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I (4–1–10 Edition) that are reasonably likely to occur proven atorlip-20 20 mg cholesterol definition pdf, the bility to the product being produced at processor shall reassess the adequacy the facility buy cheap atorlip-20 20 mg on line average cholesterol daily. Such changes may include 20mg atorlip-20 visa ldl cholesterol definition, ity is limited on a processing vessel or but are not limited to changes in: Raw at a remote processing site discount 20 mg atorlip-20 visa average cholesterol per meal, the records materials or source of raw materials, may be transferred to some other rea- product formulation, processing meth- sonably accessible location at the end ods or systems, finished product dis- of the seasonal pack but shall be imme- tribution systems, or the intended use diately returned for official review or consumers of the finished product. All records re- by an individual or individuals who quired by this part and all plans and have been trained in accordance with procedures required by this part shall §123. Processing and other information are not subject to the requirements of shall be entered on records at the time this section unless they are used to ful- that it is observed. These records are subject similar document that is specific to to the requirements of §123. An importer rately reflects the current situation be- may hire a competent third party to tween the signing parties, and is func- assist with or perform any or all of the tioning and enforceable in its entirety; verification activities specified in para- or graph (a)(2) of this section, including (2) Have and implement written writing the importer’s verification pro- verification procedures for ensuring cedures on the importer’s behalf. The importer shall main- they offer for import into the United tain records, in English, that document States were processed in accordance the performance and results of the af- with the requirements of this part. The firmative steps specified in paragraph procedures shall list at a minimum: (a)(2)(ii) of this section. These records (i) Product specifications that are de- shall be subject to the applicable provi- signed to ensure that the product is not sions of §123. There Federal Food, Drug, and Cosmetic Act must be evidence that all fish and fish- because it may be injurious to health ery products offered for entry into the or have been processed under insani- United States have been processed tary conditions, and, under conditions that comply with this part. Processors shall maintain chemical contamination, natural tox- records that document that all shucked ins, and related food safety hazards, molluscan shellfish have met the re- processors shall include in their quirements of this section. The tag shall bear, at a Subpart D [Reserved] minimum, the information required in §1240. In place of Subpart E—Production and Process the tag, bulk shellstock shipments may Controls be accompanied by a bill of lading or 129. These records shall document: Subpart A—General Provisions (1) The date of harvest; (2) The location of harvest by State §129. I (4–1–10 Edition) holding, and shipping of bottled drink- (g) Primary container means the im- ing water are in conformance with or mediate container in which the product are operated or administered in con- water is packaged. For the purposes of this part, the fol- (j) Shipping case means a container in lowing definitions apply: which one or more primary containers (a) Approved source when used in ref- of the product are held. The presence in the plant of current certifi- Subpart B—Buildings and Facilities cates or notifications of approval from the government agency or agencies §129. Conveyor open- ages, or other containers and offered ings shall not exceed the size required for sale for human consumption, in- to permit passage of containers. Records of (a) Product water and operations approval of the source water by govern- water—(1) Product water. The product ment agencies having jurisdiction, water supply for each plant shall be records of sampling and analyses for from an approved source properly lo- which the plant is responsible, and cated, protected, and operated and records describing corrective measures shall be easily accessible, adequate, taken in response to a finding of E. If different from jurisdiction over the approval of the the product water supply, the oper- water source, and shall be consistent ations water supply shall be obtained with the minimum requirements set from an approved source properly lo- forth in §165. Firms that use a public water system (3) Product water and operations water for source water may substitute public from approved sources. Additionally, (ii) Firms that do not use a public source water obtained from other than water system as the source of their a public water system is to be sampled water may reduce the frequency of and analyzed for total coliform at least their testing of that source, as well as once each week. If any coliform orga- the number of chemical contaminants nisms are detected, follow-up testing for which they test the source water, if must be conducted to determine wheth- they can document that such reduction er any