Multimodální analgezie je založena na předpokladu, že benefity kombinace léků převáží nad riziky. Perioperační podávání gabapentinoidů má významné nežádoucí účinky. Gabapentinoidy v kombinaci s opioidy vykazují dokonce vyšší respirační riziko než samotné opioidy. Rutinní perioperační podávání gabapentinoidů již není doporučeno. Je velmi nepravděpodob né, že by nové klinické studie ohledně hodnocení analgetického benefitu gabapentinoidů na pooperační bolest poskytly nějaké nové důkazy.

Multimodal analgesia is predicated on interactions of medicines whereby benefits of combination exceed the risks. Perioperative gabapentinoids have significant adverse effects. Gabapentinoids, when combined with opioids, confer even greater respiratory risk than opioids alone. Routine perioperative administration of gabapentinoids is not more recommended. New clinical trials to evaluate analgesic benefits of gabapentinoids on postoperative pain are very unlikely to provide any new evidence.

• Keywords
• gabapentinoidy,
• MeSH
• Analgesia methods   MeSH
• gamma-Aminobutyric Acid analogs & derivatives   therapeutic use   MeSH
• Gabapentin * history   adverse effects   therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Humans MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Perioperative Period * MeSH
• Pain, Postoperative drug therapy   MeSH
• Pregabalin * history   adverse effects   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Diabetická neuropatie je jednou z nejčastějších komplikací diabetu. Přesná prevalence není známa, udává se rozmezí 25–90 %. Etiologie je multifaktoriální, dominantní vliv má hyperglykemie, resp. délka expozice hyperglykemii. Základním příznakem diabetické periferní senzitivní neuropatie jsou parestezie. Klinické příznaky kardiální autonomní neuropatie jsou chudé (ortostatická hypotenze, snížená tolerance námahy). Typickým projevem je klidová tachykardie, závažnou komplikací jsou maligní arytmie. Diagnosticky pomáhá vyšetření variability R‐R intervalu. Obtěžující jsou symptomy porušené sudomotoriky (návaly pocení v důsledku selhávající termoregulace). Základem terapie a zároveň prevence rozvoje diabetické neuropatie je intenzifikace léčby diabetu s co nejlepší kompenzací. Většina současné medikamentózní terapie je pouze symptomatická se zaměřením na zmírnění subjektivních obtíží. S ohledem na vysoký výskyt nežádoucích účinků je nutno při této léčbě postupovat racionálně. Jedinou současně dostupnou léčivou látkou s prokazatelným vlivem na patofyziologické procesy, které vedou k diabetické neuropatii, je kyselina thioktová.

Diabetic neuropathy is one of the most frequent complications of diabetes. Precise prevalence is not known; the range of 25–90% is reported. Etiology is multifactorial with the dominant influence of hyperglycemia, or rather the length of exposure to hyperglycemia. The primary symptom of diabetic peripheral sensory neuropathy is paresthesia. Clinical signs of cardiac autonomic neuropathy are sparse (orthostatic hypotension, lowered tolerance to strain). Typical manifestation is tachycardia at rest, and malignant arrhythmia is a severe complication. Examination of R‐R interval variability helps in the process of diagnostics. Symptoms of sudomotor dysfunction (bouts of hyperhidrosis due to failing thermoregulation) are the most bothersome symptoms. The basis of therapy and prevention of the development of diabetic neuropathy is an intensification of diabetic treatment with the best compensation possible. Most of the current drug therapy is only symptomatic, focusing on reducing subjective problems. With regards to a high occurrence of adverse effects, it is necessary to proceed rationally during treatment. Thioctic acid is the only currently available substance with proven influence on pathophysiological processes that lead to diabetic neuropathy.

