Vrednotenje varnosti dermalne in sistemske uporabe retinoidov v nosečnosti

Selan, Tajka (author), Peterlin Mašič, Lucija (mentor)

Retinoidi, vitamin A in njegovi derivati, ne predstavljajo samo pomembne skupine zdravilnih učinkovin, ki jih lahko uporabljamo sistemsko (npr. za zdravljenje okužb, kožnih in rakavih obolenj) ali dermalno (za zdravljenje kožnih obolenj), pač pa tudi kozmetično aktivne sestavine in sestavine prehranskih dopolnil. Ne glede na široko uporabnost retinoidov, pa morajo biti nosečnice pri njihovi uporabi previdne, saj lahko izpostavljenost retinoidom škoduje plodu. Nosečnice lahko preko sistemske (zdravljenje, prehranska dopolnila) ali dermalne (zdravljenje, kozmetični izdelki) uporabe pridejo v stik z retinoidi, ki so znani teratogeni. Izpostavljenost retinoidom v nosečnosti lahko povzroči malformacije ploda ali spontani splav. Vrednotenje varnosti dermalne in sistemske rabe retinoidov nam omogoča snovanje boljših smernic za nosečnice, z namenom, da bi vnesle dovolj vitamina A, ki je nujno pomemben za embriogenezo in razvoj otroka, a hkrati, da z uporabo določenih oblik ne bodo ogrozile varnosti ploda. Namen magistrske naloge je bil ovrednotiti varnost uporabe topikalnih retinoidov, ki jih uporabljamo za zdravljenje dermatoloških bolezni, topikalnih retinoidov, ki jih uporabljamo v kozmetičnih izdelkih, sistemskih retinoidov, ki jih uporabljamo za zdravljenje bolezni ter prehranskih dopolnil z vitaminom A in s tem varnih odmerkov nadomeščanja vitamina A za nosečnice. Za pregled varnostnih profilov zdravil, prehranskih dopolnil in kozmetičnih izdelkov, ki vsebujejo retinoide, smo uporabili znanstvene članke iz podatkovne baze PubMed, z iskalnim profilom »(retinoids OR vitamin A) AND pregnancy« ter raziskave omejili na pregledne članke, sistematične pregledne članke, metaanalize in klinične študije, izdane v letih 2001–2021. Izmed vseh retinoidov, ki se uporabljajo za topikalno in sistemsko zdravljenje, smo izbrali 5 zdravilnih učinkovin, ki so dostopne v Republiki Sloveniji in podrobneje raziskali varnost njihove uporabe v nosečnosti. Ugotovili smo, da je dermalna uporaba retinoidov za zdravljenje kožnih obolenj v nosečnosti odsvetovana, kljub temu, da ob pravilni uporabi zdravil obstaja majhna verjetnost za sistemske učinke. Enako velja tudi za kozmetične izdelke, ki vsebujejo retinoide, saj smo ljudje ena izmed najbolj občutljivih vrst za toksičnost retinoidov. Sistemska uporaba retinoidov za zdravljenje obolenj, pri katerih tveganje ne pretehta koristi, je v obdobju nosečnosti strogo odsvetovana, saj lahko vodi do resnih malformacij ploda. Dopolnjevanje prehrane z vitaminom A pri nosečnicah svetujemo le, v kolikor obstaja tveganja za pomanjkanje, sicer pa lahko presežek vitamina A v obliki prehranskih dopolnil prav tako predstavlja tveganje za teratogene učinke.

• Language: Slovenian
• Keywords: varnost, retinoidi, dermalna uporaba, sistemska uporaba, nosečnost
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-150951
• Publication date in RUL: 26.09.2023

Secondary language

• Language: English
• Title: Safety evaluation of dermal and systemic retinoid use in pregnancy

Abstract

Retinoids, vitamin A and its derivatives, represent not only an important group of medicinal agents that can be used systemically (e.g. for the treatment of infections, skin and cancer diseases) or dermally (for the treatment of skin diseases), but also cosmetically active ingredients and components of nutritional supplements. Regardless of the wide applicability of retinoids, pregnant women must be careful when using them, as exposure to retinoids can harm the fetus. Pregnant women can come into contact with retinoids, which are known teratogens, through systemic (treatment, nutritional supplements) or dermal (treatment, cosmetic products) use. Exposure to retinoids during pregnancy may cause fetal malformations or miscarriage. Evaluating the safety of dermal and systemic use of retinoids allows us to design better guidelines for pregnant women, with the aim that pregnant women will take in enough vitamin A, which is essential for embryogenesis and development of the child, but at the same time, that they will not endanger the safety of the fetus by using certain forms. The purpose of the master's thesis is to evaluate the safety of topical retinoids used for the treatment of dermatological diseases, topical retinoids used in cosmetic products, systemic retinoids used for the treatment of diseases and nutritional supplements with vitamin A and thus safe doses of vitamin replacement for pregnant women. To review the safety profiles of drugs, nutritional supplements and cosmetic products containing retinoids, we used scientific articles from the PubMed database with the search profile "(retinoids OR vitamin A) AND pregnancy" and limited the research to review articles, systematic review articles, meta-analyses and clinical studies published between 2001 and 2021. From among all retinoids used for topical and systemic treatment, we selected 5 active ingredients that are available in the Republic of Slovenia and investigated in more detail the safety of their use during pregnancy. We found that the dermal use of retinoids for the treatment of skin diseases in pregnancy is not recommended, despite the fact that there is a small probability of systemic effects when the drugs are used correctly. The same applies to cosmetic products containing retinoids, as humans are one of the most sensitive species to retinoid toxicity. The systemic use of retinoids for the treatment of diseases in which the risk does not outweigh the benefits is strictly advised against during pregnancy, as it can lead to serious malformations of the fetus. Supplementing the diet with vitamin A is recommended for pregnant women only if there is a risk of deficiency, otherwise an excess of vitamin A in the form of dietary supplements may also pose a risk of teratogenic effects.

• Keywords: safety, retinoids, dermal use, systemic use, pregnancy