Neurontin

W. Irmak. University of the District of Columbia.

In the case of pharmaceutical chemicals that are mostly ‘organic solutes’ cheap neurontin 400 mg overnight delivery, the liquid-liquid extraction system may very often make use of two immiscible organic solvents (e order 800 mg neurontin fast delivery. On the contrary, the ‘inorganic solutes’ normally encountered are in- variably in aqueous solutions ; therefore, it has become absolutely necessary to produce such neutral sub- stances out of them, for instance ion-association complexes and metal-chelates (using organic-ligands) that may be extracted into an appropriate organic solvent. In short, liquid-liquid extraction has been employed predominantly and effectively not only for the pre-concentration and isolation of a ‘single’ chemical entity just before its actual estimation, but also for the extraction of classes of organic compounds or groups of metals, just prior to their usual estimation either by chromatographic techniques or by atomic-absorption methods. Now, if a third substance is made to dissolve in a two-phase mixture of the solvents (i. Therefore, under these prevailing experimental parameters the ratio of the mole fractions of the solute in the two respective immiscible phases (‘a’ and ‘b’) is found to be a constant which is absolutely independent of the quantity of solute present. It is termed as the Nernst Distribution Law or the Partition Law and may be expressed as follows : []A a Concentration of solute in solvent ‘a’ Kp = =... The constant (Kp) is also known as the distribution coefficient or the partition coefficient. However, the Partition Law offers the following two limitations, namely : (a) It is not thermodynamically rigorous i. In other words, it is solely applicable to very dilute solutions in which case the ratio of the activities almost approaches unity, and (b) It does not hold good when the distributing substances encounters association or distribution in either phases (i. Consequently, a more rigorous treatment particularly specifies Kp as the ratio of the activities of the substance (A) in the two solvents instead of their concentrations. Hence, for dilute solutions, at a specified constant pressure and temperature, the mole fraction of a solute is directly proportional to its concentration in molarity or mass per unit volume ; which implies that these may be employed instead of mole-fraction in Eq. Thus, the Partition Coefficient Kp is also given by the following expression : S1 Kp =... Adequate precaution and care must be exercised in determining partition coefficients based on the solubility data as S1 is not the solubility of substance ‘A’ in pure Solvent ‘a’, but rather the solubility in Solvent ‘a’ saturated with Solvent ‘b’. Example : In order to determine the exact partition coefficient of substance ‘A’ between water and ethyl acetate, the appropriate solubilities would be those of the substance ‘A’ in 3. Solvent Pair tion Phases of Azeotrope of Azeotrope of Solvents (%) (°C) (°C) Upper Lower 1. Therefore, a number of procedures have been adopted to avoid ‘error due to the volume change’ incurred thereby, namely : (i) Measure the volume of the phase employed for the analysis and incorporate this volume in the calculations, (ii) Separate the phase quantitatively and subsequently dilute to a known volume, (iii) Separate the phase quantitatively and make use of the entire volume in the remaining steps of the ongoing analysis, and (iv) Carry a marker substance through the extraction to automatically compensate for volume changes. However, the latter procedure finds its abundant use in chromatographic methods of analysis. Let us assume that ‘x’ moles of solute present initially in a volume V2 of Solvent ‘b’. Now, this particular sample undergoes extraction with a volume V1 of Solvent ‘a’ and subsequently ‘y’ moles of com- pound are left in V2 at equilibrium. Hence, the fraction left unextracted after ‘n’ extraction may be given by the following expression : − n F V1 I fn = G Kp + 1J...... Therefore, it is absolutely necessary to take this into consideration while selecting an appropriate extraction-system. Thus, the effect of temperature