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BRIEF REPORT
Year : 2008  |  Volume : 74  |  Issue : 5  |  Page : 475-477

Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal


Department of Dermatology, PSG Hospitals, Coimbatore, India

Correspondence Address:
Reena Rai
Department of Dermatology, PSG Hospitals, Peelamedu, Coimbatore - 641 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0378-6323.44303

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  Abstract 

Background : Histamine is responsible for the wheal and flare reaction in various allergic conditions. Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H 1 and H 2 receptors may provide better relief. Aim: To compare the efficacy of levocetirizine (H 1 blocker) versus levocetirizine and ranitidine (H 2 blocker) in suppressing histamine-induced wheal. Methods: Fifteen volunteers were given a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. A pretest was performed by intradermal histamine prick test. After administration of the drugs, the prick test was repeated at 1 hour, 2, 3, 6, and 24 hours, and the size of the wheal measured and statistically analyzed. Results: At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and the combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone. Conclusion: H2 blocker potentiates the effects of an H1 blocker in suppressing histamine-induced wheal.


Keywords: Histamine1 blocker, Histamine 2 blocker, Histamine-induced wheal


How to cite this article:
Dhanya N B, Rai R, Srinivas C R. Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal. Indian J Dermatol Venereol Leprol 2008;74:475-7

How to cite this URL:
Dhanya N B, Rai R, Srinivas C R. Histamine 2 blocker potentiates the effects of histamine 1 blocker in suppressing histamine-induced wheal. Indian J Dermatol Venereol Leprol [serial online] 2008 [cited 2019 Aug 21];74:475-7. Available from: http://www.ijdvl.com/text.asp?2008/74/5/475/44303



  Introduction Top


Histamine is a major mediator in allergic reactions. It is secreted as a result of the interaction of antigens with IgE antibodies on mast cells and results in profound pharmacological effects, both locally and systemically. [1] Four histamine receptors have been identified. H 1 and H 2 receptors are found in cutaneous blood vessels, and H 3 receptors are located in the brain. [2] The function of the H4 receptor is not known. Activation of either H1 or H2 receptors increases vasodilation of vascular endothelium and elicits negative ionotropic effects on myocytes through release of nitric oxide. Nitric oxide-mediated vasodilation through the H1 receptors plays a part in the flare reaction. The action of histamine on bronchial smooth muscle and blood vessels accounts in part for allergic symptoms (H1 and H2 receptors). It also has a major role in regulation of gastric secretions by inducing acid and peptin secretion (H2 receptors), formation of edema (wheal and flare), and stimulation of sensory nerve endings (H1 and H2). [1]

Classical antihistamines are the drugs which block the H 1 receptors and are widely used in various allergic conditions, whereas H 2 blockers are mainly used for acid peptic disease. Although H 1 receptor-mediated actions of histamine are primarily responsible for vasodilatation, vasopermeability, and itching, it has been observed that combined blocking of both H 1 and H 2 receptors may provide better relief. [3] Based on this, we conducted a study to compare the efficacy of levocetirizine (H 1 blocker) versus levocetirizine and ranitidine (H 2 blocker) in suppressing histamine-induced wheal.


  Methods Top


The study was done on 15 healthy volunteers (10 males and 5 females) in the age group of 18 to 50 years after obtaining informed consent. The volunteers were not on antihistamines, steroid, and immunosuppressants for 7 days prior to the study. None of them had history of atopy, drug hypersensitivity, or use of alcohol. Pregnant and lactating women were excluded.

Volunteers were administered a single dose of levocetirizine 5 mg on day 1 and a single dose of levocetirizine 5 mg with ranitidine 150 mg twice a day on day 7. Ranitidine 150 mg was given twice a day because it is the recommended dose . A prick test was performed before administration of the drugs by the standard method using histamine 0.1% w/v solution. A drop of 0.1% w/v of histamine solution was placed on the flexor aspect of the forearm. The skin was pricked through the histamine solution with a lancet. The tip of the lancet was kept parallel to the skin surface and the skin lifted by tenting the lancet by 45 to 60.

After 1 minute, the test site was wiped with filter paper to remove the excess histamine solution. The size of wheal was calculated by measuring the maximum diameter of the wheal and the orthogonal diameter with a transparent scale. Multiple squares of size 11 cm were marked on the flexor aspect of the forearm. The prick test was repeated within the squares at 1 hour, 2, 3, 6, and 24 hours after administering the drug on day 1 and day 7. The size of the histamine-induced wheal was recorded each time.


  Results Top


The mean values of wheal size in response to intradermal histamine challenge for levocetirizine and for levocetirizine with ranitidine at 1 hour, 2, 3, 6, and 24 hours were analyzed using SPSS PC 11.5 version. Mean and standard deviations were computed.

Paired t test was used to compare the mean values. P value <0.05 was considered statistically significant.

At 1 hour, there was no statistically significant difference in the wheal size between levocetirizine alone and combination of levocetirizine and ranitidine. Levocetirizine with ranitidine resulted in statistically significant reduction of wheal size at 2, 3, 6, and 24 hours when compared with levocetirizine alone [Table 1].


