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Amitriptyline/perphenazine
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<h2 id="medical-uses">Medical uses</h2> <p>In the <a href="/facts/United_States_of_America/P0sCdLe5">United States</a> amitriptyline/perphenazine is indicated for the treatment of patients with:<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <ul><li>Moderate to severe <a href="/facts/Anxiety/Geekl883">anxiety</a> and/or agitation and <a href="/facts/Depression_(mood)/GDNFWm1L">depression</a></li> <li>Depression and anxiety in association with chronic physical disease</li> <li>Schizophrenia with prominent depressive symptoms</li></ul> <h2 id="adverse-effects">Adverse effects</h2> Common (>1% incidence) adverse effects include <a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> <ul><li>Sedation</li> <li><a href="/facts/Hypertension/wlAvBfcf">Hypertension</a></li> <li>Neurological impairments (such as <a href="/facts/Extrapyramidal_symptom/5d3lLrto">extrapyramidal side effects</a> which include <a href="/facts/Dystonia/j0jeA0XD">dystonia</a>, <a href="/facts/Akathisia/hFUb0Uqr">akathisia</a>, <a href="/facts/Parkinsonism/orfkyX69">parkinsonism</a>, muscle rigidity, etc.)</li> <li>Anticholinergic side effects such as:</li></ul> <ul><li>Blurred vision</li> <li>Constipation</li> <li>Dry mouth</li> <li>Nasal congestion</li></ul> <ul><li>Increased appetite</li> <li>Weight gain</li> <li>Nausea</li> <li>Dizziness</li> <li>Headache</li> <li>Vomiting</li></ul> Unknown frequency adverse effects include <a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> <ul><li>Diarrhoea</li> <li><a href="/facts/Alopecia/uEPKUafl">Alopecia</a></li> <li>Photophobia</li> <li>Pigmentation</li> <li>Eczema up to exfoliative dermatitis</li> <li>Urticaria</li> <li>Erythema</li> <li>Itching</li> <li><a href="/facts/Photosensitivity/dohEzKCm">Photosensitivity</a></li> <li>Hypersalivation</li> <li><a href="/facts/Hyperprolactinaemia/cTdwMNlP">Hyperprolactinaemia</a> — This may present with the following symptoms:</li></ul> <ul><li><a href="/facts/Galactorrhea/tB5rDh0B">Galactorrhea</a></li> <li><a href="/facts/Gynaecomastia/8VkLDnGD">Gynaecomastia</a></li> <li>Disturbances in menstrual cycle</li> <li>Sexual dysfunction</li></ul> <ul><li>Pigmentation of the cornea and lens</li> <li>Hyperglycaemia</li> <li>Hypoglycaemia</li> <li>Disturbed concentration</li> <li>Excitement</li> <li>Anxiety</li> <li>Insomnia</li> <li>Restlessness</li> <li>Nightmares</li> <li>Weakness</li> <li>Fatigue</li> <li>Diaphoresis — excessive/abnormal sweating.</li></ul> Uncommon/Rare adverse effects include <a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> <ul><li><a href="/facts/Tardive_dyskinesia/IAR6aJBJ">Tardive dyskinesia</a>, 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 <i>tardive</i>), involuntary, repetitive, purposeless muscle movements.</li> <li><a href="/facts/Neuroleptic_malignant_syndrome/g80RuABy">Neuroleptic malignant syndrome</a>, a potentially fatal complication of antipsychotic drug use. It is characterised by the following symptoms:</li></ul> <ul><li>Muscle rigidity</li> <li>Tremors</li> <li>Mental status change (e.g., hallucinations, agitation, stupor, confusion, etc.)</li> <li>Hyperthermia</li> <li>Autonomic instability (e.g., tachycardia, high blood pressure, diaphoresis, diarrhoea, etc.)