Statin intolerance – still more questions than answers

Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease and also in subjects with a moderate or high risk by reducing the levels of low-density lipoprotein cholesterol. Although statins are considered to be drugs with a very good safety profile, their wide use seems to evoke concerns about the compromising adverse effects overpowering proven beneficial ones. Patients frequently discontinue statin therapy without medical advice due to unfavorable events, thereby substantially increasing their risk of cardiovascular events. Statin discontinuation is a great problem and appears to be growing. Complete statin intolerance is relatively rare. Step-by-step approach that includes careful examination of all possible statin-intolerance increasing factors would help patients to continue statin therapy even if experiencing statin-associated side effects

Pharmacological therapy as a supplement to reduction diet and physical activity for weight reduction

Farmakološka terapija može biti korisna kao dodatak redukcijskoj prehrani i tjelesnoj aktivnosti u smanjenju tjelesne mase. Međutim, treba imati na umu da farmakološka terapija ne bi smjela biti jedini način za smanjenje tjelesne mase. Redukcijska prehrana i tjelesna aktivnost su ključni za zdrav i održiv gubitak tjelesne mase. Farmakološka terapija treba biti korištena samo pod nadzorom stručnjaka i u slučajevima kada druge strategije za gubitak tjelesne mase nisu uspješne. Pandemija pretilosti i povećanja tjelesne mase nastavlja rasti alarmantnom brzinom. Trenutni dokazi za preporuku specifičnih dijeta i kombinacija dijete i lijekova za mršavljenje te kombinacija lijekova i tjelesnih aktivnosti i dijeta i dalje slabi, što se djelomično može pripisati razlikama u prehrambenim protokolima, razlikama u praćenju tjelesne aktivnosti i različitim vremenima praćenja u dostupnim ispitivanjima. Budući da su modifikacije stila i načina života ograničene u svom uspjehu u održavanju gubitka tjelesne mase, farmakoterapija igra važnu ulogu u postizanju klinički značajnog gubitka tjelesne mase. Farmakoterapija za smanjenje tjelesne mase indicirana je kao dodatak dijeti sa smanjenim unosom kalorija i povećanoj tjelesnoj aktivnosti u odraslih osoba s ITM ≥30 kg/m², ali i u osoba s preuhranjenošću s ITM-om ≥27 do 35 kg/m² s komorbiditetima ili ITM >40 kg/m2 s komorbiditetima ili bez njih. Farmakoterapija pretilosti značajno se razvila u posljednjih 60 godina. Federalna uprava za lijekove (FDA) je za sada odobrila šest lijekova za dugotrajno liječenje pretilosti. Malo je vjerojatno da će jedno farmakološko sredstvo biti učinkovito u liječenju pretilosti. Stoga će buduće strategije za liječenje pretilosti morati potaknuti učinkovit gubitak težine i vjerojatno će zahtijevati istodobnu primjenu lijekova koji djeluju kroz različite mehanizme. Ciljevi kontrole tjelesne mase naglašavaju važnost realističnog pristupa mršavljenju kako bi se postiglo smanjenje zdravstvenih rizika, a uključuju promicanje gubitka tjelesne mase, održavanje postignute niže tjelesne mase i prevenciju ponovnog debljanja. Ako se želi smanjiti tjelesnu masu, potrebno je pristupiti tome s više različitih strategija, uključujući i farmakološku terapiju.Pharmacological therapy can be useful as an adjunct to a reduction diet and physical activity in reducing body weight. However, it is important to note that pharmacological therapy should not be the only way to reduce body weight. Diet and physical activity are key to healthy and sustainable weight loss. Pharmacological therapy should only be used under expert supervision and in cases where other strategies for weight loss are unsuccessful. The obesity and weight gain pandemic continues to grow at an alarming rate. Current evidence to recommend specific diets and combinations of diet and medication for weight loss and combination of medication and physical activity and diet remains weak, which may be partially attributable to differences in dietary protocols, differences in monitoring of physical activity, and different follow-up times in the available trials. Because lifestyle modifications are limited in their success in maintaining weight loss, pharmacotherapy plays an important role in achieving clinically significant weight loss. Pharmacotherapy for weight loss is indicated as an addition to a diet with reduced calorie intake and increased physical activity in adults with BMI ≥30 kg/m², but also in obese individuals with BMI ≥27 to 35 kg/m² with comorbidities or BMI > 40 kg/m2 with or without comorbidities. Pharmacotherapy of obesity has developed significantly in the last 60 years. The Federal Drug Administration (FDA) has so far approved six drugs for the long-term treatment of obesity. It is unlikely that a single pharmacological agent will be effective in the treatment of obesity. Therefore, future strategies for the treatment of obesity will need to promote effective weight loss and will likely require the simultaneous use of drugs that work through different mechanisms. Weight control goals emphasize the importance of a realistic approach to weight loss to reduce health risks, and include promoting weight loss, maintaining weight loss, and preventing weight gain. If one wants to reduce body weight, it is necessary to approach with several different strategies, including pharmacological therapy

Drug - drug interaction in a patient with epilepsy and newly diagnosed paroxysmal atrial fibroundulation

Cytochrome P450 isoenzymes have a major role in the metabolism of xenobiotics. They are mostly found in hepatocytes and oxidize majority of drugs, thus shifting them into their inactive form. Some of them can influence cytochromes’ activity while getting oxidized, simultaneously inducing or inhibiting them. This way, drug activity can be altered and their benefit in the management of the disease limited

Do statins lead to increased myopathy and changes in physical performance in athletes?

