Proceedings of the Western Pharmacology Society最新文献

Aminoglycosides such as streptomycin or gentamycin are employed to treat stubborn infections. In México, tuberculosis patients are successfully treated with 1 g/day for over 6 months. Ototoxicity is often seen as a consequence of prolonged treatment with aminoglycosides. In young people STP damages the vestibule of the ear; in elder patients it diminishes hearing and balance. These effects are due to streptidine, a metabolite of STP produced in elder patients and detected in blood by liquid chromatography. On occasion, sudden deafness is established after only a short treatment period as the result of the presence of a single nucleotide mutation in the mitochondrial 12S rRNA gene. In patients with this polymorphism, aminoglycosides produce a stereotypic conformation similar to the bacterial 16S rRNA thus inhibiting the synthesis of proteins. Many aminoglycoside-sensitive mutations have been described in several ethnic groups, causing sudden deafness. We started similar studies in Mexican individuals, treated or not with an aminoglycoside, to determine whether similar alterations could be detected. To date in over 60 individuals analyzed we found only one case of polymorphism in a streptomycin treated patient. We developed a simple method to identify such mitochondrial gene in a larger population to make recommendations to use an alternative treatment which do not cause ototoxicity in the mutation bearing patient.

Information related to adverse drug effects caused by ocular medications and ocular adverse effects of systemically administered drugs has increased over the last several decades. Here we review the medical literature over the last four decades to both quantitatively and qualitatively determine the adverse effects of ocular drugs and ocular toxicity of non-ocular drugs. A systematic bibliographic review of the literature was performed with the following terms: "drug treatment", "drug therapy", "ocular adverse effects", "ocular side effects", "ocular toxicity", "systemic side effects", "systemic adverse effects", "systemic toxicity", "ocular drug" and "ophthalmic drug" using the Boolean operators or, and, not. Searches focused on: (1) Ocular side/adverse effects of ophthalmic drugs; (2) Ocular side/adverse effects of systemic drugs; (3) Systemic side/adverse effects of ophthalmic drugs. PubMed was used to perform searches. Limits included: species, human and field tag, abstract/title, dates from 01/01/1971 to 31/12/2010. A sub-selection of references was made by discarding articles that were irrelevant for the topics listed above. Adverse effects of alpha2-adrenergic agonists, beta-adrenergic antagonists, quinine derivatives and antituberculosis agents appear in the literature throughout the period of the review. Adverse effects of newer drugs such as amiodarone, phosphodiesterase 5 inhibitors, antiepileptics, tamoxifen, and its interactions have been published principally in the last two decades. It is imperative for patient safety that knowledge of the adverse effects of drugs on the eye whether topically or systemically administered, and the possible systemic effects of drugs given as ophthalmic medications be emphasized to clinicians.

Tissue degeneration, infection, inflammation, cancer, trauma, surgery and limb fractures all produce pain. Each of these physiological abnormalities requires a therapeutic approach different from the last. In acute pain, caused by fracture, several classes of analgesics have been utilized. These basic remedies for analgesia, however, are still confined to a small number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids. In addition, most of these drugs have side effects, limiting their use in clinical practice. The purpose of this study was to compare the efficacy of three NSAIDs to relief acute pain caused by ankle fracture. Sixty subjects with ankle fracture were randomized to receive ketorolac, diclofenac, or etoricoxib, every 12 hours in a prospective, double-blind study. Forty-nine patients completed the study. The subjects' assessments of ankle pain on the visual analog scale and a Likert scale showed a significant reduction from baseline over 24 hr, regardless the treatment group. All treatments showed a similar profile in pain reduction. Etoricoxib, diclofenac and ketorolac twice daily are a rapid and effective treatment for acute pain. All the regimens were well tolerated in this study.

This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + uridine + cytidine + vitamin B12 (Group DN, n=40) or uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck.

Struthanthus venetus (Sv) from family Loranthaceae is employed in traditional medicine to treat coughs. In previous studies, a methanol extract of Sv shows hypotensive effects and changes in heart rate in rats. The purpose of this study was to determine the effect of a methanol extract of Sv on the electrocardiogram (EKG), and histological changes in the guinea pig heart. Male Hartley guinea pigs anesthetized with sodium pentobarbital received 50 mg/kg ip of Sv extract. An EKG was taken before and after the ip application of Sv extract. The EKG showed changes in QRS morphology, ST segment and T wave, Q wave in DI and AVL, data of ischemia, and myocardial injury. Guinea pigs were sacrificed after 1-93 days; the hearts were prepared for histopathological study with HE, PAS, Masson and Gallegos staining. The methanol extract of Sv causes apoptosis of myocardial fibers, degeneration of muscle fibers, staying only the fibro vascular skeleton, necrosis areas, hyperplasia of endothelial cells and mitotic figures in vascular endothelial cells and myocardial fibers. Changes in the EKG of the guinea pig could explain the hypotensive effects of Sv in rats. Sv extract causes cardio toxicity, apoptosis, autophagic and mitogenic activity in guinea pig heart, suggesting regeneration of the heart.