of the coliform organisms are is consistent with a State-issued waiv- Escherichia coli. I (4–1–10 Edition) that are likely to result from such in sanitary closures and kept clean treatment. Federal Food, Drug, and Cosmetic Act (d) Filling, capping, closing, sealing, dealing with adulterated foods. Whenever air done in a sanitary manner so as to pre- under pressure is directed at product clude contamination of the bottled water or a product water-contact sur- drinking water. When em- and utensils shall be suitable for their ployee locker and lunchrooms are pro- intended use. This includes all collec- vided, they shall be separate from tion and storage tanks, piping, fittings, plant operations and storage areas and connections, bottle washers, fillers, shall be equipped with self-closing cappers, and other equipment which doors. The rooms shall be maintained may be used to store, handle, process, in a clean and sanitary condition and package, or transport product water. Storage tanks shall be of May 29, 2009] the type that can be closed to exclude all foreign matter and shall be ade- §129. All itary condition of such surfaces and to treatment of product water by distilla- assure they are kept free of scale, evi- tion, ion-exchanging, filtration, ultra- dence of oxidation, and other residue. All such proc- containers, utensils, and disassembled esses shall be performed in and by piping and equipment shall be trans- equipment and with substances which ported and stored in such a manner as will not adulterate the bottled product. Prod- (1) Steam in enclosed system: At uct water samples shall be taken after least 170 °F for at least 15 minutes or at processing and prior to bottling by the least 200 °F for at least 5 minutes. The methods of analysis (3) Chemical sanitizers shall be shall be those approved by the govern- equivalent in bactericidal action to a 2- ment agency or agencies having juris- minute exposure of 50 parts per million diction. Chemical sanitizers applied as a cleaned, sanitized, and inspected just spray or fog shall have as a minimum prior to being filled, capped, and 100 parts per million of available chlo- sealed. Containers found to be unsani- rine at 57 °F or its equivalent in bac- tary or defective by the inspection tericidal action. Records of physical the surface of the container by a rins- maintenance, inspections and condi- ing procedure. The final rinse, prior to tions found, and performance of the filling the container with product mechanical washer shall be maintained water, shall be performed with a dis- by the plant. Each procedures shall be performed as often unit package from a batch or segment as necessary to maintain the cases in of a continuous production run of bot- satisfactory condition. The production Cleaning and sanitizing solutions uti- code shall identify a particular batch lized by the plant shall be sampled and or segment of a continuous production tested by the plant as often as is nec- run and the day produced. The plant essary to assure adequate performance shall record and maintain information in the cleaning and sanitizing oper- as to the kind of product, volume pro- ations. Records of these tests shall be duced, date produced, lot code used, maintained by the plant. During by chemical means or by any other the process of filling, capping or seal- means such as circulation of live steam ing either single-service or multi- or hot water, shall be adequate to ef- service containers, the performance of fect sanitization of the intended prod- the filler, capper or sealer shall be uct water-contact surfaces and any monitored and the filled containers other critical area. The plant should visually or electronically inspected to maintain a record of the intensity of assure they are sound, properly capped the sanitizing agent and the time dura- or sealed, and coded and labeled. Con- tion that the agent was in contact with tainers which are not satisfactory shall the surface being sanitized. Only lowing times and intensities shall be nontoxic containers and closures shall considered a minimum: be used. All quired documents shall be available for samples shall be free of coliform orga- official review at reasonable times. Foods (2) For chemical, physical, and radio- logical purposes, take and analyze at 130. The representtive Subpart A—General Provisions sample(s) consists of primary con- tainers of product of unit packages of §130. The plant such terms when used in regulations shall maintain records of date of sam- promulgated under the act. For ex- to substantiate the information in his ample, all regulations under section 401 petition, at a public hearing on the contemplate that the food and all arti- matter, the Commissioner may either cles used as components or ingredients (1) withdraw the regulation and termi- thereof shall not be poisonous or dele- nate the proceeding or (2) if he con- terious and shall be clean, sound, and cludes that it is in accordance with the fit for food. A provision in such regula- requirements of section 401 of the act, tions for the use of coloring or fla- continue the proceeding and introduce voring does not authorize such use evidence to substantiate such informa- under circumstances or in a manner tion.

