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English to Turkish: a scientific literature sample General field: Medical Detailed field: Nutrition
Source text - English GiRi§
Doksilamin siiksinat (DS) refetesiz satilabilen ve FDA tarafindan
1978’de yetijkinlerde uyku bozuklugu tedavisinde
onaylanmij, spesifik olmayan antikolinerjik ve sedatif etkili
birinci kujak H1 antagonistidir. Orta derece sedatif etkisinin
yam sira yarilanma omrii gorece uzun (10-15 saat) oldugundan
gep kullamldigmda sabah sersemlik gibi artik etki gosterebilmektedir.
Zamanla sedatif etkilerine karji tolerans gelijebilmektedir.
Antikolinerjik etkinlige sahip olmasi nedeni
ile bilinp sislenmesi (konfiizyon), gorme bulamkligi ve idrar
retansiyonuna yol apabilir. Iki haftadan daha uzun sure kullanimi
onerilmemektedir (Yetkin 2016).
DS’nin repetesiz satilmasi, repetesiz satilan pogu ilapta oldugu
gibi hastalara doktora gitmeden ktiptik rahatsizliklan
yonetebilme kolayligi saglamaktadir. Hastalar doktor tarafindan
verilmeyen bir ilacin daha masum ve zararsiz olabilecegini
diijunerek doksilamin siiksinat ve dimenhidrinat
gibi antihistaminikleri kotiiye kullanabilirler (Coombes ve
Cooper 2019). Ayrica ajiri kullamm nedeniyle fiziksel veya
psikolojik bagimlilik gelijtirebilirler. Antihistaminiklerin HI
reseptor antagonizmasi iizerinden nukleus akkumbens’te dopamin
norotransmisyonunu aktive ederek kotiiye kullamm ve
bagimliliga neden olabilecegi diijiiniilmektedir (Bahji ve ark.
2021). Literatiirde dimenhidrinat (DH) ve difenhidramin
gibi antihistaminik bagimhhgi ile ilgili vakalar tammlanmijtir
(Thomas ve ark. 2009, Gracious ve ark. 2010, Schifano ve
ark. 2021). Doksilamin bagimlihgimn yayginhgi ile ilgili 90k
fazla palijmaya rastlanmamakla beraber eczanede repetesiz satilan
ilaplar ile ilgili yapilan bir pahjmada DS kullanan 36 kijinin
%72,2’sinin 1 aydan, %61,5’inin 6 aydan daha uzun sure
kullandigi, bir kijinin DSM-lV’e gore bagimlilik kriterlerini
karjiladigi ve 4 yildir DS kullandigi belirtilmijtir (Roussin ve
ark. 2013). Tiirkiye’de ise antihistaminiklerle ilgili feniramin
ve dimenhidrinat bagimlilik vakalari bildirilmijtir (Bilici ve
ark. 2012, Kaya 2014). Bildigimiz kadariyla bu Tiirkiye’de
Geli§ Tarihi: 18.04.2021, Kabul Tarihi: 01.08.2021, ^evrimi^i Yaym Tarihi: 21.12.2021
^Uzm., Antalya Ataturk Devlet Hastanesi, Psikiyatri AD., ^Dr. Ogr. Uyesi, Akdeniz Univ. Tip Fak., Ruh Sagligi ve Hastaliklari AD., Antalya.
AUY: littps://ordd.org/0000-0002-5076-6106, BC: littps://ordd.org/0000-0001-6480-l454
Dr. Asena Uzdu Yajar, e-posta: uzduasena(3)gmail.com
211
bildirilen ilk doksilamin siiksinat bagimliligi olgusudur. Bu
yazida 5 yildir araliksiz DS kullanan bir hasta sunulmujtur.
OLGU
43 yajinda, evli ve iki focuklu, ogretmen olarak falijan erkek
hasta son 3 yil 125 mg/giin olacak jekilde 5 yildir araliksiz
her giin doksilamin suksinat kullanmasina ragmen iki iif aydir
olan uykuya dalarken zorlanma jikayeti ile poliklinigimize
bajvurdu. DS almadiginda huzursuzluk, mide bulantisi, terleme,
baj agrisi ve uykusuzluk jikayeti oldugu ipin ilacini almaya
devam ediyordu. Evde en az 10 adet DS kutusu bulundurmak,
onerilen dozun (25-50 mg/giin) 90k iistiinde ila9 kullanmak,
bir yere gideceginde mutlaka ilacini yanina aimak, azaltmayi
istemesine ragmen birakamamak ve almadiginda yoksunluk
semptomlari yajamak, ila9siz kaldiginda ilaci bulana kadar tiim
nobetpi eczaneleri gezmek gibi ilap kotiiye kullammi belirtilerini
gosterdigi ipin hastada DSM-5’e gore Sedatif, Hipnotik
ve Anksiyolitik ile Ilijkili Bozukluk (ICD-lO’a gore FI3.20
Sedatif, Hipnotik veya Anksiyolitik Bagimliligi) diijiiniildii.
