Nowadays, most of the newly developed active pharmaceutical ingredients (APIs) consist of cohesive particles with a mean particle size of <100μm, a wide particle size distribution (PSD) and a tendency to agglomerate, therefore they are difficult to handle in continuous manufacturing (CM) lines. The current paper focuses on the impact of various glidants on the bulk properties of difficult-to-handle APIs. Three challenging powders were included: two extremely cohesive APIs (acetaminophen micronized (APAPμ) and metoprolol tartrate (MPT)) which previously have shown processing issues during different stages of the continuous direct compression (CDC)-line and a spray dried placebo (SD) powder containing hydroxypropylmethyl cellulose (HPMC), known for its sub-optimal flow with a high specific surface area (SSA) and low density. Four flow-enhancing excipients were used: a hydrophilic (Aerosil® 200) and hydrophobic (Aerosil® R972) fumed silica grade, a mesoporous silica grade (Syloid® 244FP), and a calcium phosphate excipient (TRI-CAFOS® 200-7). The APIs and binary API/glidant blends (varied between 0.5-2.75 w/w%) were characterized for their bulk properties relevant for CDC. The results indicated that optimizing different bulk parameters (e.g., density, flow, compressibility..) of an API required varying weight percentages of the glidant (e.g., different surface area coverage (SAC)) depending on the APIs. Moreover, even at similar SAC, the impact of the glidant on the bulk characteristic of the APIs depended on the glidant type properties. While nano-sized silicon dioxide were effective for improving the flowability of a powder, other glidants (mesoporous silica and tricalcium phosphate (TCP)) showed also promise as alternatives. Additionally, an excess of glidant, referred to as oversilication, negatively impacted some bulk parameters, but other characteristics were unaffected. Finally, to determine the appropriate concentration of the different classes of glidants, SAC calculations, an understanding of the glidant's working mechanism, and knowledge about the API's characteristics (i.e., morphology, compressibility, flowability, aeration, density, and wall friction) are required. This study confirmed the necessity of including various material characterization techniques to assess the impact of glidants on the bulk characteristics of APIs.
- MeSH
- deriváty hypromelózy * chemie MeSH
- farmaceutická chemie metody MeSH
- fosforečnany vápenaté * chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- metoprolol * chemie MeSH
- nerozplněné léky MeSH
- oxid křemičitý chemie MeSH
- paracetamol * chemie MeSH
- pomocné látky * chemie MeSH
- prášky, zásypy, pudry * MeSH
- příprava léků metody MeSH
- reologie * MeSH
- velikost částic * MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- antidota klasifikace terapeutické užití MeSH
- benzodiazepiny otrava MeSH
- otrava alkoholem diagnóza farmakoterapie klasifikace MeSH
- otrava houbami diagnóza farmakoterapie klasifikace MeSH
- otrava * diagnóza etiologie farmakoterapie klasifikace ošetřování MeSH
- paracetamol otrava MeSH
- uštknutí hadem farmakoterapie klasifikace MeSH
- Publikační typ
- přehledy MeSH
Je dobře známo, že suboptimální léčba hypertenze zvyšuje nemocnost a úmrtnost pacientů a že NSA patří mezi léky, které mohou krevní tlak zvyšovat. Do nedávné doby byl paracetamol považován za analgetikum, které takové účinky nemá. Některé nové informace však vzbuzují obavy o bezpečnost alespoň u části pacientů s arteriální hypertenzí při podávání paracetamolu. Tento přehledový článek předkládá informace o možném vlivu paracetamolu i NSA na krevní tlak hypertoniků i pacientů bez hypertenze. Z dostupných údajů vyplývá, že negativní vliv NSA je zřejmě intenzivnější než vliv paracetamolu.
It is well known that suboptimal treatment of hypertension increases patient morbidity and mortality and that NSAIDs belong to the drugs that can raise blood pressure. Until recently, paracetamol was considered an analgesic that does not have such effects. However, some new information raises concerns about the safety of at least some patients with arterial hypertension when taking paracetamol. This review article presents information on the possible effect of paracetamol and NSAIDs on the blood pressure of hypertensive and non-hypertensive patients. From the available data, it appears that the negative impact of NSAIDs is more intense than the effect of paracetamol.