• MeSH
• Amines therapeutic use   MeSH
• Antidepressive Agents adverse effects   therapeutic use   MeSH
• Antioxidants therapeutic use   MeSH
• Pain drug therapy   MeSH
• Diabetes Mellitus MeSH
• Diabetic Neuropathies * drug therapy   physiopathology   MeSH
• gamma-Aminobutyric Acid analogs & derivatives   therapeutic use   MeSH
• Hyperglycemia physiopathology   MeSH
• Thioctic Acid * therapeutic use   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• Keywords
• klimakterický syndrom,
• MeSH
• gamma-Aminobutyric Acid * analogs & derivatives   pharmacology   therapeutic use   MeSH
• Gabapentin MeSH
• Climacteric * drug effects   MeSH
• Humans MeSH
• Breast Neoplasms drug therapy   complications   MeSH
• Hot Flashes drug therapy   MeSH
• Pregabalin therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Female MeSH

Lower plant species including some green algae, non-vascular plants (bryophytes) as well as the oldest vascular plants (lycopods) and ferns (monilophytes) possess a unique aldehyde dehydrogenase (ALDH) gene named ALDH21, which is upregulated during dehydration. However, the gene is absent in flowering plants. Here, we show that ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP+ -dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinic semialdehyde, an intermediate of the γ-aminobutyric acid (GABA) shunt pathway, into succinate in the cytosol. NAD+ is a very poor coenzyme for ALDH21 unlike for mitochondrial SSALDHs (ALDH5), which are the closest related ALDH members. Structural comparison between the apoform and the coenzyme complex reveal that NADP+ binding induces a conformational change of the loop carrying Arg-228, which seals the NADP+ in the coenzyme cavity via its 2'-phosphate and α-phosphate groups. The crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg-121 and Arg-457, and a hydrogen bond with Tyr-296. While both arginine residues are pre-formed for substrate/product binding, Tyr-296 moves by more than 1 Å. Both R121A and R457A variants are almost inactive, demonstrating a key role of each arginine in catalysis. Our study implies that bryophytes but presumably also some green algae, lycopods and ferns, which carry both ALDH21 and ALDH5 genes, can oxidize SSAL to succinate in both cytosol and mitochondria, indicating a more diverse GABA shunt pathway compared with higher plants carrying only the mitochondrial ALDH5.

• MeSH
• Bryophyta enzymology   genetics   MeSH
• Phylogeny MeSH
• gamma-Aminobutyric Acid analogs & derivatives   metabolism   MeSH
• Ferns enzymology   genetics   MeSH
• Protein Conformation MeSH
• Succinic Acid metabolism   MeSH
• Genes, Plant genetics   physiology   MeSH
• Substrate Specificity MeSH
• Succinate-Semialdehyde Dehydrogenase genetics   metabolism   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH

A simple, sensitive and robust method for simultaneous determination of antiepileptic drugs (gabapentin, pregabalin and vigabatrin) in human serum using GC-MS was developed and validated for clinical toxicology purposes. This method employs an emerging class of derivatization agents - alkyl chloroformates allowing the efficient and rapid derivatization of both the amino and carboxylic groups of the tested antiepileptic drugs within seconds. The derivatization protocol was optimized using the Design of Experiment statistical methodology, and the entire sample preparation requires less than 5 min. Linear calibration curves were obtained in the concentration range from 0.5 to 50.0 mg/L, with adequate accuracy (97.9-109.3%) and precision (<12.1%). The method was successfully applied to quantification of selected γ-aminobutyric acid analogs in the serum of patients in both therapeutic and toxic concentration ranges.

