A wonderful world with with my whole heart. I am alone, and feel the charm of existence in this spot, which was created for the bliss of souls like mine. I am so happy, my dear friend, so absorbed in the exquisite sense of mere tranquil existence, that I neglect my talents. I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now.

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth, a thousand unknown plants are noticed by me.

DEVELOP THE ECONOMY 

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

[blockquote align=”left” author=”Penci Design” style=”font-size: 30px”]To take a trivial example, which of us ever undertakes laborious physical exercise, except to obtain some advantage from it?[/blockquote]

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words.

MODERN NEWS & MAGAZINE

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

 

To an English person, it will seem like simplified English, as a skeptical Cambridge friend of mine told me what Occidental is.The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words. Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators.


How To Achieve Zero Carbon Emission

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth.

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A wonderful world with with my whole heart. I am alone, and feel the charm of existence in this spot, which was created for the bliss of souls like mine. I am so happy, my dear friend, so absorbed in the exquisite sense of mere tranquil existence, that I neglect my talents. I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now.

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth, a thousand unknown plants are noticed by me.

DEVELOP THE ECONOMY 

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

[blockquote align=”left” author=”Penci Design” style=”font-size: 30px”]To take a trivial example, which of us ever undertakes laborious physical exercise, except to obtain some advantage from it?[/blockquote]

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words.

MODERN NEWS & MAGAZINE

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

 

To an English person, it will seem like simplified English, as a skeptical Cambridge friend of mine told me what Occidental is.The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words. Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators.


How To Achieve Zero Carbon Emission

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth.

0 yorumlar
0 FacebookTwitterPinterestE-posta

A wonderful world with with my whole heart. I am alone, and feel the charm of existence in this spot, which was created for the bliss of souls like mine. I am so happy, my dear friend, so absorbed in the exquisite sense of mere tranquil existence, that I neglect my talents. I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now.

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth, a thousand unknown plants are noticed by me.

DEVELOP THE ECONOMY 

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

[blockquote align=”left” author=”Penci Design” style=”font-size: 30px”]To take a trivial example, which of us ever undertakes laborious physical exercise, except to obtain some advantage from it?[/blockquote]

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words.

MODERN NEWS & MAGAZINE

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

 

To an English person, it will seem like simplified English, as a skeptical Cambridge friend of mine told me what Occidental is.The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words. Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators.


How To Achieve Zero Carbon Emission

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth.

0 yorumlar
0 FacebookTwitterPinterestE-posta

A wonderful world with with my whole heart. I am alone, and feel the charm of existence in this spot, which was created for the bliss of souls like mine. I am so happy, my dear friend, so absorbed in the exquisite sense of mere tranquil existence, that I neglect my talents. I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now.

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth, a thousand unknown plants are noticed by me.

DEVELOP THE ECONOMY 

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

[blockquote align=”left” author=”Penci Design” style=”font-size: 30px”]To take a trivial example, which of us ever undertakes laborious physical exercise, except to obtain some advantage from it?[/blockquote]

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words.

MODERN NEWS & MAGAZINE

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

 

To an English person, it will seem like simplified English, as a skeptical Cambridge friend of mine told me what Occidental is.The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words. Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators.


How To Achieve Zero Carbon Emission

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth.

0 yorumlar
0 FacebookTwitterPinterestE-posta

A wonderful world with with my whole heart. I am alone, and feel the charm of existence in this spot, which was created for the bliss of souls like mine. I am so happy, my dear friend, so absorbed in the exquisite sense of mere tranquil existence, that I neglect my talents. I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now.

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth, a thousand unknown plants are noticed by me.

DEVELOP THE ECONOMY 

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

[blockquote align=”left” author=”Penci Design” style=”font-size: 30px”]To take a trivial example, which of us ever undertakes laborious physical exercise, except to obtain some advantage from it?[/blockquote]

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words.

MODERN NEWS & MAGAZINE

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

 

To an English person, it will seem like simplified English, as a skeptical Cambridge friend of mine told me what Occidental is.The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words. Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators.


How To Achieve Zero Carbon Emission

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth.