BACKGROUND: Adequate postoperative pain treatment is important for quality of life, patient satisfaction, rehabilitation, function, and total opioid consumption, and might lower both the risk of chronic postoperative pain and the costs for society. Prolonged opioid consumption is a well-known risk factor for addiction. Previous studies in upper extremity surgery have shown that total opioid consumption is a third of the amount prescribed, which can be explained by package size. The aim of this study was to examine whether implementation of prepacked takehome analgesia bags reduced the quantity of prescribed and dispensed opioids. MATERIAL AND METHODS: We introduced prepacked take-home analgesia bags for postoperative pain treatment in outpatient surgery. The bags came in two sizes, each containing paracetamol, etoricoxib, and oxycodone. The first 147 patients who received the prepacked analgesia bags were included in the study, and received a questionnaire one month after surgery covering self-assessed pain (visual analog scale of 0-10) and satisfaction (0-5), as well as opioid consumption. Prescription data after introducing the analgesia bags were compared with data before the bags were introduced. RESULTS: Of the 147 patients included in the study, 58 responded. Compared to standard prescription (small bag group: 14 oxycodone immediate release capsules (5 mg), large bag group: additional 28 oxycodone extended release tablets (5 mg), based on the smallest available package), the patients in the small analgesia bag group received 50% less oxycodone and 67% less for the large bag group. Patients with small bags consumed a median of 0.0 mg oxycodone and those with large bags consumed a median of 25.0 mg oxycodone. The median satisfaction was 5.0 (range: 2-5) and the median pain score was acceptable at the first postoperative day. Prescription data showed a significant reduction of 60.0% in the total amount of prescribed opioids after the introduction of prepacked analgesia bags. CONCLUSIONS: The introduction of prepacked analgesia bags dramatically reduced the quantity of opioids prescribed after outpatient hand surgery. Patient satisfaction was high and the postoperative pain level was acceptable. KEY WORDS: analgesia, hand surgery, opioids, outpatint surgery, wrist surgery.
- MeSH
- ambulantní chirurgické výkony * metody MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- management bolesti metody MeSH
- měření bolesti MeSH
- opioidní analgetika * aplikace a dávkování MeSH
- oxykodon aplikace a dávkování MeSH
- paracetamol aplikace a dávkování terapeutické užití MeSH
- pooperační bolest * prevence a kontrola farmakoterapie MeSH
- ruka chirurgie MeSH
- spokojenost pacientů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- analgetika aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- antirevmatika aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- bolest * farmakoterapie MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- metamizol aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- paracetamol aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- tramadol aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
A multi-residue UHPLC-MS/MS analytical method, previously developed for monitoring 52 pharmaceuticals in drinking water, was used to analyse these pharmaceuticals in wastewater originating from healthcare facilities in the Czech Republic. Furthermore, the methodology was expanded to include the evaluation of the effectiveness of drug removal in Czech wastewater treatment plants (WWTPs). Of the 18 wastewater samples analysed by the validated UHPLC-MS/MS, each sample contained at least one quantifiable analyte. This study reveals the prevalence of several different drugs; mean concentrations of 702 μg L-1 of iomeprol, 48.8 μg L-1 of iopromide, 29.9 μg L-1 of gabapentin, 42.0 μg L-1 of caffeine and 82.5 μg L-1 of paracetamol were present. An analysis of 20 samples from ten WWTPs revealed different removal efficiencies for different analytes. Paracetamol was present in the inflow samples of all ten WWTPs and its removal efficiency was 100%. Analytes such as caffeine, ketoprofen, naproxen or atenolol showed high removal efficiencies exceeding 80%. On the other hand, pharmaceuticals like furosemide, metoprolol, iomeprol, zolpidem and tramadol showed lower removal efficiencies. Four pharmaceuticals exhibited higher concentrations in WWTP effluents than in the influents, resulting in negative removal efficiencies: warfarin at -9.5%, indomethacin at -53%, trimethoprim at -54% and metronidazole at -110%. These comprehensive findings contribute valuable insights to the pharmaceutical landscape of wastewater from healthcare facilities and the varied removal efficiencies of Czech WWTPs, which together with the already published literature, gives a more complete picture of the burden on the aquatic environment.
