Abstract
Relevance. Today, the pharmacotherapy of many diseases is significantly expanded. However, the amount of pathological conditions associated with the use of drugs has increased. Drug related problems in some cases can be fatal and increase health care costs. It is necessary to be able to anticipate in advance the possibility of developing such conditions, to prevent them. Therefore, the analysis of the causes and mechanisms of development of these conditions is relevant.
 Objective. To find out the most common causes of drug related problems and consider the mechanisms of such states.
 Methods. Analysis of scientific publications in PubMed by keywords for the period 2001-2018.
 Results. The therapeutic index is the ratio of the dose that causes toxic effects in 50% of patients to the dose that causes the expected therapeutic effect in 50% of patients. The therapeutic index ≤ 3 is an indicator that defines drugs with narrow (small) therapeutic index. These drugs include insulin, digoxin, warfarin, levothyroxine, aminoglycoside antibiotics, carbamazepine, lithium, phenytoin, etc.
 The risks associated with these drugs are: the use of generic drugs with insufficient bioequivalence, pharmacokinetic interaction and polymorphism of genes of drug metabolism. The main mechanisms of their pharmacokinetic interaction at the stages of absorption (alteration of digestive tract motility, influence on the activity of P-glycoprotein), distribution (competition for blood plasma proteins and tissue proteins), and biotransformation (inhibition or induction of metabolism). The role of polymorphism of genes encoding the activity of isoenzymes cytochrome P450 2C9 and 1A2 and glycoprotein P in the development of adverse drug reactions of drugs with a narrow therapeutic index is presented.
 Conclusion. Risk management of using drugs with a narrow therapeutic index should include therapeutic drug monitoring of especially generic drugs, assessment of the risks of pharmacokinetic interaction, widespread introduction pharmacogenetic tests for determine the polymorphism of the genes of metabolism enzymes and drug transporters in the clinical practice.
Highlights
Ïðè ïðèéîì3 öèïðîôëîêñàöèíó ïîòð3áíî çíèæóâàòè äîçè òåîô3ë3íó òà âàðôàðèíó ÷è ôåí3òî¿íó
Äëÿ ìåíåäæìåíòó äàíèõ ðèçèê3â âàæëèâî çàáåçïå÷èòè òåðàïåâòè÷íèé ë3êàðñüêèé ìîí3òîðèíã ë3êàðñüêèõ çàñîá3â (ËÇ) 3ç ÂÒ2, îñîáëèâî ãåíåðè÷íèõ ïðåïàðàò3â, çä3éñíþâàòè îö3íêó ðèçèê3â âçàoìîä3¿ ËÇ (çîêðåìà, ôàðìàêîê3íåòè÷íî¿), à òàêîæ øèðøå âïðîâàäæóâàòè ó êë3í3÷íó ïðàêòèêó ôàðìàêîãåíåòè÷í3 òåñòè äëÿ âèçíà÷åííÿ ïîë3ìîðô3çìó ãåí3â ôåðìåíò3â ìåòàáîë3çìó òà òðàíñïîðòåð3â ËÇ
Summary
Ïðåäñòàâëåíî ðîëü ïîë3ìîðô3çìó ãåí3â, ùî êîäóþòü àêòèâí3ñòü 3çîôåðìåíò3â öèòîõðîìó Ð450 2C9 òà 1À2, à òàêîæ ãë3êîïðîòå¿íó Ð ó ðîçâèòêó ïîá3÷íèõ ðåàêö3é ËÇ 3ç âóçüêèì òåðàïåâòè÷íèì 3íäåêñîì. Ìåíåäæìåíò ðèçèê3â ïðè çàñòîñóâàíí3 ë3êàðñüêèõ çàñîá3â 3ç âóçüêèì òåðàïåâòè÷íèì 3íäåêñîì ïîâèíåí âêëþ÷àòè òåðàïåâòè÷íèé ë3êàðñüêèé ìîí3òîðèíã, îñîáëèâî ãåíåðè÷íèõ ïðåïàðàò3â, îö3íêó ðèçèê3â ôàðìàêîê3íåòè÷íî¿ âçàoìîä3¿, øèðîêå âïðîâàäæåííÿ ó êë3í3÷íó ïðàêòèêó ôàðìàêîãåíåòè÷íèõ òåñò3â äëÿ âèçíà÷åííÿ ïîë3ìîðô3çìó ãåí3â ôåðìåíò3â ìåòàáîë3çìó òà òðàíñïîðòåð3â ë3êàðñüêèõ çàñîá3â. Òåðàïåâòè÷íèé 3íäåêñ ≤ 3 o ïîêàçíèêîì, ÿêèé âèä3ëÿo ËÇ 3ç ÂÒ2 [7, 24], äî íèõ â3äíîñÿòüñÿ 3íñóë3í, äèãîêñèí, âàðôàðèí, ëåâîòèðîêñèí, àì3íîãë3êîçèäí3 àíòèá3îòèêè, êàðáàìàçåï3í, ë3ò3é, ôåí3òî¿í òîùî [19].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
