Tadalafil entfaltet seine Wirkung über eine selektive Hemmung der PDE5, wodurch die Konzentration von cGMP im glatten Muskelgewebe stabil bleibt. Diese biochemische Modulation resultiert in einer langanhaltenden Relaxation der Gefäßwände. Der Wirkstoff wird nach oraler Einnahme effizient resorbiert, mit einer Bioverfügbarkeit von rund 80 %. Seine Halbwertszeit von bis zu 36 Stunden ist innerhalb dieser Substanzklasse außergewöhnlich. Abgebaut wird er in der Leber, hauptsächlich durch CYP3A4, mit anschließender biliärer Exkretion. Typische unerwünschte Wirkungen entstehen durch eine verstärkte Vasodilatation, etwa Kopfschmerzen oder Flush. Pharmakologisch wird cialis generika vor allem durch die verlängerte Wirkungsdauer charakterisiert.

Multimodality treatment of allergic rhinitis

‡ Allergic rhinitis affects approximately 50 million people in the U.S., and the prevalence is rising.
‡ Allergies represent the 2nd leading cause of chronic disease in the U.S., costing the healthcare system $18 billion annually.
‡ 3.4 million days lost from work annually and 2 ‡ The head and neck region is the “shock organ” ‡ Sneezing – 84%‡ Anterior rhinorrhea – 76%‡ Itchy eyes – 71% ‡ Nasal congestion – 70%‡ Itchy nose – 56% ‡ Sinus pressure – 52%‡ Headache – 49%‡ Watery eyes – 49% Sneezing
Rhinorrhea
Congestion
Symptoms
„ Competitive H1 binding„ Lipophilic (crosses the BBB) „ Anticholinergic effect (urinary retention, xerostomia) „ Diphenhydramine, chlorpheniramine, hydroxyzine „ Non-competitive H1 binding„ Lipophobic (less sedation, improved performance) „ Terfenadine, fexofenadine, loratadine (des), azelastine, „ Cardiac effects (macrolides, systemic antifungals) Itchiness, airway smooth muscle contraction „ Binds to alpha-1 and alpha-2 receptors „ Displaced norepinephrine from receptors Cetirizine = fexofenadine > loratadine Effects on the task of driving: diphen.>EtOH>fex=placebo Response time: EtOH>diphen>fex=placebo Testing scores in children (10-12): non-atopic>loratadine>diphen ‡ Levels peak - 2 hours (½ life 3-4 hours) ‡ Local potency greater than with systemic ‡ Risks – rhinitis medicamentosa (>7 days) ‡ May produce urinary retention or insomnia „ Phenylephrine (Neo-synephrine®)„ Oxymetazoline (Afrin, Dristan®) ‡ Use with caution in patients with a history of: HTN, CAD, glaucoma, hyperthyroidism, „ Naphazoline (Privine®)„ Epinephrine (Primatene®) MAO inhibitor use, urinary retention, CVA ‡ Pseudoephendrine is only available choice ‡ Binds to intracellular receptors (mRNA, ‡ Prevents initiation of the allergic cascade ‡ Major side effects include HA, nosebleeds „ Decreased recruitment and migration of ‡ Posterior subcapsular cataracts not proven ‡ Use when congestion is a major symptom ‡ Chronic use leads to growth suppression in „ Decreased activity of basophils and mast cells „ Decreased migration of APC, T-cells, B-cells ‡ Initially identified in the 1930’s – called ‡ Combination with antihistamine has been ‡ Effects of cysteinyl leukotrienes (C4,D4,E4) ‡ Low side effect profile - Isolated cases of liver toxicity and Churg-Strauss syndrome „ LTE4 attracts neutro, eos in asthmatic patients ‡ Useful in nasal polyposis +/- ASA triad? ‡ Topical ipratropium bromide (Atrovent®) ‡ Useful before anticipated antigen exposure ‡ Cromolyn sodium (Nasalcrom®, Intal®) ‡ Begin with AM loading dose, repeat in 6 ‡ Use with caution in elderly patients, „ Late phase inhibition of eos and neutrophils „ Try a non-sedating AH ± decongestant or a leukotriene „ Consider intranasal steroid alone or combined „ Inadequate response to initial therapy „ Significant impact on the quality of life„ Co-morbidities are occurring „ Combined therapy ± oral corticosteroids, antibiotics ‡ In general, the lowest effective dose of a ‡ You must be aware of side effects, safety ‡ Medication strategies must be tailored to ‡ You may have to follow a moving target!
  • Pathways of Allergic Inflammation
  • Leukotriene Receptor Antagonists
  • Topical Nasal Sprays & Montelukast
  • Pharmacotherapy – Other Modalities
  • Source: http://www.entnyc.com/allergy_pharm.pdf

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