Fizik muayenesi olagandi. Tam kan sayimi, bobrek, karaciger
ve tiroid fonksiyon testleri, serum ferritin, B12 ve D vitamini
seviyelerini olpen laboratuvar testleri yapildi. TSHdeki hafif
yiikseklik (6,10 ulU/mF) (laboratuvar referans araligi: 0,35-
5,50 ulU/mF) dijinda tiim degerler normal simrlardaydi.
TSH degerlerinin donem donem yiikseldigi ve dahiliye boliimii
tarafindan takipli oldugu ogrenildi. Yetersiz laboratuvar
ekipmam nedeni ile DS kan diizeyi bakilamadi.
Hastanin uykusuzluk jikayeti 21 yajindayken yajadigi ilk romantik
ilijkisi sonlandiktan sonra bajlamij. Bu donemde herhangi
bir tedavi almamij. Iki yil sonra evlendiginde uykusuzluk
jikayeti gepmij. Uykusuzlugu, 36 yajinda iken eji ile problemleri
bajladiginda yinelemij. Uykuya dalmakta zorlanma, sik sik
uyanma ve yeniden yatamama jikayetleri ile gittigi psikiyatrist
essitalopram 10 mg/giin bajlamij. Ilaptan 90k fayda gormiij ve
6 ay kadar kullanmij. Iki yil sonra ilijkisinde problemler yajadigi
bir donemde uykusuzluk jikayeti tekrar bajlamij ve eczacisinin
onerisiyle DS almij. Ilk alti ay 25 mg/giin aliyorken,
zamanla giinliik dozunu yiikseltmij. Son ii9 yildir 125 mg/giin
aliyormuj. §ehir dijina 9ikacagi zaman en az alti kutu DS yanina
aliyor ve evde her zaman en az 10 kutu bulunduruyormuj.
Hasta poliklinigimize diizenli ve yiiksek doz DS kullanimina
ragmen devam eden uykusuzluk jikayeti ile bajvurdu. Bu
jikayete ek olarak birkap aydir keyifsizlik, pokkiin duygudurum,
ilgi ve istek kaybimn oldugu ve uygulanan Hamilton
Depresyon Olpeginden (HAM-D) 27 puan aldigi goriildii.
Venlafaksin 75 mg/giin ve ketiapin 25 mg/giin ile ayaktan takibine
bajlandi ve ihtiyap duydugu takdirde en fazla 75 mg/
giin DS almasi onerildi. Iki hafta sonra yapilan kontrol muayenesinde
75 mg/giin DS aldiginda uykusuzluk, huzursuzluk
ve ip sikintisi jikayetleri oldugu ipin 125 mg/giin almaya
devam ettigi ogrenilen hastada ketiapin kesilerek diazepam 5
mg/giin bajlandi. Yoksunluk belirtileri yajadigi takdirde ilk iki
hafta 50 mg/giin, son iki hafta 25 mg/giin DS almasi onerildi.
Dort hafta sonra depresif jikayetlerinde kismen azalma
(HAM-D: 14) olan hastanin ilk iki hafta 50 mg/giin aldigi ve
son iki haftada da haftalik 3-4 giin 25 mg/giin DS aldigi ve DS
almadigi giinlerde de jiddetli huzursuzluk ve uykusuzluk yajamadigi
goriildii. Mevcut tedavisine mirtazapin 15 mg/giin eklendi.
Dort hafta sonraki kontroliinde depresif jikayetlerinin
geptigi (HAM-D: 7), DS ile ilgili herhangi bir yoksunluk belirtisi
yajamadigi ancak eji ile tartijtigi bir giin huzursuzluk
yajadigi sirada 25 mg/giin DS aldigi ogrenildi. Diazepam bir
hafta ipinde kademeli olarak kesilerek venlafaksin 75 mg ve
mirtazapin 15 mg ile tedavisine devam edildi. Hastanin tedavisinin
2. aymdan 5. ayin sonuna kadar pogunlukla stres yajadigi
bir olayi takiben 5 defa DS 25 mg/giin aldigi ve son bir
aydir DS alma arzusu duymadigi ve DS almadigi ogrenildi.
