Rezumat

Majoritatea substanþelor psihotrope suferã metabolizare la nivel hepatic, fenomen care presupune posibilitatea apariþiei fenomenelor adverse de tip hepatocitolitic sau colestatic fie direct, fie prin interacþiunile farmacokinetice cu alte medicamente administrate concomitent. Monitorizarea transaminazelor este necesarã pentru a evita instalarea unor reacþii severe ireversibile, atunci când existã date în literatura de specialitate referitoare la potenþialul hepatotoxic al respectivelor medicamente. Antidepresivele, antipsihoticele tipice ºi atipice, benzodiazepinele, inhibitorii de acetilcolinesterazã, timostabilizatoarele ºi substanþele cu potenþial de dependenþã sunt analizate din perspectiva incidenþei efectelor hepatotoxice, a mecanismelor prin care se produc acestea ºi a consecinþelor pe termen scurt sau lung ale reacþiilor adverse induse.

Abstract

Many of the psychotropic drugs are metabolized in the liver, a phenomenon that involves the possibility of hepatocytolitic or cholestatic adverse events. These reactions could be provoked either through a direct mechanism, or through the pharmacokinetic interactions with other co-administered drugs. The monitoring of the transaminases level is usefull in order to avoid serious and irreversible reactions, whenever there are data in the literature sustaining the existence of hepatotoxicity associated to the currently used drugs. Asntidepressants, antipsychotics, both typical and atypical, benzodiazepines, acetylcholynesterase inhibitors, anticonvulsants and dependence associated drugs are analysed using variables like the incidence, mechanisms and short and long term prognosis of the hepatotoxic reactions.

Cuvinte cheie:

hepatotoxicitate, hepatocitolizã, colestazã, efecte adverse, antidepresive, antipsihotice

Keywords:

hepatotoxicity, antidepressants, drugs of abuse, antipsychotics

Rezumat: În trecut, pacientele cu boli colagen-vasculare erau sfãtuite sã evite sarcina. În prezent, dacã boala reumatismalã este controlatã terapeutic, sarcina poate fi permisã. Aceste sarcini prezintã riscuri materno-fetale: pusee evolutive, hipertensiune arterialã gestaþionalã, preeclampsie, tromboze, avort, întârziere de creºtere ºi dezvoltare intrauterinã, moarte fetalã, prematuritate. Gravidele cu boli de colagen-vasculare necesitã o monitorizare complexã antenatalã, realizatã de obstetrician, reumatolog, nefrolog, pediatru.

Abstract: In the past, the women with collagen-vascular diseases were advised to avoid pregnancy. In present, if the rheumatic disease is well controlled, the pregnancy will be permitted. These pregnancies present maternal-fetal risks: disease flares, gestational hypertension, pre-eclampsia, thrombosis, abortion, intrauterine growth restriction, still birth, premature delivery. The pregnant women with collagen-vascular diseases need a complex antenatal monitoring, performed by the obstetrician, rheumatologist, nephrologist, pediatrist.

Cuvinte cheie: boli de colagen-vasculare, sarcinã

Key words: collagen-vascular diseases, pregnancy

Rezumat

Boala ficatului gras non-alcoolic cuprinde un spectru larg al afecþiunilor hepatice, nelegate de consumul de alcool in cantitati care ar iniþia leziuni ale ficatului, spectru care cuprinde steatoza hepatica, steatohepatita non-alcoolica si ciroza hepatica, având potenþial evolutiv cãtre carcinomul hepatocelular.

Boala ficatului  gras non-alcoolic este asociata cu componentele sindromului metabolic: obezitatea, diabetul zaharat tip II si rezistenta la insulina, hipertensiunea arteriala si dislipidemia. Rezistenta la insulina ar fi factorul de legãtura intre boala grasa a ficatului non-alcoolic si alte stãri patologice ca sindromul apneei in somn si sindromul ovarului polichistic.

In ultimul deceniu, studiile efectuate au adus clarificãri in ceea ce priveºte patogenia bolii ficatului gras non-alcoolic. In esenþa, obezitatea conduce la instalarea rezistentei la insulina la nivel muscular, ceea ce are ca efect eliberarea unor cantitati mari de insulina de cãtre celulele β pancreatice. Aceste cantitati de insulina duc la sinteza crescuta de acizi graºi liberi la nivelul ficatului, ceea ce conduce la steatoza hepatica. Steatoza hepatica poate avea evoluþie variata la diferiþi indivizi, la o parte din bolnavi putându-se constata dezvoltarea apoptozei, necrozei, infiltratului inflamator si a fibrozei. Aceasta din urma evoluþie s-ar datora lipotoxicitatii. Deºi mecanismele lipotoxicitatii nu sunt complet intelese, un rol important in dezvoltarea leziunilor se pare ca revine disfuncþiei mitocondriale, in care sunt implicate peroxidarea lipidelor, expresia crescuta a TNFα si a speciilor reactive de oxigen.

Diagnosticul complet al bolii hepatice ar trebui sa includã si examenul histopatologic, pentru stabilirea stadiului si prognosticului bolii.

Mijloacele terapeutice actuale sunt adresate mai mult sindromului metabolic. Înþelegerea mai profunda a patogeniei bolii încurajeazã desfãºurarea unor trialuri cu agenþi terapeutici adresaþi ficatului.

In stadiile avansate ale bolii, ultima soluþie ramâne transplantul hepatic, cu riscul recurentei leziunilor pe ficatul transplantat daca factorii ce au iniþiat injuria hepatica nu sunt bine controlaþi.

Abstract

Non- alcoholic fatty liver disease (NAFLD) means a large spectrum of liver affections, non-related to alcohol consumption in such amounts  which could produce liver injuries, spectrum which includes liver steatosis, non-alcoholic steatohepatitis and liver cirrhosis, with possible evolution to hepatocellular carcinoma.

NAFLD is associated with the  components  of the metabolic syndrome: obesity, type 2 diabetes mellitus and  insulin resistance, arterial hypertension and dislipidemia. Insulin resistance seems to be the connection factor between NAFLD and other pathological conditions like sleep apnea syndrome and policystic ovary syndrome.

In the last decade, studies could clarify  the pathogenesis of NAFLD. Brief, obesity induces the insulin resistance in muscles, which is responsible for the releasing of large amounts of insulin in the β pancreatic cells. These large amounts of insulin lead to the increased synthesis of free fatty acids in liver, which induces liver steatosis. Liver steatosis has various evolutions in different patients; some patients develop apoptosis,  necrosis,  inflammatory infiltrate and fibrosis. This evolution could be the consequence of the lipotoxicity. The mechanisms of lipotoxicity are not yet well known, but an important role in liver injuries outcomes is owned by the mitochondrial impairment, due to lipid peroxidation, the increased expression of  TNF α and of reactive oxygen species.

The complete diagnosis of NAFLD must include the histological examination, in order  to establish the stage and the prognosis of the disease.

The therapies used by now are addressed more to the components of the metabolic syndrome and less directly to the liver. The better understanding of the pathogenesis of the NAFLD encourages the trials with drugs addressed to the liver.

In the advanced stages of the disease, the last solution seems to be liver transplantation, but the risk of  injuries recurrence on the transplanted liver remains, if the factors which initiated the disease are not well controlled.

Cuvinte cheie: boala grasa a ficatului non-alcoolic, steatohepatita non-alcoolica, sindrom metabolic, disfuncþie mitocondriala, leziuni hepatice,terapie adresata ficatului

Key-words: non- alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome, mitochondrial impairment, liver injuries, therapies addressed to the liver.