Farmakoterapija prehlade i gripa

Acute upper respiratory tract viral infections are frequently manifested through the common cold and influenza, a mainly mild and a potentially life-threatening clinical syndrome, respectively. Cough and fever (>37.8 °C) in an influenza-like illness, especially in the context of an influenza epidemic, suggest the existence of an influenza syndrome. While the available treatments against the common cold are purely symptomatic (alleviation of sore throat, sneezing, rhinorrhoea, nasal congestion, watery eyes, cough, headache, chilliness and fever), the annual seasonal trivalent vaccine and neuraminidase inhibitors are usually effective measures against influenza. It is hypothesized that frequent colds may reduce the likelihood of infection with influenza and hence be protective. In this vein, the complete prevention may be worse than the inconvenience due to illness and it seems reasonable to try and reduce the public health burden of common cold, but surely not eliminate the common colds altogether. In regard to the influenza, the epidemiological experience warn us that the generally positive results of prophylactic and therapeutic measures during the last pandemic (2009-2010) do not preclude the appearance of some newer genetic reassortments of the virus in the future, possibly threatening the whole population.Virusne infekcije gornjih disajnih puteva često se manifestuju kao klinički sindromi prehlade (uglavnom blagi), odnosno gripa (potencijalno životno ugrožavajući). Kašalj i groznica (temperatura >37,8 °C) u gripu-sličnom stanju, posebno u uslovima proglašene epidemije gripa, sugerišu postojanje sindroma gripa. Dok su dostupni tretmani protiv prehlade čisto simptomatski (ublažavanje gušobolje, kijanja, curenja nosa, kongestije nosa, suzenja očiju, kašlja, glavobolje, jeze i groznice), godišnja 'sezonska' trovalentna vakcina i inhibitori neuraminidaze su obično efektivne profilaktičke, odnosno terapijske mere protiv gripa. Postavljena je hipoteza da česte prehlade mogu da smanje verovatnoću infekcije virusom gripa i da stoga mogu da imaju zaštitnu ulogu. U tom smislu, potpuna prevencija prehlada bi mogla da ima lošije posledice od neprijatnosti usled same bolesti. Stoga, mere smanjenja opterećenja za javno zdravlje koje nose prehlade jesu potrebne, ali se ne čini racionalnim eventualno eliminisanje prehlade uopšte. U odnosu na grip, epidemiološko iskustvo nas upozorava da generalno pozitivni rezultati profilaktičkih i terapijskih mera tokom poslednje pandemije (2009-2010) ne isključuju mogućnost pojave nekih novih genetskih resortiranja virusa u budućnosti, koja bi mogla da ugroze celu populaciju

Memory Effects of Benzodiazepines: Memory Stages and Types Versus Binding-Site Subtypes

Benzodiazepines are well established as inhibitory modulators of memory processing. This effect is especially prominent when applied before the acquisition phase of a memory task. This minireview concentrates on the putative subtype selectivity of the acquisition-impairing action of benzodiazepines. Namely, recent genetic studies and standard behavioral tests employing subtype-selective ligands pointed to the predominant involvement of two subtypes of benzodiazepine binding sites in memory modulation. Explicit memory learning seems to be affected through the GABAA receptors containing the α1 and α1 subunits, whereas the effects on procedural memory can be mainly mediated by the α1 subunit. The pervading involvement of the α1 subunit in memory modulation is not at all unexpected because this subunit is the major subtype, present in 60% of all GABAA receptors. On the other hand, the role of α5 subunits, mainly expressed in the hippocampus, in modulating distinct forms of memory gives promise of selective pharmacological coping with certain memory deficit states

Antiepileptici u terapiji neuropatskog bola

Neuropathic pain, a form of chronic pain, caused by injury or disease of the peripheral or central nervous system, is a therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Basic research of pathophysiological mechanisms of neuropathic pain has shown many similarities between the morphological and biochemical changes observed in epilepsy and neuropathic pain, which gave the rational for examination and use of antiepileptic drugs (AED) in management of neuropathic pain disorders. Carbamazepine was the first AED studied in clinical trials, achieving positive results predominantly in the treatment of trigeminal neuralgia, and took its place in therapy of this particular neuropathic pain disorder. Gabapentin, a newer AED, has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia and is considered the first choice of therapy for neuropathic pain. There is increasing evidence that effect in both experimental and clinical studies. Due to less frequency and severity of adverse effects it is considered as an alternative to carbamazepine in a treatment of neuropathic pain. There is insufficient evidence about efficacy of phenitoin, lamotrigine and some others AED in the treatment of neuropathic pain disorders. Future advances in treatment of neuropathic pain are directed on understanding the pathophysiological mechanisms underlying neuropathic pain and further examining the mechanisms of action of AED, and their efficacy and safety in treatment of neuropathic pain.Neuropatski bol je oblik hroničnog bola izazvan povredom ili oboljenjem perifernog ili centralnog nervnog sistema. Predstavlja terapijski izazov za kliničare, jer se primenom konvencionalnih analgetika u terapiji ovog tipa bola ne postižu zadovoljavajući rezultati. Bazična istraživanja patofizioloških mehanizama neuropatskog bola pokazala su mnoge sličnosti između morfoloških i biohemijskih promena koje se javljaju kod neuropatskog bola i onih koje se javljaju kod epilepsije, što čini osnovu za ispitivanje i upotrebu antiepileptika u terapiji ovog tipa bola. Prvi klinički ispitani antiepileptik, karbamazepin, ostvario je pozitivne rezultate prevashodno u terapiji neuralgije trigeminusa, gde je i našao svoje mesto u kliničkoj praksi. Lek novije generacije, gabapentin, je za sada najjasnije pokazao analgetičko dejstvo kod neuropatskog bola, posebno kod dijabetičke neuropatije i postherpetičke neuralgije i danas se smatra lekom prvog izbora u terapiji neuropatskih bolnih stanja. Sve je više dokaza o analgetičkom dejstvu okskarbazepina, koji je keto-derivat karbamazepina. U eksperimentalnim i kliničkim ispitivanjima okskarbazepin se pokazao kao moguća zamena za karbamazepin u terapiji neuropatskog bola, zbog niže učestalosti i manjeg intenziteta neželjenih efekata. Znatno je manje dokaza o efikasnosti fenitoina, lamotrigina i nekih drugih antiepileptika u suzbijanju neuropatskog bola. Dalje usavršavanje terapije neuropatskog bola usmereno je ka rasvetljavanju njegovih složenih patofizioloških mehanizama, kao i daljem ispitivanju mehanizama dejstva, efikasnosti i bezbednosti primene antiepileptika u terapiji neuropatskog bola