Solid lipid nanoparticles in lymph and plasma after duodenal administration to rats 20 mg atorlip-20 free shipping cholesterol levels diet and exercise. Biodistribution of stealth and non-stealth solid lipid nanoparticles after intravenous administration to rats discount atorlip-20 20 mg fast delivery cholesterol medication withdrawal symptoms. Intravenous administration to rabbits of non-stealth and stealth doxorubicin loaded solid lipid nanoparticles at increasing concentration of stealth agent: Pharmacokinetics and distribution of doxorubicin in brain and in other tissues discount 20mg atorlip-20 overnight delivery foods eat low cholesterol diet. Transport in lymph and blood of solid lipid nanoparticles after oral administration in rats cheap 20 mg atorlip-20 visa cholesterol levels uk 5.3. Presented at the Proceedings of the 24th International Symposium on Controlled Release of Bioactive Materials, Stockholm; 1997:179–180. Preparation and evaluation in vitro of colloidal lipo- spheres containing pilocarpine as ion-pair. Evaluation in vitro/in vivo of colloidal lipospheres containing pilocarpine as ion-pair. Highly efficient cellular uptake of c-myb antisense oligonucleotides through specifically designed polymeric nanospheres. Nanoparticle formulation enhances the delivery and activity of a vascular endothelial growth factor antisense oligonucleotide in human retinal pigment epithelial cells. Idarubicin solid lipid nanospheres administration to rats by duodenal route: Pharmacokinetics and tissues distribution. Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection. Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems. Microemulsions – Modern colloidal carrier for dermal and transdermal drug delivery. Effects of phospholipids based formulations on in vitro and in vivo percutaneous absorption of methyl nicotinate. Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream. Bicontinuous sucrose ester microemulsion: A new vehicle for topical delivery of niflumic acid. Transdermal permeation of apomorphine through hairless mouse skin from microemulsions. Transdermal apomorphine permeation from microemulsions: A new treatment in Parkinson’s disease. Nocturnal anomalous movement reduction and sleep microstructure analysis in parkinsonian patients during 1-night transdermal apo- morphine treatment. Although nanoparticles are per- haps the simplest of nanostructures, nanoparticle-based technologies are broadly covering different fields, ranging from environmental remediation, energy genera- tion, and storage all the way to applications in bioscience (1–5). The need to fine-tune different nanoparticle properties to make them suitable for specific applications has sparked a large number of worldwide research efforts aimed at their tailoring. However, full use of these structures in these applications requires more detailed information and a feedback of data coming from reliable characterization techniques (6–8). Several methods have been applied to obtain this information and some of them are described in different chapters of this book. In this contribution, an overview of the recent progress in nanoparticle charac- terization is presented. Some of the aforementioned methods will be introduced and the kind of information that can be obtained from them will be discussed. However, a detailed account of a specific characterization method and its variations is outside the scope of this review. Therefore, if imaging at consider- ably higher resolution is required, electromagnetic radiation of shorter wavelengths must be used. The development of electron microscopes has resulted in instruments that are able to routinely achieve magnifi- cations of the order of 1 million and that can disclose details with a resolution of up to about 0. When an electron beam interacts with a sample, many measurable signals are generated and electrons can be transmitted, backscattered, and diffracted. Depend- ing on the sample thickness, transmitted electrons pass through it without suffer- ing significant energy loss. Since the attenuation of the electrons depends mostly on the density and thickness of the sample, the transmitted electrons form a two- dimensional projection of the sample. Elec- trons can also get diffracted by particles if these are favorably oriented toward the electron beam; the crystallographic information that can be obtained from these diffracted electrons is the basis for electron diffraction. Finally, the electrons in the primary beam can collide with atoms in the sample and be scattered back, or, in turn, remove more electrons from these atoms (secondary