Statini su jedni od najčešće prepisivanih lijekova današnjice s obzirom na njihovu golemu ulogu u primarnoj, ali i sekundarnoj prevenciji kardiovaskularnih incidenata, glavnog uzroka smrti u današnjoj populaciji „zahvaljujući“ sve zastupljenijem nezdravom stilu života. Međutim, pojavila se zabrinutost u vezi s njihovim potencijalnim nuspojavama, posebice njihovim utjecajem na miopatiju I promjene u tjelesnoj izvedbi, osobito kod sportaša. Ovaj rad ima cilj istražiti odnos između uporabe statina i miopatije te potencijalne učinke na fizički performans kod sportaša. Sveobuhvatnim pregledom literature analizirane su različite studije kako bi se utvrdila prevalencija i mehanizmi miopatije izazvane statinima. Dostupni dokazi sugeriraju da statini izazivaju uočljivu miopatiju makar ona varira ovisno o čimbenicima kao što su vrsta statina, doza i individualna osjetljivost. Dodatno, rad istražuje temeljne mehanizme kojima statini mogu doprinijeti miopatiji, uključujući poremećaj puta mevalonata i mitohondrijske disfunkcije. Što se tiče utjecaja upotrebe statina na fizičku izvedbu među sportašima, pokazalo se da pate od povećanog rizika za razvoj miopatije jer fizička aktivnost znatno pridonosi njezinoj pojavnosti i intenzitetu. Navedeno može dovesti do prekida trenažnog procesa što u profesionalnih sportaša svakako nije poželjno, a u ovome radu opisane su određene strategije koje mogu ublažiti potencijalnu miopatiju uz očuvanje performansi. To uključuje personalizirani odabir statina, prilagodbu doze, razne suplementacije u vidu koenzima Q10 ili intervencija u prehrani, od kojih mnoge metode tek zahtijevaju dodatnu pažnju u istraživanjima kako bi se potvrdila njihova učinkovitost. Kada je u pitanju učinak statina na kvalitetu fizičkog performansa, provedene su višestruke studije koje analiziraju izdržljivost i mišićnu snagu kod sportaša koji uzimaju statine, no, nije primijećen zamjetan utjecaj na iste I kvaliteta fizičkog performansa nije se pokazala ugroženom, unatoč pojavi miopatije. Međutim, bitno je naglasiti kako se ova tema relativno kratko istražuje i zbog dosadašnjega manjka kvalitetno provedenih ispitivanja ne može se sa sigurnošću ustvrditi postoji li zaista toliko minimalna, zanemariva povezanost između navedenih varijabli, pogotovo u slučaju dugogodišnje primjene statinske terapije, kada bi se kumulativni učinak ovih lijekova na mišiće očitovao tek nakon određenoga vremenskoga perioda.Statins are one of the most commonly prescribed drugs today, given their enormous role in the primary and secondary prevention of cardiovascular incidents, the main cause of death in today’s population thanks to an increasingly prevalent unhealthy lifestyle. However, concerns have arisen regarding their potential side effects, especially their impact on myopathy and alternation in physical performance, particularly in athletes. This article’s attention is to investigate the relationship between statin use and myopathy while looking into potential effects on physical performance. A broad literature review analyzed numerous studies to determine the prevalence and mechanisms of statin induced myopathy. The available evidence suggests that statins cause noticeable myopathy, although this varies depending on elements such as type of statin, dose and individual sensitivity. Additionally, the article explores the fundamental mechanisms by which statins may contribute to myopathy, as well as interference of the mevalonate pathway and mitochondrial dysfunction. Additionally, the affect of statin use on physical performance among athletes is assesed. Multiple studies analyzing endurance, muscle power, and exercise volume in athletes taking statins have not found significant decreases in muscle strength and endurance in individuals. In order to diminish potential statin-induced myopathy while preserving performance, this article proposes certain strategies. These incorporate personalized statin selection, dose alterations, coenzyme Q10 supplementation and lifestyle moderation such as exercise and dietary customizations. Several studies have examined the impact of statins on physical performance in athletes, specifically endurance and muscle strength. However, despite the occurrence of myopathy, no noticeable effect on these factors or compromise in the quality of physical performance has been observed. However, it is worth noting that this topic has been studied for a relatively brief duration and due to the current absence of well-designed trials, it cannot be definitively asserted whether there truly exists such a minimal, insignificant association between the mentioned variables, particularly in the context of prolonged use of statin therapy, where the cumulative impact of these medications on muscles may only become evident after a certain timeframe