0 yorumlar
0 FacebookTwitterPinterestE-posta

A wonderful world with with my whole heart. I am alone, and feel the charm of existence in this spot, which was created for the bliss of souls like mine. I am so happy, my dear friend, so absorbed in the exquisite sense of mere tranquil existence, that I neglect my talents. I should be incapable of drawing a single stroke at the present moment; and yet I feel that I never was a greater artist than now.

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth, a thousand unknown plants are noticed by me.

DEVELOP THE ECONOMY 

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

[blockquote align=”left” author=”Penci Design” style=”font-size: 30px”]To take a trivial example, which of us ever undertakes laborious physical exercise, except to obtain some advantage from it?[/blockquote]

When I hear the buzz of the little world among the stalks, and grow familiar with the countless indescribable forms of the insects and flies, then I feel.

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words.

MODERN NEWS & MAGAZINE

Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators. To achieve this, it would be necessary to have uniform grammar, pronunciation and more common words. If several languages coalesce, the grammar of the resulting language is more simple and regular than that of the individual languages. The new common language will be more simple and regular than the existing European languages. It will be as simple as Occidental; in fact, it will be Occidental.

 

To an English person, it will seem like simplified English, as a skeptical Cambridge friend of mine told me what Occidental is.The European languages are members of the same family. Their separate existence is a myth. For science, music, sport, etc, Europe uses the same vocabulary. The languages only differ in their grammar, their pronunciation and their most common words. Everyone realizes why a new common language would be desirable: one could refuse to pay expensive translators.


How To Achieve Zero Carbon Emission

When, while the lovely valley teems with vapour around me, and the meridian sun strikes the upper surface of the impenetrable foliage of my trees, and but a few stray gleams steal into the inner sanctuary, I throw myself down among the tall grass by the trickling stream; and, as I lie close to the earth.

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TC Sağlık Bakanlığı Halk Sağlığı Genel Müdürülüğü tarafından 2014- 2020 yıllarına ait ULUSAL ZEHİR DANIŞMA MERKEZİ (UZEM) RAPORLARI yayınlandı. TATD Toksikoloji Çalışma grubu olarak bu raporların yayınlanmasını uzun süredir merakla bekliyorduk. Toplam 728 sayfa olan rapor  Halk Sağlığı Genel Müdürlüğü Ulusal Zehir Danışma Merkezi Sorumlusu Dr. İbrahim Koç ve yayın ekibi tarafından büyük bir titizlikle hazırlanmış. İçeriğinde 208 tablo ve 180 grafik var. Bu verilerin yayınlanmasındaki amacı önsözde  Halk Sağlığı Genel Müdürü Doç. Dr. Fatih Kara “Üniversiteler, Hastaneler, Tüm Kamu Kurum ve Kuruluşlarında, Türkiye’deki zehirlenmeler ve zehirlenme profilleriyle ilgili bilgiyi kolay ulaşılabilir hale getirmek, ayrıca yapılacak bilimsel çalışmalara zemin hazırlamak amaçlanmıştır. “ olarak özetlemişler. Raporda göreceksiniz ki KKTC’ den yapılan bildirimler de var. Maruz kalınan toksinler akrep zehirinden ayak bakım ürünleri veya fondöten gibi makyaj malzemelerine kadar değişiyor. Verileri özetler halinde TATD Toksikoloji çalışma grubu sitemizde sizlere sunacağız. Ancak sizler de bir göz atmak isterseniz buraya tıklayarak raporlara ulaşabilirsiniz.
İyi Okumalar Dilerim.
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Antikoagülan

Antikoagülan Zehirlenmelerinin Yönetimi‘ 

WEBINARI

Antikoagülan Zehirlenmelerinin Yönetiminin tüm detaylarının konuşulduğu WEBINARımız

30 Eylül 2021, Saat 20:00’da

DoktorClub üzerinden canlı yayınlanacaktır

Moderatör:

Doç. Dr. Serkan Emre EROĞLU

Konuşmacılar:

Doç. Dr. Serkan Emre EROĞLU

Uzm. Dr. Emir ÜNAL

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Pekçok ilaçta kişinin yaşı, cinsiyeti, ailesel ve genetik özellikleri, çevresel koşulları  gibi etmenler ile ilaca bağlı istenmeyen yan etkiler oluşur. Bunun en bariz örneği cinsiyete bağlı olan yan etkilerdir.  Advers ilaç reaksiyonları hakkında yapılmış ve cinsiyete göre farklı olan bildirimler ise Tablo 1’ de mevcuttur. Bu tabloya ait referansların listesi en altta olup faklı makale ve kaynak kitaplardan erişilebilir olacak şekilde listelenmiştir.  Burada  Tablo 2’ de görüleceği gibi cinsiyete bağlı olarak fizyolojik ve metabolik farklılıklar mevcuttur. Altta yatan bu süreçlerin kadın, erkek veya gebede farklı olduğunu kısaca özetlemek istedim. Referans olarak kullanılacağını ümit ederim.

