antihistamine (1)

antihistamine (1)

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  Assignment on Autacoids Pharmacology-1 Phrm 301 SubmittedTo: Dr. Sufia Islam, Associate Professor, East West University Submitted By: Name ID NO: Shahanaj Ferdous , 2014-3-70-003 Fahmida Maliha, 2014-3-70-011 Jannatun Nur Mishu, 2014-3-70-030 Sabayet Jahan, 2014-3-70-037 Nusrat Jahan, 2014-3-70-039 Nadia Yeasmine, 2014-3-70-050 Md.Asaduzzaman, 2014-3-70-045
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  2 Abstract: The learningobjective of this assignment on autacoids is know about the autacoids, classification, histamine receptors and histamine synthesis , their release mechanism , their action on different sites, antihistamine, types of receptor antagonists , specifically H1 antagonists elaborately release mechanism ,uses and adverse effect. 1st, 2nd and 3rd generation antihistamine and their action comparison with each other. Then, we also tried to compare between histamine and antihistamine. Finally the 5 different drugs with their producing pharmaceutical industry.
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  3 AUTCOIDS The term autacoidis used for a group of hormone like substances, which originate from tissues, and produce effects at the site of release. Autacoids can have many different biological actions including modulation of the activity of smooth muscles, glands, nerves, platelets and other tissues. 1.CLASSIFICATION OF AUTACOIDS: # Biogenic Amine autacoids: Histamine, serotonin # Phospholopids autacoids: Prostaglandins # Polypeptides autacoids: Angiotensin # Others: Gastrin, Cytokines etc. 2. HISTAMINE RECEPTORS AND SITE OF ACTION: Histamine exerts its effects by binding to histamine receptors on cells’ surfaces. There are four types of histamine receptor: H1, H2, H3 and H4. The binding of histamine to these receptors stimulates them to produce functional responses and these are described in more detail below: 2.1.H1 Histamine Receptor: The H1 histamine receptor plays an important role in allergic response and is widely distributed throughout the peripheral nervous system, particularly the smooth muscle, where its activation causes vasoconstriction. Activation of the H1 receptor also causes blood vessel dilation, increased vessel permeability, stimulation of sensory nerves in the airways and bronchoconstriction. In addition, activation of this receptor promotes the chemo taxis of eosinophils, which can lead to nasal congestion, sneezing and rhinorrhea. Once activated in the cerebral cortex, the H1 receptor can inhibit potassium channels in neuronal cell membranes, depolarizing the neurons and increasing neuronal excitation. It also increases calcium ion. 2.2. H2 Histamine Receptor: The H2 receptor is found on the parietal cells within the stomach, heart and to a limited extent, in immune cells and vascular smooth muscle. Activation of the H2 receptor stimulates vasodilation and release of the gastric acids required for digestion. Physical responses to the H2 receptor include a decrease in the chemo taxis and activation of neutrophils and basophils, stimulation of suppressor T cells, lymphocyte proliferation and natural killer cell activity. Combined activation of H1 and H2 receptors contributes to rhinorrhea and swelling of the nasal airways. It increases cAMP level and gastric acid secretions and capillary permeability.
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  4 2.3. H3 HistamineReceptor: TheH3 histamine receptor is a presynaptic autoreceptor found on nerve cells that contain histamine. It is widely distributed throughout the central nervous system, with the greatest expression found in the cortex, caudate nucleus, thalamus, hypothalamus, olfactory tubercle and hippocampus. The diverse distribution of the H3 receptor throughout the cortex suggests this receptor is able to modulate many neurotransmitters such as dopamine, GABA, acetylcholine and norepinephrine in the central and peripheral nervous systems.H3 receptor decreases cAMP level and histamine release secretions 2.4. H4 Histamine Receptor: The H4 histamine receptor is a member of G-protein coupled receptor. It is found highly in bone marrow and white blood cells. It’s also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea. The Histamine H4 receptor has been shown to be involved in mediating eosinophil shape change and mast cell chemotaxis. This occurs via the βγ subunit acting at phospholipase C to cause actin polymerisation and eventually chemotaxis. 3. HISTAMINE SYNTHESIS: Histamine is an important mediator of many biological action. It is an endogenous substance synthesized, stored in and released by mast cells, which are abundant in the skin, GI, and the respiratory tract and basophiles in the blood. Mainly, histamine is formed by decarboxylation of the amino acid L-histidine in a reaction catalyzed by the enzyme histidine decarboxylase. Histidine decarboxylase generates histamine by catalyzing the removal of the carboxyl group from the amino acid L-histidine . Fig 3: Histamine synthesis
