Amitriptyline/perphenazine

Amitriptyline/perphenazine (Duo-Vil, Etrafon, Triavil, Triptafen) is a formulation that contains the tricyclic antidepressant amitriptyline and the medium-potency typical (first-generation) antipsychotic, perphenazine. In the United States amitriptyline/perphenazine is marketed by Mylan Pharmaceuticals Inc. and Remedy Repack Inc.[1][2]

Amitriptyline/perphenazine
Combination of
AmitriptylineTricyclic antidepressant
PerphenazineTypical antipsychotic
Clinical data
Trade namesDuo-Vil, Etrafon, Triavil, Triptafen
AHFS/Drugs.comConsumer Drug Information
License data
Pregnancy
category
  • US: D (Evidence of risk)
    Routes of
    administration    		Oral
    Legal status
    Legal status
    Identifiers
    CAS Number
    UNII
    KEGG

    Medical uses

    In the United States amitriptyline/perphenazine is indicated for the treatment of patients with:[1][2][3]

    • Moderate-severe anxiety and/or agitation and depression
    • Depression and anxiety in association with chronic physical disease
    • Schizophrenia with prominent depressive symptoms

    Adverse effects
    Common (>1% incidence) adverse effects include
    [1][2][4]
    • Sedation
    • Hypertension — high blood pressure.
    • Neurological impairments (such as extrapyramidal side effects which include dystonia, akathisia, parkinsonism, muscle rigidity, etc.)
    • Anticholinergic side effects such as:
    - Blurred vision
    - Constipation
    - Dry mouth
    - Nasal congestion
    • Increased appetite
    • Weight gain
    • Nausea
    • Dizziness
    • Headache
    • Vomiting
    Unknown frequency adverse effects include
    [1][2][4]
    • Diarrhoea
    • Alopecia — hair loss
    • Photophobia
    • Pigmentation
    • Eczema up to exfoliative dermatitis
    • Urticaria
    • Erythema
    • Itching
    • Photosensitivity (increased sensitivity of affected skin to sunlight)
    • Hypersalivation — excessive salivation.
    • Hyperprolactinaemia — elevated blood prolactin levels. This may present with the following symptoms:
    - Galactorrhea — the release of milk that is not associated with pregnancy or breastfeeding
    - Gynaecomastia — the development of breast tissue in males
    - Disturbances in menstrual cycle
    - Sexual dysfunction
    • Pigmentation of the cornea and lens
    • Hyperglycaemia — elevated blood glucose (sugar) levels.
    • Hypoglycaemia — low blood glucose (sugar) levels.
    • Disturbed concentration
    • Excitement
    • Anxiety
    • Insomnia
    • Restlessness
    • Nightmares
    • Weakness
    • Fatigue
    • Diaphoresis — excessive/abnormal sweating.
    Uncommon/Rare adverse effects include
    [1][2][4]
    • Tardive dyskinesia, an often irreversible adverse effect that usually results from chronic use antipsychotic medications, especially the high-potency first-generation antipsychotics. It is characterised by slow (hence tardive), involuntary, repetitive, purposeless muscle movements.
    • Neuroleptic malignant syndrome, a potentially fatal complication of antipsychotic drug use. It is characterised by the following symptoms:
    - Muscle rigidity
    - Tremors
    - Mental status change (e.g. hallucinations, agitation, stupor, confusion, etc.)
    - Hyperthermia — elevated body temperature
    - Autonomic instability (e.g. tachycardia, high blood pressure, diaphoresis, diarrhoea, etc.)
    • Urinary retention — the inability to pass urine despite having urine to pass.
    • Blood dyscrasias e.g. agranulocytosis (a potentially fatal drop in white blood cell count), leukopaenia (a drop in white blood cell counts but not to as extreme an extent as agranulocytosis), neutropaenia (a drop in neutrophil [the cells of the immune system that specifically destroy bacteria] count), thrombocytopaenia (a dangerous drop in platelet [a cell found in the blood that plays a crucial role in the blood clotting process] counts), purpura (the appearance of red or purple discolourations of the skin that do not blanch when pressure is applied), eosinophilia (raised eosinophil [the cells of the immune system that specifically fights off parasites] count)
    • Hepatitis — inflammation of the liver
    • Jaundice
    • Pigmentary retinopathy
    • Anaphylactoid reactions
    • Oedema — the abnormal buildup of fluids in the tissues
    • Asthma
    • Coma
    • Seizures
    • Confusional states
    • Disorientation
    • Incoordination
    • Ataxia
    • Tremors
    • Peripheral neuropathy — nerve damage
    • Numbness, tingling and paresthesias of the extremities
    • Dysarthria
    • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
    • Tinnitus — falsely hearing ringing in the ears.
    • Alteration in EEG patterns
    • Paralytic ileus — cessation of the peristaltic waves that propel partially digested food through the digestive tract.
    • Hyperpyrexia (elevated body temperature)
    • Disturbance of accommodation
    • Increased intraocular pressure
    • Mydriasis