Bolest je komplikovaná subjektivní entita, kterou je obtížné kvantifikovat a léčit. Jednotlivci se prostřednictvím svých životních zkušeností učí pojmu bolesti a koncepce vnímání bolesti se u člověka mění. Přestože bolest obvykle plní adaptivní roli, může mít nepříznivé účinky na kvalitu života – na funkční, sociální a psychologickou rovnováhu. Proto je třeba respektovat sdělení jednotlivce o tom, že prožívá a cítí bolest, či sledovat různé symptomy bolesti. Perioperační léčba bolesti je dnes součástí komplexní péče o pacienty, kteří se podrobují operačním zákrokům, a je spojena s četnými benefity pro pacienta i společnost. V současnosti je k dispozici dostatek léků, lékových forem, modalit léčby i dostatek literárních údajů, vč. poznatků o organizaci léčby pooperační bolesti. Komplexní péče začíná již před operačním výkonem na specializovaných ambulancích správnou přípravou pacienta na anestezii a operační výkon. Samotná léčba pooperační bolesti je podobně jako péče o pacienta po chirurgickém výkonu multidisciplinárním týmovým úkolem, na němž se podílejí zejména ošetřující lékař, operatér, anesteziolog a sestry pooperačního oddělení. Součástí této rozsáhlé spolupráce jsou specializované týmy na léčbu akutní pooperační bolesti, které mají úlohu především konziliární, vzdělávací a organizační a pomáhají zajišťovat specializované léčebné postupy tišení bolesti. Je nutné, aby všechny specialisty spojovaly základní znalosti a jejich uplatňování v praxi.
Pain is a complicated subjective entity that is difficult to quantify and treat. Individuals learn the concept of pain through their life experience, and a person’s concept of pain perception changes. Although pain usually fulfills an adaptive role, it can have adverse effects on quality of life – functional, social and psychological balance. Therefore, it is necessary to respect the communication of the individual experiencing and feeling pain, or to monitor the various symptoms of pain. Today, perioperative pain management is part of the comprehensive care of patients undergoing surgery, and is associated with numerous benefits for the patient and society. Currently, there are enough drugs, dosage forms, treatment modalities available, as well as enough literary data, incl. knowledge about the organization of postoperative pain treatment. Comprehensive care begins even before surgery in specialized outpatient clinics with the proper preparation of the patient for anesthesia and surgery. The treatment of postoperative pain itself is similar to the care of a patient after a surgical procedure, a multidisciplinary team task, in which the attending physician, surgeon, anesthetist and nurses of the postoperative department participate in particular. Part of this extensive collaboration are specialized teams for the treatment of acute postoperative pain, which primarily have a conciliatory, educational and organizational role, and help to provide specialized treatment procedures for pain relief. It is necessary for all specialists to combine basic knowledge and their application in practice.