Tablo 1. Advers ilaç reaksiyonlarında cinsiyet farklılıkarı

İlaç sınıfı Klinik tabloların kıyaslaması
Analjezikler Kadınlarda perioperative analjeziklerde daha çok yan etki1.
Anafilaktik şok Kadınlarda nöromuskuler bloker ajanlar, hipnotikler, opioidler ve benzodiazepinler daha sık anafilaktik şoka neden olur2.
Anestetik ilaçlar Kadınlarda ADR postoperatif olarak daha sıktır 2-4
ACE inhibitorleri Kuru öksürük kadınlarda 2-3 kat daha fazla5-7. Anjiyoödem / ürtiker eşit 8.
Antiaritmikler Kadında QT uzama riski ve TdP daha fazla9-10.
Antikoagulanlar Kadınlarda daha sık ve ciddi kanamalar11-19
H1-Antihistamin grubu Kadınlarda sedasyon, uyku hali daha fazla 20-22
Antiplatelet ajanlar Kadınlarda daha sık ve ciddi kanamalar23
Antipsikotikler Kadınlarda daha fazla ekstrapiramidal ve antikolinerjik etkiler, Qtc uzaması. Erkeklerde ise daha fazla cinsel problemler bildirilmiştir24-27
Aspirin Kadınlarda kanama riski daha fazla 28. Erkeklerde ise ülser komplikasyonları daha fazla29
Beta blokerler Kadında metoprolol kan basıncını ve kalp hızını daha fazla baskılar 30.
Benzodiazepinler Diazepam kadınlarda daha fazla psikomotor becerileri bozar31. Kadında bağımlılık daha sık26
Kalsiyum kanal blokerleri Kadında ödem riski daha fazla 32. menstruasyon sırasında diazepam alanlarda entoksikasyon daha fazla33
Digoksin Kadınlarda kalp yetmezliğinde mortalite fazladır 34. Kadında trepaötik digoksin plasma düzeyleri  < 0.8 ng/mL olarak önerilir 35
Diüretikler Hipo- osmolarite, hipopotasemi ve hiponatremi kadında daha sık olup aritmiye neden olur15,35-39
Değişik ilaçlar ile  TdP Kadınlarda değişik ilaçlar ile QTc aralığı uzama riski ve  TdP oluşma riski daha sıktır 40-44
GPIIb/ IIIa inhibitorleri Kadında erkekten daha sıktır23,45
Heparin Kadınlarda kanama riski daha yüksektir 12,46,47
Opioid reseptor agonistleri Kadında daha fazla bulantı, kusma, solunum depresyonu 48-52
NSAID Erkeklerde yan etkilerin toplam prevalansı daha fazla 29,53-55
Parasetamol Kadında parasetamol zehirlenmesinde akut karaciğer yetmezliği daha sık 56

Kısaltmalar: ACE: anjiotensin-converting enzim,  NSAID: non-steroidal anti-inflammatory drug = steroid olmayan antienflamatuar ilaç, QTc: corrected QT interval,TdP: torsades de pointes.

Tablo 2. Cinsiyete bağlı farklılık gösteren fizyoloji ve metabolik parametreler 67

  Parametreler

  Cinsiyet farkı

   İlaç Biyoyararlanımı
 Emilim    E > K
 Gastrik asit sekresyonu    E > K > G.
 Gastrik boşalma    E > K > G. Estrojen gastrik boşalmayı inhibe eder.
 Gastrointestinal geçiş zamanı
 Barsak  metabolizması    E = K
   Vücut yapısı
 Vücut yüzey alanı    E > G > K. Vücut yüzeyi arttıkça emilim de artar
 Organ (kalp) boyutu    E > K
 Organ kan akımı    Erkekte iskelet kası ve karaciğere kan akımı daha fazla.