Nicorandil directly and cyclic GMP-dependently opens K+ channels in human bypass grafts

As we previously demonstrated the role of different K+ channels in the action of nicorandil on human saphenous vein (HSV) and human internal mammary artery (HIMA), this study aimed to analyse the contribution of the cGMP pathway in nicorandil-induced vasorelaxation and to determine the involvement of cGMP in the K+ channel-activating effect of nicorandil. An inhibitor of soluble guanylate cyclase (GC), ODQ, significantly inhibited nicorandil-induced relaxation, while ODQ plus glibenclamide, a selective ATP-sensitive K+ (KATP) channel inhibitor, produced a further inhibition of both vessels. In HSV, ODQ in combination with 4-aminopyridine, a blocker of voltage-gated K+ (K-V) channels, did not modify the concentration-response to nicorandil compared with ODQ, whereas in HIMA, ODQ plus iberiotoxin, a selective blocker of large-conductance Ca2+-activated K+ (BKCa) channels, produced greater inhibition than ODQ alone. We showed that the cGMP pathway plays a significant role in the vasorelaxant effect of nicorandil on HSV and HIMA. It seems that nicorandil directly opens KATP channels in both vessels and BKCa channels in HIMA, although it is possible that stimulation of GC contributes to KATP channels activation in HIMA. Contrary, the activation of K-V channels in HSV is probably due to GC activation and increased levels of cGMP

Are GABA(A) receptors containing alpha 5 Subunits contributing to the sedative properties of benzodiazepine site agonists?

Classical benzodiazepines (BZs) exert anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsive, and amnesic effects through potentiation of neurotransmission at GABA(A) receptors containing alpha(1), alpha(2), alpha(3) or alpha(5) subunits. Genetic studies suggest that modulation at the alpha(1) subunit contributes to much of the adverse effects of BZs, most notably sedation, ataxia, and amnesia. Hence, BZ site ligands functionally inactive at GABAA receptors containing the alpha(1) subunit are considered to be promising leads for novel, anxioselective anxiolytics devoid of sedative properties. In pursuing this approach, we used two-electrode voltage clamp experiments in Xenopus oocytes expressing recombinant GABAA receptor subtypes to investigate functional selectivity of three newly synthesized BZ site ligands and also compared their in vivo behavioral profiles. The compounds were functionally selective for alpha(2)-, alpha(3)-, and alpha(5)-containing subtypes of GABA(A) receptors (SH-053-S-CH3 and SH-053-S-CH3-2'F) or essentially selective for alpha(5) subtypes (SH-053-R-CH3). Possible influences on behavioral measures were tested in the elevated plus maze, spontaneous locomotor activity, and rotarod test, which are considered primarily predictive of the anxiolytic, sedative, and ataxic influence of BZs, respectively. The results confirmed the substantially diminished ataxic potential of BZ site agonists devoid of alpha(1) subunit-mediated effects, with preserved anti-anxiety effects at 30 mg/kg of SH-053-S-CH3 and SH-053-S-CH3-2'F. However, all three ligands, dosed at 30 mg/kg, decreased spontaneous locomotor activity, suggesting that sedation may be partly dependent on activity mediated by alpha(5)-containing GABAA receptors. Hence, it could be of importance to avoid substantial agonist activity at alpha(5) receptors by candidate anxioselective anxiolytics, if clinical sedation is to be avoided

Farmakologija insulina

Insulin is anabolic and anti-catabolic hormone which has an important role in the metabolism of carbohydrates, proteins and lipids. In addition, insulin is the only agent used in all forms of diabetes mellitus for blood sugar control. Further, insulin is critical for the management of diabetic ketoacidosis, and it has an important role in the treatment of hyperglycemic, nonketotic coma and in the perioperative management of diabetic patients. Commercial insulin preparations, used today, represent result of recombinant DNA technology and have amino acid sequence identical to human insulin. Also, insulin analogs are produced by modifications in insulin molecule in order to improve pharmacokinetic properties. In this article, insulin preparations are described including their classification, characteristics and safety of use in a pregnancy