Duygudurumu otimik olan ve depresif jikayetleri tamamen
gepen hastanin aylik takiplerine devam edilmektedir.
TARTI§MA
Uykusuzluk uykuya dalmakta giipliik, yeterli zaman ya da
firsat olmasina karjm uykunun siiresinde, biitiinliigiinde
ve kalitesinde yetersizlik ile tammlamr. Uykusuzluk oldukpa
yaygin goriilen bir yakinmadir. Toplumun %30-50’sinde
kisa siireli uykusuzluk goriiliirken, %10-15’inde kronik uykusuzluga
rastlamr (Yetkin 2016). Uyku bozuklugu yajayan
kijilerin yaklajik %25’i repetesiz satilan uykuya yardimci olabilecek
ilaplari kullanmaktadirlar. Repetesiz satilan uyku yardimcilari
olarak pok sik kullanilan DH ve DS ipin 2 haftadan
fazla kullamm onerilmemekle birlikte pok sayida yetijkin bu
ilaplari kronik olarak kullamr (Krystal ve ark. 2019). Kronik
kullammi arajtiran bir palijmada 18-64 yaj arasmdaki kijilerin
%21’i, 65-74 yaj arasmdaki kijilerin %37si ve 75 yajin
iizerindeki kijilerin %47’si onceki ay 15 giinden fazla repetesiz
uyku yardimcisi kullandigim bildirmijtir. Yajh yetijkinlerin
ejzamanh antikolinerjik ilap kullamm olasihgi ve genp yetijkinlerin
alkol kullanma sikligi goz oniinde bulundurularak
antihistaminiklerin kronik kullammimn ozellikle yan etkiler
apisindan dikkate ahnmasi onerilmijtir (Albert ve ark. 2017).
Antihistaminiklerin laboratuvar testlerinde antidepresan gibi
davrandigi veya psikiyatri hastalarinda anksiyolitik etkilere
sahip oldugu bildirilmijtir. Farmakolojik olarak etkisinin sadece
histamin sistemi ile sinirli olmayacagi dtijuniilmektedir.
Antihistaminiklerin asetilkolin, serotonin, norepinefrin, dopamin
ve opioid sistemi ile etkilejime girebilecegine dair kamtlar
vardir. Bu durum depresyon ve anksiyete iizerindeki etkilerini
apiklayabilir (Roussin ve ark. 2013).
Translation - Turkish INTRODUCTION
Doxylamine succinate (DS) is a non-prescription drug that is approved by the FDA in 1978 for treatment of sleep disorders in adults. It is a non-specific anticholinergic and sedative first generation H1 antagonist. Its sedative effect is moderate and has a half-life that is relatively longer (10 - 15 hours), exhibiting dizziness - like effects when used in late hours. Tolerance to sedative effect may develop in time. It may cause confusion, blurred vision and urinary retention due to anticholinergic effect, and it is not recommended to be used for more than 2 weeks (Yetkin, 2016).
Since it is not a prescription drug, it provides the comfort for the patients to manage small discomforts by themselves without consulting a doctor. Patients may suppose that a non-prescription drug is harmful, allowing an increased rate of abusing them (Coombes and Cooper, 2019). Physical and psychological addiction may develop due to excessive use.
Antihistaminics activate dopamin neurotransmission in nucleus accumbens via H1-recepter antagonism, and may possibly lead to abuse and addiction (Bahji et al., 2021). Literature reports of cases for Dimenhydrinate (HD) and difenhydramine dependency are available (Thomas et al., 2009; Gracious et al., 2010; Schifano et al., 2021). Reports for doxylamine addiction are not very common; however, a study conducted on non-prescrtiption drugs reported that 72.2% and 61.5% of 36 patients receiving DS have used them for longer than 1 month and 6 months, respectively, one person meeting the addiction criteria according to DSM-IV who has been using the drug for 4 years (Roussin et al., 2013). Feniramin and dimenhydrate are the antihistaminics for which addiction cases have been reported (Bilici et al., 2012; Kaya, 2014). As far as we are concerned, this is the first reported doxylamine succinate addiction case in Turkey. This report presents a patients using DS for 5 years straight.
