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Fluoxetine

Discussion in 'Drug Articles' started by chibi curmudgeon, Feb 27, 2012.

  1. chibi curmudgeon

    chibi curmudgeon Gold Finger Gold Member

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    Fluoxetine HCl (Prozac, Sarafem) is probably the most well-known antidepressant and the archetypal selective serotonin reuptake inhibitor (SSRI). It is used for the pharmacological treatment of several mental disorders, most notably depression and anxiety, and sometimes neuropathy.

    Introduction to [var]PAGENAME[/var]

    [​IMG]Fluoxetine is a highly selective inhibitor of the serotonin transporter (SERT,) preventing serotonin in the synapse from being taken back into the presynaptic neuron. This increases the amount of serotonin available to postsynaptic receptors. Fluoxetine is a relatively safe antidepressant with few serious side effects, although combinations with other serotonergic drugs can result in possibly fatal serotonin syndrome. Fluoxetine has by far the longest half-life of all SSRIs. Fluoxetine is a first-line treatment for major depressive disorder and is less likely to cause a discontinuation syndrome than any other SSRI.

    Using [var]PAGENAME[/var]


    Ways of Administration


    Fluoxetine is available in immediate-release capsules and tablets in dosages of 10, 20, and 40 mg, a delayed-release capsule containing 90 mg fluoxetine in enteric-coated pellets (Prozac Weekly,) and an oral solution containing 20 mg fluoxetine/5 ml.[1]

    Effects of [var]PAGENAME[/var]


    As with other antidepressants, fluoxetine may take 2 or more weeks to produce a noticeable effect; single doses have minimal utility. Fluoxetine's psychoactive effects are usually subtle; euphoria and CNS stimulation or depression are estimated to occur in 1/100-1/1000 patients and thus the drug is considered to have minimal recreational potential. Emotional blunting, an inability to feel extreme emotions of any kind, is often reported.

    There is controversy regarding the efficacy of fluoxetine and other SSRIs; in some clinical trials there is little to no statistically significant difference between the effects of fluoxetine and a placebo.

    Combinations with [var]PAGENAME[/var]


    Fluoxetine is commercially available in combination with the 2nd-generation antipsychotic olanzapine, as Symbyax, for depressive episodes of bipolar disorder. Symbyax contains either 6 or 12 mg olanzapine with either 25 or 50 mg fluoxetine.

    Different Uses for [var]PAGENAME[/var]


    In the U.S., fluoxetine is approved for major depressive disorder, obsessive-compulsive disorder, bulimia nervosa, and panic disorder alone and with agoraphobia, and premenstrual dysphoric disorder, and sometimes prescribed off-label for selective mutism, post-traumatic stress disorder (PTSD), social anxiety disorder, chronic neuropathic pain, fibromyalgia, and Raynaud's phenomenon.

    Pharmacology of [var]PAGENAME[/var]


    LD[SUB]50[/SUB] (mg/kg) as hydrochloride :
    Mice : 248 (orally)
    Rat : 452 (orally)

    Fluoxetine inhibits serotonin reuptake almost exclusively, having no clinically appreciable effect on adrenergic, dopaminergic, muscarinic, or histaminergic receptors.

    It is available as a racemic mixture of R and S enantiomers, which are mostly pharmacologically equivalent. Fluoxetine in plasma is approximately 94.5% bound to proteins, including albumin and alpha-1-glycoprotein.

    Fluoxetine is effectively absorbed thorugh oral administration, with bioavailability of at least 60-80%. Time to peak plasma concentrations is between 4-8 hours following oral administration of normal therapeutic preparations and doses.

    Fluoxetine is a substrate and inhibitor of cytochrome P450 2D6, and inhibits several other isoforms as well. It is extensively metabolized by the liver to norfluoxetine and several inactive metabolites. S-norfluoxetine is also a potent SSRI.

    The half-life of fluoxetine ranges from 1 to 6 days, depending on acute or chronic administration, and norfluoxetine's may be as long as 16 days. Hence weekly dosing is feasible with fluoxetine, missed daily doses are rarely problematic, and SSRI discontinuation syndrome is unlikely.

    Chemistry of [var]PAGENAME[/var]

    Column 1 Column 2
    Systematic(IUPAC) name: N-Methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine
    Synonyms: Prozac, Sarafem, Fontex,
    Molecular Formula: C[SUB]17[/SUB]H[SUB]18[/SUB]F[SUB]3[/SUB]NO
    Molar mass: 309.33 g/mol.
    CAS Registry Number: 54910-89-3
    Melting Point: 179-182 ℃
    Boiling Point: 395 ℃
    Flash Point: 192.757 °C
    Solubility: Sparingly soluble in Water and in Dichloromethane (DCM); Freely soluble in Ethanol and in methanol; practically insoluble in Ether


    Column 1 Column 2
    Title compound: [var]PAGENAME[/var]
    Systematic (IUPAC) name: N-Methyl-[gamma]-[4-(trifluoromethyl)phenoxy]benzenepropanamine
    Synonyms: (±)-N-methyl-3-phenyl-3-[([alpha],[alpha],[alpha]-trifluoro-p-tolyl)oxy]propylamine, dl-N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine; LY-110140, Adofen, Fluctin, Fluneurin, Fluoxeren, Fluox-Puren, Flusol, Fluxet, Fontex, Foxetin, Lovan, Prozac, Reconcile, Sarafem (hydrochloride)
    Molecular Formula: C[sub]17[/sub]H[sub]18[/sub]F[SUB]3[/SUB]NO
    Molar mass: 309.33 g/mol, 345.79 g/mol (hydrochloride)
    CAS Registry Number: 54910-89-3, 59333-67-4 (hydrochloride)
    Melting Point: 158.4-158.9°C (hydrochloride)
    Boiling Point: no data
    Flash Point: no data
    Solubility: Hydrochloride (mg/mL) : methanol, ethanol > 100; acetone, acetonitrile, chloroform 33-100; dichloromethane 5-10; ethyl acetate 2-2.5; toluene, cyclohexane, hexane 0.5-0.67; maximum solubility in water 14; practically insoluble in ether
    Additionnal data: none
    Notes: hydrochloride aspect : white to off white crystalline powder. There is mention of an oxalate salt (mp 179-182°C).
    [1]