electrons). These two pro- cesses (backscattering and generation of secondary electrons) are more effective as the atomic number of the atom increases. More recently, changes in nanoparticle structure as a result of interactions with gas-, liquid-, or solid-phase substrates can now be monitored by this technique (11). In recent years, a large number of new and novel developments have been made in electron microscopy for nanotechnology. This includes new techniques such as in situ microscopy used for imaging dynamic processes, quantitative chem- ical mapping, holographic imaging of electric and magnetic fields, and ultrahigh- resolution imaging (12). For instance, the study of nanoparticles can be greatly improved with the use of aberration-corrected lenses, enabling image resolutions at levels sometimes lower than 1 A˚ (13,14). This level of image resolution yields a new level of understanding of the behavior of matter at the nanoscale. Beam sus- ceptibility makes it very difficult sometimes to carry out electron diffraction studies on nanoparticles that are prone to beam damage. In this case, by using low electron beam currents, it is possible to obtain lattice fringe images and electron diffraction. Figure 1 shows an example of a study using an aberration-corrected elec- tron microscope to study the structure and morphology of AuPd bimetallic par- ticles (16). The authors matched the experimental intensities of atomic columns with theoretical models of three-layered AuPd nanoparticles in different orienta- tions. Based on this information, the authors indicated that the surface layer of the metallic nanoparticles contains kinks, terraces, and steps at the nanoscale. The inset indicates the authors’ proposed sketch of element-rich locations in the layers. The inten- sity profile through a typical AuPd nanoparticle is displayed in Figure 1(B), and it depends on the atomic number and the column thickness. The contrast is due to a core–shell structure consisting of three layers as sketched in the inset. When this occurs, the surrounding matrix usually tends to mask the supported nanopar- ticles. In some special cases, however, the existence of an epitaxial relationship between the nanoparticles and their support can be used to obtain size and shape information (17). Moreover, nanoparticles can be susceptible to damage under the electron beam irradiation conditions normally used for high-resolution imaging. Problems become even more exacerbated when the nanoparticles under study have tendency to adhere strongly to each other, forming agglomerates. Consequently, bulk-sensitive methods that provide information regard- ing the quality, size, and structural properties of a given sample must be employed. Among these methods, Raman spectroscopy and optical absorption deliver the most comprehensive results.

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In order to flip the rotating nuclear axis with regard to the magnetic field an oscillating radio-frequency field buy discount atorlip-20 20 mg on line cholesterol ratio 1.9 good, supplied by low power atorlip-20 20mg sale cholesterol test fasting, crystal-controlled oscillator is strategically placed at right angles that would be perpendicular to the plane of the paper purchase atorlip-20 20 mg mastercard cholesterol uptake. The coil that transmits the radio-frequency field is made into two- halves to allow insertion of the sample holder generic atorlip-20 20mg on-line streefwaarde cholesterol ratio, and the two halves are placed in the gap of the magnetic poles. A few turns of wire wound tightly around the sample tube forms a separate radio-frequency coil which picks up the resonant signals emitted from the sample. The receiver coil is perpendicular to both the stationary field and the radio-frequency transmitter coil so as to minimise pick-up from these fields. Thus, energy is absorbed from these receiver coils when nuclear transitions are induced. Absorption of energy causes the radio-frequency voltage across the receiver coil to drop. This voltage change is amplified and detected by a high-gain-radio frequency amplifier and a diode-detector which is tuned to the same frequency as the ratio frequency transmitter. Hence, any apparent deviations of the spectrum of a sample under investigation vis- a-vis the spectrum of the pure and the authentic pharmaceutical substance usually give rise to an enormous information not only confined to the true identity of the substance but also the probable nature of the impu- rities it possesses. The quantitative determination is carried out by comparing the peak area