Levocetirizine

12,043 views

Published on

A short presentation I gave for my medical school pharmacology. A little rough in places, but I really just wanted to try this service.

Published in: Health & Medicine
2 Comments
15 Likes
Statistics
Notes
  • thanx for such nice presentation there is a gud xplanation of levocetirizine in dis
    dis wuj hv been more informative.
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Fioricet is often prescribed for tension headaches caused by contractions of the muscles in the neck and shoulder area. Buy now from http://www.fioricetsupply.com and make a deal for you.
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
No Downloads
Views
Total views
12,043
On SlideShare
0
From Embeds
0
Number of Embeds
1,862
Actions
Shares
0
Downloads
1,967
Comments
2
Likes
15
Embeds 0
No embeds

No notes for slide
  • Levocetirizine

    1. 1. LEVOCETIRIZINE A histamine H 1 -receptor antagonist
    2. 2. Primary Questions
    3. 3. Primary Questions <ul><li>What is the problem? </li></ul>
    4. 4. Primary Questions <ul><li>What is the problem? </li></ul><ul><li>What are the treatment options? </li></ul>
    5. 5. Primary Questions <ul><li>What is the problem? </li></ul><ul><li>What are the treatment options? </li></ul><ul><li>What is unique about Levocetirizine? </li></ul>
    6. 6. Histamine Endogenous Vasoactive Amine •  Mediates the increase in capillary permeability associated with the contraction of endothelial cells in postcapillary venules that occurs with mild injuries • Released from granules in mast cells, basophils, and platelets •  Degranulation is usually a localized event in response to acute insult, therefore inflammation remains site specific Gartner and Hiatt. “Color Textbook of Histology” Second Ed. 2001
    7. 7. Histamine Histamine Receptor Subtypes Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004 Eosinophils, neutrophils, CD4 T-cells H 4 Presynaptic: brain, neurons H 3 Gastric mucosa, cardiac muscle, mast cells, brain H 2 Smooth muscle, endothelium, brain H 1 Distribution Receptor subtype
    8. 8. Histamine <ul><li>H 1 Receptors </li></ul><ul><li>Similar to muscarinic and 5-HT 1 receptors </li></ul><ul><li>Mediate pain and itching </li></ul><ul><li>BP changes are caused by vasodilation action of histamine on arterioles </li></ul><ul><li>Postcapillary vessel separation  Histamine induced edema (urticaria) </li></ul><ul><li>Agonism can cause bronchoconstriction </li></ul>Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004
    9. 9. Allergic Rhinitis
    10. 10. Allergic Rhinitis Clinical Presentation
    11. 11. Allergic Rhinitis <ul><li>Clinical Presentation </li></ul><ul><li>Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation. </li></ul><ul><li>Symptoms include: </li></ul><ul><li>Rhinnorrhea </li></ul><ul><li>Nasal obstruction* </li></ul><ul><li>Nasal itching and sneezing </li></ul>“ Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.” Allergy 2009: 64: 85: 9 5
    12. 12. Allergic Rhinitis IgE-mediated inflammation 1. Mast cell sensitization: • exposure to antigen  production of specific IgE antibodies • IgE attaches to the surface of mast cells 2. Mast cell degranulation: • Subsequent exposure  binding of antigen to surface IgE, signaling granule release of histamine Mast cell depicted using Single Particle Tracking (SPT) Image courtesy of: http://www.nanopicoftheday.org/ “ Lippincott’s Illustrated Review: Pharmacology.” Harvey and Champe Eds. 4th edition. 2009
    13. 13. Allergic Rhinitis <ul><li>Ubiquitous Allergens </li></ul>
    14. 14. Allergic Rhinitis *Nasal Obstruction
    15. 15. Allergic Rhinitis Co-morbidities and Associated Findings • Asthma • Otitis Media • Sinusitis Reduced Quality of life: • sleep disturbance • impaired cognitive function • depression and anxiety “ Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.” Allergy 2009: 64: 85: 9 5
    16. 16. Allergic Rhinitis Burden-of-illness • $2-5 billion USD annually in direct costs • $5-9 billion USD annually in indirect costs “ The economic burden of allergic rhinitis: a critical evaluation of the literature.” Reed SD, Lee TA, McCrory DC. Pharmacoeconomics . 2004;22(6):345-61. Review.
