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- a tricyclic antidepressant drug (trade name Elavil) with serious side effects; interacts with many other medications (同)amitriptyline_hydrochloride, Elavil
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/08 11:36:52」(JST)
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| Systematic (IUPAC) name | |
|---|---|
| 3-(10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine | |
| Clinical data | |
| Trade names | Amitrip, Elavil, Endep, Levate |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a682388 |
| Licence data | US FDA:link |
| Pregnancy cat. |
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| Legal status |
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| Routes | Oral, intramuscular |
| Pharmacokinetic data | |
| Bioavailability | 30–60% due to first pass metabolism |
| Protein binding | 96%[1][2][3][4] |
| Metabolism | Hepatic (CYP2D6)[1][2][3][4] |
| Half-life | 22.4 hr (26 hr for active metabolite, nortriptyline)[1][2][3][4] |
| Excretion | Renal[1][2][3][4] |
| Identifiers | |
| CAS number | 50-48-6 Y 549-18-8 (hydrochloride) |
| ATC code | N06AA09 |
| PubChem | CID 2160 |
| IUPHAR ligand | 200 |
| DrugBank | DB00321 |
| ChemSpider | 2075 Y |
| UNII | 1806D8D52K Y |
| KEGG | D07448 Y |
| ChEBI | CHEBI:2666 Y |
| ChEMBL | CHEMBL629 Y |
| Chemical data | |
| Formula | C20H23N |
| Mol. mass | 277.403 g/mol |
|
SMILES
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InChI
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| Y (what is this?) (verify) | |
Amitriptyline /ˌæmɪˈtrɪptɪliːn/[5] (Elavil, Endep, Levate and many others) is a tricyclic antidepressant (TCA). It is the most widely used TCA.
It is used to treat a number of mental disorders including: major depressive disorder, anxiety, and less commonly psychosis, attention deficit hyperactivity disorder, and bipolar disorder. Other uses include: prevention of migraines and post herpetic neuralgia and less commonly insomnia.[6]
Side effects may include: seizures, an increased risk of suicide in those less than 25 years of age, urinary retention, and a number of heart issues. They should not be taken with MAO inhibitors or cisapride.[6] In the United States and Australia they are pregnancy category C which means that may cause problems during pregnancy.[7] Use during breastfeeding does not appear to be a problem.[8]
It was originally developed by Merck, first synthesised in 1960 and was first approved by the United States Food and Drug Administration (FDA) on 7 April 1961.[9][10] It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[11]
Contents
- 1 Medical uses
- 1.1 Investigational uses
- 2 Adverse effects
- 2.1 Common (≥1% frequency)
- 2.2 Uncommon (0.1–1% frequency)
- 2.3 Rare (<0.1% frequency)
- 2.4 Unknown frequency
- 2.5 Contraindications
- 2.6 Interactions
- 2.7 Overdose
- 3 Mechanism of action
- 4 Pharmacokinetics
- 5 Pharmacogenetics
- 6 Brand names
- 7 Synthesis
- 8 See also
- 9 Notes
- 10 References
- 11 Further reading
Medical uses
Amitriptyline is used for a number of medical conditions including major depressive disorder (MDD) which is its only FDA-labeled indication.[1] This is also a TGA- and MHRA-labelled indication.[12][13] Some evidence suggests that amitriptyline may have superior efficacy compared to other antidepressants,[14] including the SSRIs,[15] although it is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants such as the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).[12]
It is TGA-labeled for migraine prophylaxis, as it is also is in cases of neuropathic pain disorders,[12] fibromyalgia[16] and nocturnal enuresis.[12][17] Amitriptyline is a popular off-label treatment for irritable bowel syndrome.[18] Although it is most frequently reserved for severe cases of abdominal pain in patients with IBS due to the fact that it needs to be taken regularly to work and has a generally poor tolerability profile, although a firm evidence base supports its efficacy in this indication.[18] Amitriptyline can also be used as an anticholinergic drug in the treatment of early stage Parkinson disease if depression also needs to be treated.[19]
Investigational uses
- Eating disorders[2] The few randomized controlled trials investigating its efficacy in eating disorders have been discouraging.[20]
- Pseudobulbar affect. A new agent containing a combination of dextromethorphan and quinidine is currently under development for the treatment of pseudobulbar affect.[21]
- Insomnia. Owing to the development of tolerance and the potential for adverse effects such as constipation, its use in the elderly for this indication is recommended against.[12]