attributed by ethylene of (I) at 5. It is, however, pertinent to mention here that the assay results were fairly in agreement with British Pharmacopoeial method of analysis. It is, however, interesting to observe that additional sources of variability are usually incorpo- rated into an assay employing external standardization, and the same has been duly shown in the results thus obtained i. Hence, it is possible to measure accurately the integration curve given out by the combined C-1, and C-2 glyceride methylene protons that occurs almost separately at 4. Now, employing these as an internal calibration one may determine conveniently the following two vital informations, such as : (a) the total number of alkenyl protons, which is a measure of degree of unsaturation, and, (b) the total number of protons, which is a measure of the average molecular weight. How would you carry out the ‘assay’ of the following pharmaceutical products : (a) Quinidine in mixtures of hydroquinidine, (b) Methsuximide and Phensuximide Capsules, (c) Trimethoprim and Sulfamethoxazole Tablets, (d) Meprobamate and Mebutamate, and (e) Meclizine and Methaqualone. The fundamental fact of emission spectroscopy is very simple, wherein the atoms present in a sample undergo excitation due to the absorption of either electrical or thermal energy. Subsequently, the radiation emitted by atoms in an excited sample is studied in an elaborated manner both qualitatively and quantitatively. Therefore, emission spectroscopy is considered to be an useful analytical tool for the analysis of : (i) elemental analysis of metals, (ii) identification and quantitative determination of metallic elements, (iii) estimation of metalloids e. In short, emission spectroscopy is considered to be the most accurate, precise and reliable means of quantitative analysis of elements as on date. If proper skill, precautions and wisdom are applied together this method may be adopted safely and conveniently to analyze approximately seventy elements from the ‘periodic table’ at a concentration as low as 1 ppm. This particular light after passing through either a prism or a grating when studied directly with the help of a spectroscope, gives rise to a spectrum, that is termed as emission spectrum. It has been noticed that a few lines are missing in the observed spectrum thereby leaving either dark bands or lines at their respective places. Because the light of wavelength exactly corresponding to these dark bands (or lines) is found to be absorbed by the substance through which light is passed, the resulting spectrum is called as an absorption spectrum. In fact, a band spectrum com- prises of groups of lines so near to one another that under normal circumstances they more or less seem to appear as continuous bands. However, in emission spectroscopy the band spectra provided by molecules may be elimi- nated completely by giving energy to the corresponding molecules so that they may be split- up into separate atoms. The thermal radiation of this nature is termed as black-body radiation, which has the following three characteristic features, namely : (a) Dependent more on the temperature of the emitting surface than the material of which the surface is made of, (b) Caused by the innumerable atomic and molecular oscillations excited in the condensed solid by the thermal energy, and (c) Independent of the chemical composition of the substance. Hence, it is pertinent to mention here that the continuous spectrum cannot be employed effectively for spectrochemical analysis and these spectra may be eliminated completely by volatalizing the material (sam- ple) before excitation. As the line spectrum depends solely upon the type of an atom, hence it enjoys the status of a predominant type of emission spectroscopy. For a Na atom the single-outer-electron in the lowest ground state G is situated in the 3s orbital. Consequently, the energy level E1 might designate the energy of the atom when this ‘single electron’ has been duly raised to the 3p state by virtue of its absorption of thermal, electrical or radiant energy. This phenomenon has been clearly shown with the help of the dotted-line in Figure : 24. In the case of Na atom E2 designates the highly energetic 4p state and the radiation λ2 obtained therefrom will appear at a relatively shorter wavelength. The horizontal lines are due to the many excited vibrational states whereas the energy differences due to rotational states have not been shown in the said Figure. Thus, the multitude of various energy states is clearly shown by the solid lines in Figure 24. Therefore, we may have the