{"id":2089,"date":"2021-06-21T23:43:59","date_gmt":"2021-06-21T20:43:59","guid":{"rendered":"https:\/\/tatd.org.tr\/tatdtoks\/2021\/06\/21\/ilaclarin-istenmeyen-etkilerinin-cinsiyete-gore-dagilimi\/"},"modified":"2022-01-06T12:15:35","modified_gmt":"2022-01-06T09:15:35","slug":"ilaclarin-istenmeyen-etkilerinin-cinsiyete-gore-dagilimi","status":"publish","type":"post","link":"https:\/\/tatd.org.tr\/toksikoloji\/2021\/06\/21\/ilaclarin-istenmeyen-etkilerinin-cinsiyete-gore-dagilimi\/","title":{"rendered":"\u0130la\u00e7lar\u0131n \u0130stenmeyen Etkilerinin Cinsiyete G\u00f6re Da\u011f\u0131l\u0131m\u0131"},"content":{"rendered":"

Pek\u00e7ok ila\u00e7ta ki\u015finin ya\u015f\u0131, cinsiyeti, ailesel ve genetik \u00f6zellikleri, \u00e7evresel ko\u015fullar\u0131\u00a0 gibi etmenler ile ilaca ba\u011fl\u0131 istenmeyen yan etkiler olu\u015fur. Bunun en bariz \u00f6rne\u011fi cinsiyete ba\u011fl\u0131 olan yan etkilerdir.\u00a0 Advers ila\u00e7 reaksiyonlar\u0131 hakk\u0131nda yap\u0131lm\u0131\u015f ve cinsiyete g\u00f6re farkl\u0131 olan bildirimler ise Tablo 1<\/strong>\u2019 de mevcuttur. Bu tabloya ait referanslar\u0131n listesi en altta olup fakl\u0131 makale ve kaynak kitaplardan eri\u015filebilir olacak \u015fekilde listelenmi\u015ftir.\u00a0 Burada\u00a0 Tablo 2<\/strong>\u2019 de g\u00f6r\u00fclece\u011fi gibi cinsiyete ba\u011fl\u0131 olarak fizyolojik ve metabolik farkl\u0131l\u0131klar mevcuttur. Altta yatan bu s\u00fcre\u00e7lerin kad\u0131n, erkek veya gebede farkl\u0131 oldu\u011funu k\u0131saca \u00f6zetlemek istedim. Referans olarak kullan\u0131laca\u011f\u0131n\u0131 \u00fcmit ederim.<\/p>\n

Tablo 1.<\/strong> Advers ila\u00e7 reaksiyonlar\u0131nda cinsiyet farkl\u0131l\u0131kar\u0131<\/p>\n