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  5 4. HISTAMINE RELEASEMECHANISM: Histamine is released from storage granules as a result of the interaction of antigen with immunoglobulin E (IgE) antibodies on the mast cell surface,Histamine plays a central role in immediate hypersensitivity and allergic responses.The actions of histamine on bronchial smooth muscle and blood vessls account for many of the symptoms of the allergic responses.In addition, certain clinically useful drugs can act directly on mast cells to release histamine, thereby explaining some of their untoward effects. Histamine has a major role in the regulation of gastric acid secretion and also modulates neurotransmitter release. Fig4: Histamine release mechanism 5. ANTIHISTAMINES: An antihistamine is a type of pharmaceutical drug that opposes the activity of histamine receptors in the body.Antihistamine includes four types of drugs: 1.H1-receptor antagonists 2.H2-receptor antagonists 3.H3 -receptor antagonists & 4.H4 - receptor antagonists
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  6 5.1. H1 RECEPTORANTAGONISTS: It is located throughout the body, specifically in smooth muscles, on vascular endothelial cells, in the heart and the CNS. It mediates decrease in vascular permeability at sites of inflammation induced by histamine.It is used in allergies, nausea, sleep disorders.For example: Dimetindene, Ebastine, Doxylamine, Hydroxyzine, Meclozine etc. 5.2. Mechanism of Action of H1 Antagonists: Histamine exerts its biological effects by binding to and activating four distinct separate rhodopsin-like G protein-coupled receptors-histamine H1 receptor. The H1 receptor couples to Gq/11(heterotrimeric G-protein subunit) activated phospholipase C. Acting on a membrane phospholipid, phospholipase C cleaves off IP3, which is a small polar molecule. Only diacylglycerol (DAG) situates on the membrane and IP3 cross the ER and then bind with ligand gated ca++ ion channel,At last, when IP3 binds, channel is opened and calcium can go into the membrane to give different cellular activity,The remaining DAG in the membrane activates protein kinase C by phosphorylation. 5.2. Figure: Mechanism of Action: H1 Antagonists 5.3 Theraputic Uses of H1 Antagonists: They are used primarily to treat disorders where abnormal or excessive histamine release by inflammatory cells is thought to underly illness. This includes conditions such as: 1. Allergic rhinitis & common cold 2. Allergic dermatitis, itching, urticaria
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  7 3. Wasp stings/bite:pain and itching decreases 4. Mild blood transfusion reactions 5. Allergic conjunctivitis 6. Motion sickness: dimenhydrinate, promethazine 7. Morning sickness: promethazine 8. Vertigo: cinnarizine 9. Chronic urticaria 10. Appetite stimulant: cyprohepatidine 11.Drug induced parkinsonism 5.3.Toxic Reaction and Side Effects of H1 Antagonists: 1. Side effects are frequent but mild. 2. Sedation, diminished alertness and concentration, light headedness, motor incordination, fatigue and tendency fall asleep. 3. Anticholinergic properties- dryness of mouth, alteration of bowel movement, urinary hesitancy and blurring of vision. 4. Epigastric distress and headache. 5. Acute overdose causes excitation, tremors, hallucinations, macular incardination, convulsions, flushing, hypotension,death. 5.4. HISTAMINE H2 RECEPTOR ANTAGONIST: It is located in more specific locations in the body mainly in gastric parietal cells, a low level can be found in vascular smooth muscle, neutrophils, CNS, heart, uterus. It decreases the release of gastric acid which is the treatment of stomach ulcers. For example: Cimetidine, Ranitidine, Famotidine, Nizatidine etc. 5.5.HISTAMINE H3 RECEPTOR ANTAGONIST: H3 receptor antagonist is a classification of drugs used to block the action of histamine at the H3 receptor. Unlike the H1 and H2 receptors which have primarily peripheral actions, but do
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  8 not cause sedation.H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. For example: Ciproxifan, pitolisant, clobenpropit, conessine etc. 5.6 HISTAMINE H4 RECEPTOR ANTAGONISTS: H4 receptor antagonists in treating a variety of disease indications. These include allergic and inflammatory conditions affecting the lung, skin and gastrointestinal system, inflammatory and neuropathic pain. For example: Thioperamide etc. 6. FIRST GENERATION ANTIHISTAMINE: First generation antihistamines are the oldest H1-antihistaminergic drugs. They are widely available and also inexpensive. They are effective in the relief of allergic symptoms, but are moderately to highly potent muscarinic acetylcholine receptor antagonists as well. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes. Adverse drug reactions are most commonly associated with the first-generation H1-antihistamines. This is due to their relative lack of selectivity for the H1 receptor and their ability to cross the blood brain barrier. Some common adverse effects in first-generation H1-antihistamines include dizziness, tinnitus, blurred vision, euphoria, uncoordination, anxiety, increased appetite leading to weight gain, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination etc. Some commonly used antihistamines are: Chlorpheniramine, Cyclizine, Doxepin, Benadryl, Dramamine, Hydroxyzine, Karbinal ER, Sominex etc. 7. SECOND GENERATION ANTIHIATAMNIE: Second-generation H1-antihistamines are newer drugs that are much more selective for peripheral H1 receptors as opposed to the central nervous system H1 receptors and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions, such as sedation, while still providing effective relief of allergic conditions.