on the partition coefficient may be estimated conveniently from its effect on the solubilities of the substance in the two respective solvents. The effect of inert solutes, such as : calcium chloride, magnesium chloride and sucrose, can also be employed judiciously and efficaciously in the development of solutions to difficult extraction problems by allowing efficient extractions from the water into such solvents as acetone, ethanol and methanol that are found to be completely miscible with water in the absence of salt. Matkovitch and Cristian* found the above three inert solutes to be the best agents for salting acetone out of water. It has been observed that the acetone layer that separated from a saturated aqueous solution of CaCl2 exclusively contained 0. Thus, these neutral and ionic forms may not have the same identical partition coefficients in a second solvent ; therefore, the quantity of a substance being extracted solely depends upon the position of the acid-base equilibrium and ultimately upon the pH of the resulting solution. Hence, extraction coefficient (E) may be defined as the ratio of the concentrations of the substance in all its forms in the two respective phases in the presence of equilibria ; and it can be expressed as follows : Σ[]Si 2 E = Extraction Coefficient =... In conclusion, it may be observed that the pH for an ‘extraction system’ must be selected in such a fashion so that the maximum quantum of the analyte is present in the extractable form, that obviously suggests that the analyte should always be in the form of either a free base or a free acid. From the actual practical experience it has been noticed that a good-working range lies between 95 to 97% present in the extractable form. In true sense, ion-pair may be regarded as a close association of an anion and cation, and therefore, it usually takes place either in a polar or a non-polar solvent. In reality, the ion-pairs are invariably formed by virtue of the union between comparatively large organic anions and (much smaller) cations. Interestingly, the resulting ion-pairs have been found to show their appreciable solubility in polar solvents ; and hence, these species may be extracted conveniently under such experimental parameters where neither individual compo- nent ion could. A few vital criteria towards the formation of an improved aqueous extractable ionic species are, namely : • Formation of a neutral metal-chelate complex or by ion association, and • Creation of larger and more hydrophobic molecular species.

They may androgens reduce the number of prolactin receptors or may bind competi- Nausea and vomiting tively to those that are available buy 400mg neurontin amex. Fluid retention Androgens may inhibit estrogen synthesis or competitively bind caused by sodium reten- at estrogen receptors generic neurontin 400 mg visa. Just for women Pharmacotherapeutics Women may develop: • acne Androgens are indicated for the palliative treatment of advanced • clitoral hypertrophy breast cancer, particularly in postmenopausal women with bone metastasis. Just for kids Children may develop: Pharmacokinetics • premature epiphyseal closure After oral administration, antiandrogens are absorbed rapidly and completely. Antiandrogens are metabolized rapidly and extensively and ex- creted primarily in urine. Pharmacotherapeutics Antiandrogens are used with a gonadotropin-releasing hor- mone analogue, such as leuprolide, to treat metastatic prostate cancer. Special feature: no flareup Concomitant administration of antiandrogens and a gonadotropin- releasing hormone analogue may help prevent the disease flare that occurs when the gonadotropin-releasing hormone analogue is used alone. How- ever, flutamide and bicalutamide may affect prothrombin time (a test to measure clotting factors) in a patient receiving warfarin. Adverse These drugs include: reactions to • hydroxyprogesterone caproate antiandrogens • medroxyprogesterone acetate • megestrol acetate. When antiandro- gens are used with gonadotropin-releasing Pharmacokinetics hormone analogues, the When taken orally, megestrol acetate is well absorbed. Progestins are metabolized in the liver and • nausea excreted