\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\u0130la\u00e7 s\u0131n\u0131f\u0131<\/strong><\/td>\nKlinik tablolar\u0131n k\u0131yaslamas\u0131<\/strong><\/td>\n<\/tr>\n
Analjezikler<\/td>\nKad\u0131nlarda perioperative analjeziklerde daha \u00e7ok yan etki1<\/sup>.<\/td>\n<\/tr>\n
Anafilaktik \u015fok<\/td>\nKad\u0131nlarda n\u00f6romuskuler bloker ajanlar, hipnotikler, opioidler ve benzodiazepinler daha s\u0131k anafilaktik \u015foka neden olur2<\/sup>.<\/td>\n<\/tr>\n
Anestetik ila\u00e7lar<\/td>\nKad\u0131nlarda ADR postoperatif olarak daha s\u0131kt\u0131r 2-4<\/sup><\/td>\n<\/tr>\n
ACE inhibitorleri<\/td>\nKuru \u00f6ks\u00fcr\u00fck kad\u0131nlarda 2-3 kat daha fazla5-7<\/sup>. Anjiyo\u00f6dem \/ \u00fcrtiker e\u015fit 8<\/sup>.<\/td>\n<\/tr>\n
Antiaritmikler<\/td>\nKad\u0131nda QT uzama riski ve TdP daha fazla9-10<\/sup>.<\/td>\n<\/tr>\n
Antikoagulanlar<\/td>\nKad\u0131nlarda daha s\u0131k ve ciddi kanamalar11-19<\/sup><\/td>\n<\/tr>\n
H1-Antihistamin grubu<\/td>\nKad\u0131nlarda sedasyon, uyku hali daha fazla 20-22<\/sup><\/td>\n<\/tr>\n
Antiplatelet ajanlar<\/td>\nKad\u0131nlarda daha s\u0131k ve ciddi kanamalar23<\/sup><\/td>\n<\/tr>\n
Antipsikotikler<\/td>\nKad\u0131nlarda daha fazla ekstrapiramidal ve antikolinerjik etkiler, Qtc uzamas\u0131. Erkeklerde ise daha fazla cinsel problemler bildirilmi\u015ftir24-27<\/sup><\/td>\n<\/tr>\n
Aspirin<\/td>\nKad\u0131nlarda kanama riski daha fazla 28<\/sup>. Erkeklerde ise \u00fclser komplikasyonlar\u0131 daha fazla29<\/sup><\/td>\n<\/tr>\n
Beta blokerler<\/td>\nKad\u0131nda metoprolol kan bas\u0131nc\u0131n\u0131 ve kalp h\u0131z\u0131n\u0131 daha fazla bask\u0131lar 30<\/sup>.<\/td>\n<\/tr>\n
Benzodiazepinler<\/td>\nDiazepam\u00a0kad\u0131nlarda daha fazla psikomotor becerileri bozar31<\/sup>. Kad\u0131nda ba\u011f\u0131ml\u0131l\u0131k daha s\u0131k26<\/sup><\/td>\n<\/tr>\n
Kalsiyum kanal blokerleri<\/td>\nKad\u0131nda \u00f6dem riski daha fazla 32<\/sup>. menstruasyon s\u0131ras\u0131nda diazepam alanlarda entoksikasyon daha fazla33<\/sup><\/td>\n<\/tr>\n
Digoksin<\/td>\nKad\u0131nlarda kalp yetmezli\u011finde mortalite fazlad\u0131r 34<\/sup>. Kad\u0131nda trepa\u00f6tik digoksin plasma d\u00fczeyleri\u00a0 < 0.8 ng\/mL olarak \u00f6nerilir 35<\/sup><\/td>\n<\/tr>\n
Di\u00fcretikler<\/td>\nHipo- osmolarite, hipopotasemi ve hiponatremi kad\u0131nda daha s\u0131k olup aritmiye neden olur15,35-39<\/sup><\/td>\n<\/tr>\n
De\u011fi\u015fik ila\u00e7lar ile\u00a0 TdP<\/td>\nKad\u0131nlarda de\u011fi\u015fik ila\u00e7lar ile QTc aral\u0131\u011f\u0131 uzama riski ve\u00a0 TdP olu\u015fma riski daha s\u0131kt\u0131r 40-44<\/sup><\/td>\n<\/tr>\n
GPIIb\/ IIIa inhibitorleri<\/td>\nKad\u0131nda erkekten daha s\u0131kt\u0131r23,45<\/sup><\/td>\n<\/tr>\n
Heparin<\/td>\nKad\u0131nlarda kanama riski daha y\u00fcksektir 12,46,47<\/sup><\/td>\n<\/tr>\n
Opioid reseptor agonistleri<\/td>\nKad\u0131nda daha fazla bulant\u0131, kusma, solunum depresyonu 48-52<\/sup><\/td>\n<\/tr>\n
NSAID<\/td>\nErkeklerde yan etkilerin toplam prevalans\u0131 daha fazla 29,53-55<\/sup><\/td>\n<\/tr>\n
Parasetamol<\/td>\nKad\u0131nda parasetamol zehirlenmesinde akut karaci\u011fer yetmezli\u011fi daha s\u0131k 56<\/sup><\/td>\n<\/tr>\n<\/tbody>\n<\/table><\/div>\n

K\u0131saltmalar:<\/strong>\u00a0ACE: anjiotensin-converting enzim, \u00a0NSAID: non-steroidal anti-inflammatory drug = steroid olmayan antienflamatuar ila\u00e7,\u00a0QTc: corrected QT interval,TdP: torsades de pointes.<\/p>\n

Tablo 2.<\/strong> Cinsiyete ba\u011fl\u0131 farkl\u0131l\u0131k g\u00f6steren fizyoloji ve metabolik parametreler 67<\/sup><\/p>\n

