A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

Effects of Sucrose Palmitate on the Physico-Chemical and Mucoadhesive Properties of Buccal Films.

In our current research, sucrose palmitate (SP) was applied as a possible permeation enhancer for buccal use. This route of administration is a novelty as there is no literature on the use of SP in buccal mucoadhesive films. Films containing SP were prepared at different temperatures, with different concentrations of SP and different lengths of hydroxypropyl methylcellulose (HPMC) chains. The mechanical, structural, and in vitro mucoadhesive properties of films containing SP were investigated. Tensile strength and mucoadhesive force were measured with a device and software developed in our Institute. Positron annihilation lifetime spectroscopy (PALS) and X-ray powder diffractometry (XRPD) were applied for the structure analysis of the films. Mucoadhesive work was calculated in two ways: from the measured contact angle and compared with direct mucoadhesive work, which measured mucoadhesive force, which is direct mucoadhesion work. These results correlate linearly with a correlation coefficient of 0.98. It is also novel because it is a new method for the determination of mucoadhesive work.

Qualitative and quantitative research of medication review and drug-related problems in Hungarian community pharmacies: a pilot study.

BACKGROUND: Pharmaceutical care is the pharmacist's contribution to the care of individuals to optimize medicines use and improve health outcomes. The primary tool of pharmaceutical care is medication review. Defining and classifying Drug-Related Problems (DRPs) is an essential pillar of the medication review. Our objectives were to perform a pilot of medication review in Hungarian community pharmacies, a DRP classification was applied for the first time. Also, our goal was the qualitative and quantitative description of the discovered DRPs, and of the interventions for their solution in order to prove the safety relevance of the service and to map out the competence limits of GPs and community pharmacists to drug therapy. METHODS: The project took place in Hungarian community pharmacies. The study was performed with patients taking vitamin K antagonist (VKA) and/or ACE inhibitor and NSAID simultaneously (ACEI-NSAID). 61 pharmacists and 606 patients participated in the project. Pharmacists reviewed the medication for 3 months and the classification of DRPs was performed (category of DRP1 - DRP6). Patient data were statistically analyzed. RESULTS: Patients consumed on average 7.9 ± 3.1 medications and other products. 571 DRPs were detected in 540 patients, averaging 1.06 DRPs per patient (SD = 1.07). The highest frequency category was DRP5 (non-quantitative safety problem; 51.0%). The most common root cause was an interaction (42.0%) and non-adherence (19.4%.). The most commonly used intervention was education (25.4%) and medication replacement by the pharmacist (20.1%). The changing of the frequency and dosage in any direction were negligible. CONCLUSIONS: Patients are struggling with many DRPs that can be assessed and categorized by this system and which remain unrecognizable without pharmacists. Further projects need to be developed to assist in the development of physician-pharmacist cooperation and the widespread dissemination of pharmaceutical care.

Microstructural Distinction of Electrospun Nanofibrous Drug Delivery Systems Formulated with Different Excipients.

The electrospun nanofiber-based orally dissolving webs are promising candidates for rapid drug release, which is due to the high surface area to volume ratio of the fibers and the high amorphization efficacy of the fiber formation process. Although the latter is responsible for the physical and/or chemical instability of these systems. The primary aim of the present study was to elucidate how the addition of polysorbate 80 (PS80) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) influenced the electrospinning process, the properties, and the behavior of the obtained nanofibers. In order to reveal any subtle changes attributable to the applied excipients, the prepared samples were subjected to several state of the art imaging and solid state characterization techniques at both macroscopic and microscopic levels. Atomic force microscopy (AFM) revealed the viscoelastic nature of the fibrous samples. At relatively low forces mostly elastic deformation was observed, while at higher loads plasticity predominated. The use of polysorbate led to about two times stiffer, less plastic fibers than the addition of cyclodextrin. The 1H-13C nuclear magnetic resonance (NMR) cross-polarization build-up curves pointed out that cyclodextrin acts as an inner, while polysorbate acts as an outer plasticizer and, due to its "liquid-like" behavior, can migrate in the polymer-matrix, which results in the less plastic behavior of this formulation. Positron annihilation lifetime spectroscopy (PALS) measurements also confirmed the enhanced mobility of the polysorbate and the molecular packing enhancer properties of the cyclodextrin. Solid-state methods suggested amorphous precipitation of the active ingredient in the course of the electrospinning process; furthermore, the nature of the amorphous systems was verified by NMR spectroscopy, which revealed that the use of the examined additives enabled the development of a molecularly dispersed systems of different homogeneities. An accelerated stability study was carried out to track physical state related changes of the incorporated drug and the polymeric carrier. Recrystallization of the active ingredient could not be observed, which indicated a large stress tolerance capacity, but time-dependent microstructural changes were seen in the presence of polysorbate. Raman mapping verified homogeneous drug distribution in the nanofibrous orally dissolving webs. The performed dissolution study indicated that the drug dissolution from the fibers was rapid and complete, but the formed stronger interaction in the case of the PVA-CD-MH system resulted in a little bit slower drug release, compared to the PS80 containing formulation. The results obviously show that the complex physicochemical characterization of the polymer-based fibrous delivery systems is of great impact since it enables the better understanding of material properties including the supramolecular interactions of multicomponent systems and consequently the rational design of drug-loaded nanocarriers of required stability.

