Mangarova, M.

Mihova, V.

Varbanov, G.

Zheljazkov, D.

Zheljazkova, M.

English

Varna Medical University Press: Journals

DRUGS AND LABORATORY TESTS: I . INTERACTION OF PHENAMIN AND A C E T Y S A L WITH DETERMINATION OF F R E E F A T T Y ACIDS D. Zheljazkov, V. Mihova, M. Zheljazkova, M. Mangarova, G. Varbanov Key-words: free fatty acids — Phenamin—Acetysal—hepatic cirrhosis—chronic renal failure The influence of many drugs on plasma levels of free fatty acids ( F F A ) ( F . P . Kup ieck i , 1971; A . B izz i et a l . , 1964) presents possibilities as wel l for imitat ion or interference wi th l ipid metabolism changes in certain pathological processes as for difficulties and mistakes in their diagnosis or prognosis. The literature data ( L . A . Carlson and J . Ostman, 1961; R . Santi and G . Fassina, 1965) about some changes in total plasma F F A after Phenamin or Acetysal application direc­ted us to the comparison of the effects both drugs on total concentration and levels of 7 individual F F A with the changes of the same indexes in 2 patients' groups; wi th hepatic cirrhosis (HC) and wi th chronic renal failure ( C R F ) ( 3 r d — 4 t h degree). Our attention was paid to Acetysal as a drug belonging to the wide-spread group of non-steroid antiinflammatory agents. I ts basic mechanism of action is the inhibit ion of prostaglandin synthetase ( D . Metzler, 1980). The often non-controlled use of Acetysal can lead the physician to false interpretations of labo­ratory findings. The duration of prostaglandin synthetase inhibit ion after a sin­gle dose Acetysal is 5—7 days long ( J . Hirsch, 1977) what is of importance for the c l in ica l practice. The Phenamin was chosen as a representative of indirect sympathomimetic amines the use of which as regards of their doping and anorexigenic action can be left out of control by physicians. Material and methods The study was carried out on 108 persons divided into 5 groups as followed: 1 s t one — 50 healthy; 2 n d — 9 volunteers treated wi th a single dose of 10 mg Phe­namin; 3 r d — 9 volunteers given Acetysal (total dose 3,0 g, thrice dai ly divided in equal 6 hours intervals) 4 t h — 24 patients wi th H C , and 5 t h one — 16 pa­tients wi th C R F . I n any persons the following F F A were determined: myrist ic Ql 4 : 0 ; palmitic C i 6 . 0 ; palmitoleic C 1 6 . -/, stearic C 1 8 . 0 ; oleic C 1 8 . x ; linoleic C 1 8 . 2 ; and arachidic С 2 0 : 4 . The changes in both saturated and unsaturated F F A and in the arachidic acid level were followed up and the ratio between the linoleic acid as a precursor of arachidic acid and the arachidic acid itself (index C 1 8 . 2 / C 2 o : 4 ) was calculated. The arachidic acid was taken into special consideration because of its importance as an immediate precursor in prostaglandin synthe­sis for the second series. The F F A were determined by using gas chromatography wi th the apparatus Chrom-4. The extraction was perfomed according to Dole's method (1960) and Drugs and laboratory tests: I . Interaction of. 21 the methylizing of F F A — by using diazomethane syntesized from acetamide in our laboratory. . Y . . , , . • • The calculations were made according to an intrinsic standard arachinic acid ( C 2 0 . o)-Results and discussion The received results show that the total amount of F F A is significantly in­creased, as well after Phenamin and Acetysal treatment as in H C or C R F patients Free fatty acids сно lCt6 o' Ci8 0 '' Ci6 i'' °i6>i,Cte г'Сго* /J22 Fig . 1 U16QQ -UQO -1200 -| / ш -^ 800 -£ 500 -К 400 -200-496 ¥ i 716 1100 946 Healthy Ph Acet ЛС CRF Fig . 2 400 ^ зоо ^ 200 4 °- too Шаге Ph A afterp* Ж ZZO zi6 W9 /72 m ! 326 I n i I i n comparison wi th that in healthy individuals (fig. 1). Th i s increase is in both patients' groups wi th in the range of drug-mediated changes. The relative share of saturated and non-saturated F F A and arachidic acid varies in this total in-\ 22 D. Zheljazkov, V . Mihova, M. Zheljazkova. crease. After treatment wi th Phenamin (fig. 2) and Acetysal (fig. 3) the enhanc­ing is due exclusively to the G > 0 . 4 . Probably, the Acetysal inhibit ion of prosta­glandin synthetase blockades the involving of this acid in its further metabolism, WOO 800 ^ 600 5 400 200 /107 CZ3 before Acet ШИ after Acet /89 /68 220 24& Ж л о Fig . З two woo 400 ^ 300 zoo IOOV / » + / ? * / » /7 + Г • n Ы.о °wo Lre.o °/6o %t °ie2 1107 71 306 • Healthy 282 E 3 Acet Шр/1 Ш CRF CD tic F i g . 