\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

\u00a0 Parametreler<\/strong><\/p>\n<\/th>\n

\n

\u00a0 Cinsiyet fark\u0131<\/p>\n<\/th>\n<\/tr>\n<\/thead>\n

\u00a0 \u00a0\u0130la\u00e7 Biyoyararlan\u0131m\u0131<\/strong><\/td>\n<\/tr>\n
\u2003Emilim<\/td>\n\u00a0 \u00a0E > K<\/td>\n<\/tr>\n
\u2003Gastrik asit sekresyonu<\/td>\n\u00a0 \u00a0E > K > G.<\/td>\n<\/tr>\n
\u2003Gastrik bo\u015falma<\/td>\n\u00a0 \u00a0E > K > G. Estrojen gastrik bo\u015falmay\u0131 inhibe eder.<\/td>\n<\/tr>\n
\u2003Gastrointestinal ge\u00e7i\u015f zaman\u0131<\/td>\n<\/tr>\n
\u2003Barsak \u00a0metabolizmas\u0131<\/td>\n\u00a0 \u00a0E = K<\/td>\n<\/tr>\n
\u00a0 \u00a0V\u00fccut yap\u0131s\u0131<\/strong><\/td>\n<\/tr>\n
\u2003V\u00fccut y\u00fczey alan\u0131<\/td>\n\u00a0 \u00a0E > G > K. V\u00fccut y\u00fczeyi artt\u0131k\u00e7a emilim de artar<\/td>\n<\/tr>\n
\u2003Organ (kalp) boyutu<\/td>\n\u00a0 \u00a0E > K<\/td>\n<\/tr>\n
\u2003Organ kan ak\u0131m\u0131<\/td>\n\u00a0 \u00a0Erkekte iskelet kas\u0131 ve karaci\u011fere kan ak\u0131m\u0131 daha fazla.<\/p>\n

Kad\u0131nda ya\u011f dokusuna kan ak\u0131m\u0131 fazla.<\/p>\n

Gebelikte kan ak\u0131m\u0131 artar<\/td>\n<\/tr>\n

\u2003Total v\u00fccut s\u0131v\u0131s\u0131<\/td>\n\u00a0 \u00a0E > G > K<\/td>\n<\/tr>\n
\u2003Plazma hacmi<\/td>\n\u00a0 \u00a0G > E > K. Menstrual siklus ve gebelikte de\u011fi\u015fken<\/td>\n<\/tr>\n
\u2003V\u00fccut ya\u011f oran\u0131<\/td>\n\u00a0 \u00a0K> E<\/td>\n<\/tr>\n
\u2003Kardiyak at\u0131m<\/td>\n\u00a0 \u00a0E > G > K.<\/td>\n<\/tr>\n
\u2003Pulmoner fonksiyon<\/td>\n\u00a0 \u00a0E > G > K.<\/td>\n<\/tr>\n
\u00a0 \u00a0Da\u011f\u0131l\u0131m<\/strong><\/td>\n<\/tr>\n
\u2003Da\u011f\u0131l\u0131m hacmi (Vd)<\/td>\n\u00a0 \u00a0K >E.\u00a0 Lipofilik ila\u00e7lar i\u00e7in<\/td>\n<\/tr>\n
\u00a0 \u00a0E > K. Hidrofilik ila\u00e7lar i\u00e7in<\/td>\n<\/tr>\n
\u00a0 \u00a0Plazma proteinin\u00a0 ba\u011flanma yeri<\/strong><\/td>\n<\/tr>\n
\u2003Albumin<\/td>\n\u00a0 \u00a0E = K. Gebelik ve estrojen plazma albumini azalt\u0131r. Serbest ila\u00e7 artar.<\/td>\n<\/tr>\n
\u2003\u03b11-asid\u00a0 glikoprotein<\/td>\n\u00a0 \u00a0E > K. Estrojen ve gebelikte plazma d\u00fczeyi azal\u0131r<\/td>\n<\/tr>\n
\u2003Globulin<\/td>\n\u00a0 \u00a0Estrojen,\u00a0\u00a0 cinsiyet hormonlar\u0131, kortikosteroid ve tiroksin ba\u011flay\u0131c\u0131 globulinleri art\u0131r\u0131r<\/td>\n<\/tr>\n
\u00a0 \u00a0Drug\/ ila\u00e7 ta\u015f\u0131y\u0131c\u0131lar<\/strong><\/td>\n<\/tr>\n
\u2003Hepatik P-glikoprotein<\/td>\n\u00a0 \u00a0E > K<\/td>\n<\/tr>\n
\u2003OCT2<\/td>\n\u00a0 \u00a0E > K.<\/td>\n<\/tr>\n
\u2003OATP1B1-3<\/td>\n\u00a0 \u00a0E > K<\/td>\n<\/tr>\n
\u00a0 \u00a0Metabolizan enzimler ve ta\u015f\u0131y\u0131c\u0131lar<\/strong><\/td>\n<\/tr>\n
\u2003Faz I metabolik reaksiyonlar<\/strong> (hydroliz, oksidasyon, reduksiyon) cytochrome P450 (CYP) isoformlar\u0131 arac\u0131l\u0131k eder<\/td>\n\u00a0 \u00a0CYP1A2: E > K. Gebelikte ve estrojen ile azal\u0131r<\/td>\n<\/tr>\n
\u00a0 \u00a0CYP2B6: K > E<\/td>\n<\/tr>\n
\u00a0 \u00a0CYP2C9: E = K<\/td>\n<\/tr>\n
\u00a0 \u00a0CYP2C19: E = K<\/td>\n<\/tr>\n
<\/td>\n<\/tr>\n
\u00a0 \u00a0CYP3A4: K > E.<\/td>\n<\/tr>\n
\u00a0 \u00a0CYP2D6: E > K. Estrojen ind\u00fckler<\/td>\n<\/tr>\n
\u00a0 \u00a0CYP2E1: E > K.<\/td>\n<\/tr>\n
\u2003Faz \u00a0II metabolizma enzimleri<\/strong><\/td>\n<\/td>\n<\/tr>\n
\u2003\u2003Uridin difosfat\u00a0 glukuronosil-transferaz<\/td>\n\u00a0 \u00a0E > K. Gebelikte ve Estrojen ile artar<\/td>\n<\/tr>\n
\u2003\u2003N<\/em>-Asetiltransferaz<\/td>\n\u00a0 \u00a0E= K<\/td>\n<\/tr>\n
\u2003\u2003Katekol-O-metiltransferaz<\/td>\n\u00a0 \u00a0E > K<\/td>\n<\/tr>\n
\u2003\u2003Asetil-butiril-kolinesteraz<\/td>\n\u00a0 \u00a0E > K<\/td>\n<\/tr>\n
\u2003\u2003Xantin-oxidaz<\/td>\n\u00a0 \u00a0K > E<\/td>\n<\/tr>\n
\u2003\u2003Gastrik alkol\u00a0 dehidrojenaz<\/td>\n\u00a0 \u00a0E > K. Kad\u0131nda plazmada alkol d\u00fczeyleri daha y\u00fcksektir<\/td>\n<\/tr>\n
\u00a0 \u00a0Drug\/ ila\u00e7 at\u0131l\u0131m <\/strong><\/td>\n<\/tr>\n
\u00b7\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0Renal kan ak\u0131m\u0131<\/p>\n

