Fluphenazine

Template:Short description Template:Use dmy dates Template:Cs1 config Template:Drugbox Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication.<ref name=AHFS2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is used in the treatment of chronic psychoses such as schizophrenia,<ref name=AHFS2015/><ref name=TGA>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine.<ref>Template:Cite journal</ref> It is given by mouth, injection into a muscle, or just under the skin.<ref name=AHFS2015/> There is also a long acting injectable version that may last for up to four weeks.<ref name=AHFS2015/> Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Common side effects include movement problems, sleepiness, depression and increased weight.<ref name=AHFS2015/> Serious side effects may include neuroleptic malignant syndrome, low white blood cell levels, and the potentially permanent movement disorder tardive dyskinesia.<ref name=AHFS2015/> In older people with psychosis as a result of dementia it may increase the risk of dying.<ref name=AHFS2015/> It may also increase prolactin levels which may result in milk production, enlarged breasts in males, impotence, and the absence of menstrual periods.<ref name=AHFS2015/> It is unclear if it is safe for use in pregnancy.<ref name=AHFS2015/>

Fluphenazine is a typical antipsychotic of the phenothiazine class.<ref name=AHFS2015/> Its mechanism of action is not entirely clear but believed to be related to its ability to block dopamine receptors.<ref name=AHFS2015/> In up to 40% of those on long term phenothiazines, liver function tests become mildly abnormal.<ref>Template:Cite journal</ref>

Fluphenazine came into use in 1959.<ref name=Mc2007>Template:Cite book</ref> The injectable form is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> It is available as a generic medication.<ref name=AHFS2015/> It was discontinued in Australia in 2017.<ref name=Au2017>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical use

A 2018 Cochrane review found that fluphenazine was an imperfect treatment and other inexpensive drugs less associated with side effects may be an equally effective choice for people with schizophrenia.<ref>Template:Cite journal</ref> Another 2018 Cochrane review found that there was limited evidence that newer atypical antipsychotics were more tolerable than fluphenazine.<ref name="s408">Template:Cite journal</ref> Intramuscular depot injection forms are available as both the decanoate and enanthate esters.<ref name="y335">Template:Cite journal</ref>

Side effects

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">Template:Cite book</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>Template:Cite book</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>Template:Cite journal</ref> It may also result in reoccurrence of the condition that is being treated.<ref>Template:Cite book</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>

Pharmacology

Pharmacodynamics

Fluphenazine acts primarily by blocking post-synaptic dopaminergic D₂ receptors in the basal ganglia, cortical and limbic system. It also blocks α₁ adrenergic receptors, muscarinic M₁ receptors, and histaminergic H₁ receptors.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

citation

CitationClass=web }}</ref>
Site	Ki (nM)	Action	Ref
5-HT1A	145–2829	Template:Abbr	<ref name="PDSP" />
5-HT1B	334	Template:Abbr	<ref name="PDSP" />
5-HT1D	334	Template:Abbr	<ref name="PDSP" />
5-HT1E	540	Template:Abbr	<ref name="PDSP" />
5-HT2A	3.8–98	Template:Abbr	<ref name="PDSP" />
5-HT2B	Template:Abbr	Template:Abbr	<ref name="PDSP" />
5-HT2C	174–2,570	Template:Abbr	<ref name="PDSP" />
5-HT3	4,265– >10,000	Template:Abbr	<ref name="PDSP" />
5-HT5A	145	Template:Abbr	<ref name="PDSP" />
5-HT6	7.9–38	Template:Abbr	<ref name="PDSP" />
5-HT7	8	Template:Abbr	<ref name="PDSP" />
D1	14.45	Template:Abbr	<ref name="PDSP" />
D2	0.89	Template:Abbr
D2L		Template:Abbr	<ref name="PDSP" />
D3	1.412	Template:Abbr	<ref name="PDSP" />
D4	89.12	Template:Abbr	<ref name="PDSP" />
D5	95–2,590	Template:Abbr	<ref name="PDSP" />
α1A	6.4–9	Template:Abbr	<ref name="PDSP" />
α1B	13	Template:Abbr	<ref name="PDSP" />
α2A	304–314	Template:Abbr	<ref name="PDSP" />
α2B	181.6–320	Template:Abbr	<ref name="PDSP" />
α2C	28.8–122	Template:Abbr	<ref name="PDSP" />
β1	>10,000	Template:Abbr	<ref name="PDSP" />
β2	>10,000	Template:Abbr	<ref name="PDSP" />
H1	7.3–70	Template:Abbr	<ref name="PDSP" />
H2	560	Template:Abbr	<ref name="PDSP" />
H3	1,000	Template:Abbr	<ref name="PDSP" />
H4	>10,000	Template:Abbr	<ref name="PDSP" />
M1	1,095-3,235.93	Template:Abbr	<ref name="PDSP" />
M2	2,187.76–7,163	Template:Abbr	<ref name="PDSP" />
M3	1441–1445.4	Template:Abbr	<ref name="PDSP" />
M4	5,321	Template:Abbr	<ref name="PDSP" />
M5	357	Template:Abbr	<ref name="PDSP" />
Template:Abbrlink	Template:Abbr	Template:Abbr	<ref name="PDSP" />
Template:Abbrlink	Template:Abbr	Template:Abbr	<ref name="PDSP" />
Template:Abbrlink	Template:Abbr	Template:Abbr	<ref name="PDSP" />
[[NMDA receptor|Template:Abbr (Template:Abbr)]]	Template:Abbr	Template:Abbr	<ref name="PDSP" />
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except 5-HT3 (rat), D4 (human/rat), H3 (guinea pig), and NMDA/PCP (rat).<ref name="PDSP" />

History

Fluphenazine came into use in 1959.<ref name=Mc2007/>

Availability

The injectable form is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st" /> It is available as a generic medication.<ref name=AHFS2015/> It was discontinued in Australia in 2017.<ref name=Au2017/>

Veterinary

In horses, it is sometimes given by injection as an anxiety-relieving medication, though there are many negative common side effects and it is forbidden by many equestrian competition organizations.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>