following expression : P = kC where, P = Radiant power, C = Total concentration of the species, and k = Constant of proportionality The aforesaid relationship forms the basis of quantitative emission spectroscopy. Exactly in a similar manner, the full-fledged complete spectrum is obtained possibly only when the energy equivalent to the ionization potential is ab- sorbed by a molecule. However, it has a serious drawback because most of the spectral lines invariably fall within the vacuum-ultraviolet region thereby rendering their critical studies rather difficult. In ac- tual practice, it has been observed that the spectra of alkali-metals, like : K, Na, Li, Rb appear to be very simple and hence they may be studied conveniently without any difficulty. It is also pertinent to mention here that these spectra usually comprise of 13 to 14 adequately spaced lines having reasonably good sensitivity and possessing wavelengths. In the specific case of sodium the resulting emission spectrum shall exhibit characteristic yellow lines. The spectrum is so highly sensitive that even the traces of Na show yellow lines distinctly. In the case of other elements, for instance : Uranium, the emission spectrum normally displays thousands of narrowly spaced lines. However, the emission source possesses a fixed amount of energy which shall be spread up eventually amongst the thousands of lines thereby mini- mizing the sensitivity of each line. Hence, it is rather difficult to examine the less sensitive complex spectra of elements such as uranium. Flames are comparatively inexpensive and cater for both stable and reproducible sources of excitation that can effectively handle a wide-range of typical analytical problems. However, the temperature of the flame is guided by a number of vital factors, such as : • Types of Fuel and Oxidant, • Fuel to Oxidant Ratio, • Type of Burner Employed, and • Zone (or region) in flame which is focussed into the entrance-slit of spectral-isolation-unit. A = An Ammeter (Range 3 to 30 A), B = Inductance Coil, C = Variable Resistance (Range 10 to 40 Ω) D = Arc Gap (Range from 20 mm to 1 cm), and E = Direct Current Source (Range 110 to 220 V at 3 to 30 A). Procedure : The various procedural steps are as follows : • Current is passed across the arc-gap in series with the help of a variable resistor C (10 – 40 Ω) and an inductance coil B. Once the current picks up flow, the temperature across the arc-gap shoots up promptly. The electrodes are pulled apart leaving a gap of 20 mm to 1 cm, thereby establishing the electric arc whose tempera- ture varies from 4000 to 8000° K. Where, A = Ammeter (Range 3 to 30 A) B = Variable Resistance, C1 = Variable Inductance in the Primary Circuit, C2 = Inductance Coil in the Main Circuit, D = Arc Gap (Range from 20 mm to 1 cm), E = Primary Circuit, and F = Step-up Transformer (Range 2000 to 5000 V). Procedure : The procedural details are stated below : • Step-up transformer (F) maintains a high voltage of 2000 to 5000 V, which helps the arc to jump the gap, • Variable inductance (C1) is adjusted duly to maintain a current of 1 to 5 A in the primary circuit, • Current in the main circuit is alternating at a frequency of 60 Hz thereby extinguishing the arc 120 times in one second, and • After each cycle the arc picks out a new surface area whereby the entire surface of the sample under examination, is exhaustively arced and subsequently excited. It is worthwhile noting that the arc-gap temperature in this case is considerably lower than the direct- current arc, due to the stop-and start nature of the source, which ultimately offers a much lower sensitivity. Examples : Pure metal powders may be compressed into solid discs or cylinders which can be used as electrodes. These electrodes have centre posts which minimises wandering-of-the-arc source thereby improving the reproducibility ; and their narrow neck improves the sensitivity appreciably. On passing the electrical discharge the material (sample) is first vaporised into the body of the discharge and subsequently the spectrographic emission occurs. Note : (1) Both types are found to be suitable for either aqueous or non-aqueous solvents, and (2) Samples dissolved in organic solvents usually ignite in the discharge which may produce erratic emission. Prism monochromators normally bring forth two serious shortcomings which are discussed briefly here, namely : First, when light from a single emission-line (of one particular wavelength) is made to pass through a quartz (or glass) prism, it emerges from the other side of the prism as two different lines as shown in Figure 24.