\u00b7\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0\u00a0Glomerular filtrasyon h\u0131z\u0131<\/p>\n

\u00b7\u00a0\u00a0\u00a0\u00a0 \u00a0\u00a0\u00a0\u00a0Tubular sekresyon\/ reabsorbsiyon<\/td>\n

\u00a0 \u00a0E > K. Renal klerens gebelikte artar<\/td>\n<\/tr>\n
\u00a0 \u00a0Renal at\u0131l\u0131mda aktif olarak sekrete olan ila\u00e7lar cinsiyete g\u00f6re farkl\u0131 olabilir.<\/td>\n<\/tr>\n<\/tbody>\n<\/table><\/div>\n

K\u0131saltmalar:<\/strong> E: Erkek, K: Kad\u0131n, G: Gebelik<\/p>\n

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\u0130la\u00e7lar\u0131n kullan\u0131m\u0131na ba\u011fl\u0131 geli\u015fen toksitelerin \u00f6nemli bir k\u0131sm\u0131 ilac\u0131n molek\u00fcler \u00f6zelliklerinden ba\u011f\u0131ms\u0131z olarak v\u00fccutta ge\u00e7irdi\u011fi metabolik ve enzimatik s\u00fcre\u00e7lerde bireysel farkl\u0131l\u0131klara dayanmaktad\u0131r. G\u00fcn\u00fcm\u00fczde ki\u015fiye \u00f6zel \u201ctarget tedavilerin ilerlemesi ve genetik tedavi y\u00f6ntemlerinin\u201d geli\u015ftirilmesi bu felsefe \u00fczerinden ilerlemektedir. Asl\u0131nda biz acil t\u0131pta genetik veya metabolik bireye \u00f6zel\u00a0 tedaviler yapamasak da kar\u015f\u0131m\u0131za drug\/ ila\u00e7 toksisitesi ile gelmi\u015f bir hastada beklenen semptomlar\u0131 \u00f6nden tahmin edebiliriz.<\/p>\n","protected":false},"author":1538,"featured_media":2090,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[10010,10014],"tags":[103,192,441],"class_list":["post-2089","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-slider","category-akademik-blog-yazisi","tag-cinsiyet-farki","tag-ilac-yan-etkileri","tag-yan-etki"],"acf":[],"_links":{"self":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/2089","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/users\/1538"}],"replies":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/comments?post=2089"}],"version-history":[{"count":0,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/2089\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media\/2090"}],"wp:attachment":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media?parent=2089"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/categories?post=2089"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/tags?post=2089"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}