- Urinary incontinence. An accepted use for amitriptyline in Australia is the treatment of urinary urge incontinence.[12]
- Cyclic vomiting syndrome[22][23]
- Tinnitus[24]
- Chronic cough[25]
- Preventive treatment for patients with recurring biliary dyskinesia (sphincter of Oddi dysfunction)[26]
- Attention deficit/hyperactivity disorder (in addition to, or sometimes in place of ADHD stimulant drugs)[27]
Adverse effects
Adverse effects include the following:[1][2][3][4][12][13]
Common (≥1% frequency)
- Weight gain
- Anticholinergic side effects (it tends to produce more anticholinergic effects than the other TCAs) such as:
- Constipation
- Xerostomia (dry mouth)
- Mydriasis (dilated pupils)
- Blurred vision
- Urinary hesitancy
- Reduced GI motility
- Anticholinergic delirium (particularly in the elderly and in Parkinson's disease)
- Dizziness
- Headache
- Somnolence (drowsiness) it tends to be a more sedating TCA.[28][29]
- Decreased lacrimation
- Orthostatic hypotension
- Sinus tachycardia
- Impotence
- Loss of libido
- Other sexual adverse effects
- Tremor
- Sweating
- Agitation
- Insomnia
- Anxiety
- Confusion
Uncommon (0.1–1% frequency)
- Slowed cardiac conduction
- T wave inversion or flattening (particularly at high doses)
- Arrhythmias
- Sinus tachycardia
- Nausea
- Hyperglycemia
- Gynaecomastia (breast enlargement in men)
- Breast enlargement and galactorrhoea (milk leakage) in females
- Allergic skin reactions
- Mania
- Hypomania
Rare (<0.1% frequency)
- Cardiomyopathy
- Hepatitis
- Liver failure
- Jaundice
- Lupus-like syndrome (migratory arthritis, positive ANA and rheumatoid factor)
- Hypotension (low blood pressure)
- Syncope (fainting)
- Hypertension
- Tachycardia
- Palpitations
- Myocardial infarction
- Heart block
- Stroke
- Agranulocytosis
- Leukopaenia
- Thrombocytopaenia
- Purpura
- Eosinophilia
- Neuroleptic malignant syndrome
Unknown frequency
- Hypoglycaemia
- Skin rash
- Urticaria (hives)
- Photosensitization
- Oedema
- Seizures
- Testicular swelling
- Increased or decreased libido
- Urinary retention
- Dilatation of the urinary tract
- Disturbance of accommodation[clarification needed]
- Increased intraocular pressure
- Paralytic ileus
- Epigastric distress
- Stomatitis
- Peculiar taste
- Parotid swelling
- Black tongue
- Alopecia (hair loss)
- Urinary frequency
- Diaphoresis
- Myocardial infarction
- Coma
- Hallucinations
- Delusions
- Weight loss
- Weakness
- Fatigue
- Headache
- Increased perspiration
- Urinary frequency
- Confusional states
- Disorientation
- Incoordination
- Ataxia
- Tremors
- Peripheral neuropathy
- Numbness
- Tingling
- Paraesthesias
- Extrapyramidal symptoms
- Tardive dyskinesia
- Dysarthria
- Disturbed concentration
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Hyponatraemia
- Tinnitus (ringing in the ears)
- Alteration in EEG patterns
Contraindications
The following are the known contraindications of amitriptyline.[4]
- Hypersensitivity to tricyclic antidepressants or to any of its excipients
- History of myocardial infarction
- History of arrhythmias, particularly heart block to any degree
- congestive heart failure
- Coronary artery insufficiency
- Mania
- Severe liver disease
- Children under 7 years
- Breast feeding
- Patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.
Interactions
Amitriptyline is known to interact with:[3]
- Monoamine oxidase inhibitors as it can potentially induce a serotonin syndrome
- CYP2D6 inhibitors and substrates such as fluoxetine due to the potential for an increase in plasma concentrations of the drug to be seen.
- Guanethidine — as it can reduce the antihypertensive effects of this drug.
- Anticholinergic agents such as benztropine, hyoscine (scopolamine) and atropine. Due to the fact that the two might exacerbate each other's anticholinergic effects, including paralytic ileus and tachycardia.
- Antipsychotics due to the potential for them to exacerbate the sedative, anticholinergic, epileptogenic and pyrexic (fever-promoting) effects. Also increases the risk of neuroleptic malignant syndrome
- Cimetidine due to the potential for it to interfere with hepatic metabolism of amitriptyline and hence increasing steady-state concentrations of the drug.
- Disulfiram due to the potential for the development of delirium
- ECT may increase the risks associated with this treatment
- Antithyroid medications — may increase the risk of agranulocytosis
- Thyroid hormones — potential for increased adverse effects such as CNS stimulation and arrhythmias.
- Analgesics, such as tramadol due to the potential for an increase in seizure risk.
- Medications that are subject to gastric inactivation (e.g. levodopa) due to the potential for amitriptyline to delay gastric emptying and reduce intestinal motility
- Medications that may be subject to increased absorption given more time in the small intestine (e.g. anticoagulants)
- Serotoninergic agents such as the SSRIs and triptans due to the potential for serotonin syndrome.
Overdose
Main article: Tricyclic antidepressant overdose
The symptoms and the treatment of an overdose are largely the same as for the other TCAs, including the presentation of serotonin syndrome and adverse cardiac effects. The British National Formulary notes that amitriptyline can be particularly dangerous in overdose,[13] thus it and other tricyclic antidepressants are no longer recommended as first line therapy for depression. Alternative agents, SSRIs and SNRIs are safer in overdose, though they are no more efficacious than TCAs. English folk singer, Nick Drake, died from an overdose of Tryptizol in 1974.
The possible symptoms of amitriptyline overdose include:[3]
- Drowsiness
- Hypothermia (low body temperature)
- Tachycardia (high heart rate)
- Other arrhythmic abnormalities, such as bundle branch block
- ECG evidence of impaired conduction
- Congestive heart failure
- Dilated pupils
- Convulsions (e.g. seizures, myoclonus)
- Severe hypotension (very low blood pressure)
- Stupor
- Coma
- Polyradiculoneuropathy
- Changes in the electrocardiogram, particularly in QRS axis or width
- Agitation
- Hyperactive reflexes
- Muscle rigidity
- Vomiting
The treatment of overdose is mostly supportive as there is no specific antidote for amitriptyline overdose.[3] Activated charcoal may reduce absorption if given within 1–2 hours of ingestion.[3] If the affected person is unconscious or have an impaired gag reflex a nasograstic tube may be used to deliver the activated charcoal in the stomach.[3] ECG monitoring for cardiac conduction abnormalities is essential and if one is found close monitoring of cardiac function is advised.[3] Body temperature should be regulated with measures such as heating blankets if necessary.[3] Likewise cardiac arrhythmias can be treated with propanolol and should heart failure occur digitalis may be used.[3] Cardiac monitoring is advised for at least five days after the overdose.[3] Amitriptyline increases the CNS depressant action but not the anticonvulsant action of barbiturates; therefore, an inhalation anaesthetic or diazepam is recommended for control of convulsions.[3] Dialysis is of no use due to the high degree of protein binding with amitriptyline.[3]
Mechanism of action
| Receptor | Ki [nM][Note 1] (amitriptyline)[30][29] |
Ki [nM][Note 2] (nortriptyline)[29][30] |
|---|---|---|
| SERT | 3.13 | 16.5 |
| NET | 22.4 | 4.37 |
| DAT | 5380 | 3100 |
| 5-HT1A | 450 | 294 |
| 5-HT1B | 840 | - |
| 5-HT2A | 4.3 | 5 |
| 5-HT2C | 6.15 | 8.5 |
| 5-HT6 | 103 | 148 |
| 5-HT7 | 114 | - |
| H1 | 1.1 | 15.1 |
| H3 | 1000 | - |
| H4 | 33.6 | - |
| M1 | 12.9 | 40 |
| M2 | 11.8 | 110 |
| M3 | 25.9 | 50 |
| M4 | 7.2 | 84 |
| M5 | 19.9 | 97 |
| α1 | 24 | 55 |
| α2 | 690 | 2030 |
| D1 | 89 | - |
| D2 | 1460 | 2570 |
| D3 | 206 | - |
| D5 | 170 | - |
| σ | 300 | 2000 |
Amitriptyline acts primarily as a serotonin-norepinephrine reuptake inhibitor, with strong actions on the serotonin transporter and moderate effects on the norepinephrine transporter.[31][32] It has negligible influence on the dopamine transporter and therefore does not affect dopamine reuptake, being nearly 1,000 times weaker on it than on serotonin.[32] It is metabolised to nortriptyline — a more potent and selective norepinephrine reuptake inhibitor — which may complement its effects on norepinephrine reuptake.[3]
Amitriptyline additionally functions as a 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, α1-adrenergic, H1, H2,[33] H4,[34][35] and mACh receptor antagonist, and σ1 receptor agonist.[36][37][38][39] It has also been shown to be a relatively weak NMDA receptor negative allosteric modulator at the same binding site as phencyclidine.[40] Amitriptyline inhibits sodium channels, L-type calcium channels, and Kv1.1, Kv7.2, and Kv7.3 voltage-gated potassium channels, and therefore acts as a sodium, calcium, and potassium channel blocker as well.[41][42]
