Quetiapinum

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**Quetiapinum**
Natura chemica


Formula chemica	C ₂₁H ₂₅N ₃O ₂S
Massa molaris	383.5099 g/mol
PubChem	5002
DrugBank	DB01224
Natura pharmacologica
Codex ATC	N05AH04 (WHO)
Tempus semivitae biologicum	7 h Norquetiapinum: 9-12 h
Metabolismus	iecore (hepaticus): CYP3A4
Metabolitus	Norquetiapinum (N-Desalcylquetiapinum)
Excretio	renibus (73%), faecibus (20%)
Ad usum therapeuticum
Applicatio	per os
MedlinePlus	a698019 (Anglice)

Quetiapinum est substantia antipsychotica et propterea medicamentum, quod cogitari potest, ad therapiam schizophreniarum, interruptionum bipolarium^[1] sicut depressionum velut delirii^[2]. Interdum insomniae quoque adhibetur, quamquam usus illius non ubilibet approbatur^[3]^[4].

Historia

Ab anno 1970 diversae substantiae antipsychoticae atypica quoque vocatae sunt, primo enim Clozapinum. Haec "atypica", cum Olanzapino (1971, demum in usu medici ab 1996), cum receptoria D₂ tum receptoria serotonini 5-HT_1A obsidentes, praeterea minius effectus adversaria ostendentes. Anno 1985 dibenzothiazepino derivata Quetiapinum, simul Clozapino Olanzapinoque simile sed cum grege adiecto, divulgatum est.^[5]

Synthesis

Synthesis Quetiapini ab uno dibenzothiazepinonorum orditur. Ad fabricandum dibenzothiazepinum primo lactamum cum phosphoryl chlorido tractatur. Deinde per substitutionem nucleophilicam molecula lateraliter additur.

Natura Quetiapini

Natura chemica

Quetiapinum est thiazepinum. Nomen IUPAC suum est 2-(2-(4-dibenzo[b,f][1,4]thiazepine-11-yl-1-piperazinyl)ethoxy)ethanol, quod est thiazepinum (anulus chemicus cum sulphure et nitrogenio et quinque atomis carboniorum), cum duobus anulis aromatici (benzenum) et piperazino (anulus heterocyclus cum duobus atomis nitrogeniorum) et ethanolo.

Quetiapinum est substantia alba et crystallina, massa molaris sua 383.5099 g/mol.

Natura pharmacologica

Quetiapinum est medicamentum cum virtutibus antipsychoticis et antidepressivis. Codex ATC est N05AH04 (WHO).

Pharmacodynamica

Receptorium	Quetiapini affinitas ligandi, K_i (nM)^[6]	Norquetiapini affinitas ligandi, K_i (nM)	Actio
dopamini D₁	712^[7] - 994.5	99.8 (receptorium ratti)	antagonista
D₂	245^[7] - 379	196	antagonista
D_2L	712^[7]		antagonista
D_2S	390^[7]		antagonista
D₃	340	-	antagonista
D₄	1,202^[7] - 2,019	1297	antagonista
5-HT_1A	394.2	45	antagonista partialis
5-HT_2A	118	48	antagonista
5-HT_2C	1,843	107	antagonista
5-HT₄	nondum determinata	nondum determinata	antagonista
5-HT₆	33 / 1,864	-	antagonista
5-HT₇	307	76	antagonista
α_1A	22	144	antagonista
α_1B	14.6	46.4 (receptorium ratti)	antagonista
α_2A	3,630	237	antagonista
α_2C	28.85	-	antagonista
ß₁	> 10,000	> 10,000	nondum inquisita
ß₂	> 10,000	> 10,000	nondum inquisita
H₁	6.9	3.5	antagonista
H₂	41.24	-	antagonista
H₃	>10,000	>10,000	nondum inquisita
H₄	>10,000	>1,660	nondum inquisita
M₁	489 - 858	38.3 (receptorium ratti)	antagonista
M₂	1,339 - 1,631.5	453	nondum inquisita
M₃	1,631.5 - >10,000	23	antagonista
M₄	542	110	nondum inquisita
M₅	1,942	23	antagonista
SERT	>10000^[7]	927	situm obsidens
NET	>10000^[7]	12	situm obsidens

