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Histamines/antihis

UVa med pharmacology block 2

QuestionAnswer
Diphenhydramine Benadryl 1st gen H1 antag allergic rhinits/rxns, sedation, motion sickness physfx: block VSMC fxs, antemesis, anti-tussive, block itch/edema, anti-muscarinic, local anesthesia T1/2 4-6hrs met'd liver sidefx: CNS tox, excess dryness/sedation
Dimenhydrinate Dramamine 1st gen H1 antag allergic rhinits/rxns, sedation, motion sickness physfx: block VSMC fxs, antemesis, anti-tussive, block itch/edema, anti-muscarinic, local anesthesia T1/2 4-6hrs met'd liver sidefx: CNS tox, excess dryness/sedation
Chlorphniramine Chlor-trimeton 1st gen H1 antag allergic rhinits/rxns, sedation, motion sickness physfx: block VSMC fxs, antemesis, anti-tussive, block itch/edema, not anti-muscarinic, local anesthesia T1/2 4-6hrs met'd liver sidefx: CNS tox, excess dryness/sedation
Promethazine Phenergan1st gen H1 antag allergic rhinits/rxns, sedation, motion sickness physfx: block VSMC fxs, antemesis, anti-tussive, block itch/edema, anti-muscarinic, local anesthesia, weak α1antag T1/2 4-6hrs met'd liver sidefx: CNS tox, excess dryness/seda
Meclizine Antivert first gen H1 antag motion sickness, vertigo due to vestibular disorder phys/side fx of diphenhydramine T1/2>12hrs
Fexofenadine allegra 2nd gen H1 antag allergic rhinits/rxns (not for sedation, motion sickness) physfx: like 1st gen not antimuscarinic T1/2>12hrs oral admin met'd liver cyt P450 sidefx like 1st gen, no adverse rxns w/antifungals or ABs
Loratidine claritin2nd gen H1 antag allergic rhinits/rxns (not for sedation, motion sickness) physfx: like 1st gen not antimuscarinic T1/2>24hrs oral admin met'd liver cyt P450 sidefx like 1st gen, no adverse rxns w/antifungals or ABs
Cetirizine zyrtec 2nd gen H1 antag allergic rhinits/rxns (not for sedation, motion sickness) physfx: like 1st gen not antimuscarinic T1/2>12hrs pk conc 1-2hrs oral admin met'd liver cyt P450 sidefx like 1st gen, no adverse rxns w/antifungals or ABs
Terfenadine Seldane 2nd gen H1 antag allergic rhinits/rxns (not for sedation, motion sickness) physfx: like 1st gen not antimuscarinic T1/2>12hrs pk conc 1-2hrs oral admin met'd liver cyt P450 sidefx: Can cause cardiac arrhythmias
Levocetrizine xyzal 3rd gen H1 antag allergic rhinitis, chronic urtricaria (hives) active metabs of 2nd gen antags quick acting and more potent T1/2 24hrs excr urine/feces fewer sidefx than 1st gen, do not cross BBB CI: end stage renal disease
Desloratidine Clarinex 3rd gen H1 antag allergic rhinitis, chronic urtricaria (hives) active metabs of 2nd gen antags quick acting and more potent T1/2 27hrs excr urine/feces fewer sidefx than 1st gen, do not cross BBB CI: end stage renal disease
What is unique about Meclizine compared to other 1st generation H1 blockers? Its duration is over 12hrs, instead of 4-6 like the rest of them.
What are 1st generation H1 blockers used for clinically, that 2nd generation are not? Sedation Motion Sickness
What are special considerations for Terfenadine and Astemizole? They can cause serious Cardiac Arrhythmias. The non-metabolized form can block Delayed-Rectifier Potassium channels in heart. when not met'd slow depolarization --> Long QT interval --> Possible premature AP's --> Polymorphic Ventricular Tachycardia
What is the distribution and time to effect for 1st generation H1 Antagonists (Antihistamines)? Rapidly absorbed, wide distribution including CNS. Peaks in 1-2 hrs, effective for 4-6.
What causes Histamine release? - Cell damage (Toxins, Injury, Ischemia, Bee Sting, etc.) - Specific Antigens attached to IgE
Which 1st Generation H1 blocker is used for Parkinson's? Diphenhydramine
What are some physiological effects of 1st generation H1 Blockers? - Blocks Smooth Muscle contraction - Sedation - Block edema/itch - Bronchiospasm block is poor (Very little clinical value in Asthma) - Anti-Emetic - Local Anesthetic activity - Anti-tussive (not understood)
What are the differences between 1st and 2nd generation Antihistamines? 2nd Generation not as lipid soluble, do not cross BBB, not sedative, effective for 12-24hrs (as opposed to 4-6 for 1st gen), Not anticholinergic.
What drugs can have interactions with Terfenadine and Astemizole and limit their metabolism, thus causing cardiac side effects? Macrolide Antibiotics and certain Antifungals can inhibit Cyt. P450, and slow down metabolism of these drugs.
What are the clinical uses for Histamine? Few clinical uses (due to adverse side effects). Diagnostic uses (rarely used): - Test for Gastric Acid secretion - Pheochromocytoma (Histamine causes catecholamine release).
What are adverse side effects of Histamine use? - Anaphylactic Shock - Increased Nasal/Bronchial Mucus production - Cramps, Diarrhea (GI Motility/Increased Acid Secretion) - Asthma Exacerbation (Bronchial Constriction)
Where are H3 receptors located? Presynaptic: Brain Myenteric Plexus
What types of cells store Histamine? Mast Cells (Secretory Granules) Basophils (Secretory Granules) Gastric Mucosa Neurons in CNS (Neurotransmitter)
What are clinical uses for Histamine Antagonists? - Allergic Rhinitis (Decreased Edema/Itch, Anti-Tussive) - Allergic Reactions - Sedation - Motion Sickness (Anti-Emetic)
What are some adverse affects of 1st generation Antihistamines? CNS Toxicity Excessive Dryness Excessive Sedation
Although Histamine is in nearly all tissues, where is it found in high levels? Lung Skin GI Tract
Which 1st Generation H1 blocker is used for Motion Sickness? Meclizine
Which 1st Generation H1 Blocker is used as an Anti-Emetic? Promethazine
Where are H2 receptors located? Gastric Mucosa Cardiac Muscle
What is special about Promethazine when compared to other Antihistamines? It has weak alpha-1 adrenoceptor antagonism.
Where are H1 receptors located? Smooth Muscle Endothelium Brain
What are the actions of the H1 receptor? - Decreased TPR (Poorly sustained) - Increased Endothelial Permeability --> Edema - Increased GI Motility - Bronchial Constriction
- Decreased TPR (Poorly sustained) - Increased Endothelial Permeability --> Edema - Increased GI Motility - Bronchial Constriction - Increased Gastric Acid - Increased HR - Decreased TPR/BP (Well Sustained)
Created by: sam.mrosenfeld
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