only marginally effective for this use. Diphenhydramine also has an antitussive effect not mediated by H1-receptor antagonism. PowerPoint Presentation: Treatment of urticaria and atopic dermatitis , including hives Sedatives. Several (doxylamine, diphenhydramine) are marketed as over-the-counter (OTC) sleep aids. Prevention of motion sickness Appetite suppressants Adverse effects: Adverse effects (significantly reduced with second-generation agents) Sedation, dizziness, and loss of appetite. These agents can cause gastrointestinal upset, nausea, and constipation or diarrhea. H1-receptor antagonists produce anticholinergic effects (dry mouth, blurred vision, and urine retention). Histamine (H2)-receptor antagonists: Histamine (H2)-receptor antagonists Cimetidine Ranitidine Famotidine Nizatidine Competitive antagonists at the H2-receptor, which predominates in the gastric parietal cell. PowerPoint Presentation: Used in the treatment of: Gastrointestinal disorders, including heartburn and acid-induced indigestion. These agents promote the healing of gastric and duodenal ulcers . Pharmacokinetics : Pharmacokinetics The bioavailability of H2-antagonists goes from 50% for ranitidine and famotidine to approximately 90% for nizatidine and advised dosages take this into account. They are taken especially in the evening to reduce night gastric acidity. Their elimination is primarily renal. Cimetidine inhibits cytochrome P-450 and increases the concentrations and the effects of many other drugs. PowerPoint Presentation: Adverse effects: confined to the site of application Include: sore throat dry mouth.