Kadında yağ dokusuna kan akımı fazla.

Gebelikte kan akımı artar

 Total vücut sıvısı    E > G > K
 Plazma hacmi    G > E > K. Menstrual siklus ve gebelikte değişken
 Vücut yağ oranı    K> E
 Kardiyak atım    E > G > K.
 Pulmoner fonksiyon    E > G > K.
   Dağılım
 Dağılım hacmi (Vd)    K >E.  Lipofilik ilaçlar için
   E > K. Hidrofilik ilaçlar için
   Plazma proteinin  bağlanma yeri
 Albumin    E = K. Gebelik ve estrojen plazma albumini azaltır. Serbest ilaç artar.
 α1-asid  glikoprotein    E > K. Estrojen ve gebelikte plazma düzeyi azalır
 Globulin    Estrojen,   cinsiyet hormonları, kortikosteroid ve tiroksin bağlayıcı globulinleri artırır
   Drug/ ilaç taşıyıcılar
 Hepatik P-glikoprotein    E > K
 OCT2    E > K.
 OATP1B1-3    E > K
   Metabolizan enzimler ve taşıyıcılar
 Faz I metabolik reaksiyonlar (hydroliz, oksidasyon, reduksiyon) cytochrome P450 (CYP) isoformları aracılık eder    CYP1A2: E > K. Gebelikte ve estrojen ile azalır
   CYP2B6: K > E
   CYP2C9: E = K
   CYP2C19: E = K
   CYP3A4: K > E.
   CYP2D6: E > K. Estrojen indükler
   CYP2E1: E > K.
Faz  II metabolizma enzimleri
  Uridin difosfat  glukuronosil-transferaz    E > K. Gebelikte ve Estrojen ile artar
  N-Asetiltransferaz    E= K
  Katekol-O-metiltransferaz    E > K
  Asetil-butiril-kolinesteraz    E > K
  Xantin-oxidaz    K > E
  Gastrik alkol  dehidrojenaz    E > K. Kadında plazmada alkol düzeyleri daha yüksektir
   Drug/ ilaç atılım
·          Renal kan akımı

·          Glomerular filtrasyon hızı

·         Tubular sekresyon/ reabsorbsiyon

   E > K. Renal klerens gebelikte artar
   Renal atılımda aktif olarak sekrete olan ilaçlar cinsiyete göre farklı olabilir.

Kısaltmalar: E: Erkek, K: Kadın, G: Gebelik

Kaynaklar

1.     Richardson J, Holdcroft A. Results of forty years Yellow Card reporting for commonly used perioperative analgesic drugs. Pharmacoepidemiol Drug Saf 2007;16:687-694.

2.     Ciccone GK, Holdcroft A. Drugs and sex differences: a review of drugs relating anaesthesia. Br J Anesthes 1999;82:255-265.

3.     Kando JC, Yonkers KA, Cole JO. Gender as a risk factor for adverse events to medications. Drugs 1995;50:1-6.

4.     Buchanan MR, Rischke JA, Butt R, Turpie AG, Hirsh J, Rosenfeld J. The sex-related differences in aspirin pharmacokinetics in rabbits and man and its relationship to antiplatelet effects. Thromb Res 1983;29:125-139.

5.     Os I, Bratland B, Dahlof B, Gisholt K, Syvertsen JO, Tretli S. Female sex as an important determinant of lisinopril induced-cough. Lancet 1992;339:372.

6.     Strocchi E, Malini PL, Valtancoli G, Ricci C, Bassein L, Ambrosioni E. Cough during treatment with angiotensin-converting enzyme inhibitors. Analysis of predisposing factors. Drug Invest 1992;4:69-72.

7.     Strocchi E, Valtancoli G,  Ambrosioni E. The incidence of cough during treatment with angiotensin converting enzyme inhibitors. J Hypertens 1989:7(Suppl.);S308-309.