• MeSH
• Amines analysis   blood   MeSH
• Anticonvulsants analysis   blood   MeSH
• Computer-Aided Design MeSH
• Formates chemistry   MeSH
• gamma-Aminobutyric Acid analogs & derivatives   analysis   blood   MeSH
• Calibration MeSH
• Cyclohexanecarboxylic Acids analysis   blood   MeSH
• Humans MeSH
• Gas Chromatography-Mass Spectrometry MeSH
• Pregabalin analysis   blood   MeSH
• Vigabatrin analysis   blood   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Complex forming capabilities of [(η(6)-p-cymene)Ru(H2O)3](2+) with aminohydroxamates (2-amino-N-hydroxyacetamide (α-alahaH), 3-amino-N-hydroxypropanamide (β-alahaH) and 4-amino-N-hydroxybutanamide (γ-abhaH)) having the primary amino group in different chelatable position to the hydroxamic function were studied by pH-potentiometry, NMR and MS methods. Formation of stable [O,O] and mixed [O,O][N,N] chelated mono- and dinuclear species is detected in partially slow with α-alahaH and β-alahaH or in fast processes with γ-abhaH and the formation constants of the complexes present in aqueous solution are reported. Synthesis, spectral (NMR, IR) and ESI mass spectrometric characterization of novel dinuclear α-alaninehydroximato complexes containing the half-sandwich type Ru(II) core is described. The crystal and molecular structure of [{(η(6)-p-cymene)Ru}2(μ(2)-α-alahaH-1)(H2O)Br]Br∙H2O (1) and [{(η(6)-p-cymene)Ru}2(μ(2)-α-alahaH-1)(H2O)Cl]BF4∙H2O (2) was determined by single crystal X-ray diffraction method. In the complexes one half-sandwich core is coordinated by a hydroxamate [O,O] chelate while the other one by [Namino,Nhydroxamate] fashion of the bridging ligand. In both cases the remaining coordination sites of one of the Ru cores are taken by a halide ion whiles the other one by a water molecule. Reaction of 2 with 9-methylguanine indicates the N7 coordination of this simple DNA model. Complexes 1 and 2 were tested for their in vitro cytotoxicity using human-derived cancer cell lines (A2780, MCF-7, SKOV-3, HCT-116, HeLa) and showed no anti-proliferative activity in the micromolar concentration range.

• MeSH
• gamma-Aminobutyric Acid analogs & derivatives   chemistry   MeSH
• Guanine analogs & derivatives   chemistry   MeSH
• HCT116 Cells MeSH
• HeLa Cells MeSH
• Cations, Divalent MeSH
• Coordination Complexes chemical synthesis   pharmacology   MeSH
• Crystallography, X-Ray MeSH
• Hydroxamic Acids chemistry   MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Models, Molecular MeSH
• Monoterpenes chemistry   MeSH
• Cell Line, Tumor MeSH
• Organometallic Compounds chemical synthesis   pharmacology   MeSH
• Antineoplastic Agents chemical synthesis   pharmacology   MeSH
• Ruthenium chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Bolest jako nejvýznamnější klinický příznak onemocnění herpes zoster (HZ, pásový opar) řadíme do skupiny neuropatických bolestí. V akutním stadiu ve fázi kožního výsevu se označuje jako herpetická neuralgie (HN). Bolest se ovšem může vyskytovat již v preeruptivním období, kdy mohou být různé bolestivé symptomy chybně diagnostikovány v závislosti na lokalizaci jako řada jiných onemocnění (např. vředová choroba, ledvinové koliky, lumboischialgie, infarkt myokardu apod.). Pokud akutní bolest přejde do chronického stadia, hovoříme o postherpetické neuralgii (PHN), jejíž léčba je mnohdy velmi svízelná. Kazuistika prezentuje pacientku s neobvykle dlouhým prodromálním stadiem nemoci a současně hodnotí efekt velmi časně nasazené terapie neuropatické bolesti adjuvantním analgetikem – pregabalinem, a to jak ve vztahu k akutní HN, tak ovlivnění rozvoje PHN.

Pain as the most significant clinical symptom of herpes zoster (HZ, shingles) is classified as neuropathic pain. In the acute phase of skin eruption, it is referred to as herpetic neuralgia (HN). Pain, however, can occur as early as the pre-eruptive phase wherein various painful symptoms may be misdiagnosed, depending on the location, as a number of other conditions (e.g., ulcerous disease, renal colic, lumbar ischialgia, myocardial infarction, and others). If acute pain progresses to a chronic stage, it is referred to as post-herpetic neuralgia (PHN) the treatment of which is often very difficult. The case report presents a female patient with an unusually long prodromal phase of the disease as well as evaluates the effect of very early commencement of treatment for neuropathic pain with pregabalin, an adjuvant analgesic, both in terms of the relationship to acute HN and affecting the development of PHN.

