“Zuclopenthixol”的意思、由来-开放百科全书

Zuclopenthixol is a D₁ and D₂ antagonist, α₁-adrenergic and 5-HT₂ antagonist. While it is approved for use in Australia, Canada, Ireland, India, New Zealand, Singapore, South Africa and the UK it is not approved for use in the United States.^[3]^[4]

Medical uses

Available forms

Dosing

As a long acting injection, zuclopenthixol decanoate comes in a 200 mg and 500 mg ampoule. Doses can vary from 50 mg weekly to the maximum licensed dose of 600 mg weekly. In general, the lowest effective dose to prevent relapse is preferred. The interval may be shorter as a patient starts on the medication before extending to 3 weekly intervals subsequently. The dose should be reviewed and reduced if side effects occur, though in the short term an anticholinergic medication benztropine may be helpful for tremor and stiffness, while diazepam may be helpful for akathisia. 100 mg of zuclopenthixol decanoate is roughly equivalent to 20 mg of flupentixol decanoate or 12.5 mg of fluphenazine decanoate.

In acutely psychotic and agitated inpatients, 50 – 200 mg of zuclopenthixol acetate may be given for a calming effect over the subsequent three days, with a maximum dose of 400 mg in total to be given. As it is a long-acting medication, care must be taken not to give an excessive dose.

In oral form zuclopenthixol is available in 10, 25 and 40 mg tablets, with a dose range of 20–60 mg daily.

Side effects

Chronic administration of zuclopenthixol (30 mg/kg/day for two years) in rats resulted in small, but significant, increases in the incidence of thyroid parafollicular carcinomas and, in females, of mammary adenocarcinomas and of pancreatic islet cell adenomas and carcinomas. An increase in the incidence of mammary adenocarcinomas is a common finding for D₂ antagonists which increase prolactin secretion when administered to rats. An increase in the incidence of pancreatic islet cell tumours has been observed for some other D₂ antagonists. The physiological differences between rats and humans with regard to prolactin make the clinical significance of these findings unclear.

Other permanent side effects are similar to many other typical antipsychotics, namely extrapyramidal symptoms as a result of dopamine blockade in subcortical areas of the brain. This may result in symptoms similar to those seen in Parkinson's disease and include a restlessness and inability to sit still known as akathisia, a slow tremor and stiffness of the limbs.^[8] Zuclopenthixol is thought to be more sedating than the related flupentixol, though possibly less likely to induce extrapyramidal symptoms than other typical depots.^[5] As with other dopamine antagonists, zuclopenthixol may sometimes elevate prolactin levels; this may occasionally result in amenorrhoea or galactorrhoea in severe cases. Neuroleptic malignant syndrome is a rare but potentially fatal side effect. Any unexpected deterioration in mental state with confusion and muscle stiffness should be seen by a physician.

Zuclopenthixol decanoate induces a transient dose-dependent sedation. However, if the patient is switched to maintenance treatment with zuclopenthixol decanoate from oral zuclopenthixol or from i.m. zuclopenthixol acetate the sedation will be no problem. Tolerance to the unspecific sedative effect develops rapidly.^[9]

Pharmacology

Pharmacodynamics

Zuclopenthixol antagonises both dopamine D₁ and D₂ receptors, α₁-adrenoceptors and 5-HT₂ receptors with a high affinity, but has no affinity for cholinergic muscarine receptors. It weakly antagonises the histamine (H₁) receptor but has no α₂-adrenoceptor blocking activity.

Evidence from in vitro work and clinical sources (i.e. therapeutic drug monitoring databases) suggests that both CYP2D6 and CYP3A4 play important roles in zuclopenthixol metabolism.^[11]

References

1. ^{{cite book | author = Sneader, Walter | title = Drug discovery: a history | publisher = Wiley | location = New York | year = 2005 | page = 410 | isbn = 0-471-89980-1 | oclc = | doi = | url = https://books.google.com/?id=Cb6BOkj9fK4C&lpg=PA410&pg=PA410#v=onepage}}
2. ^{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1102|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=1102–}}
3. ^{{cite journal|last1=Green|first1=Alan I.|last2=Noordsy|first2=Douglas L.|last3=Brunette|first3=Mary F.|last4=O'Keefe|first4=Christopher|title=Substance abuse and schizophrenia: Pharmacotherapeutic intervention|journal=Journal of Substance Abuse Treatment|volume=34|issue=1|year=2008|pages=61–71|issn=0740-5472|doi=10.1016/j.jsat.2007.01.008|pmc=2930488|pmid=17574793}}
4. ^{{Cite book|editor=Sweetman, Sean C. |chapter=Anxiolytic Sedatives Hypnotics and Antipsychotics|title=The complete drug reference |edition=36th |year=2009 |pages=1040–1|publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1}}
5. ^¹{{cite web |vauthors=da Silva Freire Coutinho E, Fenton M, Quraishi SN | title = Zuclopenthixol decanoate for schizophrenia | work = The Cochrane Database of Systematic Reviews | publisher = John Wiley and Sons, Ltd. | year = 1999 | url = http://www.cochrane.org/reviews/en/ab001164.html | doi = 10.1002/14651858.CD001164 | accessdate = 2007-06-12}}
6. ^{{Cite journal |vauthors=Haessler F, Glaser T, Beneke M, Pap AF, Bodenschatz R, Reis O | title = Zuclopenthixol in adults with intellectual disabilities and aggressive behaviours | journal = British Journal of Psychiatry | volume = 190 | issue = 5 | pages = 447–448 | year = 2007 | doi = 10.1192/bjp.bp.105.016535 | pmid = 17470962 | postscript = }}
7. ^{{cite web | author = Lundbeck P/L | title = Clopixol Acuphase 50 mg/mL Injection Clopixol Acuphase 100 mg / 2 mL Injection | publisher = Lundbeck P/L | year = 1991 | url = http://home.intekom.com/pharm/lundbeck/clopixac.html | accessdate = 2007-06-12}}
8. ^¹{{cite web |vauthors=Kumar A, Strech D | title = Zuclopenthixol dihydrochloride for schizophrenia | work = The Cochrane Database of Systematic Reviews | publisher = John Wiley and Sons, Ltd. | year = 2005 | url = http://www.cochrane.org/reviews/en/ab005474.html | doi = 10.1002/14651858.CD005474 | accessdate = 2007-06-12}}
9. ^{{Cite web|url=https://www.hpra.ie/img/uploaded/swedocuments/LicenseSPC_PA0115-005-007_03062015110150.pdf|title=Summary of Product Characteristics|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}
10. ^¹²³⁴https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05705-3
11. ^{{Cite journal |vauthors=Davies SJ, Westin AA, Castberg I, Lewis G, Lennard MS, Taylor S, Spigset O | title = Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies. | journal = Acta Psychiatrica Scandinavica | volume = 122 | issue = 6 | pages = 445–453 | year = 2010 | doi = 10.1111/j.1600-0447.2010.01619.x }}