</li></ul> <ul><li><a href="/facts/Urinary_retention/YvTCprKk">Urinary retention</a></li> <li>Blood dyscrasias, e.g., <a href="/facts/Agranulocytosis/3AP5MDpD">agranulocytosis</a> (a potentially fatal drop in white blood cell count), <a href="/facts/Leukopenia/LB1Avvby">leukopaenia</a> (a drop in white blood cell counts but not to as extreme an extent as agranulocytosis), <a href="/facts/Neutropaenia/qasEurVu">neutropaenia</a> (a drop in neutrophil count), <a href="/facts/Thrombocytopaenia/qMy4o0Rz">thrombocytopaenia</a> (a dangerous drop in platelet counts), <a href="/facts/Eosinophilia/RkFrKK10">eosinophilia</a> (raised eosinophil count), <a href="/facts/Purpura/bz0qayUG">purpura</a> (the appearance of red or purple discolourations of the skin that do not blanch when pressure is applied)</li> <li><a href="/facts/Hepatitis/FIN87T5e">Hepatitis</a></li> <li>Jaundice</li> <li>Pigmentary retinopathy</li> <li>Anaphylactoid reactions</li> <li><a href="/facts/Oedema/Q6MI3KdH">Oedema</a></li> <li>Asthma</li> <li>Coma</li> <li>Seizures</li> <li>Confusional states</li> <li>Disorientation</li> <li>Incoordination</li> <li>Ataxia</li> <li>Tremors</li> <li><a href="/facts/Peripheral_neuropathy/2KjA7nyD">Peripheral neuropathy</a></li> <li>Numbness, tingling and paresthesias of the extremities</li> <li><a href="/facts/Dysarthria/UQFqqkvH">Dysarthria</a></li> <li><a href="/facts/Syndrome_of_inappropriate_antidiuretic_hormone_secretion/4sb69yBM">Syndrome of inappropriate antidiuretic hormone secretion</a> (SIADH)</li> <li><a href="/facts/Tinnitus/QNjx4EJp">Tinnitus</a></li> <li>Alteration in EEG patterns</li> <li><a href="/facts/Paralytic_ileus/1rMI0juo">Paralytic ileus</a></li> <li>Hyperpyrexia (elevated body temperature)</li> <li>Disturbance of accommodation</li> <li>Increased intraocular pressure</li> <li>Mydriasis</li></ul> <h2 id="pharmacology">Pharmacology</h2> <p class="note">See also: <a href="/facts/Amitriptyline/7YGkJGfr">Amitriptyline § Pharmacology</a>, and <a href="/facts/Perphenazine/rf2wAucn">Perphenazine § Pharmacology</a></p> <p>Binding affinities (Ki [nM]; for human cloned receptors when available)<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> </p> <table><tbody><tr><th>Molecular target</th><th>Amitriptyline</th><th><a href="/facts/Nortriptyline/predd7gA">Nortriptyline</a> (Amitriptyline's active metabolite)</th><th>Perphenazine</th><th>Notes</th></tr><tr><td><a href="/facts/Serotonin_transporter/VPh5wtCy">SERT</a></td><td>3.13</td><td>16.5</td><td>?</td><td>It is this and its NET-inhibiting action is believed to give amitriptyline its antidepressant action.</td></tr><tr><td><a href="/facts/Norepinephrine_transporter/532N8LIg">NET</a></td><td>22.4</td><td>4.37</td><td>?</td><td>See above.</td></tr><tr><td><a href="/facts/Dopamine_transporter/V9I2Uy1p">DAT</a></td><td>5380</td><td>3100</td><td>?</td><td></td></tr><tr><td><a href="/facts/5-HT1A_receptor/aMCB3tvc">5-HT1A</a></td><td>450</td><td>294</td><td>421</td><td>Binding for human brain receptors had to be substituted in amitriptyline (AMI) and nortriptyline's (NOR) cases</td></tr><tr><td><a href="/facts/5-HT2A_receptor/YfTglQKQ">5-HT2A</a></td><td>4.3</td><td>5</td><td>5.6</td><td>Binding for cloned rat receptors had to be substituted for AMI & NOR. Binding to this receptor is believed to be what gives the newer (<i>atypical</i>) antipsychotics, <a href="/facts/Clozapine/N0Lqztg1">clozapine</a>, <a href="/facts/Quetiapine/hI3hPqEH">quetiapine</a>, <a href="/facts/Olanzapine/8BhqJuPM">olanzapine</a>, <a href="/facts/Ziprasidone/armf6BDh">ziprasidone</a>, <a href="/facts/Risperidone/xpFEYzoF">risperidone</a>, <a href="/facts/Sertindole/HzAlM7W9">sertindole</a> and <a href="/facts/Zotepine/9pU3XXYj">zotepine</a> their lower extrapyramidal side effect (EPS) liability.</td></tr><tr><td><a href="/facts/5-HT2C_receptor/RuyLstWf">5-HT2C</a></td><td>6.15</td><td>8.5</td><td>132</td><td>(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.</td></tr><tr><td><a href="/facts/5-HT6_receptor/2QQJ7upp">5-HT6</a></td><td>103</td><td>148</td><td>17</td><td>Cloned rat receptor was substituted for NOR's binding.</td></tr><tr><td><a href="/facts/5-HT7_receptor/rcpLc6FL">5-HT7</a></td><td>114</td><td>?