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  9 The reason fortheir peripheral selectivity is that most of these compounds are zwitterionic at pH around 7.4. They are very polar, meaning that they do not cross the blood–brain barrier and act mainly outside the central nervous system. Some commonly used second generation antihistamines are: Cetirizine, Allerga, Claritin, Clarinex, fexofenadine, Loratadine, Levocetirizine etc. 8. THIRD GENERATION ANTIHISTAMINE: Third generation H1 – antihistamines are second generation antihistamines formally labeled third generation because the active enantiomer (Levocetirizine) or metabolite (Desloratadine) derivatives of second generation drugs intended to have increased efficacy with fewer adverse drug reactions. Examples: 1) Norastemizole ( Metabolite of astemizole) 2) Descarboethoxy loratadine ( Metabolite of loratadine) 3) Levocetirizine (Active enantiomer of cetirizine) 9. SECOND GENERATION ANTIHISTAMINES OVER FIRST GENERATION ANTIHISTAMINES:  1st generation antihistamines are highly lipid soluble, crossing the blood-brain barrier ease and antagonize H1 receptors in both CNS and periphery. On the other hand, 2nd generation antihistamines are larger molecules and less lipophilic, and thus less likely to cross the blood-brain barrier.  1st generation antihistamines block both histaminic and muscarinic receptors, Second- generation antihistamines mainly block histaminic receptors. That’s why 2nd generation antihistamines are more selective and do not produce more side effect just like 1st generation antihistamines occur.  Both first- and second-generation antihistamines are competitive antagonists to histamine at the H1-receptor site. An additional pharmacological activity of first-generation, but not second-generation antihistamines is the competitive antagonism of acetylcholine at neuronal and neuromuscular muscarinic receptors.
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  10 10. THIRD GENERATIONANTIHISTAMINES OVER FIRST GENERATION ANTIHISTAMINES:  Third generation antihistamine is generally used to treatment of allergic rhinitis and chronic urticaria, although 1st generation antihistamine is used before to treatment along with sedation but this 3rd generation antihistamine do not produce sedation. 11. HISTAMINE VS ANTIHISTAMINE: The difference between histamine and antihistamine on major points are given below: Types of Effect Histamine Antihistamine Cardiovascular effect -vasodilation -Increased permeability (edema) -Systemic hypotension -Decreased peripheral vascular resistance -prevents vasodilation -prevents increased permeability -Increased peripheral vascular resistance Smooth muscle effect -stimulates exocrine glands (increase secretion of salivary, gastric, lacrimal , bronchial, sweat ,pancreas gland) -stimulation of nerve endings -Prevents salivary, gastric, lacrimal, sweat, bronchial, pancreas secretions . Immune effect -signals to the specialized mast cells on different types of vasoconstriction and allergic response -binds to receptor and stop the release of histamine
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  11 12. 5 ANTIHISTAMINEDRUG PRODUCED IN BANGLADESH: 5 different antihistamine drugs with their producing pharmaceutical industry and their uses are given below: Drugs Brand Name and Generic Name Pharmaceutical Industry Treatment of diseases 1. Citin (Cetrizine Hydrochloride) Opsonin symptomatic relief of allergy such as hay- fever, urticaria 2.Axodin (Fexofenadine hydrochloride) Beximco relief of symptoms associated with seasonal allergic rhinitis, uncomplicated skin manifestations of chronic idiopathic urticaria in adult and children above 12 years. 3. Mebolin (Mebhydrolin Napadysylate) Acme allergic disease or symptoms, such as urticaria, pruritus of different origins, eczema, drug rash, allergic conjunctivitis, dermatitis of nutritional origin, hay -fever, vasomotor rhinitis, allergic asthma. 4. Allermine (Chlorphenamine Maleate) Renata symptomatic relief of allergy such as hay- fever, urticaria; emergency treatment of anaphylactic reactions. 5.Alervil (Pheniramine Hyrogen maleate Incepta hay fever, sneezing attack, itching, running nose, conjunctivitis urticaria with pruritus, reddening and swelling of skin, eczema. 13. CONCLUSION: All the physiological and pathophysiological effects of antihistamine due to the binding to the receptors histamine. An imbalance in their synthesis, release or in the transduction system, there may be significant condition just like as inflammation, allergy, hypersensitivity and ischemia- reperfusion. So, for the normal body function autacoids are very much important.
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  12 Reference: 1. http://www.ebi.ac.uk/interpro/entry/IPR000921 2. RANGand DALE’s pharmacology, 8th edition 3. https://en.wikipedia.org/wiki/H1_antagonist 4. https://www.drugs.com 5.Tillement J.P. “pharmacological profile of the new antihistamines.” Clinical and Experimental Allergy Review 2005; 5:7-11. 6. http://www.bdnf.org.bd/antihistamines/ 7. http://medind.nic.in/ibi/t00/i4/ibit00i4p3.pdf 8.Basic clinical pharmacology, 13th edition – by Katzung and Trevor 9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697784/
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