    17. 17. Allergic Rhinitis Burden-of-illness
    18. 18. Allergic Rhinitis <ul><li>Indirect Costs </li></ul><ul><li>Cost per employee per year for AR: $593 </li></ul><ul><ul><li>Stress: $518 </li></ul></ul><ul><ul><li>Migraine: $277 </li></ul></ul><ul><ul><li>Depression: $273 </li></ul></ul><ul><ul><li>Arthritis/rheumatism: $269 </li></ul></ul><ul><ul><li>Respiratory infections: $181 </li></ul></ul><ul><ul><li>Diabetes: $95 </li></ul></ul><ul><ul><li>Coronary heart disease: $40 </li></ul></ul>“ Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.” Allergy 2009: 64: 85: 9 5
    19. 19. Allergic Rhinitis <ul><li>Prevalence </li></ul><ul><li>10-20% of the general population </li></ul><ul><li>10-40% of the pediatric patient </li></ul><ul><li>In all likelihood, these numbers are under representations due to variability in perceived impact on lifestyle </li></ul>“ Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.” Allergy 2009: 64: 85: 9 5
    20. 20. Chronic Idiopathic Urticaria
    21. 21. Chronic Idiopathic Urticaria Clinical Presentation
    22. 22. Chronic Idiopathic Urticaria <ul><li>Clinical Presentation </li></ul><ul><li>Chronic urticaria is a disease consisting of spontaneous pruritic welts, present on all or most days for more than 6 weeks </li></ul><ul><li>Angioedema frequently occurs with CIU </li></ul><ul><li>No effective diagnostic screens </li></ul><ul><li>No clear universal therapy </li></ul><ul><li>Frustration and dismay abound in patients </li></ul><ul><li>QoL can be profoundly reduced </li></ul>“ Chronic idiopathic urticaria.” Greaves MW. Curr Opin Allergy Clin Immunol. 2003 Oct;3(5):363-8.
    23. 23. Chronic Idiopathic Urticaria A Difficult Disease To Treat “ I've had Chronic Idiopathic Urticaria for 6 years and its not going away, but getting worse. I've been to so many doctors and specialists! All these doctors do the same tests and they tell me the same thing ‘there is no cure and nothing we can do.’” http://answers.yahoo.com/question/index?qid=20080928142252AA64Xyf
    24. 24. Chronic Idiopathic Urticaria <ul><li>Two Types </li></ul><ul><li>Autoimmune: </li></ul><ul><li>- Antibodies formed against IgE receptor FcεR1 </li></ul><ul><li>- Antibodies formed against IgE (less common) </li></ul><ul><li>- Mast cell stimulation  degranulation </li></ul><ul><li>2. “True” idiopathic: </li></ul><ul><li>- Some autoimmune mechanism as yet undefined </li></ul>http://www.medscape.com/viewarticle/461843
    25. 25. Chronic Idiopathic Urticaria <ul><li>Two Types </li></ul><ul><li>- The more severe cases typically involve autoantibodies to the mast cell receptors, but this pathology constitutes nearly 50% of cases </li></ul><ul><li>There is no data linking these reactions to underlying infections or malignancies </li></ul><ul><li>Treatment options are limited to modulating the reactions: immunosuppressive therapies aiming to prevent reactions have not been demonstrated efficacious </li></ul>“ Chronic urticaria: a role for newer immunomodulatory drugs? “Am J Clin Dermatol. 2003;4(5):297-305.
    26. 26. Chronic Idiopathic Urticaria <ul><li>Triggers for CIU may include: </li></ul><ul><ul><li>Medications </li></ul></ul><ul><ul><li>Food allergies* </li></ul></ul><ul><ul><li>Insect stings </li></ul></ul><ul><ul><li>Physical stimuli </li></ul></ul>“ Urticaria and angioedema. Controlling acute episodes, coping with chronic cases.” Postgrad Med. 2005 May;117(5):25-31.