Persistent pulmonary hypertension of the newborn is defined as the failure of the normal circulatory transition that occurs after birth. It is a syndrome characterized by marked pulmonary hypertension that causes hypoxemia and right-to-left extra-pulmonary shunting of blood. In the treatment of persistent pulmonary hypertension of the newborn, the goal is to increase oxygen flow to the baby's organs to prevent serious health problems. Treatment may include medication, mechanical ventilation and respiratory therapy. We performed a retrospective, descriptive and transversal study to investigate the prevalence and treatment of neonatal patients with persistent pulmonary hypertension who were admitted at the Hospital del Niño DIF from 2004 to 2008. Data, collected from hospital charts, included demographic, clinical course and use of medication. A total of 38 patients were included (prevalence of 5.7%). The average age of patients was 8.4 +/- 1.4 days. The mortality rate was 42.1%. Data were collected and 45 different drugs were given to the pediatric patients. The median number of drugs/inpatient was 8.3 (1-18). The therapeutic class most prescribed was anti-infective (29.9% of all the prescriptions), followed by cardiovascular and renal drugs (26.4% of all the prescriptions) and gastrointestinal agents (14.6% of all the prescriptions). Ranitidine was the drug most commonly used, followed by ampicillin and midazolam. We found a high mortality rate and as in many studies, the therapeutic class most used were anti-infectives.

In this study we present the efficacy of aspiration of disc material employing the Stryker Disc Dekompressor during percutaneous microdiscectomy for the treatment of chronic spinal and radicular pain due to contained lumber disc herniation and compare the short-term outcome in such patients with those who received lumber epidural injection. A total of 50 patients with chronic lumber discogenic pain and radiculopathy were enrolled in this study and were randomized into two groups. Group 1 (n=26) underwent first time, single-level lumber discectomy at either L3-4, L4-5, or L5-S1 using the Stryker Disc Dekompressor for aspiration of disc material and Group 2 (n=24) received epidural steroid/local anesthetic injection. Data on patient demographics, operative time, length of hospitalization, incidence of postoperative complications, analgesic usage and postoperative complications were obtained. For short-term evaluation of the outcome in the two patient groups, the Visual Analogue Scale (VAS) from 0-10 for back pain and radicular pain were obtained preoperatively, 24 hr and 1-6 wk postoperatively. Also, the straight leg raising test (SLRT) was performed and recorded. A significant decrease in the radicular pain scores and an increase in SLRT degrees with a decrease in the back pain scores was seen in the disc Dekompressor group with minimal incidence of postoperative complications. In the epidural injection group, the back pain scores were significantly decreased postoperatively while the radicular pain and the SLRT degrees were insignificantly changed 24 hr postoperatively and at wk 6. We conclud that when standardized patient selection criteria are used, the disc DeKompressor is a safe and more effective treatment for radicular pain of discogenic origin than epidural injection with steroid/local anesthetic. Back pain of discogenic origin was more effectively treated with the epidural steroid/local anesthetic injection. Treatment of patients with radicular pain associated with contained disc herniation using the Dekompressor can be a safe and more effective procedure.

Acute leukemia is the most common malignancy in children, and accounts for nearly 35% of all childhood cancers. Acute myelogenous leukemia (AML) constitutes about 20% of acute leukemias. Initially, treatment of AML involves the immediate management of emergencies associated as hyperleukocytosis, tumor lysis syndrome, hemorrhages and infections. Therefore we performed a retrospective, descriptive and transversal study to investigate the drugs used in patients with AML who were admitted at the Hospital del Niño DIF from 2007 to 2008. Data were collected from hospital. The data included demographic, clinical data and drug usage. A total of 13 patients (12 male and 1 female) were included (prevalence of 16.5% among all cancers in the hospital). The mean age of patients was 6.2 +/- 4.6 years. The mortality rate was 30.8%. Twelve different drugs were given to the patients (10 antineoplastic agents, ondansetron and folinic acid). The median number of drugs/inpatient was 5.4 (range 3-9). Four-hundred thirty-one doses of antineoplastic drugs were administered in 409 sessions. The most used were cytarabine (55.9 %), followed by doxorubicin (7.2 %) and vincristine (6.7 %). Three-hundred twenty-four doses of ondansetron were administered in 409 sessions. We conclude that AML is common in our hospital with a high mortality rate. Also, the antineoplastic agent most used was the pyrimidine analogue cytarabine.

Pharmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cards for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa Ocaranza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 years. The major diagnoses found were: schizophrenia (35.7%), severe mental retardation (17 %), moderate mental retardation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case.

Calorimetry is an analytical method that measures heat flow between a heat source and sample. The sample gains or losses heat based on physical or chemical composition. Differential scanning calorimetry (DSC) compares the results of heating a sample to those for heating a reference material. DSC then measures internal energy or a sample's calorific capacity. The aim of this study was to examine the thermal characteristics of platelet activation. Blood was obtained from human volunteers by venipuncture and collected in 5 ml siliconised and citronated vacutainer tubes. Platelet counts were measured using a hemocytometer. Platelet-rich (PRP) or platelet-poor plasma (PPP) was obtained by centrifugation. Ten microliters of PRP or PPP were placed into aluminum pans for DSC with or without activation by epinephrine (5.0 microM) or CaCl2 (50 microM). To avoid a spontaneous activation of platelets samples were kept frozen, after a 5 min period of stabilization, 5 microl of aggregation-inducing agent was added. Scans were initiated at a -12 degrees C after stabilization, with an increase of a 5 degrees C/min to a maximum of 60 degrees C. The experiments were performed on a TA Differential Scanning Calorimeter (New Castle, DE, USA). The difference in heat evolved between the PRP and PPP during the process of platelet activation was 253 J/g. The difference of heat flow in the activation of PRP versus PPP may correspond to an exothermic process involved in platelet aggregation.