  Discussion Top


Levocetirizine is an active enantiomer of cetirizine, which is a widely used H 1 blocker for allergic conditions; whereas ranitidine is an H2 blocker used in acid peptic disease. Studies have shown that the combination of chlorpheniramine (H 1 antagonist) and cimetidine (H 2 antagonist) is more successful in inhibiting a histamine skin reaction when compared with an H 1 antagonist alone, and it is recommended for the treatment of chronic idiopathic urticaria. [4] Other studies using cetirizine and ranitidine, diphenhydramine and ranitidine, terfenadine and ranitidine showed similar results. [5],[6],[7] The results provided additional evidence that H2 receptors are present in the human cutaneous microcirculation and add support to the clinical observation of therapeutic efficacy of H 1 plus H 2 blockers in some patients with chronic urticaria. [8],[9] It has been suggested that the H 1 antagonist-H 2 antagonist combination inhibits the release of allergic mediators, whether IgE dependent or otherwise. [10],[11],[12]

Another view suggests that the response to the combination may be highly individual and that there could be a subpopulation of urticaria patients whose response to it is especially favorable. [13],[14]

In our study, we found that the wheal suppression started at the end of 2 hours and lasted till the end of 24 hours. Urticaria may sometimes be resistant to treatment by H1 blocker and so an H2 blocker may potentiate the effects of an H1 blocker. [15] There are also increasing reports of the beneficial effects of H 2 -antagonists, mostly in combination with H 1 -antagonists, in a variety of allergic and pseudoallergic conditions such as chronic urticaria and anaphylactoid reactions due to colloid volume substitutes, opioid analgesics, and radiographic contrast media. The combined use of H 1 - and H 2 -antagonists might not only act as specific histamine antagonism but also exert a mast cell stabilizing effect, as demonstrated in animal experiments and some clinical studies. [16] These results support the rationale of using the combination of H1- and H2-antagonists in urticarial disease not responding to H1 blockers alone. Future research may show whether the combined use of H 1 - and H 2 -antagonists will become a routine therapeutic procedure in allergy therapy.

 
  References Top

1.Babe KS, Serafin WE. Histamine, bradykinin and their antagonists. In: Hardman JG, Limbird LE, editors. The Pharmacological basis of therapeutics. 9 th ed. New York: McGraw-Hill; 1996. p. 581-600.  Back to cited text no. 1    
2.Arrang JM, Garberg M,th Schwartz JC. Auto inhibition of brain histamine release mediated by a novel (H 3 ) class of histamine receptor. Nature 1983;302:832-7.  Back to cited text no. 2    
3.Marks R, Greaves MW. Vascular reaction to histamine and compound 48/80 in human skin: suppression by a histamine H 2 receptor blocking agent. Br J Clin Pharmacol 1977;4:367-9.   Back to cited text no. 3    
4.Bleehen SS, Thomas SE, Greaves MW, Newton J, Kennedy CT, Hindley F, et al. Cimetidine and chlorpheniramine in the treatment of chronic idiopathic urticaria: A multicentre randomized double blind study. Br J Dermatol 1987;117:81-8.  Back to cited text no. 4  [PUBMED]  
5.Lin RY, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med 2000;36:462-8.   Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Lee KC, Kim DY, Lee JW, Kwon KH, Jin SM, Lee YB. Effects of histamine 2 antagonsit in the treatment of perennial allergic rhinitis. Korean J Otolaryngol-Head Neck Surg 1999;42:993-6.  Back to cited text no. 6    
7.Paul E, Pfeffer M, Bφdeker RH. Effect of terfenadine and ranitidine on histamine and suxamethonium wheals. Eur J Clin Pharmacol 1988;34:591-4.  Back to cited text no. 7    
8.Greaves M, Marks R, Robertson I. Receptors for histamine in human skin blood vessels: a review. Br J Dermatol 1977;97:225-8.   Back to cited text no. 8  [PUBMED]  
9.Harvey RP, Schocket AL . The effect of H1 and H2 blockade on cutaneous histamine response in man. J Allergy Clin Immunol 1980;65:136-9.  Back to cited text no. 9    
10.Dorsch W, Reimann HJ, Neuhauser J. Histamine 1 - histamine 2 antagonism: Effect of combined clemastine and cimetidine pretreatment on allergen and histamine-induced reactions of the guinea pig lung in vivo and in vitro. Agents Actions 1982;12:113-8.  Back to cited text no. 10  [PUBMED]  
11.Philbin DM, Moss J, Akins CW, Rosow CE, Kono K, Schneider RC, et al. The use of H 1 and H 2 histamine antagonists with morphine anesthesia: A double-blind study. Anesthesiology 1981;55:292-6.  Back to cited text no. 11  [PUBMED]  
12.Irwin RB, Lieberman P, Friedman MM, Kaliner M, Kaplan R, Bale G, et al. Mediator release in local heat urticaria: Protection with combined H 1 and H 2 antagonists. J Allergy Clin Immunol 1985;76:35-9.  Back to cited text no. 12    
13.Cook J, Shuster S. Lack of effect of H2 blockade in chronic urticaria. Br J Dermatol 1979;17:21-2.  Back to cited text no. 13    
14.Farnam J, Grant JA, Guernsey BG, Jorizzo JL, Petrusa ER. Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone. J Allergy Clin Immunol 1984;73:842-5.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Monroe EW, Cohen SH, Kalbfleisch J, Schulz CI. Combined H1 and Combined H1 and H2 antihistamine therapy in chronic urticaria. Arch Dermatol 1981;117:404-7.  Back to cited text no. 15  [PUBMED]  
16.Mansfield LE, Smith JA, Nelson HS. Greater inhibition of dermographia with a combination of H 1 and H 2 antagonists. Ann Allergy 1983;50:264-5.  Back to cited text no. 16  [PUBMED]  



 
 
    Tables

  [Table 1]

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