Different types, applications and limits of enabling excipients of pharmaceutical dosage forms.

Along with the development of novel drug delivery systems the material science is also advancing. Conventional and novel synthetic or natural excipients provide opportunities to design dosage forms of the required features including their bioavailability. Emerging trends in the design and development of drug products indicate an increasing need for the functionality-related characterization of excipients. The purpose of this review is to provide an overview of different types of excipients in relation to their application possibilities in various dosage forms with special focus on the enabling excipients. The study also summarizes the applied excipient systems of research formulations and dosage forms available on the market.

Post-authorization changes in the safety and efficacy assessment, recommended indications, and drug quality profile of adalimumab: a chronological overview.

OBJECTIVE: The intention of the present study was to demonstrate the postauthorization changes of adalimumab (European trade name: Humira), evaluating the variations in its safety, efficacy, and quality profile. METHODS: Type-II, major variations of the Summary of Product Characteristics (SmPC) from September 8, 2003 to November 19, 2015, were analyzed, which, according to Commission Regulation (EC) No. 1234/2008, have to reflect changes that may have a significant impact on the safety, efficacy, or quality profile of a medicinal product. A unique scoring system was developed to estimate the influence of post-authorization variations in the safety and efficacy assessment, recommended indications, and drug-quality profile of adalimumab. RESULTS: In the past 13 years, adalimumab has been proven to be beneficial in 12 indications. In this time period, the safety-related subsections of the SmPC expanded the most. 27.12% of the total changes were found in subsection 4.8 (Undesirable effects), 19.77% in subsection 4.4 (Special warnings and precautions for use). Section 5 (Pharmacological properties) was also significantly modified (19.77%) thanks to the numerous clinical trials studying the effects of adalimumab. Concerning the total changes in the content of the SmPC, 58.4% was safety, 29.4% efficacy, and only 1.8% was quality-related alteration. The rest, 10.4%, was considered as administrational modification. CONCLUSION: The extensive postauthorization research (both surveillance and clinical trials) significantly have increased our knowledge about the efficient and safe use of the medicine and have made adalimumab one of the top-10 selling pharmaceuticals worldwide. Regarding ongoing clinical trials, more pediatric indications are expected.

Polyvinyl alcohol nanofiber formulation of the designer antimicrobial peptide APO sterilizes Acinetobacter baumannii-infected skin wounds in mice.

Native and designer cationic antimicrobial peptides are increasingly acknowledged as host defense molecules rather than true antimicrobials. Due to their ability to activate the innate immune system, these structures are used to treat uninfected and bacterially-infected wounds, including those harboring Acinetobacter baumannii. Previously we documented that when administered intramuscularly or topically in liquid formulations, the proline-rich host defense peptide dimer A3-APO accelerates uninfected wound re-epithelization and eliminates systemic and local A. baumannii, methicillin-resistant Staphylococcus aureus and other pathogen load from infected lesions better than conventional antibiotics. In the current study we sought to produce and characterize a novel delivery system, suitable for immediate and convenient application in non-hospital environments. The APO monomer was incorporated into polyvinyl alcohol nanofibers and the complex was polymerized into a solid patch dressing. Mice were subjected to skin abrasion where the wounds were either left uninfected or were inoculated with a near lethal dose of multidrug resistant A. baumannii strain. Analyzed after 3 days, APO monomer-containing patches improved wound appearance significantly better than polymer patches without antibiotics. When compared to colistin, the APO patches accelerated wound healing, and statistically significantly reduced wound size and wound bacterial load. The in vivo antimicrobial effect was more extensive than after intramuscular administration of the peptide drug, by using only one tenth of the active pharmaceutical ingredient. These data suggest that the APO monomer-impregnated nanofiber dressing can be developed as an economical first-line treatment option to skin injuries in general and battlefield burn and blast injuries in particular.