Recently, amitriptyline has been demonstrated to act as an agonist of the TrkA and TrkB receptors.[43] It promotes the heterodimerization of these proteins in the absence of NGF and has potent neurotrophic activity both in-vivo and in-vitro in mouse models.[43][44] These are the same receptors BDNF activates, an endogenous neurotrophin with powerful antidepressant effects, and as such this property may contribute significantly to its therapeutic efficacy against depression. Amitriptyline also acts as FIASMA (functional inhibitor of acid sphingomyelinase).[45]
Pharmacokinetics
Nortriptyline, amitriptyline's chief active metabolite
Amitriptyline is readily absorbed from the gastrointestinal tract and is extensively metabolised on first-pass through the liver.[3] It is metabolised mostly via CYP2D6, CYP3A4, CYP2C19-mediated N-demethylation into nortriptyline,[3] which is another tricyclic antidepressant in its own right.[46] It is 96% bound to plasma proteins, nortriptyline is 93-95% bound to plasma proteins.[3][47] It is mostly excreted in the urine (around 30-50%) as metabolites either free or as glucuronide and sulfate conjugates.[3] Small amounts are also excreted in faeces.[2]
Pharmacogenetics
Since amitriptyline is primarily metabolized via CYP2D6 and CYP2C19, genetic variations within the genes coding for these enzymes can affect its metabolism, leading to changes in the concentrations of the drug in the body.[48] Increased concentrations of amitriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drug's efficacy.[49][50][51]
Individuals can be categorized into different types of CYP2D6 or CYP2C19 metabolizers depending on which genetic variations they carry. These metabolizer types include poor metabolizers, intermediate metabolizers, extensive metabolizers and ultrarapid metabolizers. Most individuals (~77 - 92%) are extensive metabolizers,[51] and have "normal" metabolism of amitriptyline. Poor and intermediate metabolizers have reduced metabolism of the drug as compared to extensive metabolizers - patients with these metabolizer types have an increased probability of experiencing side effects. Ultrarapid metabolizers metabolize amitriptyline much faster than extensive metabolizers - patients with this metabolizer type may have a greater chance of experiencing pharmacological failure.[49][50][51]
The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends avoiding amitriptyline in patients who are CYP2D6 ultrarapid or poor metabolizers, due to the risk for a lack of efficacy and side effects, respectively. The consortium also recommends considering an alternative drug not metabolized by CYP2C19 in patients who are CYP2C19 ultrarapid metabolizers. A reduction in starting dose is recommended for patients who are CYP2D6 intermediate metabolizers and CYP2C19 poor metabolizers. If use of amitriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments.[51] The Dutch Pharmacogenetics Working Group also recommends selecting an alternative drug or monitoring plasma concentrations of amitriptyline in patients who are CYP2D6 poor or ultrarapid metabolizers, and selecting an alternative drug or reducing initial dose in patients who are CYP2D6 intermediate metabolizers.[52]
Brand names
Brand names include (just including those used in English-speaking countries with † to indicate discontinued brands):[46][53]
- Amirol (NZ)
- Amit (IN)
- Amitone (IN)
- Amitor (IN)
- Amitrip (AU,† IN, NZ)
- Amitriptyline (UK)
- Amitriptyline Hydrochloride Caraco (US)
- Amitriptyline Hydrochloride Mutual (US)
- Amitriptyline Hydrochloride Mylan (US)
- Amitriptyline Hydrochloride Sandoz (US)
- Amitriptyline Hydrochloride Vintage (US)
- Amitriptyline Hydrochloride (UK)
- Amitrol† (AU)
- Amrea (IN)
- Amypres (IN)
- Apo-Amitriptyline (CA, HK, SG)
- Crypton (IN)
- Elavil (CA, UK,† US†)
- Eliwel (IN)
- Endep (AU, HK,† ZA,† US†)
- Enovil† (US)
- Gentrip (IN)
- Kamitrin (IN)
- Latilin (IN)
- Levate (US)
- Maxitrip (IN)
- Mitryp (IN)
- Mitryp-10 (IN)
- Odep (IN)
- Qualitriptine (HK)
- Sandoz Amitriptyline (ZA)
- Saroten (CH)
- Sarotena (IN)
- Tadamit (IN)
- Trepiline (ZA)
- Tripta (SG)
- Tryptanol (ZA)
- Tryptomer (IN)
Synthesis
Amitriptyline synthesis 1:[54][55][56] GB 858187 GB 858188 BE 584061
Amitriptyline synthesis 2: U.S. Patent 3,205,264 DE 1468138
See also
- Octriptyline
- Nortriptyline
- Cyclobenzaprine
- Tricyclic antidepressant
Notes
- ^ These Ki values are averaged binding affinities towards cloned human receptors when available.
- ^ As with amitriptyline, these Kivalues are averaged binding affinities towards cloned human receptors when available.
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- ^ a b Jang SW, Liu X, Chan CB, Weinshenker D, Hall RA, Xiao G, Ye K (June 2009). "Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity". Chem. Biol. 16 (6): 644–56. doi:10.1016/j.chembiol.2009.05.010. PMC 2844702. PMID 19549602.
- ^ "Pharmaceutical Information - AMITRIPTYLINE". RxMed. Retrieved 2013-02-16.
- ^ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer TW, Spitzer GM, Liedl KR, Gulbins E, Tripal P (2011). "Identification of novel functional inhibitors of acid sphingomyelinase". In Riezman, Howard. PLoS ONE 6 (8): e23852. doi:10.1371/journal.pone.0023852. PMC 3166082. PMID 21909365.
- ^ a b "Amitriptyline". Martindale: The Complete Drug Reference (London, UK: Pharmaceutical Press). 30 January 2013. Retrieved 2 December 2013.
- ^ "Pamelor, Aventyl (nortriptyline) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 2 December 2013.
- ^ Rudorfer MV, Potter WZ (1999). "Metabolism of tricyclic antidepressants". Cell Mol Neurobiol 19 (3): 373–409. PMID 10319193.
- ^ a b Stingl JC, Brockmoller J, Viviani R (2013). "Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function". Mol Psychiatry 18 (3): 273–87. doi:10.1038/mp.2012.42. PMID 22565785.
- ^ a b Kirchheiner J, Seeringer A (2007). "Clinical implications of pharmacogenetics of cytochrome P450 drug metabolizing enzymes". Biochim Biophys Acta 1770 (3): 489–94. PMID 17113714.
- ^ a b c d Hicks JK, Swen JJ, Thorn CF, Sangkuhl K, Kharasch ED, Ellingrod VL, Skaar TC, Muller DJ, Gaedigk A, Stingl JC (2013). "Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants". Clinical Pharmacology & Therapeutics 93 (5): 402–8. doi:10.1038/clpt.2013.2. PMC 3689226. PMID 23486447.
- ^ Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, Rongen GA, van Schaik RH, Schalekamp T, Touw DJ, van der Weide J, Wilffert B, Deneer VH, Guchelaar HJ (2011). "Pharmacogenetics: from bench to byte--an update of guidelines". Clinical Pharmacology & Therapeutics 89 (5): 662–73. doi:10.1038/clpt.2011.34. PMID 21412232.
- ^ "Amitriptyline". Drugs.com. Retrieved 2 December 2013.
- ^ Hoffsommer, R. D.; Taub, D.; Wendler, N. L. (1965). "Coupling Reactions in the Synthesis of Amitriptyline". Journal of Medicinal Chemistry 8 (4): 555. doi:10.1021/jm00328a042. PMID 5884168. edit
- ^ Hoffsommer, R. D.; Taub, D.; Wendler, N. L. (1962). "The Homoallylic Rearrangement in the Synthesis of Amitriptyline and Related Systems". The Journal of Organic Chemistry 27 (12): 4134. doi:10.1021/jo01059a004. edit
- ^ Hoffsommer, R. D.; Taub, D.; Wendler, N. L. (1963). "Synthesis of Amitriptyline and Related Substances. Hydroboration of 5-Allylidene-5H-dibenzo[a,d]-10,11-dihydrocycloheptene". The Journal of Organic Chemistry 28 (7): 1751. doi:10.1021/jo01042a004. edit
Further reading
- PubChem Substance Summary: Amitriptyline National Center for Biotechnology Information.
- TREPILINE-10 TABLETS; TREPILINE-25 TABLETS South African Electronic Package Inserts. 12 May 1978. Revised February 2004.
- SAROTEN RETARD 25 mg Capsules; SAROTEN RETARD 50 mg Capsules South African Electronic Package Inserts. December 1987. Updated May 2000.
- AMITRIP Amitriptyline hydrochloride 10 mg, 25 mg and 50 mg Capsules Medsafe NZ Physician Data Sheet. November 2004.
- Endep Consumer Medicine Information, Australia. December 2005.
- MedlinePlus Drug Information: Amitriptyline. US National Institutes of Health. January 2008.
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UpToDate Contents
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- 1. 三環系抗うつ剤および四環系抗うつ剤：薬理学、投与、および副作用 tricyclic and tetracyclic drugs pharmacology administration and side effects
- 2. 化学療法誘発性末梢神経障害の予防および治療 prevention and treatment of chemotherapy induced peripheral neuropathy
- 3. 成人における初期治療の効果がない線維筋痛症の治療 treatment of fibromyalgia in adults not responsive to initial therapies
- 4. 成人における線維筋痛症の初期治療 initial treatment of fibromyalgia in adults
- 5. ファブリー病の神経症状 neurologic manifestations of fabry disease
English Journal
- New sorbent in the dispersive solid phase extraction step of quick, easy, cheap, effective, rugged, and safe for the extraction of organic contaminants in drinking water treatment sludge.
- Cerqueira MB1, Caldas SS1, Primel EG2.Author information 1Escola de Química e Alimentos, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil.2Escola de Química e Alimentos, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil. Electronic address: eprimelfurg@gmail.com.AbstractRecent studies have shown a decrease in the concentration of pesticides, pharmaceuticals and personal care products (PCPs) in water after treatment. A possible explanation for this phenomenon is that these compounds may adhere to the sludge; however, investigation of these compounds in drinking water treatment sludge has been scarce. The sludge generated by drinking water treatment plants during flocculation and decantation steps should get some special attention not only because it has been classified as non-inert waste but also because it is a very complex matrix, consisting essentially of inorganic (sand, argil and silt) and organic (humic substances) compounds. In the first step of this study, three QuEChERS methods were used, and then compared, for the extraction of pesticides (atrazine, simazine, clomazone and tebuconazole), pharmaceuticals (amitriptyline, caffeine, diclofenac and ibuprofen) and PCPs (methylparaben, propylparaben, triclocarban and bisphenol A) from drinking water treatment sludge. Afterwards, the study of different sorbents in the dispersive solid phase extraction (d-SPE) step was evaluated. Finally, a new QuEChERS method employing chitin, obtained from shrimp shell waste, was performed in the d-SPE step. After having been optimized, the method showed limits of quantification (LOQ) between 1 and 50μgkg(-1) and the analytical curves showed r values higher than 0.98, when liquid chromatography tandem mass spectrometry was employed. Recoveries ranged between 50 and 120% with RSD≤15%. The matrix effect was evaluated and compensated with matrix-matched calibration. The method was applied to drinking water treatment sludge samples and methylparaben and tebuconazole were found in concentration <LOQ.
- Journal of chromatography. A.J Chromatogr A.2014 Apr 4;1336:10-22. doi: 10.1016/j.chroma.2014.02.002. Epub 2014 Feb 8.
- Recent studies have shown a decrease in the concentration of pesticides, pharmaceuticals and personal care products (PCPs) in water after treatment. A possible explanation for this phenomenon is that these compounds may adhere to the sludge; however, investigation of these compounds in drinking wate
- PMID 24582392
- Socioeconomic deprivation independently predicts symptomatic painful diabetic neuropathy in type 1 diabetes.
- Anderson SG1, Malipatil NS2, Roberts H2, Dunn G3, Heald AH4.Author information 1Cardiovascular Sciences Research Group, Core Technology Facility (3rd Floor), University of Manchester, 46 Grafton Street, Manchester, United Kingdom.2Department of Medicine, Leighton Hospital, Crewe, United Kingdom.3Podiatry, East Cheshire NHS Trust, Macclesfield, United Kingdom.4Department of Medicine, Leighton Hospital, Crewe, United Kingdom; School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom. Electronic address: adrian.heald@manchester.ac.uk.AbstractINTRODUCTION: Painful peripheral neuropathy in people with type 1 diabetes is a disabling and costly complication. A greater understanding of predisposing factors and prescribing may facilitate more effective resource allocation.
- Primary care diabetes.Prim Care Diabetes.2014 Apr;8(1):65-9. doi: 10.1016/j.pcd.2013.08.004. Epub 2013 Nov 8.
- INTRODUCTION: Painful peripheral neuropathy in people with type 1 diabetes is a disabling and costly complication. A greater understanding of predisposing factors and prescribing may facilitate more effective resource allocation.METHODS: The Townsend index of deprivation (numerically higher for grea
- PMID 24211151
- Determination of the cationic amphiphilic drug-DNA binding mode and DNA-assisted fluorescence resonance energy transfer amplification.
- Yaseen Z1, Banday AR2, Hussain MA2, Tabish M2, Kabir-Ud-Din3.Author information 1Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: zadn521@gmail.com.2Department of Biochemistry, Aligarh Muslim University, Aligarh 202002, India.3Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: kabir7@rediffmail.com.AbstractUnderstanding the mechanism of drug-DNA binding is crucial for predicting the potential genotoxicity of drugs. Agarose gel electrophoresis, absorption, steady state fluorescence, and circular dichroism have been used in exploring the interaction of cationic amphiphilic drugs (CADs) such as amitriptyline hydrochloride (AMT), imipramine hydrochloride (IMP), and promethazine hydrochloride (PMT) with calf thymus or pUC19 DNA. Agarose gel electrophoresis assay, along with absorption and steady state fluorescence studies, reveal interaction between the CADs and DNA. A comparative study of the drugs with respect to the effect of urea, iodide induced quenching, and ethidium bromide (EB) exclusion assay reflects binding of CADs to the DNA primarily in an intercalative fashion. Circular dichroism data also support the intercalative mode of binding. Besides quenching, there is fluorescence exchange energy transfer (FRET) in between CADs and EB using DNA as a template.
- Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2014 Mar 25;122:553-64. doi: 10.1016/j.saa.2013.11.030. Epub 2013 Nov 16.
- Understanding the mechanism of drug-DNA binding is crucial for predicting the potential genotoxicity of drugs. Agarose gel electrophoresis, absorption, steady state fluorescence, and circular dichroism have been used in exploring the interaction of cationic amphiphilic drugs (CADs) such as amitripty
- PMID 24334019
Japanese Journal
- Tricyclic Antidepressant Amitriptyline Indirectly Increases the Proliferation of Adult Dentate Gyrus-Derived Neural Precursors: An Involvement of Astrocytes
- Boku Shuken,Hisaoka-Nakashima Kazue,Nakagawa Shin,Kato Akiko,Kajitani Naoto,Inoue Takeshi,Kusumi Ichiro,Takebayashi Minoru
- Plos one 8(11), e79371, 2013-11-18
- … We have also shown that amitriptyline (AMI), a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA). …
- NAID 120005365918
- 回復期病棟入院患者の頻尿に対するアミトリプチリンの有効性の検討
- 中木村 繁,吉田 聖子,藤原 郁子 [他]
- 総合リハビリテーション 41(2), 187-190, 2013-02
- NAID 40019568053
- 夜尿症児90例の臨床的検討
- 村杉 寛子,永木 茂,大澤 眞木子,MURASUGI Hiroko,NAGAKI Shigeru,OSAWA Makiko
- 東京女子医科大学雑誌 83(E1), E205-E211, 2013-01-31
- 夜尿症90例の臨床検討を行った. 初診時年齢の分布は,6歳と9歳に2峰性のピークがみられ,男女比1.7:1,男児に多くみられる傾向にあった.一次性夜尿は88例,二次性夜尿は2例.病型分類できた83例のうち多尿型41例(49.4%),混合型42例(50.6%)であった.治療の選択薬剤は抗利尿ホルモン 44例, 抗コリン薬40例,三環系抗うつ薬34例,またアラームは4例で使用した(重複あり).生活指導 …
- NAID 110009559379
Related Links
- Amitriptyline is a tricyclic antidepressants and is used is used to treat symptoms of depression. Learn about side effects, interactions and indications. ... Amitriptyline side effects Get emergency medical help if you have any of these ...
- Amitriptyline - Amitriptyline is a tricyclic antidepressant. Amitriptyline affects chemicals in the brain that may become unbalanced. - You should not use this medication if you are allergic to amitriptyline, or if you have recently had a ...
Related Pictures
★リンクテーブル★
| リンク元 | 「抗うつ薬」「薬理学」「三環系抗うつ薬」「アミトリプチリン」 |
| 拡張検索 | 「amitriptyline hydrochloride」 |
「抗うつ薬」
- 英
- antidepressant, antidepressants
- 関
- 薬理学、そううつ病、精神疾患
作用機序
三環系抗うつ薬 tricyclic antidepressant
- ２つの説がある。
- 1. (急性作用)シナプス前膜におけるノルアドレナリン、セロトニンの再取り込み↓→シナプス間隙における薬剤濃度↑
- 2. (慢性作用)(2週間後)シナプス後膜における受容体の数↓
- 慢性作用はシナプス間隙のノルアドレナリン、セロトニン濃度が上昇した結果、シナプス後膜の受容体が減少したために出現すると考えられる。
抗うつ薬
- 三環系
- 四環系
- 非定型抗うつ薬 atypical agent
副作用
- Adams and s Principles of Neurology, Ninth Edition Allan Ropper p.1474
| 不眠、焦燥 | 鎮静 | 低血圧 | 抗コリン作用 | 消化管症状(嘔吐等) | 性機能低下 | 体重増加 | ||
| 三環系 | アミトリプチリン | ± | 2+ | 2+ | 3+ | ± | ＋ | 2+ |
| 三環系 | ドスレピン | ± | 2+ | 2+ | 2+ | ± | ＋ | 2+ |
| 三環系 | イミプラミン | 2+ | ＋ | 2+ | 2+ | ± | ＋ | 2+ |
| SSRI | フルオキセチン | 2+ | ± | ± | ＋ | 2+ | 2+ | ＋ |
| SSRI | パロキセチン | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | セルトラリン | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | フルボキサミン | 2+ | ＋ | ± | ± | 2+ | 2+ | ＋ |
| SSRI | シタロプラム | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SSRI | エスシタロプラム | 2+ | ± | ± | ± | 2+ | 2+ | ＋ |
| SNRI | デシプラミン | ＋ | ± | 2+ | ＋ | ± | ＋ | ＋ |
| SNRI | ノルトリプチリン | ＋ | ＋ | ＋ | ＋ | ± | ＋ | ＋ |
| SNRI | マプロチリン | ＋ | ± | ＋ | ＋ | ± | ＋ | 2+ |
| SNRI | ベンラファキシン | 2+ | ± | ± | ± | 2+ | 2+ | ± |
| SNRI | デュロキセチン | ± | ＋ | ± | ＋ | ＋ | ± | ± |
| NDRI | ブプロピオン | 2+ | ± | ± | ＋ | ＋ | ± | ± |
| MAOI | フェネルジン | 2+ | ＋ | 2+ | ＋ | ＋ | 2+ | ＋ |
| MAOI | トラニルシプロミン | 2+ | ＋ | 2+ | ＋ | ＋ | 2+ | ＋ |
| MAOI | イソカルボキサジド | 2+ | ± | 2+ | ＋ | ＋ | 2+ | 2+ |
| MAOI | セレギリン | ＋ | ± | ＋ | ＋ | ＋ | ＋ | ＋ |
| NaSSA | ミルタザピン | ± | 3+ | ＋ | ± | ± | ± | 3+ |
| 非定型 | ネファゾドン | ± | 2+ | ＋ | ＋ | ＋ | ± | ＋ |
| 非定型 | トラゾドン | ± | 3+ | ＋ | ± | ＋ | 2+ | ＋ |
「薬理学」
- 英
- pharmacology
- 関
- drug entries
定義
- 生物系と化学物質の選択的な相互作用を研究する学問 (SPC.2)
生物系と薬の相互作用
関連分野
- 薬物学 materia medica
- 生薬学
- 実験薬理学
- 臨床薬理学
- 動物薬理学
- 人体薬理学
- 比較薬理学
- 薬理作用学(薬力学)
- 薬物動態学
- 中毒学、毒科学
- 薬物治療学
- 処方学
薬品の命名
| Ending of the drug name | Category | Example |
| ～afil | Erectile dysfunction | sildenafil |
| ～ane | Inhalatinal general anesthetic | halothane |
| ～azepam | Benzodiaizepine | diazepam |
| ～azine | Phenothiazine (neuroleptic, antiemetic) | chlorpromazine |
| ～azole | Ailtifungal | ketoconazole |
| ～barbital | Barbiturate | phenobarbital |
| ～caine | Local anesthetic | lidocaine |
| ～cillin | Penicillin | methicillin |
| ～cycline | Antibiotic, protein syntlesis inhibitor | tetracycline |
| ～ipramine | TCA | iimipramine |
| ～navir | Protease inhibitor | saquinavir |
| ～olol | β-antagonist | propranolol |
| ～operidol | Butyrophenone ( neuroleptic ) | haloperidol |
| ～oxin | Cardiac glycoside ( inotropic agent ) | digoxin |
| ～phylline | Methylxanthine | theophylline |
| ～pril | ACE inhibitor | captopril |
| ～terol | β2 agonist | albuterol |
| ～tidine | H2 antagonist | cimtidine |
| ～triptyline | TCA | amitriptyline |
| ～tropine | Pituitary hormone | somatotropine |
| ～zosin | a1 antagonist | prazosin |
薬一覧
薬物代謝
薬理動態
神経伝達物質
神経筋接合部遮断薬(筋弛緩薬)
交感神経作動薬
交感神経遮断薬
副交感神経作動薬
副交感神経遮断薬
貧血治療薬
甲状腺関連物質
- レボチロキシン levothyroxine
- リオチニシン liothyronine
痛風治療薬
- 痛風発作予防薬
- 尿酸排泄促進薬
- 尿酸生成抑制薬
「三環系抗うつ薬」
概念
- 環状の構造を三つ持つ抗うつ薬
- 治療効果発現には2-3週間必要
種類
作用機序
副作用
- 抗コリン作用
- 視力障害、口渇、便秘、尿閉
- 頻脈
- α1ブロック作用
- 起立性低血圧
- 血中ノルアドレナリンの上昇
- 抗ヒスタミン作用
- 鎮静、眠気
「アミトリプチリン」
「amitriptyline hydrochloride」
- 同
- Elavil, Emitrip, Endep