HH11 Antihistamines Antihistamines & &

Urticaria UrticariaDr.M.Al.Ahmad ,Dr.M.Al.Ahmad ,DeDerrmatologmatolog

ististHoms Military HospitalHoms Military Hospital

21.4.200921.4.2009

Histamine is a small molecule derived from the decarboxylation of the amino acid histidine. It is destroyed by the enzyme diamine oxidase (histiminase), which is also involved in the metabolism of other bioactive amines.

ReceptorType

Major Tissue LocationsMajor Biologic Effects

H1smooth muscle, endothelial cells

acute allergic responses

H2gastric parietal cellssecretion of gastric acid

H3central nervous systemmodulating neurotransmission

H4mast cells, eosinophils, T cells, dentritic cells

regulating immune responses

MepyramineMepyramine

The first effective and safe The first effective and safe

antihistamineantihistamine..Was discovered in 1944 by Parisian Was discovered in 1944 by Parisian investigators ,Bovet and walthert.investigators ,Bovet and walthert.

ClassificationClassification

First- generation HFirst- generation H11 antihistamines. antihistamines. (Sedating-H(Sedating-H11 antihistamines). antihistamines).

Second-generation HSecond-generation H11 antihistamines. antihistamines. (None-sedating H(None-sedating H11 antihistamines) antihistamines)

First-generation HFirst-generation H11 antihistamines antihistamines..

Potent effect.Potent effect.Short- acting.Short- acting.Metabolized in liver by the microsomal cytochrome Metabolized in liver by the microsomal cytochrome P-450 system.P-450 system.

First- generation HFirst- generation H11 antihistamines antihistamines

Common side effects:Common side effects:Sedation.Sedation.Atropine like side effects:Atropine like side effects:

- - Dryness of the mouthDryness of the mouth. . - - Blurring of visionBlurring of vision..

- - ConstipationConstipation..- - Urinary retentionUrinary retention..

Others:Others:

Photosensitivity.Photosensitivity.Tachycardia.Tachycardia.Prolongation of the Q-T interval.Prolongation of the Q-T interval.

Table 1. FDA Approved Indications for First-Generation Antihistamines (7,8,9)

Drug NameFDA Approved Age

for UseIndications*Pregnancy Category

Azatadine(Optimine)

> 12 years oldPAR, SAR, CUB

Azelastine> 3 years oldPAR, SAR, VR, ACC

Brompheniramine(Dimetane)

> 6 years oldAR, HR Type 1c

Chlorpheniramine(Chlor-Trimeton)

> 2 years oldARB

Clemastine(Tavist)

> 6 years oldPAR, SAR, CUB

Cyproheptadine(Periactin)

> 2 years oldPAR, SAR, CUB

Dexchlorpheniramine(Polaramine)

> 2 years oldPAR, SAR, CUB

Hydroxyzine(Atarax, Vistaril)

Can be given < 6 years old

Pruritus, Sedation, Analgesia, Anti-emetic

C

Promethazine(Phenergan)

> 2 years oldHR Type 1, Sedation, Motion sickness,

Analgesia

C

Tripelennamine(PBZ)

> 1 month oldPAR, SAR, CUB

Second generation-HSecond generation-H11 antihistaminesantihistamines

No or low sedation when recommended No or low sedation when recommended doses are used.doses are used.No anticholenergic side effects.No anticholenergic side effects.Long- acting.Long- acting.No drug interaction.No drug interaction.No cardiac side effects.No cardiac side effects.

Table 2. FDA Approved Indications for Second- and Third-Generation Antihistamines (7,8)

Drug NameAge RestrictionIndications*Pregnancy Category

Cetirizine (Zyrtec)

> 2 years oldPAR, SAR, CIUB

Fexofenadine(Alle gra)

> 6 years oldSAR, CIUC

Loratadine(Claritin)

> 2 years oldSAR, CIUB

Levocetirizine(Xyzal)

>6years oldPAR,SAR,CIUB

Desloratadine(Clarinex)

> 12 years oldPAR, SAR, CIUC

*PAR = perennial allergic rhinitis, SAR = seasonal allergic rhinitis, CIU = chronic idiopathic urticaria

Novel second- generation HNovel second- generation H11 antihistamines. antihistamines.

-Rupatadine.-Rupatadine.

-Bilastine.-Bilastine.

HH11 antihistamines in children antihistamines in children

Second generation ones are probably safer. Second generation ones are probably safer. - -Overdose of the fist generation may cause Overdose of the fist generation may cause

severe toxicity including hyperpyrexia and severe toxicity including hyperpyrexia and convulsionconvulsion..

--First-generation ones might cause First-generation ones might cause paradoxical excitation in childrenparadoxical excitation in children..

IndicationsIndications Hypersensitivity reactions type one:Hypersensitivity reactions type one:

Perennial or seasonal allergic rhinitis.Perennial or seasonal allergic rhinitis.Vasomotor rhinitis.Vasomotor rhinitis.Allergic conjunctivitis.Allergic conjunctivitis.Urticaria.Urticaria.

Urticaria (Hives)Urticaria (Hives)

Prevalence: (adult and children ): Prevalence: (adult and children ): Acute : 15 Acute : 15 –– 25 % lifetime prevalence . 25 % lifetime prevalence . Chronic idiopathic : Up to 5 % of Chronic idiopathic : Up to 5 % of population.population.