PHENOMENON
A 43 year-old male patient is a teacher and married with children, he has been using DS for 5 years straight at a dose of 125mg/day for the last 3 years. Patient presented to outpatient clinic for insomnia for the last 2-3 months. Patient described irritability, nausea, sweating, headache and insomnia when he did not use DS; therefore, he continued to use it. Patient described symptoms of drug abuse like storing at least 10 DS boxes at home, using very higher doses than the recommended dose range (25-50 mg/day), taking the drug with him while going outside, inability to stop the medication despite the desire to do it, and showing withdrawal symptoms when not taking the medication, and visiting all pharmacies on duty at night if the drug is not available. Sedative, Hypnotic and Anxiolytic Dependency Disorder (F13.20 Sedative, Hypnotic or Anxiolytic Addiction) was considered. Physical examination was within normal limits. CBC, kidney, liver and thyroid functions tests, serum ferritin, Vitamin B12 and Vitamin-D levels were measured. TSH was mildly elevated (6.10 uIU/mF) (laboratory normal range: 0.35 – 5.50 uIU/mF). Findings were otherwise normal. TSH level has been increasing from time to time and he was followed-up by Internal Medicine. DS blood level could not be tested due to inadequate laboratory equipment.
Insomnia started when he was 21 years old after his first romantic affair at the age of 21. He did not receive any treatment at that time. He got married 2 years later and complaint disappeared. His complaint recurred when he started having problems with his wife at the age of 36. He presented to a psychiatrist with complaints of insomnia, frequent awakening and inability to sleep again, psychiatrist prescribed him Escitalopram 10 mg/day. Complaints recurred after 2 years again while having relationship problems. He used DS recommended by the pharmacist. He was using 25mg/day for 6 months; after that, he started to increase the dose. He has been using 125 mg/day for the last 3 years. He takes at least 6 boxes of DS with him when going outside the city and stores at least 10 boxes at home.
Patient presented to outpatient clinic despite use of high and regular dose of DS. He also described unhappiness, depressed mood, loss of interest and desire, and had a score of 27 at Hamilton Depression (HAM-D) scale. Venlafaxine 75mg/day and Quetiapine 25mg/day were started as outpatient, and he was recommended to use maximum 75 mg/day DS in time of need. He returned for control visit 2 weeks later and stated that he had insomnia, irritability and distress with of 75 mg DS, and still used 125mg/day. Quetiapine was stopped and Diazepam 5 mg/day was started. 50mg/day dose for 2 weeks and 25mg/day for the next 2 weeks was recommended in case of withdrawal symptoms. Depression complaints partially decrease by 4 weeks (HAM-D: 14). He used DS 50mg/day for 2 weeks and 25 mg/day for the next 2 weeks (for 3-4 days), and denied any irritability and insomnia after DS withdrawal. Mirtazapine 15 mg/day was added to regimen. Depression complaints resolved after the next 4 weeks (HAM-D: 7), he had no withdrawal symptoms related with DS and had used 25mg/day DS when he had a quarrel with his wife. Diazepam was gradually stopped in 1 week, and treatment was continued with Venlafaxine 75 mg + Mirtazapine 15 mg. He used 25 mg/day DS for 5 times after a stressful event between the second and fifth months of treatment, and did not have any desire to use DS for 1 month and never used DS during this period. He had euthymic mood and depressive complaints totally resolved. Monthly follow-up continues.
DISCUSSION
Insomnia is defined as difficulty falling asleep, and inadequate duration, integrity and quality of sleep. Insomnia is a very common condition. 30-50% of soicety has short term insomnia, while 10-15% has chronic insomnia (Yetkin, 2016). 25% of people with insomnia use non-prescription medications. DH and DS, as non-prescription drugs, are not recommended to be used for more than 2 weeks. Most adults use them chronically (Krystal et al., 2019). A study conducted on chronic use revealed that 21%, 37% and 47% of people between 18-64 years, 65-74 years and >75 years used non-prescription sleeping aids. Chronic use of anti-histaminic should be treated with extreme caution considering high rate of anticholinergic use in the elderly, and frequent use of alcohol in young adults (Albert et al. 2017).
Antihistaminic medication act like antidepressants in laboratory tests and exert anxiolytic effects in psychiatry patients. Pharmacological effects are not considered to be limited with histamin system. Evidence suggest that antihistaminics interact with acetylcolin, serotonin, norepinephrin, dopamin and opioid system. This may explain its effects on depression and anxiety (Roussin et al., 2013).
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