    The Dangers of [var]PAGENAME[/var]

    Physical Health Risks

    Physical Problem 1


    Physical Problem 2


    Overdose

    Fluoxetine has an advantage over tricyclic antidepressants and monoamine oxidase inhibitors in that overdoses are rarely fatal. Seizures, coma, and cardiac arrythmias may result, but most patients survive overdoses without sequelae.

    Reported Deaths


    Mental Health Risks

    Fluoxetine's prescribing information includes a black box warning for suicidality in children and adolescents aged under 25, and caregivers are warned to monitor patients taking fluoxetine for changes in mood and behavior. However, meta-analyses of clinical trials suggest this may not be as much of a problem as such a warning implies. The benefits of treating depression appear to outweigh the risks of no treatment.[2][3]

    Mental Health Risk 1

    In patients with bipolar disorder, fluoxetine may trigger mania, but has been successfully used as monotherapy in clinical trials.

    Mental Health Risk 2


    Side Effects

    The most common adverse events associated with fluoxetine include nausea/vomiting and diarrhea, due to the effects of 5HT3 receptors in the chemoreceptor trigger zone. Fluoxetine may also cause dry mouth, appetite loss, insomnia or somnolence, bleeding due to inhibited platelet activity, and various sexual problems including lowered libido, difficulty orgasming, and erectile dysfunction.

    Addiction

    Physical Addiction

    Mental Addiction



    Producing/Growing [var]PAGENAME[/var]


    Forms of [var]PAGENAME[/var]


    United Nations

    USA

    Fluoxetine is prescription-only but not a controlled substance.

    EU

    Other Countries


    History of [var]PAGENAME[/var]

    Fluoxetine was developed by Eli Lilly in the 1970s and was approved by the FDA in 1987.

    More [var]PAGENAME[/var] Sections


    [insights][var]PAGENAME[/var][/insights]

    The Latest [var]PAGENAME[/var] Threads


    [showthreads=10]107[/showthreads]

    [cat]Antidepressants[/cat]
    [CAT]SSRI[/CAT]

    References

    1. ^Prozac Prescribing Information (2006) Eli Lilly and Company. In Physician's Desk Reference, 61st ed. Thomson PDR, Montvale, NJ.
    2. ^Beasley CM Jr, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH Jr, Heiligenstein JH, Thompson VL, Murphy DJ, Masica DN. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. British Medical Journal. 1991 Sep 21;303(6804):685-92.
    3. ^Bridge JA, Iyengar S, Salary CB, Barbe RP, Birmaher B, Pincus HA, Ren L, Brent DA. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. Journal of the American Medical Association. 2007 Apr 18; 297(15):1683-96.

    [1]Merck Index, fifteenth edition (2013)
     
    Last edited by a moderator: Sep 10, 2017
  2. C.D.rose

    C.D.rose Palladium Member Donating Member

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    First! ;)

    I added a few more words to the article header, and I edited the introduction section. In that section I added a reference to serotonin syndrome and I removed the part that said that, due to its long half-life, fluoxetine can be taken weekly. I see that there is a sort of depot formulation of fluoxetine (Prozac Weekly), but if a reference to once-weekly use is made, it should be by pointing out that this can only be done with Prozac Weekly. I don't want anyone to read this article and think "hey, I'll just add up seven daily doses and take them all at once." This would probably be less dangerous than with some other drugs, but it would be somewhat dangerous nonetheless.

    The image of the fluoxetine molecule could maybe be placed at the top of the article, but I don't want to mess with that just now.

    C.D.
     
  3. chibi curmudgeon

    chibi curmudgeon Gold Finger Gold Member

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    Ah, good call. I'm bad at writing introductions.
     
  4. sassyspy

    sassyspy Palladium Member

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    Am I wrong in thinking the "combinations with" section is meant to contain info on the potential reactions when combined with other drugs?

    No criticism meant, but happened to be looking for examples of prozac when mixed with other drugs, and thought that was the section it was meant to be in.?
    If not, I will be needing to go back and edit my additions!:s


    Thanks much!:)
     
    Last edited by a moderator: Sep 10, 2017
  5. chibi curmudgeon

    chibi curmudgeon Gold Finger Gold Member

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    No, you're right, but I figured I'd start with the commercially available combination. I might also mention the other psych meds with which it's frequently combined. Contraindications should go there, too. I just happened to lose access to my favorite online resource right before I decided to start the wiki because the universe hates me.
     
    Last edited by a moderator: Sep 10, 2017
  6. sassyspy

    sassyspy Palladium Member

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    :vibes:not the whole universe, lovey! But I know how you feel!

    Well, thanks for saving my day... :) hate going back and editing my edits!
     
    Last edited by a moderator: Sep 10, 2017
  7. Calliope

    Calliope Fictional Member Palladium Member Supporter

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    from a nutshell, an infinite space
    adding antidepressant category, updating parts of template so rearranged some of the content, did chemistry table, bit to introduction section. uploaded two ref articles and inked them.

    I am nit sure with these particular wikis -- the pharmaceutics, antidepressants whether one id supposed to keep every section form the template in, it seems a bit odd to have, for example, producing/growing as a section. I've left all in for now, but will remove if this is the wat to go.