PATIENTS' KNOWLEDGE OF MEDICAL PATCHES IN HUNGARY.

Transdermal therapy with medical patches is a simple possibility in home medication. As the correct use of patches has a decisive impact from the point of its modulator effect.A questionnaire survey was developed to explore level of patients' knowledge of the correct use of transdermal patches. A survey was administered in thirteen Hungarian community pharmacies from October of 2012 to May of 2015. Most of the participants, men and women over 18 years of age (n = 233), used major analgesic patches (fentanyl); the remainder were given nitroglycerin, NSAID analgesics patches during the survey. For the hypothesis testing it was assumed that men were more likely to use a razor for skin depilation before patch application than women as their denser pelage hinders patch adhesion. The hypothesis testing showed no significant gender difference in razor use (X² = 0.201; p = 0.654). Pharmacists should direct patients to avoid using soap for skin cleansing before patch application because only 22 percent of the participants always avoided its use. Since only 9 tests were flawless from 233 completed questionnaires. Many patients do not understand how to correctly apply a transdermal dosage patch. Pharmacists should teach their correct application based on results.

Earlier identification of risks: cumulative probability analysis of time to safety alerts for therapeutic monoclonal antibodies.

OBJECTIVE: Previous analysis of US FDA Medwatch safety alerts for monoclonal antibody therapeutics demonstrated that premarketing clinical trials can predict more than half of safety concerns. We expanded this analysis to assess whether the predictable alerts are detected sooner than the unpredictable alerts. METHODS: Times to alert were compared using Mann-Whitney test, Kolmogorov-Smirnov test, and using curves displaying cumulative frequencies of alerts over time. RESULTS: Until December 31, 2013 inclusive, 76 Medwatch alerts for therapeutic monoclonal antibodies were reported: 43 predictable vs. 33 unpredictable. Predictable alerts were reported at a median (IQR) of 41 (19-77) months after approval vs. 53 (23-73) months for the unpredictable alerts. The mean (SE) was 52.07 (6.69) months and 55.91 (7.06) months for the predictable and unpredictable, respectively. Although the difference of 12 months between medians of time to alert was observed, the difference was not demonstrated as significant. Cumulative frequency curves show that predictable alerts were detected sooner until month 73 after approval, when ~ 80% of alerts were detected. Immunological reactions (such as infusion reactions, anaphylaxis, and reactions due to antibodies) were identified early; all 12 such alerts were released before the curves of cumulative frequencies cross at month 73. On the other hand, reactions occurring after the curves cross are predominantly late-occurring cancers and opportunistic infections. CONCLUSIONS: The results imply that focus on predictable reactions defined as potential risks may play a role in early detection of important safety concerns.

Comparison of directly compressed vitamin B12 tablets prepared from micronized rotary-spun microfibers and cast films.

Fiber-based dosage forms are potential alternatives of conventional dosage forms from the point of the improved extent and rate of drug dissolution. Rotary-spun polymer fibers and cast films were prepared and micronized in order to direct compress after homogenization with tabletting excipients. Particle size distribution of powder mixtures of micronized fibers and films homogenized with tabletting excipients were determined by laser scattering particle size distribution analyzer. Powder rheological behavior of the mixtures containing micronized fibers and cast films was also compared. Positron annihilation lifetime spectroscopy was applied for the microstructural characterization of micronized fibers and films. The water-soluble vitamin B12 release from the compressed tablets was determined. It was confirmed that the rotary spinning method resulted in homogeneous supramolecularly ordered powder mixture, which was successfully compressed after homogenization with conventional tabletting excipients. The obtained directly compressed tablets showed uniform drug release of low variations. The results highlight the novel application of micronized rotary-spun fibers as intermediate for further processing reserving the original favorable powder characteristics of fibrous systems.

Micro- and macrostructural characterization of polyvinylpirrolidone rotary-spun fibers.