    Pharmacology

    Binding affinities (Ki[nM]; for human cloned receptors when available)[5][6][7]

    MacromoleculeAmitriptylineNortriptyline
    (Amitriptyline's active metabolite)    		PerphenazineNotes
    SERT3.1316.5?It is this and its NET-inhibiting action is believed to give amitriptyline its
    antidepressant action.
    NET22.44.37?See above.
    DAT53803100?
    5-HT1A450294421Binding for human brain receptors had to be substituted in amitriptyline (AMI)
    and nortriptyline's (NOR) cases
    5-HT2A4.355.6Binding for cloned rat receptors had to be substituted for AMI & NOR. Binding
    to this receptor is believed to be what gives the newer (atypical) antipsychotics,
    clozapine, quetiapine, olanzapine, ziprasidone, risperidone, sertindole and
    zotepine their lower extrapyramidal side effect (EPS) liability.
    5-HT2C6.158.5132(Binding) As above. This action is believed to be partly responsible for the lower
    EPS liability of newer antipsychotics and also responsible for their higher weight
    gain liability compared to most typical antipsychotics.
    5-HT610314817Cloned rat receptor was substituted for NOR's binding.
    5-HT7114?23Cloned rat receptor was substituted for AMI.
    α1A245510Human brain receptors were substituted for AMI and NOR.
    α2A6902030810.5As above.
    D2146025700.16As above.
    D3206?0.13Human receptors (their source was undefined) had to be substituted for AMI.
    H11.115.18This receptor is at least partly responsible for the sedating effects of these three
    drugs and hence this combination product. Possibly also partly responsible for
    their weight gain liability.
    M112.9401500This is the main receptor responsible for the anticholinergic side effects
    mentioned above.
    M325.9501848This receptor is believed to be partly responsible for the metabolic adverse
    effects of the atypical antipsychotics.
    σ300200031.5All three values are for binding to the guinea pig brain receptors.

    See also

    References
    1. "PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Mylan Pharmaceuticals Inc.]". DailyMed. National Library of Medicine. Retrieved 7 October 2013.
    2. "PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet [REMEDYREPACK INC. ]". DailyMed. National Library of Medicine. Retrieved 7 October 2013.
    3. amitriptyline/perphenazine (Rx) - Etrafon, Triptafen, Triavil [Internet]. Medscape Reference. [cited 2013 Oct 7]. Available from: http://reference.medscape.com/drug/etrafon-triptafen-amitriptyline-perphenazine-342946
    4. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 7]. Greenwood Village, CO: Thomsen Healthcare; 2013.
    5. National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 7]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: "Archived copy". Archived from the original on 2013-11-08. Retrieved 2013-12-01.CS1 maint: archived copy as title (link)
    6. Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Twelfth Edition. McGraw Hill Professional; 2010.
    7. Taylor D, Paton C, Kapur S, Taylor D. The Maudsley prescribing guidelines in psychiatry. 11th ed. Chichester, West Sussex: John Wiley & Sons; 2012.
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