    27. 27. Chronic Idiopathic Urticaria *Elimination Diet: online.statref.com
    28. 28. Chronic Idiopathic Urticaria *Elimination Diet: online.statref.com
    29. 29. Treatment Options
    30. 30. Treatment Options Control the Allergen, or Consider Drug Therapy
    31. 31. Treatment Options Pharmacotherapy for Allergic Rhinitis Well-controlled clinical trials have shown the efficacy and safety of pharmacotherapy : • Intranasal corticosteroids • Oral or intranasal antihistamines • Oral antihistamine/decongestant combinations • Intranasal ipratropium • Intranasal cromolyn (42) •  Oral montelukast Online.statref.com
    32. 32. Treatment Options Pharmacotherapy for Allergic Rhinitis Well-controlled clinical trials have shown the efficacy and safety of pharmacotherapy: • Oral antihistamines
    33. 33. Treatment Options Pharmacotherapy for CIU
    34. 34. Treatment Options Pharmacotherapy for CIU The cornerstone of treatment for Chronic Idiopathic Urticaria is antihistamines: • Oral antihistamines Online.statref.com
    35. 35. Antihistamine Pharmacology H 1 Antagonists 1st Generation: Ethanolamines, Ethylaminediamines, Piperazine derivatives, Alkylamines, Phenothiazine derivatives, and others 2nd Generation: Piperidines, Laratidine, Cetirizine “ 3rd” Generation: Levocetirizine Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004
    36. 36. Antihistamine Pharmacology <ul><li>H 1 Antagonists </li></ul><ul><li>1st generation drugs: </li></ul><ul><li>Many enter the CNS readily </li></ul><ul><li>Some are extensively metabolized, primarily by the liver </li></ul>Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004
    37. 37. Antihistamine Pharmacology <ul><li>H 1 Antagonists </li></ul><ul><li>Actions not caused by Histamine receptor block: </li></ul><ul><ul><ul><li>Sedation </li></ul></ul></ul><ul><ul><ul><li>Antinausea and antiemetic actions </li></ul></ul></ul><ul><ul><ul><li>Antiparkinsonism effects - used with antipsychotics </li></ul></ul></ul><ul><ul><ul><li>Anticholinoceptor effects - atropine like effects </li></ul></ul></ul><ul><ul><ul><li>Adrenoceptor-blocking actions </li></ul></ul></ul><ul><ul><ul><li>Serotonin-blocking action </li></ul></ul></ul><ul><ul><ul><li>Local anesthesia </li></ul></ul></ul><ul><ul><ul><li>Inhibition of mast cell release of histamine (?) </li></ul></ul></ul>Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004
    38. 38. Antihistamine Pharmacology 1st Generation Diphenhydramine ( Benadryl ) - inverse agonist at H 1 receptor - anticholinergic - antiemetic, sedative, hypnotic - treatment for RA, hives - cheap, effective, available - significant drowsiness “ Lippincott’s Illustrated Review: Pharmacology.” Harvey and Champe Eds. 4th edition. 2009
    39. 39. Antihistamine Pharmacology <ul><li>H 1 Antagonists </li></ul><ul><li>2nd generation drugs: </li></ul><ul><li>Several are metabolized by CYP3A4, which is important for drug interactions </li></ul><ul><li>Considerably less lipid soluble, and therefore do not readily cross the BBB </li></ul>Katzung. “Basic and Clinical Pharmacology.” 9th edition. 2004
    40. 40. Antihistamine Pharmacology 2nd Generation Cetirizine ( Zyrtec ) - racemic compound - treatment for allergies, hay fever, angioedema, and urticaria - available OTC - less CNS effects than 1st generation antihistamines - mild drowsiness www.wikipedia.org/cetirizine
    41. 41. Antihistamine Pharmacology “ Heritage” - Following administration of hydroxyzine, a 1st generation antihistamine, the major metabolite in the blood is cetirizine - Cetirizine is a racemic mixture of dextrocetirizine and levocetirizine
    42. 42. Antihistamine Pharmacology Levocetirizine Levocetirizine is the active R-enantiomer of cetirizine. Levocetirizine Cetirizine Images: www.wikipedia.org/cetirizine
    43. 43. Antihistamine Pharmacology Levocetirizine Levocetirizine is the active R-enantiomer of cetirizine. Levocetirizine Cetirizine Images: www.wikipedia.org/cetirizine
    44. 44. Antihistamine Pharmacology Levocetirizine - While both cetirizine and hydroxyzine possess high affinity at the H 1 receptor, the R-configured levocetirizine has much slower dissociation rate from the H 1 receptor than R-hydroxyzine, making it an insurmountable antagonist. - Levocetrizine and cetirizine have longer half-lives, and can be administered once daily. “ Physicochemical, pharmacological and pharmacokinetic properties of the zwitterionic antihistamines cetirizine and levocetirizine.” Curr Med Chem. 2008;15(21):2173-91.