20%20% of these have symptoms >10 yearsof these have symptoms >10 years..

Acute urticariaAcute urticaria

--symptoms present for <6 weekssymptoms present for <6 weeks --More common in Young'sMore common in Young's

--More common in atopic vs non atopicMore common in atopic vs non atopic

Chronic urticariaChronic urticaria

- -Symptoms continuously or intermittently Symptoms continuously or intermittently present for> 6 weekspresent for> 6 weeks..

--66 weeks is not an absolute demarcationweeks is not an absolute demarcation..--Female : male : 4 : 1Female : male : 4 : 1

--No increase in incidence in atopicsNo increase in incidence in atopics . .

Causes Causes Allergic :Allergic :Food. Food. -Food additive / preservatives.-Food additive / preservatives.Drugs. Drugs. Others: (venom, latexOthers: (venom, latex…… ). ).

Infections : Infections : viralviral parasitic.parasitic. Questionable :(Questionable :(H-pylori, sinusitis ,others )H-pylori, sinusitis ,others )

Non Non –– allergic release of histamines: allergic release of histamines: Drugs : Drugs :

- - AspirinAspirin . . - - ACE inhibitorsACE inhibitors . .

Narcotics. Narcotics. Radiocntrast media.Radiocntrast media.

Systemic illnesses/ conditions:Systemic illnesses/ conditions:

Complememt deficiencies.Complememt deficiencies. Cryoglobulinemia Cryoglobulinemia serum sickness.serum sickness.Rhumatological.Rhumatological.

IdiopathicIdiopathic

More than 50% of cases.More than 50% of cases.

Pharmacological treatmentPharmacological treatment First line :First line :

- - Non Non –– sedating H1 antihistamines sedating H1 antihistamines . . Double the dose if not respondingDouble the dose if not responding . .

- - Sedating H1 antihistamines at nightSedating H1 antihistamines at night . .

Results: 12 itemsResults: 12 items ·· 11 . .Quality of life in adults with chronic idiopathic urticaria receiving Quality of life in adults with chronic idiopathic urticaria receiving

desloratadine: a randomized, double-blind, multicentre, placebo-controlled desloratadine: a randomized, double-blind, multicentre, placebo-controlled study.study.Grob JJ, Auquier P, Dreyfus I, Ortonne JP.Grob JJ, Auquier P, Dreyfus I, Ortonne JP.J Eur Acad Dermatol Venereol; 2008 Jan ; 22(1):87-93. PubMed ID: 18181978J Eur Acad Dermatol Venereol; 2008 Jan ; 22(1):87-93. PubMed ID: 18181978

[[Abstract[ ][ ]Full Text[ ][ ]Related]]·· 22 . .Increasing the dose of cetirizine may lead to better control of chronic Increasing the dose of cetirizine may lead to better control of chronic

idiopathic urticaria: an open study of 21 patients.idiopathic urticaria: an open study of 21 patients.Kameyoshi Y, Tanaka T, Mihara S, Takahagi S, Niimi N, Hide M.Kameyoshi Y, Tanaka T, Mihara S, Takahagi S, Niimi N, Hide M.Br J Dermatol; 2007 Oct ; 157(4):803-4. PubMed ID: 17627798Br J Dermatol; 2007 Oct ; 157(4):803-4. PubMed ID: 17627798

[No Abstract][No Abstract][ [ Full Text[ ][ ]Related]]·· 33 . .The effect of fexofenadine hydrochloride on productivity and quality of The effect of fexofenadine hydrochloride on productivity and quality of

life in patients with chronic idiopathic urticaria.life in patients with chronic idiopathic urticaria.Spector SL, Shikiar R, Harding G, Meeves S, Leahy MJ.Spector SL, Shikiar R, Harding G, Meeves S, Leahy MJ.Cutis; 2007 Feb ; 79(2):157-62. PubMed ID: 17388220Cutis; 2007 Feb ; 79(2):157-62. PubMed ID: 17388220

[[Abstract[ ][ ]Full Text[ ][ ]Related]]·· 44 . .Efficacy and safety of desloratadine in adults with chronic idiopathic Efficacy and safety of desloratadine in adults with chronic idiopathic

urticaria: a randomized, double-blind, placebo-controlled, multicenter trial.urticaria: a randomized, double-blind, placebo-controlled, multicenter trial.Ortonne JP, Grob JJ, Auquier P, Dreyfus I.Ortonne JP, Grob JJ, Auquier P, Dreyfus I.Am J Clin Dermatol; 2007 ; 8(1):37-42. PubMed ID: 17298105Am J Clin Dermatol; 2007 ; 8(1):37-42. PubMed ID: 17298105[[Abstract] [Full Text] [Related]] [Full Text] [Related]

·· 55 . .Levocetirizine is an effective treatment in patients suffering from chronic Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study.multicenter study.Kapp A, Pichler WJ.Kapp A, Pichler WJ.Int J Dermatol; 2006 Apr ; 45(4):469-74. PubMed ID: 16650180Int J Dermatol; 2006 Apr ; 45(4):469-74. PubMed ID: 16650180[Abstract] [Full Text] [Related][Abstract] [Full Text] [Related]

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