as metabolites in urine. Researchers believe the drugs bind to a specific receptor to act on hormonally sensitive cells. Adverse They aren’t exhibitionists reactions to Because progestins don’t exhibit a cytotoxic activity (destroying progestins or poisoning cells), they’re considered cytostatic (they keep the cells from multiplying). Mild fluid retention is probably the most com- Pharmacotherapeutics mon reaction to prog- estins. Other adverse re- Progestins are used for the palliative treatment of advanced en- actions include: dometrial, breast, prostate, and renal cancers. Oil issues • Hydroxyprogesterone taken with dantrolene and other liver- Patients who are hyper- toxic drugs increases the risk of liver toxicity. Gonadotropin-releasing hormone analogues Gonadotropin-releasing hormone analogues are used for treat- ment of advanced prostate cancer. Pharmacokinetics Goserelin is absorbed slowly for the first 8 days of therapy and rapidly and continuously thereafter. Adverse reactions to gonadotropin-releasing hormone analogues Hot flashes, impotence, and decreased sexual Flares and flashes desire are commonly reported reactions to Disease symptoms and pain may worsen or gonadotropin-releasing hormone analogues. The flare can be fatal in pa- Goserelin and • peripheral edema tients with bony vertebral metastasis. Because prostate tumor cells are stimulated by testosterone, the reduced testosterone level inhibits tumor growth. Then there’s triptorelin Triptorelin is a potent inhibitor of gonadotropin secretion. In men, testosterone declines to a level typically seen in surgically castrat- ed men. The drugs lower the testosterone level without the adverse psychological effects of castration or the adverse cardiovascular effects of diethylstilbe- strol. Drug interactions No drug interactions have been identified with goserelin, leupro- lide, or triptorelin. They do their work during the M phase, which is the phase of mitosis, or cell Vinca alkaloids division. These drugs are cell cycle–specific for the M phase and include: • vinblastine • vincristine • vinorelbine. Metabolism and excretion Vinca alkaloids undergo moderate liver metabolism before being eliminated through different phases, primarily in stool with a small percentage eliminated in urine. As a result, formation of the mitot- ic spindle is prevented, and the cells can’t complete mitosis (cell Adverse division). There- Nausea, vomiting, consti- fore, vinca alkaloids are cell cycle–specific for the M phase. Inter- pation, and stomatitis ruption of the microtubule function may also impair some types of may occur in patients cellular movement, phagocytosis (engulfing and destroying micro- taking vinca alkaloids. Muscle matters • Vincristine is used in combination therapy to treat Hodgkin’s Neuromuscular abnor- disease, non-Hodgkin’s lymphoma, Wilms’ tumor, rhabdomyosar- malities commonly occur coma, and acute lymphocytic leukemia. It vinorelbine and, occa- may also be used in the treatment of metastatic breast cancer, sionally, with vinblastine cisplatin-resistant ovarian cancer, and Hodgkin’s disease. Tumor trouble Drug interactions Vinblastine may produce Vinca alkaloids can interact with other drugs. The pain • Calcium channel blockers enhance vincristine accumulation, in- usually lasts 20 minutes creasing the tendency for toxicity. Teniposide shows Etoposide is effective in the treatment of testicular cancer, non- some activity in Hodgkin’s lymphoma, lung cancer, and acute leukemia. Teniposide treating brain has demonstrated some activity in treating Hodgkin’s disease, lym- tumors!