    45. 45. Antihistamine Pharmacology <ul><li>Levocetirizine </li></ul><ul><li>No measurable muscarinic effects </li></ul><ul><li>No induction of liver enzymes </li></ul><ul><li>Almost entirely excreted unchanged by the kidneys </li></ul><ul><li>In vitro studies indicate a 2-fold increase in affinity for H 1 receptors over cetirizine </li></ul><ul><li>Clinical studies in the pediatric and geriatric populations are ongoing, but promising </li></ul>http://www.rxlist.com/xyzal-drug.htm
    46. 46. Antihistamine Pharmacology <ul><li>Levocetirizine </li></ul><ul><li>High bioavailability </li></ul><ul><li>Rapid onset of action </li></ul><ul><li>Limited distribution </li></ul><ul><li>Physically limited from the CNS by the BBB at therapeutic doses </li></ul>“ A review of the role of levocetirizine as an effective therapy for allergic disease.” Expert Opinion on Pharmacotherapy. April 2008, Vol. 9, No. 5, Pages 859-867 “ Peripheral and central H1 histamine receptor occupancy by levocetirizine, a non-sedating antihistamine; a time course study in the guinea pig.” British Journal of Pharmacology (2007) 151, 1129–1136; doi:10.1038/sj.bjp.0707318; published online 11 June 2007
    47. 47. Antihistamine Pharmacology <ul><li>Levocetirizine vs Cetirizine </li></ul><ul><li>Studies show significant improvement in subjective rating of symptoms following a course of Levocetirizine or Cetirizine compared to placebo </li></ul><ul><li>One 12 week program demonstrated statistically significant superiority in relieving symptoms using cetirizine in 6-12 year old population* </li></ul>“ The comparison of cetirizine, levocetirizine and placebo for the treatment of childhood perennial allergic rhinitis” Pediatr Allergy Immunol. 2008 Sep 30. [Epub ahead of print].
    48. 48. Antihistamine Pharmacology Levocetirizine vs Cetirizine: Side Effects http://www.rxlist.com/xyzal-drug.htm
    49. 49. Antihistamine Pharmacology Levocetirizine vs Cetirizine http://www.rxlist.com/xyzal-drug.htm
    50. 50. Antihistamine Pharmacology Levocetirizine vs Cetirizine  negative impact =  patient comfort
    51. 51. Antihistamine Pharmacology Levocetirizine: CIU Therapy
    52. 52. Antihistamine Pharmacology <ul><li>Levocetirizine: CIU Therapy </li></ul><ul><li>Levocetirizine is more efficacious in reducing CIU symptoms than desloratadine </li></ul><ul><li>- Levocetirizine was found not only to be a potent inhibitor of the histamine-induced weal and flare reaction, following both initial and repeated doses, but also to be demonstrably free from disruptive and sedative effects on objective measures of psychomotor and cognitive function </li></ul>Comparison of the efficacy of levocetirizine 5 mg and desloratadine 5 mg in chronic idiopathic urticaria patients. Allergy. 2008 Nov 22. [Epub ahead of print]. Current Medical Research and Opinion. Volume 22, Number 4
    53. 53. Antihistamine Pharmacology <ul><li>Levocetirizine: CIU Therapy </li></ul><ul><li>The effects of levocetirizine against histamine-induced skin reactions and skin blood flow are measurably longer than other antihistamine classes </li></ul><ul><li>24 hours for loratadine and desloratadine, two days for fexofenadine, and 3-4 days for cetirizine and levocetirizine </li></ul>“ The effect of 5-days of cetirizine, desloratadine, fexofenadine 120 and 180 mg, levocetirizine, loratadine treatment on the histamine-induced skin reaction and skin blood flow--a randomized, double-blind, placebo controlled trial]” Pol Merkur Lekarski. 2006 Nov;21(125):449-53.
    54. 54. Antihistamine Pharmacology <ul><li>Levocetirizine: CIU Therapy </li></ul><ul><li>Levocetirizine is more potent and consistent than other popular H1 antihistamines ebastine, fexofenadine, loratadine, mizolastine for blocking the cutaneous response to histamine in healthy men </li></ul>“ A double-blind, randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine, loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response during 24 hours in healthy male subjects.” Ann Allergy Asthma Immunol. 2002 Feb;88(2):190-7.