ENCEPHALOPATHY CAUSED BY THE APPLICATION OF METRONIDAZOLE

Metronidazol je antibiotik koji se koristi u liječenju anaerobnih bakterijskih i parazitarnih infekcija. Kao rijetka nuspojava primjene ovog lijeka može se javiti encefalopatija. Najčešće primijećeni klinički simptomi uključuju dizartriju, nestabilnost u hodu i/ili ataksiju. Encefalopatiju uzrokovanu primjenom metronidazola potrebno je diferencijalno dijagnostički razlikovati od drugih mogućih uzroka encefalopatije. Uz kliničku sliku i podatak o primjeni metronidazola od pomoći su magnetska rezonancija mozga (MRI) - T2 i prikaz FLAIR te neurološka dijagnostika koja uključuje elektroencefalografi ju (EEG), laboratorijsku obradu i lumbalnu punkciju. Tipični nalazi MRI mozga u T2 i FLAIR tehnici pokazuju hiperintenzitet koji u većini slučajeva zahvaća nucleus dentatus malog mozga, dijelove moždanog debla te splenium corpus callosuma. Ponekad je potrebno učiniti i gensko testiranje kako bi se isključili i vrlo rijetki uzroci encefalopatije. Neurološke promjeneuzrokovane primjenom metronidazola najčešće su reverzibilne i povlače se nakon ukidanja metronidazola iz terapije. U liječenju ove vrste encefalopatije može se primijeniti metilprednizolon.Metronidazole is an antibiotic used for treating anaerobic bacterial and parasitic infections. A rare side effect of using this drug is encephalopathy. The most commonly observed symptoms include dysarthria, gait instability, and/or ataxia. Metronidazole induced encephalopathy should be differentiated from other possible causes of encephalopathy. Clinical picture with data on metronidazole application, as well as magnetic resonance imaging (MRI) of the brain, T2 and FLAIR sequences, neurological diagnostic procedures such as electroencephalography (EEG), laboratory tests and lumbar puncture should be performed. Typical brain MRI fi ndings in T2 and FLAIR technique show hyperintensity, which in most cases affects dentate nucleus of the cerebellum, parts of brainstem, and splenium corporis callosi. Genetic testing is sometimes required to distinguish some rare causes of encephalopathy. Neurological changes due to metronidazole application are most often reversible and vanish after metronidazole withdrawal. Use of methylprednisolone in treating this type of encephalopathy is sometimes helpful

ENCEPHALOPATHY CAUSED BY THE APPLICATION OF METRONIDAZOLE

Metronidazol je antibiotik koji se koristi u liječenju anaerobnih bakterijskih i parazitarnih infekcija. Kao rijetka nuspojava primjene ovog lijeka može se javiti encefalopatija. Najčešće primijećeni klinički simptomi uključuju dizartriju, nestabilnost u hodu i/ili ataksiju. Encefalopatiju uzrokovanu primjenom metronidazola potrebno je diferencijalno dijagnostički razlikovati od drugih mogućih uzroka encefalopatije. Uz kliničku sliku i podatak o primjeni metronidazola od pomoći su magnetska rezonancija mozga (MRI) - T2 i prikaz FLAIR te neurološka dijagnostika koja uključuje elektroencefalografi ju (EEG), laboratorijsku obradu i lumbalnu punkciju. Tipični nalazi MRI mozga u T2 i FLAIR tehnici pokazuju hiperintenzitet koji u većini slučajeva zahvaća nucleus dentatus malog mozga, dijelove moždanog debla te splenium corpus callosuma. Ponekad je potrebno učiniti i gensko testiranje kako bi se isključili i vrlo rijetki uzroci encefalopatije. Neurološke promjeneuzrokovane primjenom metronidazola najčešće su reverzibilne i povlače se nakon ukidanja metronidazola iz terapije. U liječenju ove vrste encefalopatije može se primijeniti metilprednizolon.Metronidazole is an antibiotic used for treating anaerobic bacterial and parasitic infections. A rare side effect of using this drug is encephalopathy. The most commonly observed symptoms include dysarthria, gait instability, and/or ataxia. Metronidazole induced encephalopathy should be differentiated from other possible causes of encephalopathy. Clinical picture with data on metronidazole application, as well as magnetic resonance imaging (MRI) of the brain, T2 and FLAIR sequences, neurological diagnostic procedures such as electroencephalography (EEG), laboratory tests and lumbar puncture should be performed. Typical brain MRI fi ndings in T2 and FLAIR technique show hyperintensity, which in most cases affects dentate nucleus of the cerebellum, parts of brainstem, and splenium corporis callosi. Genetic testing is sometimes required to distinguish some rare causes of encephalopathy. Neurological changes due to metronidazole application are most often reversible and vanish after metronidazole withdrawal. Use of methylprednisolone in treating this type of encephalopathy is sometimes helpful