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İnsanlık tarihinde yüzyıllardır şifalı bitki ve otlar çeşitli amaçlar için kullanılıyor. Günümüzde kullandığımız modern ilaçların büyük bir kısmı bitkisel kaynaklı. Her ilaç bir zehir potansiyeli de taşıdığı için şifalı diye adlandırılan, kullanılan bitkilerin toksik etkilerini de incelemek önem taşıyor. Bu yazıda  “Cancer Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 5 of 5” 1  başlıklı makaleyi inceleyeceğiz. Başlıktan da anlaşılacağı üzere genelde otların kanserle ilişkileri derlenmiş ancak birçoğunun organlar üzerine toksik etkileri de mevcut. İyi Okumalar…

Giriş

Bu derleme aslında bir yazı dizisinin 5. Bölümü. İlk makalede besin takviyelerinin ve otların etkinliği, güvenilirliği incelenmiş arkasından karaciğer, böbrek ve kardiyak toksisite yapan ve kanser ilişkili olan 3 vaka bildirimi incelenmiş ve son olarak bu otlar ve besin takviyeleri bu yazıda tablo haline getirilmiş.

Tamamlayıcı ve alternatif tıbba olan ilgi her geçen gün artıyor ve günümüzde tamamlayıcı tıp da kendini akupunktur, besin takviyesi, ot, masaj, yoga, meditasyon, dua, enerji tıbbı, hipnoz vb araç ve yollarla tamamlıyor. Bu alanların kombinasyonlarına Hindistan’da Ayurvedic tıbbı, Japonya’da Kanpo veya Kampo, Çin’de Geleneksel Çin Tıbbı ismi veriliyor. Botanik bilimi tabi ki bu alanlarda çok önemli bir yere sahip çünkü günümüzde kullandığımız ilaçların %25-30’u bitkisel kaynaklı. Kanser konusunda ise bitkiler üzerinde yoğun araştırmalar mevcut. Amerikan Ulusal Kanser Ajansı ve Birleşik Devletler Ziraat Departmanı  15.000 bitkiden elde edilen 115.000 ekstreyi antikanser ajanı olarak test eden bir proje yürütüyorlar. Antiproliferatif özellik araştıran yüzlerce invitro çalışma halen devam etmekte. Bir çok botanik ürün güvenli olarak değerlendirilse de bir çok “doğal” ürün ise maalesef güvenilir değil.

Yöntem

Çalışma için PubMed’de, Ulusal Toksikoloji Programı (National Toxicology Program) , Dünya Kanser Araştırma Fonu (World Cancer Research Fund) ve Amerikan Kanser Araştırma Enstitüsü (American Institute of Cancer Research) veri tabanlarında “bitki ekstreleri”, “kanser”, “toksisite”, “ot”, “besin takviyesi” daha sonra bunlar “karsinojenik” anahtar kelimesiyle birleştirip seçilen vaka bildirimleri daraltılmaya çalışılmış. Eğer birden fazla bitkisel ürün karışımı varsa bunlar çalışmaya alınmamış. Mantarlar, zehirli olduğu bilinen bitkiler, suisid girişimleri, doz aşımları (vitamin/mineral harici), legal veya illegal madde kullanımları tabloya alınmamış.

Sonuçlar

1 Mayıs 2017 itibariyle PubMed’de; bitki ekstresi (152.425) , bitki ekstresi ve kanser (16.606), bitki esktresi ve kanser ve toksisiste (2.312), özet karşılarına çıkmış. Bu yöntemlerle bulunan otlar; aloevera, aristolochic asid, eğreltiotu, mavi devedikeni, öksürükotu, eşekkulağı, kanarya otu, Hint dutu, Kökboya bitkisi, Yerba Mate (Paraguay Çayı), Tesbih çiçeği, soya, sassafras ağacı. Son 50 yılda sadece 1 ot (guang fang ji- aristolochia kökü) üroepitelyal sarkom için, 2 besin (eğrelti otu ve sıcak mate çayı karsinojenik etkisiyle vaka bildirimleri bulunmuş.

Guang Fang Ji (Aristolochic asid ve içeren bitkiler)

Üriner sistem karsinomlarıyla ilişkili bulunmuş. Aynı zamanda Balkan Endemik Nefropatisine ( Bosna Hersek, Bulgaristan, Hırvatistan ve Sırbistan’daki çiftçilerde sık görülen bir nefropati türü) sebep olduğu; bu bölgedeki üroepitelyal kanserlerin sık görülmesinin tarlalarda aristolochic asid içeren bitkilerle olan temas olduğu düşünülüyormuş.