4 i . e. in prostaglandin synthesis. I n both patients' series the three F F A groups increase. Here, s imi lar ly to drug effects, the part of arachidic acid is the largest one. I t is fourfold increased in H C patients and even more — in C R F ones. The com­parison of absolute amounts of this acid shows a marked s imi la r i ty of the levels in both patients' groups and Phenamin (fig. 4) treated individuals . I n regard to the mechanisms determining the pathological changes of the F F A levels one can presume a larger analogy wi th the selective adrenergic mediated adipokinesis realized by Phenamin than wi th the Acetysal action. Drugs and laboratory tests: I . Interaction of. 23 The received data demonstrate certain one-way changes of the index C 1 8 : ^ C 2 o: 4 (fig- 5) in the series studied. The sharp increase of the relative part of arachidi acid in the group under Acetysal treatment and the s imi la r i ty of indices in at Index cto Jilt* I 1 1 1 1 1 I x i 1 2 3 5 5 П & Fig . 5 patients and individuals under Phenamin treatment is clearly outlined. The data showing a significant diminution of the ratio C 1 8 : 2 / C 2 o : 4 point out that th-liberation of the C 2 0 : 4 and the eventual transformation of the C i 8 . 2 into C 2 0 . 4 in a l l groups studied is accomplished considerably more rapidly than the transfor mation of C 2 0 : 4 into prostaglandins. Conclusions 1. Phenamin which is a representative of catecholamines liberating or ago­nist adrenergic act iv i ty carrying drugs, increases the level of plasma F F A , espe­c i a l l y of the arachidic acid as an immediate precursor in prostaglandin synthesis. 2. Acetysal which is a prototype of prostaglandin synthetase inhibi t ing drugs, causes also an increase of the level of plasma F F A by means of selective enhancing of arachidic acid concentration. 3. The interaction between Phenamin and Acetysal wi th plasma levels of F F A is indirect and it is realized by means of pharmacological mechanisms. 4. The increase of F F A levels and the distribution of F F A after Phenamin or Acetysal application is similar to the changes established in H C and C R F . T h i s circumstance make the interpretation of fhe results from the studies of F F A by the physician difficult, indeed. R E F E R E N C E S 1. М е ц л е р , Д . Биохимия. M. , Мир, 1980, т. 2, с. 554. — 2. В i z z i , A . , A . M. C o d e g o n i e t a l . Nature (London) 204, 1964, 1205. — 3. С a r l s о n, L . A . , J . О s t -m a n . J . Metabol., 10, 1961, 781. — 4. D o l e , V . P . , H . A c i n e t z . J . Biol. Cfiem., 235, I960, 2595. — 5. H i r s с h, J . In : Thromboembolism. Eds. J . R . A. Mitchell and J . G . 24 D. Zheljazkov, V . Mihova, M. Zheljazkova. Domenet. Academic Press, 1977, p. 128. — 6. К u p i е с к i , F . P . Progr. Biochem- Phar­macol., 6, 1971, 274. — 7. S a n t i , R . , G . F a s s i n a. J . Pharm. Pharmacol., 17, 1965, 596. Л Е К А Р С Т В А И Л А Б О Р А Т О Р Н Ы Е Т Е С Т Ы : I . В З А И М О Д Е Й С Т В И Е Ф Е Н А М И Н А И А Ц Е Т И З А Л А С О П Р Е Д Е Л Е Н И Е М С В О Б О Д Н Ы Х Ж И Р Н Ы Х КИСЛОТ Д . Желязков, В. Михова, М. Желязкова, М. Мангарова, Г. Варбанов Р Е З Ю М Е Газово-хроматографическим способом был исследован уровень плазмы семи индиви­дуальных жирных кислот 108 лиц, распределенных в 5 групп. К первой группе относились здоровые лица. Второй контрольной группе людей вводили фенамин в дозе 10 мг. К третьей контрольной группе относились люди, которым вводили ацетизал в дозе З г. Четвертая груп­па включала больных циррозом печени. К пятой группе относились больные хронической почечной недостаточностью. Установлено, что свободные жирные кислоты лиц, относящих­ся к I I , I I I , I V и V группам, увеличены по сравнению с их уровнем у людей 1-ой группы. Обнаружены различия в распределении индивидуальных свободных жирных кислот, а так­же и в стоимостях индекса линолевой/арахидоновой кислот. Фенамин вызывает селектив­ный, направленный к арахидоновой кислоте адипокинез. Ацетизал повышает уровень сво­бодных жирных кислот и в особенности арахидоновой кислоты, являющейся ингибитором простогландинсинтетазы. Подобные изменения устанавливаются у больных циррозом пе­чени и хронической почечной недостаточностью, что осложняет интерпретацию результа­тов исследования свободных жирных кислот у больных, перечисленных к вышеуказанным группам. . . 

DRUGS AND LABORATORY TESTS: I. INTERACTION OF PHENAMIN AND ACETYSAL WITH DETERMINATION OF FREE FATTY ACIDS

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DRUGS AND LABORATORY TESTS: I. INTERACTION OF PHENAMIN AND ACETYSAL WITH DETERMINATION OF FREE FATTY ACIDS

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