• MeSH
• Amines administration & dosage   adverse effects   therapeutic use   MeSH
• gamma-Aminobutyric Acid analogs & derivatives   administration & dosage   adverse effects   MeSH
• Herpes Zoster * diagnosis   etiology   complications   MeSH
• Comorbidity MeSH
• Humans MeSH
• Neuralgia diagnosis   etiology   therapy   MeSH
• Neuralgia, Postherpetic * diagnosis   complications   therapy   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Pregabalin (PGB) je léčebná látka užitná ve více situacích. Původně jako antiepileptikum je použitelná i v léčbě neuropatické bolesti. Neuropatická bolest na rozdíl od somatické vzniká díky získané hypersenzibilizaci a hyperexcitabilitě neuronů. PGB navyšuje hlavní inhibitor GABA a snižuje množství excitačních neurotransmiterů, čímž snižuje interneuronální konektivitu. Podobně je tato účinnost PGB využita i u generalizované úzkostné poruchy (GAD), kde taktéž dochází k projevům přílišné interneuronální konektivity. PGB v době spánku navyšuje množství NREM3 na úkor REM i NREM1, zabraňuje redukci intrakortikální ale i spinální inhibice, čímž snižuje k nutkání do pohybu – RLS, PLMD. Inhibice interneuronální konektivity tedy může probíhat na všech úrovních periferního i centrálního nervového systému, zahrnout sem lze epilepsii, ale i GAD, neuropatii, RLS a PLMD. Vzájemné diagnostické přesahy dobře reagují na léčbu PGB, uvažován je synergický efekt.

Pregabalin(PGB) is a medical substance usefull in more situations. Initialy was used as anticolvulsant medication, but it is used in therapy of neuropatic pain too. Neuropatic pain unlike to somatic pain arises due to gained hypersensibility and hyperexcitability of neurons. PGB increases main inhibitor GABA and decreases quantity of excitate neurotransmitters, which cause decreasing of interneuronal communication. At Generalised anxiety disorder (GAD) is used this effectiveness similarly, where also exhibitions of excessive interneuronal communication is common. PGB in sleeptime increases quantity of NREM3 and simultaneously decreses REM a NREM1, prevents reduction of intracortical, but spinal inhibition too – RLS,PLMD. Inhibition of interneuronal communication is happening at all levels of peripheral and central nervous system. We can involve Epilepsy, also GAD, neuropathy, RLS and PLMD too. Mutual diagnostic overlaps have good response to the treatment with PGB. There is considering synergic effect.

• MeSH
• Headache drug therapy   MeSH
• Adult MeSH
• gamma-Aminobutyric Acid * analogs & derivatives   administration & dosage   therapeutic use   MeSH
• Humans MeSH
• Young Adult MeSH
• Neuralgia * drug therapy   MeSH
• Paresthesia drug therapy   MeSH
• Nocturnal Myoclonus Syndrome * drug therapy   MeSH
• Sleep Wake Disorders drug therapy   MeSH
• Pregabalin MeSH
• Restless Legs Syndrome * drug therapy   MeSH
• Anxiety Disorders drug therapy   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Neuropatická bolest je definována jako bolest, která vzniká jako přímý důsledek léze nebo choroby postihující somatosenzitivní systém (Treede, 2008). Dle anatomické lokalizace lze neuropatickou bolest dělit na centrální a periferní a dále podle etiologie. U některých poruch se může vyskytovat smíšený typ s nociceptivní i neuropatickou komponentou. Neuropatická bolest má své specifické příznaky a na rozdíl od nociceptivní bolesti nevyžaduje stimulaci receptorů bolesti, i když jejich stimulace může tuto bolest vyvolávat nebo zvýrazňovat . Pro pacienty jde o symptom, který přetrvává a může je výrazně limitovat v každodenním životě. Terapie neuropatické bolesti je komplikovaná a měla by být vždy pečlivě a individuálně volená. Z farmakoterapie jsou doporučovány pro neuropatickou složku bolesti jako léky první volby antidepresiva (SNRI inhibitory zpětného vychytávání serotoninu a noradrenalinu a TCA tricyklická antidepresiva) a antiepileptika (modulátory α2δ podjednoty napětově řízených kalciových kanálů) a jako léky druhé volby opioidy. Uvedené dvě kazuistiky popisují případy pacientů s neuropatickou bolestí, v prvním případě diabetického původu a v druhém případě vertebrogenního původu. Jde o jedny z nejčastějších typů periferních neuropatických bolestí. U obou pacientů byla zvolena léčba pregabalinem, v různých schématech. V obou případech pacienti hodnotili léčbu pozitivně, uváděli výrazné zlepšení svého klinického stavu. Ovšem, vždy byla léčba komplexní, bylo nutné důkladné postupné titrování dávek nebo zvolit kombinace léků. V druhém případě bylo součástí léčby invervenční řešení.