Balkanlardan ziyade Asya’da ve bir dönem Avrupa’da bu bitkilerin kullanıldığı bir çok bölge mevcut. 90larda Belçika’da bir diyet kliniğinin zayıflatmak için kullandığı otlardan biri buymuş ve bu hastaların %3-5’inde böbrek hasarı gelişmiş. 100’den fazla vaka bu grupta bildirilmiş. Vakaların 3’te 1’inin diyaliz ihtiyacı olmuş, 3’te 1’i böbrek nakline gitmiş kalan kısmı ise kronik böbrek hastası olarak kalmış. 2-6 yıl arasında ise bu vakaların %40-46’sında üroepitelyal karsinom gelişmiş.

Bu vakalardan sonra Geleneksel Çin Tıbbı uygulayıcıları Belçikalıların reçeteyi düzgün hazırlamadıkları için bu sonuç ortaya çıktığını söylese de, Tayvan üst üriner sistem kanserlerinin dünyada en çok görüldüğü ülke olarak biliniyor.

2001 yılından bu yana Aristolochic Asid ve içerikli ürünlerin ABD’ye girişi yasaklanmış ve dünyada bir çok ülke bu konuda Amerika’yı takip ediyor.

Hayvanlarda Kansere Sebep Olan Otlar

Bu makale insandaki kansere sebep olan maddeleri incelese de araştırma sırasında 9 bitkinin laboratuvar hayvanlarında kanserle ilişkili olduğu saptanmış.

  • Aloe vera
  • Öksürük otu
  • Eşekkulağı
  • Mabet bğacı
  • Altın Mühür bitkisi
  • Kanarya otu
  • Kava bitkisi
  • Kök boya
  • Sasafras

Ek olarak 1 besin takviyesinin (Avlimil) farelere implante edilen insan meme kanseri hücrelerini stimüle ettiği bulunmuş. Bu yazı insan vaka bildirimlerini incelese de bu örnekler değerlendirilmeye alınmış çünkü potansiyel karsinojenlerin hepsi hayvan deneyleriyle belirleniyor.

Aloe Vera

İnsanlarda güneş yanığı ve yara iyileşmesinde uzun süredir kullanılan aloe vera yaprakları ve ekstresinin son zamanlarda içecekler ve takviye kapsül formları dahi mevcut. İnsanlarda yapılan çalışma yok ancak ratlarda oral yolla alındığında kolon adenoca ile ilişkili bulunmuş.

Öksürük Otu

Öksürük, bronşit, üst solunum yolu inflamasyonlarında sıklıkla kullanılan ot, ratlarda karaciğer hemanjioendotelyal sarkoma sebep olduğu bulunmuş.

Eşekkulağı

Almanlar eşekkulağı bitkisini yara-sıyrıklarda eksternal kullanımını onaylamış ancak Physician Desk Reference for Herbal Medicines (bir altenatif tıp kitabı) ratlarda karaciğer toksisitesi ve karaciğer kanserine sebep olabildiği için dikkatli olunması gerektiğini söylüyor. İnternetten satın alınabilen bir ot ancak FDA önermiyor; içeriğindeki pirolizidin alkaloidinin hayvanlarda hepatotoksik olduğu biliniyor.

Mabet Ağacı (Ginkgo Biloba)

Hafıza kaybı ve demans için kullanılan bu bitkinin yaprak ekstreleri yüzlerce yıldır Geleneksel Çin Tıbbında kullanılmasına rağmen insan çalışmaları henüz yeterli değil ve hayvanlarda ise karaciğer kanseri riskini artırdığı bulunmuş.

Altın Mühür Bitkisi (Goldenseal)

Amerikan yerliler gastrointestinal sistem enfeksiyonları, ishal ve cilt enfeksiyonları için kullanıyorlar. Rat çalışmaları karaciğer kanseri riskini artırdığını belirtmiş.

Kanarya otu

Kuzeybatı Amerika ve Meksika’da kolik ağrı ve epilepsi için kullanılıyor, hepatotoksik olduğu biliniyor.

Kava Bitkisi

Fare çalışmaları karaciğer kanseri riskini artırdığını belirlemiş

Kök boya (Rubia tinctorum L)

Kırmızı kök boya bitkisi renk verici olarak kullanılıyor, ratlarda hem böbrek hem de karaciğer kanseriyle ilişkilendirilmiş.

Sassafras

Kuzey Amerika ve Asya’da bulunan ağaçlarından elde edilen Safrole; bira ve çayda aroma verici olarak kullanılıyor. 60’larda laboratuvar hayvanlarında karaciğer kanseri ile ilişkilendirilmiş, aynı zamanda plasentayı geçtiği ve sütle de yenidoğana geçebildiği hayvanlar üzerinde tespit edilmiş. PubMed literatüründe çayının tüketilmesinden sonra insanlarda aşırı terleme vakası bildirilmiş. FDA’in, ABD’de kullanılmasını yasakladığı bir ürün daha.

İnsanlarda Kanserle İlişkili Besinler

Araştırmacılar ABD’deki kansere bağlı ölümlerin 3’te 1’inin diyet düzenlemesi yaparak önlenebileceğini öngörüyorlar. Bazı diyet parametreleri, besinler bazı kanserlerin oranını azaltıyor veya artırıyor (Tablo 5).

Ulusal Kanser Araştırma Ajansı (IARC) 45 yılı aşkın süredir bu konu üzeirnde çalışmalar yapıyor ve 1000’den fazla neden tanımlanmış durumda. Bunların arasında gün ışığı, tütün, ilaç, hormonlar, alkol, parazitler, mantarlar, bakteriler, virüsler, talaş, tuzlanmış balık, bazı otlar vb.

Amerikan Kanser Araştırma Enstitüsü (AIRC) ve Dünya Kanser Araştırma Fonu (WCRF) ise obezite, sedanter yaşam şekli, kırmızı ve işlenmiş etin fazla tüketimi, azalmış meyve sebze tüketimi, yetersiz anne sütü alımını kanser ilişkili olarak tanımlamış.

Eğreltiotu

Dünyada bir çok ülkede yetişiyor ve bir çok kişi kullanıyor.Mesane ve intestinal kanserlerle ilişkili kendisine FDA veri tabanında zehirli bitki olarak yer edinmiş.

Sıcak Maté

Çaya benzeyen Güney Amerikada yaygın olarak tüketilen kafein bazlı içecek.Brezilya ve Uruguay bölgesinde oral-özefagial kanserlerle ilişkilendirilmiş.

Soya Besinleri ve Genistein

Yapılan 2 farklı metaanalizde soya alımının meme kanseri rekürrensiyle ilişkili olmayıp, bazı vakalarda riski azalttığı belirlenmiş ve tamoksifen ve anastrozole tedavisinde çalışmalar sürmekteymiş (Chi et al., 2013; Magee & Rowland,

2012). Genistein ise bir antioksidan olarak bilinmekte ancak yapılan çalışmalardan hala anlamlı veri elde edilememiş.

İlaç Etkileşimleri

Doktorlar ve hastalar besin takviyelerinin tedavilerle çakışabileceğinin farkında olmalılar. Her zaman olduğu gibi; daha fazla bilgi sahibi olana kadar; karaciğer, böbrek, kalp,  kanser hastaları, organ nakli olanlar, gebeler, emzirenler, başka ilaç kullananlar takviye besin veya bitkileri doktorları önermedikçe kullanmamalıdırlar.

Kısıtlılıklar

Çalışma ağırlıklı olarak PubMed ile sınırlı kalmış ve tüm literatürü göstermemekte. Dolayısıyla bitkilerin daha sık kullanıldığı Çin, Hindistan, Japon kaynaklarından bilgi yok sayılıyor. Bitki isimleri bölgeden bölgeye farklılıklar gösterebiliyor. Dolayısıyla burada olanlar ABD’de tanımlananlarla sınırlı. Bir diğer kısıtlama ise küflerin çalışmaya alınmamış olması. Çünkü küfler de besinler üzerinde bulunabiliyor ve potansiyel olarak karsinojenik olabilirler.

Kaynak

  • Amy C. Brown (2018) Cancer Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 5 of 5, Journal of Dietary Supplements, 15:4, 556-581, DOI: 10.1080/19390211.2017.1355865
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