Urticaria

1. Urticaria DR.A.Asilian

2. Mechanism of Allergy TH1 TH2 Infections Allergy

3. Mechanism of Allergy II Peanut antigen TH2 B cell Plasma cell

4. Mechanism of Allergy III Plasma Cell IgE

5. Mechanism of Allergy IV Mast Cell IgE

6. Mechanism of Allergy V Mast Cell

7. Mechanism of Allergy VI Peanut antigen Exploding Mast Cell Histamine

8. Mechanism of Allergy VII Urticaria

9. Urticaria • Affects 20% of population • Occurs across the age spectrum1 • Sometimes possible to identify a trigger such as food, drug, insect sting or infection • More than 2/3 of cases are self-limiting

10. Characteristics • Pruritic (most severely at night) • Erythematous • Often exhibit central pallor • Blanches • Oval, round or irregular shape or plaques • Plaques “move” to different locations over minutes to hours • Last less than 24 hours • Leave no residual marks (other than those created by scratching)

15. Urticaria

16. Hives or angioedema

17. Hives and angioedema

18. Men and women

19. Young and elderly

20. Classification • Acute versus Chronic Urticaria • Acute episodes < 6 weeks • more likely to have an identifiable trigger • Chronic episodes last > 6 weeks • less likely to have an identifiable trigger

21. Treatment of Urticaria • H1 antihistamines First generation: diphenhydramine, chlorpheniramine, hydroxyzine Second generation: cetirizine, loratadine, fexofenadine

22. Treatment of Urticaria (cont) • First generation antihistamines: • more sedating, require more frequent dosing • Second generation antihistamines: • higher dosing than standard dosing to obtain positive effects • Can be sedating at higher dosages

23. Treatment of Urticaria (cont) • Pregnant women or those breastfeeding may use loratidine or cetirizine

24. Treatment of Urticaria (cont) • Consider use of H2 blocker as well although data is not particularly supportive • ranitidine, nizatidine, famotidine and cimetidine (note cimetidine can increase drug levels in other medications taken concurrently)

28. Neotadin

29. Neotadin(Desloratadine) Active & Potent metabolite of Loratadin New Second generation H1 receptor antagonist

30. CLINICAL PHARMACOLOGY

31. Mechanism of Action A long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity A study in guinea pigs showed that desloratadine did not readily cross the blood brain barrier.

32. Pharmacodynamics Exhibits an antihistaminic effect by 1 hour This effect persists for as long as 24 hours.

33. PHARMACOKINETICS Absorption : Tmax : 3 hr Neither food nor grapefruit juice had an effect on the bioavailability (Cmax and AUC) of desloratadine Distribution : 82% - 87% bind to plasma protein Elimination : Half-life : 27 hr equally distributed in urine and feces as metabolic products

34. INDICATIONS AND USAGE: • Seasonal Allergic Rhinitis: • relief of nasal and non-nasal symptoms in patients 2 years of age and older • Perennial Allergic Rhinitis: • relief of nasal and non-nasal symptoms in patients 6 months of age and older • Chronic Idiopathic Urticaria: • symptomatic relief of pruritus, reduction in the number of hives, and size of hives in patients 6 • months of age and older

35. DOSAGE • Adults and Adolescents 12 Years of Age and Over: • • Neotadin Tablets - one 5 mg tablet once daily or • • Neotadin Oral Solution - 2 teaspoonfuls (5 mg in 10 mL) once daily • Children 6 to 11 Years of Age: • • Neotadin Oral Solution - 1 teaspoonful (2.5 mg in 5 mL) once daily • Children 12 Months to 5 Years of Age: • • Neotadin Oral Solution - 1/2 teaspoonful (1.25 mg in 2.5 mL) once daily • Children 6 to 11 Months of Age: • • Neotadin Oral Solution - 2 mL (1 mg) once daily

36. DOSAGE FORMS AND ADMINISTRATION • NeotadinTablets - 5 mg • Neotadin Oral Solution - 0.5 mg/1 mL • Take tablet immediately after opening the blister • may be taken without regard to meals, with or without water

37. Contraindication Hypersensitivity

38. WARNINGS AND PRECAUTIONS Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported. In such cases, stop Neotadin at once and consider alternative treatments.

39. ADVERSE REACTIONS • The most common adverse reactions (reported in ≥2% of adult • and adolescent patients with allergic rhinitis and greater than • placebo) were: • Pharyngitis, • dry mouth, • myalgia, • fatigue, • somnolence, • Dysmenorrhea • With Chronic Idiopathic Urticaria: • Headache, nausea, fatigue, dizziness, pharyngitis, dyspepsia , myalgia

40. USE IN SPECIFIC POPULATIONS* • Renal impairment: dosage adjustment is recommended • Hepatic impairment: dosage adjustment is recommended • A starting dose of one 5-mg tablet every other day • Pregnancy: category C • Desloratadine was not teratogenic in animals • Desloratadin passes into breast milk • Geriatric : dose selection for an elderly patient should be cautious

41. NO DRUG INTERACTIONS

42. Important notes: • FDA approved >6 months old • No CNS suppression (selective H1 antagonist) • Limited penetration of BBB(no anticholinergic effects) • Active & potent metabolite of Loratadine • 2nd generation Antihistamines : the first choice in guidelines for AR & CIU • Once daily (Half-life=27 Hours) • Absorption is unaffected by food • Not metabolized by CytP450 • Excellent compliance

43. Thank You! Questions?