- MeSH
- analgetika aplikace a dávkování farmakologie klasifikace MeSH
- analgezie metody MeSH
- antiflogistika nesteroidní aplikace a dávkování farmakologie klasifikace škodlivé účinky MeSH
- chirurgie operační škodlivé účinky MeSH
- hormony kůry nadledvin aplikace a dávkování MeSH
- lidé MeSH
- metamizol aplikace a dávkování MeSH
- morfin aplikace a dávkování MeSH
- opioidní analgetika aplikace a dávkování klasifikace MeSH
- paracetamol aplikace a dávkování MeSH
- perioperační péče metody MeSH
- pooperační bolest * farmakoterapie terapie MeSH
- pooperační péče * metody MeSH
- urychlená pooperační rehabilitace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Nesteroidní antirevmatika (NSA) jsou široce využívána v léčbě bolesti jak akutní, tak chronické. Dlouhodobé systémové podávání NSA může být provázeno řadou závažných nežádoucích účinků, které významně limitují možnosti dlouhodobé terapie. Tato postižení nelze omezit na alteraci trávicího traktu, NSA poškozují kardiovaskulární systém (hypertenze, progrese ischemické choroby srdeční) a ledviny (otoky, renální insuficience aj.). Potenciální toxicita NSA se jeví jako klinicky závažná především u starší populace, jež představuje většinu uživatelů NSA. Opioidy, včetně tramadolu, patří mezi nejbezpečnější analgetika. Nejsou toxické pro parenchymatózní orgány, hematopoézu a nezasahují do funkce koagulačního systému; jsou to analgetika vhodná pro polymorbidní pacienty. K nežádoucím účinkům opioidů patří obstipace, dechová deprese, narušení spánkové architektury a vznik fyzické závislosti. Opatrnosti je třeba u vyššího dávkování a rychlého navyšování dávek pacientem, velké opatrnosti je třeba u geriatrických pacientů, kde je třeba individualizovat terapii. Riziko je možné snížit užitím co nejnižších dávek tramadolu potencovaných paracetamolem. Vždy je třeba zvažovat individuální prospěch a rizika léčby u konkrétního pacienta a usilovat o aktivní management rizik léčby.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of both acute and chronic pain. Long-term systemic administration of NSAIDs may be accompanied by a number of serious adverse effects that significantly limit the options for long-term therapy. These complications cannot be limited to alterations of the gastrointestinal tract; NSAIDs damage the cardiovascular system (hypertension, progression of ischemic heart disease) and the kidneys (oedema, renal insufficiency, etc.). The potential toxicity of NSAIDs appears to be clinically significant, particularly in the elderly population, which represents the majority of NSAID users. Opioids, including tramadol, are among the safest analgesics. They are not toxic to parenchymatous organs, haematopoiesis, and do not interfere with the function of the coagulation system; they are analgesics suitable for polymorbid patients. Adverse effects of opioids include constipation, respiratory depression, disturbance of sleep patterns, and the development of physical dependence. Caution is needed with higher dosages and rapid dose escalation by the patient; great care is needed in geriatric patients where therapy needs to be individualized. The risk can be reduced by using the lowest possible doses of tramadol potentiated with paracetamol. It's essential to always weigh the individual benefits and risks of treatment for each patient and to actively manage potential treatment risks.
- MeSH
- antiflogistika nesteroidní farmakologie klasifikace škodlivé účinky MeSH
- chronická bolest * diagnóza etiologie farmakoterapie MeSH
- fixní kombinace léků * MeSH
- lidé MeSH
- opioidní analgetika * farmakologie škodlivé účinky MeSH
- paracetamol farmakologie terapeutické užití MeSH
- tramadol farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
Acetaminophen (APAP) belong among the most used analgesics and antipyretics. It is structurally derived from p-aminophenol (PAP), a potent inducer of kidney toxicity. Both compounds can be metabolized to oxidation products and conjugated with glutathione. The glutathione-conjugates can be cleaved to provide cysteine conjugates considered as generally nontoxic. The aim of the present report was to synthesize and to purify both APAP- and PAP-cysteine conjugates and, as the first study at all, to evaluate their biological effects in human kidney HK-2 cells in comparison to parent compounds. HK-2 cells were treated with tested compounds (0-1000 μM) for up to 24 h. Cell viability, glutathione levels, ROS production and mitochondrial function were determined. After 24 h, we found that both APAP- and PAP-cysteine conjugates (1 mM) were capable to induce harmful cellular damage observed as a decrease of glutathione levels to 10% and 0%, respectively, compared to control cells. In addition, we detected the disappearance of mitochondrial membrane potential in these cells. In the case of PAP-cysteine, the extent of cellular impairment was comparable to that induced by PAP at similar doses. On the other hand, 1 mM APAP-cysteine induced even larger damage of HK-2 cells compared to 1 mM APAP after 6 or 24 h. We conclude that cysteine conjugates with aminophenol are potent inducers of oxidative stress causing significant injury in kidney cells. Thus, the harmful effects cysteine-aminophenolic conjugates ought to be considered in the description of APAP or PAP toxicity.
- MeSH
- aminofenoly * toxicita MeSH
- cystein MeSH
- glutathion MeSH
- ledviny MeSH
- lidé MeSH
- paracetamol * toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
