tricyclic antidepressant (TCA)
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Indications
Contraindications
- avoid use within 6 months of coronary syndrome
Dosage
Pharmacokinetics
- metabolism by cyt P450 2D6 > 2C9, 2C10, 2C19
- slow onset of action with several weeks to achieve full effects
Adverse effects
- anticholinergic effects
- tinnitus
- constipation
- confusion
- mydriasis
- tachycardia
- in general, NOT a good class of agents for the elderly
- arrhythmic effects[3][5]
- overdose results in prolongation of the QT interval
- patients with a bundle branch block are at higher risk
- risk of torsades de pointes
- avoid use within 6 months of coronary syndrome
- cholinergic symptoms with abrupt withdrawal
- increased risk of seizures[2]
- orthostatic hypotension
- galactorrhea, hyperprolactinemia[3]
- clinical manifestations
- progressive somnolence, hypotension, widened QRS interval, seizures, & parasympatholytic signs (fever, tachycardia, mydriasis, diminished peristalsis)
- case report of cardiac arrest in a young woman with irregular, wide-complex rhythm, & a QRS width of up to 220 msec[6]
- management
- early endotracheal intubation, hyperventilation
- fluid resusitation
- gastric lavage followed by activated charcoal even with delayed presentation
- EKG monitoring: QRS complex > 100 msec predicts seizures
- bicarbonate
- bolus 1-2 meq/kg every 3-5 minutes until QRS complex narrows or blood pressure improves
- bicarbonate drip titrated to QRS width & blood pressure
- monitor serum K+, signs of fluid overload
- norepinephrine for hypotension not responsive to bicarbonate
- lidocaine for ventricular arrhythmias
- benzodiazepines for seizures
- avoid phenytoin
- propofol or barbiturates for refractory seizures
- drug adverse effects of tricyclic antidepressants
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- TCA may potentiate adverse effects of opiate agonists
- flumazenil (Romazicon) may potentiate toxic effects of TCA
- TCA block the uptake of guanethidine, guanadrel
- TCA inhibit the action of centrally-acting antihypertensives:
- alpha-methyldopa
- SSRI: paroxetine, fluoxetine (metabolized by same P450s)
- class 1A antiarrhythmic agents
- effects additive with EtOH
- drug interaction(s) of tricyclic antidepressants with physostigmine
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of antidepressant with opiates
Laboratory
- CYPD2D6 genotyping may be indicated
- CYPD2C19 genotyping may be indicated
- tricyclic antidepressants in specimen
- tricyclic antidepressants in blood (suspected overdose)
- may increase plasma metanephrine & plasma normetanephrine[7]
Mechanism of action
- Histamine H1 antagonist
- serotonin antagonist
- alpha-1-adrenergic receptor antagonist
- nortriptyline, its metabolite, is a norepinephrine reuptake inhibitor
More general terms
More specific terms
- amitriptyline (Elavil, Endep)
- amoxapine (Asendin)
- clomipramine (Anafranil)
- desipramine (Norpramin, Pertofrane)
- dothiepin (Prothiaden)
- doxepin (Sinequan, Adapin, Zonalon, Silenor)
- imipramine (Tofranil, Janimine)
- maprotiline (Ludiomil)
- nortriptyline (Aventyl, Pamelor)
- protriptyline (Vivactil, Concordin)
- tianeptine
- trimipramine (Surmontil)
Additional terms
- amitriptyline/chlordiazepoxide (Limbitrol)
- amitriptyline/perphenazine (Etrafon, Triavil)
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
- tricyclic antidepressants (TCA) in serum/plasma
References
- ↑ 1.0 1.1 Journal Watch 23(1):11, 2003 Furukawa TA et al, Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review BMJ 325:991, 2002 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12411354 <Internet> http://bmj.com/cgi/content/full/325/7371/991
- ↑ 2.0 2.1 Medications Can Cause Seizures Prescriber's Letter 10(3):16 2003 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=190320&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 3.0 3.1 3.2 Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 18 American College of Physicians, Philadelphia 2006, 2009, 2012, 2018.
- ↑ The Washington Manual of Medical Therapeutics, 33rd edition Foster C et al (eds) Lippincott, Williams & Wilkins, Philadelphia, 2010, pg 957
- ↑ 5.0 5.1 Body R, Bartram T, Azam F, Mackway-Jones K. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J. 2011 Apr;28(4):347-68 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21436332
- ↑ 6.0 6.1 Goldstein JN, Dudzinski DM, Erickson TB, Linder G. Case 12-2018: A 30-Year-Old Woman with Cardiac Arrest. N Engl J Med 2018; 378:1538-1549. April 19, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29669228 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcpc1800322
- ↑ 7.0 7.1 NEJM Knowledge+ Question of the Week. December 18, 2018 https://knowledgeplus.nejm.org/question-of-week/803/