</td><td>23</td><td>Cloned rat receptor was substituted for AMI.</td></tr><tr><td><a href="/facts/Alpha-1A_adrenergic_receptor/R6Qr1DF5">α1A</a></td><td>24</td><td>55</td><td>10</td><td>Human brain receptors were substituted for AMI and NOR.</td></tr><tr><td><a href="/facts/Alpha-2A_adrenergic_receptor/csNJEymK">α2A</a></td><td>690</td><td>2030</td><td>810.5</td><td>As above.</td></tr><tr><td><a href="/facts/Dopamine_D2_receptor/SmmP3QyU">D2</a></td><td>1460</td><td>2570</td><td>0.16</td><td>As above.</td></tr><tr><td><a href="/facts/Dopamine_D3_receptor/e1L1KnJq">D3</a></td><td>206</td><td>?</td><td>0.13</td><td>Human receptors (their source was undefined) had to be substituted for AMI.</td></tr><tr><td><a href="/facts/Histamine_H1_receptor/L6DzvF7A">H1</a></td><td>1.1</td><td>15.1</td><td>8</td><td>This 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.</td></tr><tr><td><a href="/facts/Muscarinic_acetylcholine_receptor_M1/ne0YBBqI">M1</a></td><td>12.9</td><td>40</td><td>1500</td><td>This is the main receptor responsible for the anticholinergic side effects mentioned above.</td></tr><tr><td><a href="/facts/Muscarinic_acetylcholine_receptor_M3/LNq0EXqE">M3</a></td><td>25.9</td><td>50</td><td>1848</td><td>This receptor is believed to be partly responsible for the metabolic adverse effects of the <a href="/facts/Atypical_antipsychotics/PQYUYXMu">atypical antipsychotics</a>.</td></tr><tr><td><a href="/facts/Sigma_receptor/JpFeF344">σ</a></td><td>300</td><td>2000</td><td>31.5</td><td>All three values are for binding to the guinea pig brain receptors.</td></tr></tbody></table> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Flupentixol%2fmelitracen/aXmXzq7d">Flupentixol/melitracen</a></li> <li><a href="/facts/Olanzapine%2ffluoxetine/4ug300tF">Olanzapine/fluoxetine</a></li> <li><a href="/facts/Tranylcypromine%2ftrifluoperazine/X4axzcjY">Tranylcypromine/trifluoperazine</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Mylan Pharmaceuticals Inc.]". DailyMed. National Library of Medicine. Retrieved 7 October 2013. <a href="http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e2937445-c015-c9a5-52f8-a2959da97290" target="_blank">http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e2937445-c015-c9a5-52f8-a2959da97290</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet [REMEDYREPACK INC. ]". DailyMed. National Library of Medicine. Retrieved 7 October 2013. <a href="http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ca5598e4-4226-45ab-abd1-e961707ae457" target="_blank">http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ca5598e4-4226-45ab-abd1-e961707ae457</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Mylan Pharmaceuticals Inc.]". DailyMed. National Library of Medicine. 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Available from: http://reference.medscape.com/drug/etrafon-triptafen-amitriptyline-perphenazine-342946 <a href="http://reference.medscape.com/drug/etrafon-triptafen-amitriptyline-perphenazine-342946" target="_blank">http://reference.medscape.com/drug/etrafon-triptafen-amitriptyline-perphenazine-342946</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>"PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Mylan Pharmaceuticals Inc.]". DailyMed. National Library of Medicine. Retrieved 7 October 2013. <a href="http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e2937445-c015-c9a5-52f8-a2959da97290" target="_blank">http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e2937445-c015-c9a5-52f8-a2959da97290</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>"PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet [REMEDYREPACK INC. ]". DailyMed. National Library of Medicine. 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