Mechanism of action: Relaxes smooth muscles of the bronchi- oles by stimulating β2-adrenergic receptors purchase neurontin 100 mg on-line. Contraindications: Hypersensitivity to adrenergic compounds buy neurontin 800mg mastercard, tachycardia (idiopathic or from digitalis). Mechanism of action: Scopolamine blocks acetylcholine effects at muscarinic receptors throughout the body. If dose is missed, patient should not double subsequent dose when it is remembered. Adverse reactions • Common: dry mouth, blurred vision, (decreased accommoda- tion), drowsiness, tachycardia, urinary hesitancy. Clinically important drug interactions • Drugs that increase effects/toxicity of scopolamine: antihista- mines, antidepressants, disopyramide, quinidine, alcohol, opioids, sedative-hypnotics. Gradually decrease carbidopa–levodopa dosage (10–30%) 2–3 days after initiating selegiline. Onset of Therapeutic Action Duration <1 h 24–72 h Food: Patients should avoid foods that contain tyramine (aged cheese, Chianti wine, pickled herring, chopped liver, broad beans). Contraindications: Hypersensitivity to selegiline and those who are taking opioid-type drugs, especially meperidine. Adverse reactions • Common: nausea (20%), dizziness, abdominal pain (8%), dry mouth (66%). Warnings/precautions • Use with caution in patients with diabetes mellitus, seizures, liver, kidney disease. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Adverse reactions • Common: insomnia, drowsiness, nausea, diarrhea, dry mouth, male sexual dysfunction. Mechanism of action: Enhances effect of nitric oxide by inhibit- ing phosphodiesterase in corpus cavernosum. Onset of Action Peak Effect Duration 30 min 60–120 min 4 h Food: Take on empty stomach. Contraindications: Concomitant use of nitrates, including patch; hypersensitivity to sildenafil. Advice to patient • Practice safe sex as drug has no effect on disease transmission. Clinically important drug interactions • Drugs that increase effects/toxicity of sildenafil: cimetidine, erythromycin, itraconazole, ketoconazole. Editorial comments • Sildenafil, an extremely popular drug, has proven to provide beneficial responses in patients with impotence associated with diabetes, cardiovascular disease, spinal cord injury, radical prostatectomy and in patients taking drugs for hypertension, depression, or psychosis. Cardiovascular events described with the drug’s use have generally occurred in the setting of preex- isting disease. Warnings/precautions • Use with caution in patients with hypersensitivity to silver sul- fadizine, kidney and liver disease. May have cross-sensitivity with thiaziades, sulfonylaurate, sulfonylureal anhydrase inhibitors. Your physician may recommend coverings over the area being treated with silver sulfadiazine. Clinically important drug interactions: Silver sulfadiazine reduces effects of fibrinolysin, deoxyribonuclease, collagenase, sutilains, papain. Editorial comments: It should be noted that appreciable amounts of silver sulfadiazine may be absorbed and produce systemic adverse reactions. Contraindications: Hypersensitivity to statins, active liver dis- ease or unexplained persistent elevations of serum transaminase, pregnancy, lactation. Warnings/precautions • Use with caution in patients with renal insufficiency, history of liver disease and in alcohol abusers. Values should be obtained prior to and periodically after treat- ment begins to ascertain drug efficacy. It may be advisable to take a liver biopsy if transami- nase elevation persists after drug is discontinued. Onset of Action in Serum Potassium Duration Oral 2–12 h 6–24 h Rectal 2–12 h No data Food: Administer sodium polystyrene sulfonate with water or sor- bitol, not with orange juice. Contraindications: Hypersensitivity to sodium polysterene sul- fonate or components, hypokalemia. Warnings/precautions • Use with caution in patients with sodium intake restriction (severe heart failure, marked edema, hypertension), constipation. Advise patients experiencing constipation to increase intake of fluids and to consume high-fiber foods (bran, wholegrain bread, raw vegetables and fruits). Clinically important drug interactions • Drugs that increase effects/toxicity of sodium polysterene sul- fonate: magnesium hydroxide, aluminum carbonate, other aluminum- and magnesium-containing antacids and laxatives. Mechanism of action: Stimulates linear growth in children with growth hormone deficiency. Contraindications: Growth promotion in children with closed epiphyses (if used for growth stimulation [girls 14–15, boys 15–16]), intracranial lesion with ongoing neoplastic activity, hypersensitivity to m-cresol or glycerin (present in somatropin), critically ill patients. If hypothyroidism develops, it may be nec- essary to use thyroid replacement therapy.

