Hidroksizin

Hidroksizin
Klinični podatki
Blagovne znamke	Vistaril
AHFS/Drugs.com	monograph
MedlinePlus	a682866
Nosečnostna; kategorija	AU: A ; ZDA: C (možna škodljivost) ; ;
Način uporabe	peroralno, i.m.
Oznaka ATC	N05BB01 (WHO) ;
Pravni status
Pravni status	samo na recept;
Farmakokinetični podatki
Biološka razpoložljivost	visoka (in vivo)
Vezava na beljakovine	93%
Presnova	skozi ledvice
Razpolovni čas	20,0 ± 4,1 h
Izločanje	s sečem, blatom
Identifikatorji
	IUPAC ime (±)-2-(2-{4-[(4-klorofenil)-fenilmetil]piperazin-1-il}etoksi)etanol;
Številka CAS	68-88-2;
PubChem CID	3658;
DrugBank	DB00557;
ChemSpider	3531;
UNII	30S50YM8OG;
KEGG	D08054;
ChEBI	CHEBI:5818;
ChEMBL	ChEMBL896;
CompTox Dashboard (EPA)	DTXSID8023137 ;
ECHA InfoCard	100.000.630
Kemični in fizikalni podatki
Formula	C21H27ClN2O2
Mol. masa	374,904 g/mol
3D model (JSmol)	Interactive image;
	SMILES Clc1ccc(cc1)C(c2ccccc2)N3CCN(CC3)CCOCCO;
	InChI InChI=1S/C21H27ClN2O2/c22-20-8-6-19(7-9-20)21(18-4-2-1-3-5-18)24-12-10-23(11-13-24)14-16-26-17-15-25/h1-9,21,25H,10-17H2; Key:ZQDWXGKKHFNSQK-UHFFFAOYSA-N;

Hidroksizin (pod zaščitenima imenoma Vistaril, Atarax) je antihistaminik prve generacije, ki so ga prvič sintetizirali na Union Chimique Belge leta 1956, istega leta pa ga je v ZDA utržilo farmacevtsko podjetje Pfizer.^[2] Je derivat piperazina, sintetična snov z antispastičnim (preprečuje krče) in antifibrilacijskim delovanjem (preprečuje fibrilacijo srca).^[3]

Zaradi antagonističnega delovanja na različne receptorje v osrednjem živčevju izkazuje tudi izrazito anksiolitično, antiobsesivno in antipsihotično delovanje.^[4] Danes se uporablja zlasti za simptomatsko lajšanje tesnobe in napetosti zaradi nevroze ter pri boleznih organskega izvora z izraženo tesnobnostjo. Zaradi antihistaminskega delovanja se lahko uporablja tudi za zdravljenje hude oblike srbenja, hiperalgezije ali slabosti zaradi potovalne bolezni.^[5]^[6]

Mehanizem delovanja

Poglavitni mehanizem delovanja hidroksizina je močan inverzni agonizem na histaminskih receptorjih H₁ (K_i = 2 nM).^[7]^[8]^[9]^[10] Za razliko od drugih antihistaminikov prve generacije izkazuje le zanemarljivo afiniteto do muskarinskih receptorjev (K_i = >10,000 nM) in zato ne povzroča klinično pomembnih antiholinergičnih učinkov.^[8]^[9]^[10]^[11]^[12] Poleg antihistaminskega delovanja izkazuje tudi antagonistične učinke na receptorje 5-HT_2A, (K_i = ~50 nM), D₂ (K_i = 378 nM) in α₁-adrenergične receptorje (K_i = ~300 nM).^[8]^[9]^[11]

Njegovo anksiolitično delovanje je verjetno posledica antiserotonegičnih učinkov.^[13]^[14] Drugi antihistaminiki brez zaviralnega učinka na serotoninske receptorje namreč ne izkazujejo tega delovanja.^[14]

Neželeni učinki

Hidroksizin lahko povzroči hudo omotico. Zaspanost običajno izzveni po nekaj dneh uporabe zdravila. Blažji neželeni učinki so suha usta, drhtavica in drugi neželeni gibi, zlasti pri visokih odmerkih.^[15]