Neuropathic pain is defined as a pain arising as a direct consequence of a lesion or disease affecting the somatosensory system (Treede, 2008). According to the anatomical localization neuropathic pain can be sorted into central and peripheral and then by etiology. In some cases there can occur both nociceptive and neuropathic component. Neuropathic pain has its specific symptoms and in contrast to nociceptive pain does not require the stimulation of pain receptors, though stimulation of nociceptive receptors can cause or emphasize the neuropathic pain. For patients, it is a symptom that persists and can significantly limit daily life. Therapy of neuropatic pain is complicated and should always be carefully and individually chosen. In terms of pharmacotherapy, antidepressants (SNRI serotonin–norepinephrine reuptake inhibitors and TCA tricyclic antidepressants) and antiepileptics (modulators of α2δ subunit of voltage-gated calcium channels) are recommended as first line therapy and opioids as second line therapy. The two case reports represent patients with neuropathic pain of diabetic origin in the first case and of spinal origin in the second case. These are the ones of the most common types of peripheral neuropathic pain. In both cases pregabalin was chosen as a therapy, in various schemes. Both patients rated the treatment positively, reported a significant improvement of their conditions. However, the treatment was always complete, it was necessary to carefully and gradually titrate the dose or choose a combination of drugs. In the second case, it was included interventional treatment solution.

• Keywords
• adjuvantní analgetika, Oxycodon,
• MeSH
• Analgesics * therapeutic use   MeSH
• Pain * drug therapy   MeSH
• Back Pain drug therapy   MeSH
• Diabetes Mellitus, Type 2 complications   MeSH
• Diabetic Neuropathies drug therapy   MeSH
• gamma-Aminobutyric Acid analogs & derivatives   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Neuralgia * drug therapy   classification   MeSH
• Pregabalin MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

Je prezentována kazuistika pacienta se závislostí na zolpidemu a abúzem alkoholu, kterému k abstinenci pomohla léčba duální diagnózy – generalizované úzkostné poruchy pregabalinem a motivačními rozhovory v kombinaci s autogenním tréningem.

Presented is a case report of a patient with a dependence on zolpidem and harmful use of alcohol. We suppose that the treatment of dual diagnosis – generalized anxiety disorder (GAD) by pregabaline and motivational interviewing in combination with autogenous training helped the patient to recovery and abstinence.

• MeSH
• Diagnosis, Differential MeSH
• gamma-Aminobutyric Acid * analogs & derivatives   adverse effects   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• International Classification of Diseases MeSH
• Substance-Related Disorders * drug therapy   complications   MeSH
• Psychotherapy methods   MeSH
• Pyridines administration & dosage   adverse effects   therapeutic use   MeSH
• Statistics as Topic MeSH
• Anxiety Disorders * diagnosis   drug therapy   complications   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH