Anti histamines.pptx.....................

histamine and its charactristics

1. OBJECTIVES Classify anti-histamines Differentiate between first and second generation anti-histamines Describe the pharmacologic effects of H1- receptor antagonists Describe the clinical uses of H1-receptor antagonists Enlist the adverse effects of H1-receptor antagonists Describe the drug interactions of H1-receptor antagonists  

2. Histamine: a chemical messenger mostly generated in mast cells Mediates a wide range of cellular responses Allergic and inflammatory reactions Gastric acid secretion Neurotransmission in parts of the brain.

3. Histamine is present in practically all tissues, with significant amounts in the lungs, skin, blood vessels, and GI tract Found at high concentration in mast cells an d basophils A neurotransmitter in the brain Also occurs as a component of venoms and in secretions from insect stings

4. Synthesis Histamine is formed by the decarboxylation of histidine by histidine decarboxylase In mast cells, histamine is stored in granules If histamine is not stored, it is rapidly inactivated by the enzyme amine oxidase

5. Release of histamine Most often, histamine is just one of several chemical mediators released in response to stimuli The stimuli for release of histamine from tissues may include destruction of cells as a result of cold, toxins from organisms, venoms from insects and spiders, and trauma Allergies and anaphylaxis can also trigger significant release of histamine.

6. First-generation Diphenhydramine Meclizine Doxylamine Promethazine Clemastine Dimenhydrinate Hydroxyzine Chlorpheniramine Cyproheptadine Second-generation Loratadine Desloratadine Cetirizine Levocetirizine Azelastine Fexofenadine Ketotifen

7. Mechanism of action Released in response to certain stimuli and binds to various types of histamine receptors (H1, H2, H3, and H4 ) H1 and H2 receptors are widely expressed and are the targets of clinically useful drugs H1 receptors are important in producing smooth muscle contraction and increasing capillary permeability Histamine promotes vasodilation of small blood vessels by causing the vascular endothelium to release nitric oxide Can enhance secretion of proinflammatory cytokines in several cell types and in local tissues H1 receptors mediate many pathological processes, including allergic rhinitis, atopic dermatitis, conjunctivitis, urticaria, bronchoconstriction, asthma, and anaphylaxis Histamine stimulates the parietal cells in the stomach, causing an increase in acid secretion via the activation of H2 receptors.

8. Histamine causes contraction of airway smooth muscle, stimulation of secretions, dilation and increased permeability of the capillaries, and stimulation of sensory nerve endings If the release of histamine is slow enough to permit its inactivation before it enters the bloodstream, a local allergic reaction results If histamine release is too fast for inactivation, a full-blown anaphylactic reaction occurs.

9. The H1-receptor blockers can be divided into first- and second generation drugs. First generation drugs Penetrate the CNS and cause sedation Interact with other receptors, producing a variety of unwanted adverse effects Second-generation agents Specific for peripheral H1 receptors Do not penetrate the BBB causing less CNS depression than the first generation drugs Desloratadine, fexofenadine and loratadine show the least sedation Cetirizine and levocetirizine are partially sedating

10. The action of all the H1-receptor blockers is qualitatively similar Block the receptor-mediated response of a target tissue Much more effective in preventing symptoms than reversing them Have additional effects due to binding to cholinergic, adrenergic, or serotonin receptors Cyproheptadine also acts as a serotonin antagonist on the appetite center, sometimes used off label as an appetite stimulant and in treating anorgasmy associated with SSRIs Antihistamines such as azelastine and ketotifen also have mast cell–stabilizing effects

11. Therapeutic uses Allergic and inflammatory conditions Motion sickness and nausea Somnifacients

12. Allergic and inflammatory conditions: H1-receptor blockers are useful in treating and prev e nting all e rgi c rea c tion s cause d b y antig e ns acting on IgE antibody Oral antihistamines are the drugs of choice in controlling the symptoms of allergic rhinitis and urticaria because histamine is the principal mediator released by mast cells Ophthalmic antihistamines are useful for the treatment of allergic conjunctivitis Not implicated in asthma

13. Motion sickness and nausea Diphenhydramine, dimenhydrinate, cyclizine, meclizine and promethazine are effective for prevention of the symptoms of motion sickness Not effective if symptoms are already present Taken prior to expected travel Antihistamines prevent or diminish nausea and vomiting mediated by the chemoreceptor and vestibular pathways The antiemetic action is due to blockade of central H1 and M1 muscarinic receptors Meclizine is useful for the treatment of vertigo associated with vestibular disorders

14. Somnifacients Many first-generation antihistamines , such as diphenhydramine and doxylamine have strong sedative properties Used in the treatment of insomnia Available OTC without a prescription Use is contraindicated in individuals working in jobs in which wakefulness is critical Antihistamines are not the medications of choice

15. H1-receptor blockers are well absorbed after oral administration, with maximum serum levels occurring at 1 to 2 hours Average t1/2 is 4 to 6 hours, except for that of meclizine and the second generation agents which is 12 to 24 hours First-generation H1- receptor blockers are distributed in all tissues, including CNS Most are metabolized by the hepatic CYP450 system Cetirizine and levocetirizine are excreted largely unchanged in urine Fexofenadine is excreted largely unchanged in feces Some are available as ophthalmic or intranasal formulations Pharmacokinetics

16. First-generation H1-receptor blockers have a low specificity, interacting with histamine, muscarinic cholinergic, α-adrenergic and serotonin receptors The extent of interaction with receptors varies Some side effects may be undesirable, and others may be of therapeutic value Incidence and severity of adverse reactions for a given drug varies between individual subjects

17. Sedation: (First-generation H1 antihistamines) Diphenhydramine may cause paradoxical hyperactivity in young children Fatigue, dizziness, lack of coordination, and tremors First-generation antihistamines exert anticholinergic effects, Dryness of mouth , blurred vision and retention of urine The most common adverse reaction associated with second-generation antihistamines is headache Topical diphenhydramine can cause hypersensitivity such as contact dermatitis when applied to the skin.

18. Drug interactions: Potentiation of effects of other CNS depressants, including alcohol Patients taking MAOIs should not take antihistamines 1 st generation antihistamines with anticholinergic actions may decrease effectiveness of cholinesterase inhibitors

19. Overdoses: The margin of safety of H1-receptor blockers is relatively high, and chronic toxicity is rare Acute poisoning is relatively common, especially in young children The most common and dangerous effects of acute poisoning are those on the CNS, including hallucinations, excitement, ataxia, and convulsion If untreated, the patient may experience a deepening coma and collapse of the cardiorespiratory system

20. Have little, if any, affinity for H1 receptors. Clinical use: inhibitors of gastric acid secretion in treatment of ulcers and heartburn Include: Cimetidine Ranitidine Famotidine Nizatidine