    55. 55. Antihistamine Pharmacology <ul><li>Levocetirizine: CIU Therapy </li></ul><ul><li>Levocetirizine is a cost effective treatment for CIU </li></ul><ul><li>A net gain of €91.93 per patient per month compared to placebo </li></ul>Medscape today: Clinical Drug Investigation Cost Effectiveness of Levocetirizine in Chronic Idiopathic Urticaria
    56. 56. Antihistamine Pharmacology Allergic Rhinitis
    57. 57. Antihistamine Pharmacology Allergic Rhinitis • “ Consider intranasal corticosteroids, oral antihistamines, intranasal antihistamines, oral antihistamine/oral decongestant combination products, oral leukotriene modifiers, or intranasal cromolyn as first-line pharmacotherapy” - 6 first-line therapies?!? What should you use? Online.statref.com
    58. 58. Antihistamine Pharmacology Allergic Rhinitis
    59. 59. Antihistamine Pharmacology <ul><li>Allergic Rhinitis </li></ul><ul><li>Tailor the treatment to the patient. </li></ul><ul><ul><li>Be mindful of drug interactions. Levocetirizine is a particularly safe option in this regard, but the dose should be reduced in patients with moderate renal complications, and is contraindicated in patients with renal failure . </li></ul></ul><ul><ul><li>Utilize side effects if applicable. Drowsiness may help decrease sleep latency in patients with sleep difficulty. </li></ul></ul><ul><ul><li>Cost management* </li></ul></ul>
    60. 60. Antihistamine Pharmacology <ul><li>*Cost Management </li></ul><ul><li>According to drugpriceinfo.com: </li></ul><ul><ul><li>Levocetirizine = $79/month </li></ul></ul><ul><ul><li>Cetirizine = $71/month </li></ul></ul><ul><ul><li>Benazepril = $14/month </li></ul></ul>
    61. 61. Antihistamine Pharmacology <ul><li>Allergic Rhinitis </li></ul><ul><li>Levocetirizine </li></ul><ul><ul><li>Reduced side effect profile </li></ul></ul><ul><ul><li>Preliminary indications of comparable if not better symptom relief </li></ul></ul><ul><ul><li>Societal cost savings* </li></ul></ul>
    62. 62. Antihistamine Pharmacology <ul><li>Allergic Rhinitis </li></ul><ul><li>Long term treatment with Levocetirizine compared to placebo </li></ul><ul><ul><li>Cost without treatment: 355 euros/month </li></ul></ul><ul><ul><li>Cost with Levocetirizine: 202 euros/month </li></ul></ul>“ Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.” Allergy 2009: 64: 85: 9 5
    63. 63. Antihistamine Pharmacology <ul><li>Levocetirizine: Beyond H 1 Antagonism </li></ul><ul><li>Reduces expression of IL-6, IL-8, and GM-CSF </li></ul><ul><li>Reduces percentage representation of cell phenotypes known to contribute to inflammatory tissue damage (eosinophils, CD4+CD29+, CD4+CD212+, and CD4+CD54+) and expands percentages of CD4+CD25+ </li></ul><ul><li>Inhibits production of rhinovirus-induced ICAM-1 and NF-kappaB expression </li></ul>“ Influence of cetirizine and levocetirizine on two cytokines secretion in human airway epithelial cells.” Allergy Asthma Proc. 2008 Sep-Oct;29(5):480-5. “ Levocetirizine modulates lymphocyte activation in patients with allergic rhinitis.” Pharmacol Sci. 2008 Oct;108(2):149-56. “ Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and viral replication in airway epithelial cells.” Antiviral Res. 2008 Dec 25. [Epub ahead of print]
    64. 64. Antihistamine Pharmacology <ul><li>Asthma </li></ul><ul><li>Bronchial Hyperreactivity, the cardinal feature of asthma, is frequently present in patients with chronic rhinitis </li></ul><ul><li>70% reduction in asthma attacks in children using Levocetirizine </li></ul>Levocetirizine in persistent allergic rhinitis and asthma: effects on symptoms, quality of life and inflammatory parameters. Clin Exp Allergy. 2006 Sep;36(9):1161-7. Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity. Allergy. 2009 Jan 28. [Epub ahead of print]
    65. 65. Thank you Questions?

    ×