The application of high-speed rotary spinning can offer a useful mean for either preparation of fibrous intermediate for conventional dosage forms or drug delivery systems. Polyvinylpyrrolidone (PVP) and poly(vinylpyrrolidone-vinylacetate) (PVP VA) micro- and nanofibers of different polymer concentrations and solvent ratios were prepared with a high-speed rotary spinning technique. In order to study the influence of parameters that enable successful fiber production from polymeric viscous solutions, a complex micro- and macrostructural screening method was implemented. The obtained fiber mats were subjected to detailed morphological analysis using scanning electron microscope (SEM), and rheological measurements while the microstructural changes of fiber samples, based on the free volume changes, was analyzed by positron annihilation lifetime spectroscopy (PALS) and compared with their mechanical characteristics. The plasticizing effect of water tracked by ortho-positronium lifetime changes in relation to the mechanical properties of fibers. A concentration range of polyvinylpyrrolidone solutions was defined for the preparation of fibers of optimum fiber morphology and mechanical properties. The method enabled fiber formulation of advantageous functionality-related properties for further formulation of solid dosage forms.

EFFECT OF STORAGE TEMPERATURE ON THE STABILITY OF TOTAL PARENTERAL NUTRITION ADMIXTURES PREPARED FOR INFANTS.

Physical, chemical and microbiological stability of total parenteral nutrient (TPN) admixtures was studied as a function of storage time and temperature. Particle size analysis and zeta potential measurements were carried out to evaluate the possible changes in the kinetic stability of the emulsions as a function of storage time and temperature. The concentration changes of the applied additives, those of the ascorbic acid and L-alanyl-L-glutamine, were also determined under different storage conditions. Our results indicate that there were no significant differences in the particle size and zeta potential values of admixtures stored at the three examined temperatures. The best results were obtained in the case of admixtures stored at 30°C temperature. Rapid decomposition of vitamin C was found while the glutamine showed adequate stability as a function of storage time and temperature. According to the results of the physicochemical examinations 10-day storage period of this type of TPN admixtures can be accepted at room temperature. Their storage does not require refrigeration (2-8°C) thus they can be administered without special preheating ensuring better physiological tolerance. Ascorbic acid can be added to the system preceding the administration to the patient because of its rapid decomposition.

[Drug compliance of patients on anticoagulant treatment]. / Alvadásgátló kezelésben részesülo betegek gyógyszer-adherenciája.

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

[Development possibilities of hormone-containing implants for gynecological applications: A review]. / Nogyógyászati célra szánt, hormontartalmú implantátumok fejlesztési lehetoségeinek áttekintése: irodalmi áttekintés.

Implantable gynecological drug delivery devices are applied for contraceptive, hormone replacement purposes and for the treatments of other gynecological diseases, e.g. endometriosis. The review provides a comprehensive overview about the indications, advantages, limitation of application and the applied technologies of hormone-containing implants, as well. The study comprises the relevant patents and the recently published papers.

[Introduction of Functional Foods--Types, Manufacturing Methods and Quality Assurance]. / Funkcionális élelmiszerek típusai, eloállítá'si módszerei és minoségbiztosításuk.

Because of the beneficial effects to health functional foods are important elements of health promotion. The positive effect of the functional components should be based on scientific evidence-based. In addition to the traditional food processing technology new technologies have appeared, e.g. microencapsulation, edible coatings and orodispersible films, nano-technology, vacuum impregnation. In the present study, probiotics and the structure, the production and the impact of prebiotic functional cereals are discussed in more detail. In addition to their numerous advantages in connection with the safe application, several questions arise because of inadequate quality control measures prior to coming onto the market.

Cyclodextrin encapsulation enabling the anticancer repositioning of disulfiram: Preparation, analytical and in vitro biological characterization of the inclusion complexes.

Drug repositioning is a high-priority and feasible strategy in the field of oncology research, where the unmet medical needs are continuously unbalanced. Disulfiram is a potential non-chemotherapeutic, adjuvant anticancer agent. However, the clinical translation is limited by the drug's poor bioavailability. Therefore, the molecular encapsulation of disulfiram with cyclodextrins is evaluated to enhance the solubility and stability of the drug. The present work describes for the first time the complexation of disulfiram with randomly methylated-ß-cyclodextrin. A parallel analytical andin vitrobiological comparison of disulfiram inclusion complexes with hydroxypropyl-ß-cyclodextrin, randomly methylated-ß-cyclodextrin and sulfobutylether-ß-cyclodextrin is conducted. A significant drug solubility enhancement by about 1000-folds and fast dissolution in 1 min is demonstrated. Thein vitrodissolution-permeation studies and proliferation assays demonstrate the solubility-dependent efficacy of the drug. Throughout the different cancer cell lines' characteristics and disulfiram unspecific antitumoral activity, the inhibitory efficacy of the cyclodextrin encapsulated drug on melanoma (IC50 about 100 nM) and on glioblastoma (IC50 about 7000 nM) cell lines differ by a magnitude. This pre-formulation screening experiment serves as a proof of concept of using cyclodextrin encapsulation as a platform tool for further drug delivery development in repositioning areas.

Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model.

The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7-14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization.

Pharmaceutical care for patients with acute myocardial infarction in Hungary.

OBJECTIVE: To obtain informationon the main causatives of acute myocardialinfarction (AMI), the background needs to be analyzed. Our aim was to identify those pharmaceutical aspects of this polymorbidity where the pharmacist can contribute. Earlier and recent European and Hungarian studies show similar results: cardiovascular (CV) death is still the leading cause of mortality. The quality of life is much lower and life expectancy is shorter in the investigated Borsod-Abaúj Zemplén county population compared to the whole of the country. After pharmaceutical care has been defined, its role should be established. METHODS: A retrospective hospital-based survey was carried out. Medical records of 659 patients treated for myocardial infarction at the 1st Department of Internal Medicine-Cardiology of Borsod-Abaúj-Zemplén County Hospital and University Hospital were analyzed. Data were obtained using the MedWorkS integrated hospital information system and were selected based on Social Security Number (TAJ) and The International Statistical Classification of Diseases and Related Health Problems (ICD). We focused on the therapy and medication of patients. RESULTS: The obtained results are consistent with those of previous Hungarian studies (OLEF 2000) and statistical analyses. Based on the present study we suggest that pharmacists should work more closely with the medical staff. In studying the medication, we concentrated on antiplatelet therapy and studied the use of aspirin alone compared to aspirin plus clopidogrel. Of the 659 patients only 172 received aspirin as a preventive agent. We noticed that during this study only a low number of patients received ASA treatment and it could be seen in the outcome of the illness. We also found that dual antiplatelet therapy did not decrease the incidence of reinfarction in patients with AMI. DISCUSSION: In this study the theory (guidelines, other studies) and the clinical practice of the therapy and medication of AMI were compared. ASA therapy did not produce any significant effect. Our results are similar to those studies which concluded that ASA did not decrease the risk of cardiovascular events. CONCLUSION: Most patients with AMI suffer from polymorbidity. Since the occurrence of underlying chronic diseases is high, not only AMI must be treated, but therapy and medication must be complex. Complex therapeutic management is the key to the success of pharmaceutical care in the community pharmacy following hospital treatment.

A randomized, controlled trial of a clinical pharmacist intervention in microdiscectomy surgery - Low dose intravenous ketamine as an adjunct to standard therapy.

AIM: The hypothesis that postoperative pain would be reduced by using 1 µg/kg/min of ketamine, both intra- and post-operatively, for lumbar microdiscectomy surgery was assessed by measuring morphine consumption. Patient side effects were reported. METHODS: Forty-five patients undergoing microdiscectomy surgery were randomized under double-blind conditions into three groups: Group1 (G1) received normal saline, Group 2 (G2) ketamine (1 µg/kg/min) intra-operatively and Group 3 (G3) ketamine (1 µg/kg/min) both intra- and post-operatively. Morphine consumption, pain scores, nausea and vomiting, CNS disorders were recorded for 24 h post surgery. This study was conducted by applying the concept of a clinical pharmacist intervention. RESULTS: The time for the first analgesia demand dose was significantly shorter (P < 0.05) in G117 ± 1.7 min than for G2 and G3. In G3 morphine consumption 6, 12, and 24 h after surgery was 3 ± 2.26, 9.2 ± 2.11 and 26.9 ± 2.71 mg. Total morphine consumption was significantly lower for G3 than for G1 or G2 (P < 0.05). The visual analog scale score (VAS) values were significantly lower in G3 (P < 0.05) than for the other groups during the first 24 h. The rate of nausea and vomiting was significantly higher in G1 vs G3 (P < 0.05). No difference in drug induced CNS disturbances was observed among the groups. CONCLUSIONS: Using 1 µg/kg/min of ketamine hydrochloride intra- and post-operatively for microdiscectomy surgery could be an adjunct therapy to reduce postoperative morphine consumption minimizing its side effects. Collaborative clinical pharmacy practice on the basis of pharmacology had an effective role in improving the general outcome of microdiscectomy surgery.