Viri

↑ Simons FE; Simons KJ; Frith EM (1984). »The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine«. The Journal of Allergy and Clinical Immunology. 73 (1 Pt 1): 69–75. PMID 6141198.
↑ Shorter, Edward (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-536874-6.
↑ http://lsm1.amebis.si/lsmeds/novPogoj.aspx?pPogoj=hidroksizin^{[mrtva povezava]}, Slovenski medicinski e-slovar, vpogled: 1. 1. 2012.
↑ Schram, WS: "Use of hydroxyzine in psychosis". Dis Nerv Syst 20: 126 (1959).
↑ FDA DrugInfo: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=51459
↑ »Hydroxyzine Facts and Comparisons at Drugs.com«.
↑ Gillard M; Van Der Perren C; Moguilevsky N; Massingham R; Chatelain P (2002). »Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194)«. Molecular Pharmacology. 61 (2): 391–399. doi:10.1124/mol.61.2.391. PMID 11809864.
↑ ^8,0 ^8,1 ^8,2 Snowman AM; Snyder SH (1990). »Cetirizine: actions on neurotransmitter receptors«. The Journal of Allergy and Clinical Immunology. 86 (6 Pt 2): 1025–1028. doi:10.1016/S0091-6749(05)80248-9. PMID 1979798.
↑ ^9,0 ^9,1 ^9,2 Kubo N; Shirakawa O; Kuno T; Tanaka C (1987). »Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay«. Japanese Journal of Pharmacology. 43 (3): 277–282. doi:10.1254/jjp.43.277. PMID 2884340.
↑ ^10,0 ^10,1 White RP; Boyajy LD (1960). »Neuropharmacological comparison of atropine, scopolamine, banactyzine, diphenhydramine and hydroxyzine«. Archives Internationales De Pharmacodynamie et De Thérapie. 127: 260–273. PMID 13784865.
↑ ^11,0 ^11,1 Haraguchi K; Ito K; Kotaki H; Sawada Y; Iga T (1997). »Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic acetylcholine receptor occupancies«. Drug Metabolism and Disposition: the Biological Fate of Chemicals. 25 (6): 675–684. PMID 9193868. Arhivirano iz prvotnega spletišča dne 28. avgusta 2021. Pridobljeno 1. januarja 2013.
↑ Orzechowski RF; Currie DS; Valancius CA (2005). »Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models«. European Journal of Pharmacology. 506 (3): 257–264. doi:10.1016/j.ejphar.2004.11.006. PMID 15627436.
↑ Olasov Rothbaum, Barbara; Stein, Dan J.; Hollander, Eric (2009). Textbook of Anxiety Disorders. American Psychiatric Publishing, Inc. ISBN 1-58562-254-0.
↑ ^14,0 ^14,1 Lamberty Y; Gower AJ (2004). »Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip«. Pharmacology, Biochemistry, and Behavior. 79 (1): 119–124. doi:10.1016/j.pbb.2004.06.015. PMID 15388291.
↑ http://www.ehow.com/facts_5525129_side-effects-hydroxyzine-hcl.html, vpogled: 1. 1. 2012.

[pmid6141198-1] Simons FE; Simons KJ; Frith EM (1984). »The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine«. The Journal of Allergy and Clinical Immunology. 73 (1 Pt 1): 69–75. PMID 6141198.

[isbn0-19-536874-6-2] Shorter, Edward (2009). Before Prozac: the troubled history of mood disorders in psychiatry. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-536874-6.

[3] ttps://lsm1.amebis.si/lsmeds/novPogoj.aspx?pPogoj=hidroksizin^{[mrtva povezava]}, Slovenski medicinski e-slovar, vpogled: 1. 1. 2012.

[4] Schram, WS: "Use of hydroxyzine in psychosis". Dis Nerv Syst 20: 126 (1959).

[5] FDA DrugInfo: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=51459

[urlHydroxyzine_Facts_and_Comparisons_at_Drugs.com-6] »Hydroxyzine Facts and Comparisons at Drugs.com«.

[pmid11809864-7] Gillard M; Van Der Perren C; Moguilevsky N; Massingham R; Chatelain P (2002). »Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194)«. Molecular Pharmacology. 61 (2): 391–399. doi:10.1124/mol.61.2.391. PMID 11809864.

[pmid1979798-8] 8,0 ^8,1 ^8,2 Snowman AM; Snyder SH (1990). »Cetirizine: actions on neurotransmitter receptors«. The Journal of Allergy and Clinical Immunology. 86 (6 Pt 2): 1025–1028. doi:10.1016/S0091-6749(05)80248-9. PMID 1979798.

[pmid2884340-9] 9,0 ^9,1 ^9,2 Kubo N; Shirakawa O; Kuno T; Tanaka C (1987). »Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay«. Japanese Journal of Pharmacology. 43 (3): 277–282. doi:10.1254/jjp.43.277. PMID 2884340.

[pmid13784865-10] 10,0 ^10,1 White RP; Boyajy LD (1960). »Neuropharmacological comparison of atropine, scopolamine, banactyzine, diphenhydramine and hydroxyzine«. Archives Internationales De Pharmacodynamie et De Thérapie. 127: 260–273. PMID 13784865.

[pmid9193868-11] 11,0 ^11,1 Haraguchi K; Ito K; Kotaki H; Sawada Y; Iga T (1997). »Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic acetylcholine receptor occupancies«. Drug Metabolism and Disposition: the Biological Fate of Chemicals. 25 (6): 675–684. PMID 9193868. Arhivirano iz prvotnega spletišča dne 28. avgusta 2021. Pridobljeno 1. januarja 2013.

[pmid15627436-12] Orzechowski RF; Currie DS; Valancius CA (2005). »Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models«. European Journal of Pharmacology. 506 (3): 257–264. doi:10.1016/j.ejphar.2004.11.006. PMID 15627436.

[isbn1-58562-254-0-13] Olasov Rothbaum, Barbara; Stein, Dan J.; Hollander, Eric (2009). Textbook of Anxiety Disorders. American Psychiatric Publishing, Inc. ISBN 1-58562-254-0.

[pmid15388291-14] 14,0 ^14,1 Lamberty Y; Gower AJ (2004). »Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip«. Pharmacology, Biochemistry, and Behavior. 79 (1): 119–124. doi:10.1016/j.pbb.2004.06.015. PMID 15388291.

[15] ttps://www.ehow.com/facts_5525129_side-effects-hydroxyzine-hcl.html, vpogled: 1. 1. 2012.

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