Mementote et Quetiapinum et metabolitum suum Norquetiapinum effectus pharmacologicos exercere. Quetiapinum potissime receptoria H₁, praeterea metabolitus activus Norquetiapinum (quod est N-Desalcylquetiapinum) receptoria D₂ et noradrenalini transportatorem (breve: NET, inhibitio noradrenalini^[8] reabsorptionis) et receptoria 5-HT_2A serotonini et 5-HT_2c serotonini obsidet.

Receptorium histamini 1

Antagonista receptoriorum H₁ (H1R) ut Quetiapinum lassitudinem, famis incrementum efficit^[9].

Pharmacocinetica

Tempus semivitae biologicum $t_{\frac {1}{2}}$ .^[10] circa 7 h (norquetiapinum 9-12 h) est. Excretio est per urinas (73%) et biles (20%).

Effectus Quetiapini

Cum uso Quetiapini animum advertere ad effectus secundarios et interactiones necesse est.

Effectus secundarii

Exempla sunt:

Saepissmime (>10%)

Siccitas oris (xerostomia)
Vertigo, dysequilibrium, (prae-)syncope
Capitis dolor (cephalalgia)
Somnolentia

Saepe (1%-10%)

Pressio sanguinis nimia
Hypotensio orthostatica
Pulsus celer
Cholesteroli copiae nimiae in sanguine
Triglyceridorum copiae nimiae in sanguine
Dolor abdominalis
Dysphagia
Fatigatio
Insomnia

Alia (<1%)

Symptomata extrapyramidalia
Hyponatraemia
Intervallum QT prolongatum^[11]
Ponderis incrementum

Interactiones

Cum Quetiapinum subtratum enzymi CYP3A4 esset, inhibitores CYP3A4 effectus Quetiapini augere possint, inductores invicem diminuere, per exemplum:

Pharmaca cum effectibus Quetiapini substrati
Inhibitores cum Quetiapini effectibus fortioribus	Inductores cum Quetiapini effectibus minoribus
Antihypertensiva Calcii canalium inhibitores Diltiazemum Felodipinum Antiarrhythmica Amiodaronum Dronedaronum Antidepressiva Fluvoxaminum Nefazodonum (forte) Diuretica/Hormonta Conivaptanum (forte) Antibiotica Ciprofloxacinum Macrolida Clarithromycinum (forte) Erythromycinum (forte) Telithromycinum (forte) Antiemetica Aprepitantum Fungicida/-statica Fluconazolum Ketoconazolum (forte) Isavuconazolum Itraconazolum (forte) Posaconazolum (forte) Voriconazolum (forte) Proteasis inhibitores Atazanavirum-Ritonavirum Boceprevirum (forte) Cobicistatum (forte) Indinavirum (forte) Lopinavirum cum Ritonaviro (forte) Nelfinavirum (forte) Ritonavirum (forte) Saquinavirum (forte) Telaprevirum (forte) Idelalisibum (forte) Imatinibum Nilotinibum Ribociblibum (forte) Glucocorticoides Dexamethasonum (forte) Verapamilum Hormonta GH Plantae Fructus averrhoae carambolae Silybum marianum	Anticonvulsiva Carbamazepinum (forte, quoque P-gp) Phenytoinum (forte) Fosphenytoinum (forte) Oxcarbazepinum (forte) Eslicarbazepinacetatum Topiramatum Phenobarbitalum (forte) Primidonum (forte) Antidepressiva Hypericum perforatum (forte, quoque P-gp) Antihypertensiva Bosentanum (forte, endothelini receptoris inhibitor) Substantiae antiretrovirales Efavirenzum (forte) Etravirinum (forte) Nevirapinum (forte) Substantiae antineoplasticae Dabrafenibum Enzalutamidum Mitotanum (forte) Antibiotica Rifabutinum (forte) Rifapentinum (forte) Nafcillinum (forte) Rifampicinum (forte) Hormonta Triiodthyroninum (T3) Antiandrogena Apalutamidum Modafinilum Quercetinum Capsaicinum