The question is thus one of understanding how these types of knowledge appear cheap neurontin 400 mg amex, disappear and are transformed in the cycle in relation to the actors who convey them neurontin 600 mg amex. From this standpoint, according to Barbier and Galatanue,18 a semantic and pragmatic consideration of the types of knowledge is needed, a consideration that must deal with their status, how they are used, the contexts in which they appear, and their social functions. To grasp their meaning, it is necessary frst to identify the context and then describe how the different types of knowledge appear in it and how they develop in relation to the conditions under which they are mobilized and enunciated. Consequently, sociological studies deal with the various practices that occur in scientifc investigations as well as with the history of facts and controversies, with the rhetoric of discourse both written and oral, and with the laboratories’ modes of operation. In the feld of cognitive psychology and social representations in particular, Moscovici,22 Wagner,23 and others24 bring out the fact that scientifc and common-sense knowledge develop interdependently. As Bangerter25 puts it, they develop and connect with each other in a “multilevel” organizational system. If the types of knowledge are associated with social representations that include both their conceptual and pragmatic dimensions,26 this theory can be a useful contribution to their study. Furthermore, scientifc knowledge and the construction of such knowledge are therefore as much an object of study as common-sense knowledge. Generally speaking, the object of study here is the circulation of knowledge among the various actors along the medication cycle; in order to understand the social dynamics between actors and groups of actors around knowledge, researchers must examine each one’s practices in the place they are produced. It is thus necessary to explore how diverse types of knowledge are positioned within each group and between groups and circulate among them. Galatanu, Savoirs, capacités, compétences: Des concepts d’analyse ou des concepts pour l’action. Lynch, Technical work and critical inquiry: investigations in a scientifc laboratory Social Studies of Science. Bangerter, Transformation between Scientifc and Social Representations of Conception: The Method of Serial Reproduction. Moscovici, Social Representations and pragmatic communication: Symposium on social representations. However, in this article we shall examine only how scientifc research laboratories develop this knowledge and present it to the other actors involved in the cycle in relation to the development of specifc drugs. The study on the circulation of knowledge In this study, the question we are asking is how knowledge circulates within the laboratory and outwards from the laboratory. What we are thus seeking to do is examine the ways that knowledge and the circulation of knowledge are organized. The forms of organization may be relatively standardized or differentiated or may appear to be idiosyncratic depending on the laboratory. To answer our question, we conducted exploratory research drawing on the work of Latour and Woolgar27 and Knorr Cetina28, among others, regarding the study of laboratory life and its relationship to knowledge. At the outset, as these authors have shown, knowledge is constructed out of a certain diversity of facts, inscriptions and statements. These in turn stem from laboratory researchers’, other staff’s and students’ activities in a physical and social setting that determines them, notably through the technological elements that provide the framework for the activities. As Lynch29 points out, “Such ‘knowledge’ is not a prerefective cognitive content since it is embodied in the environment of an inquiry and is the very structure of instrumental accessibility. We have selected these two basic factors of scientifc investigation, which, in a manner of speaking, constitute the knowledge that circulates in and between laboratories. In the case we are concerned with, the laboratories are molecular-biology laboratories behind the development of substances in the medication cycle To this end, we selected indicators of the bases of knowledge (technology and networks), the transformations (of the objects, in this case the substances under investigation in the laboratories) and the circulation of knowledge inside and outside the laboratory. In particular, we selected the three following indicators of the management of the space: the premises, which are basically characterized by high-tech instrumentation defning the tasks to be performed; the actors in the space and how they function (networks); and the objects they are working on, which are expressed as statements in publications. General description of the laboratory The investigations, part of a broader, ethnographic, multi-case study of knowledge in different types of laboratories involved in drug development, were conducted in three laboratories. Two are interdependent biochemistry laboratories; one is a university biochemistry laboratory, and the 27 B. Lynch, Technical work and critical inquiry: investigations in a scientifc laboratory Social Studies of Science. From their current research, we specifcally selected the studies on the antiangiogenic properties of two substances used in treating cancer, Neovastat and green tea catechin. The third laboratory, located in a regional university (in a northern area near a boreal forest), is, among other things, exploring the anticancer properties of substances extracted from such essential oils as balsam fr and tamarack larch as well as bog myrtle and yellow balsam. The frst two have a special arrangement with a dual location comprising a molecular-medicine laboratory in a children’s hospital and a biochemistry laboratory in a university. The dual location indicates the presence of a many-sided, public-private partnership and a mixed basic-and clinical-research commitment. The staff of the Montreal-area university laboratory includes 1 senior researcher/laboratory director, 1 senior researcher/project director, 1 animal technician, 1 secretary and 2 professional researchers. The director of this laboratory also heads the children’s-hospital laboratory that includes 4 senior researchers/project directors with a background in biochemistry, biology and physiology, and one technician. Attached to the two laboratories, there are also 8 masters and 5 doctoral students, most with a background in biochemistry and a few in physiology and agri-food. As for the third laboratory, it includes 2 researchers (1 full professor and 1 associate professor), 1 postdoctoral fellow, 4 doctoral students, 11 masters’ students, and 2 bachelors students.