Notae

↑ Anglice: bipolar disorder; hic formae fem. pluralis, quia haec diagnosis duas interruptiones saltim postulat
↑ Hawkins SB, Bucklin M, Muzyk AJ (2013). "Quetiapine for the treatment of delirium". J Hosp Med 8 (4): 215-20 .
↑ Gugger JJ, Cassagnol M (2008). "Low-dose quetiapine is not a benign sedative-hypnotic agent". Am J Addict 17(5): 454-5
↑ Tak LM, van Berlo-van de Laar IR, Doornbos B (2013). "Geen quetiapine bij slaapstoornissen". Ned Tijdschr Geneeskd 157: A5740 (Batavice).
↑ Raviña E (2010). The Evolution of drug discovery, Wiley-VCH .
↑ https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php
1 2 3 4 5 6 7 Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (2008). "N-Desalkylquetiapine, a Potent Norepinephrine Reuptake Inhibitor and Partial 5-HT_1A Agonist, as a Putative Mediator of Quetiapine's Antidepressant Activity". Neuropsychopharmacology 33: 2303-12 .
↑ noradrenalinum = norepinephrinum
↑ Sato H, Ito C, Hiraoka K, Tashiro M, Shibuya K, H1 Funaki Y, Yoshikawa T, Iwata R, Matsuoka H, Yanai K (2015). "Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers". Psychopharmacology (Berl) 232 (19): 3497-505 .
↑ http://goldbook.iupac.org/B00658.html
↑ Hasnain M, Vieweg WV, Howland RH, Kogut C, Breden Crouse EL, Koneru JN, Hancox JC, Digby GC, Baranchuk A, Deshmukh A, Pandurangi AK (2014). "Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports". Ther Adv Psychopharmacol 4(3): 130-8 .

[1] Anglice: bipolar disorder; hic formae fem. pluralis, quia haec diagnosis duas interruptiones saltim postulat

[2] Hawkins SB, Bucklin M, Muzyk AJ (2013). "Quetiapine for the treatment of delirium". J Hosp Med 8 (4): 215-20 .

[3] Gugger JJ, Cassagnol M (2008). "Low-dose quetiapine is not a benign sedative-hypnotic agent". Am J Addict 17(5): 454-5

[4] Tak LM, van Berlo-van de Laar IR, Doornbos B (2013). "Geen quetiapine bij slaapstoornissen". Ned Tijdschr Geneeskd 157: A5740 (Batavice).

[5] Raviña E (2010). The Evolution of drug discovery, Wiley-VCH .

[6] ttps://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php

[JENSEN-7] 1 2 3 4 5 6 7 Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (2008). "N-Desalkylquetiapine, a Potent Norepinephrine Reuptake Inhibitor and Partial 5-HT_1A Agonist, as a Putative Mediator of Quetiapine's Antidepressant Activity". Neuropsychopharmacology 33: 2303-12 .

[8] radrenalinum = norepinephrinum

[9] Sato H, Ito C, Hiraoka K, Tashiro M, Shibuya K, H1 Funaki Y, Yoshikawa T, Iwata R, Matsuoka H, Yanai K (2015). "Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers". Psychopharmacology (Berl) 232 (19): 3497-505 .

[10] ttp://goldbook.iupac.org/B00658.html

[11] Hasnain M, Vieweg WV, Howland RH, Kogut C, Breden Crouse EL, Koneru JN, Hancox JC, Digby GC, Baranchuk A, Deshmukh A, Pandurangi AK (2014). "Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports". Ther Adv Psychopharmacol 4(3): 130-8 .

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