It’s widely used to treat or prevent preeclamptic and eclamptic sei- zure activity and is used to treat ventricular arrhythmias such as torsades de pointes purchase atorlip-20 20 mg line cholesterol lowering drugs definition. It’s also used to treat seizures cheap 20mg atorlip-20 with visa foods for high cholesterol diet, severe toxe- mia order atorlip-20 20mg on-line cholesterol elevated, and acute nephritis in children safe 20 mg atorlip-20 definition high cholesterol levels. Diuretics and tap water enemas can also de- plete sodium, particularly when fluids are replaced by plain water. The salt flats Sodium also can be lost in trauma or wound drainage, adrenal When I’m out gland insufficiency, cirrhosis of the liver with ascites, syndrome of jogging, I lose inappropriate antidiuretic hormone, and prolonged I. Sodium can help me replace depleted Calling all chlorides fluids and maintain Sodium is typically replaced in the form of sodium chloride. Pharmacokinetics Oral and parenteral sodium chloride are quickly absorbed and distributed widely throughout the body. Pharmacodynamics Sodium chloride solution replaces deficiencies of the sodi- um and chloride ions in the blood plasma. Adverse A welcome infusion reactions Severe symptomatic sodium deficiency may be treated by I. Adverse reactions to Drug interactions sodium include: • pulmonary edema (if No significant drug interactions have been reported with sodium given too rapidly or in chloride. Alkalinizing and acidifying drugs Alkalinizing and acidifying drugs act to correct acid-base imbal- ances in the blood. Odd couple Alkalinizing and acidifying drugs have opposite effects: • An alkalinizing drug will increase the pH of the blood and de- crease the concentration of hydrogen ions. Some of these drugs also alter urine pH, making them useful in treating some urinary tract infections and drug overdoses. Alkalinizing drugs Alkalinizing drugs are used to treat metabolic acidosis and to in- crease blood pH. These include: • sodium bicarbonate • sodium citrate • sodium lactate • tromethamine. Metabolism and excretion Therefore, to raise Sodium citrate and sodium lactate are metabolized to the active the pH, you use an ingredient, bicarbonate. Pharmacodynamics Sodium bicarbonate separates in the blood, providing bicarbonate ions that are used in the blood buffer system to decrease the hy- Alkalinizing drogen ion concentration and raise blood pH. Hitching up with hydrogen Tromethamine acts by combining with hydrogen ions to alkalinize the blood; the resulting tromethamine–hydrogen ion complex is excreted in urine. Pharmacotherapeutics Alkalinizing drugs are commonly used to treat metabolic acidosis. Other uses include raising urine pH to help remove certain sub- stances, such as phenobarbital, after an overdose. Drug interactions The alkalinizing drugs sodium bicarbonate, sodium citrate, and sodium lactate can interact with a wide range of drugs to increase or decrease their pharmacologic effects. Adverse reactions to alkalinizing drugs Adverse reactions to alkalinizing drugs vary. Sodium lactate • Metabolic alkalosis (with overdose) Sodium bicarbonate • Extravasation • Bicarbonate overdose • Water retention or edema (in patient with • Cerebral dysfunction, tissue hypoxia, and kidney disease or heart failure) lactic acidosis (with rapid administration for diabetic ketoacidosis) Tromethamine • Water retention and edema • Hypoglycemia • Respiratory depression Sodium citrate • Extravasation • Metabolic alkalosis, tetany, or aggravation of • Hyperkalemia existing heart disease (with overdose) • Toxic drug levels (if given for more than • Laxative effect (with oral administration) 24 hours) Acidifying drugs When your Acidifying drugs are used to correct metabolic alkalosis. These stomach include: doesn’t feel quite right, you • acetazolamide (used in treatment of acute mountain sickness) might need • ammonium chloride. Absorption, metabolism, and excretion Orally administered ammonium chloride is absorbed completely in 3 to 6 hours. Break it down Acetazolamide inhibits the enzyme carbonic anhydrase, which blocks hydrogen ion secretion in the renal tubule, resulting in in- creased excretion of bicarbonate and a lower pH. Acetazolamide also acidifies urine but may produce metabolic acidosis in normal patients. Adverse • Ascorbic acid directly acidifies urine, providing hydrogen ions reactions to and lowering urine pH. Overdose may A patient with metabolic alkalosis requires therapy with an acidi- lead to acidosis. Acetazolamide • Drowsiness Safe and easy • Seizures Most patients receive both types of ions in oral or parenteral dos- • Anorexia es of ammonium chloride, a safer drug that’s easy to prepare. Ammonium chloride Oral forms of • Metabolic acidosis Drug interactions ammonium and loss of electrolytes, Acidifying drugs don’t cause clinically signifi- chloride are safer and especially potassium cant drug interactions. However, concurrent easier to (with large doses) use of ammonium chloride and spironolac- prepare. Hypokalemia is a common occurrence in conditions that increase potassium excretion or depletion, such as adminis- tration of glucocorticoid, I. Potassium should be used cautiously in patients re- ceiving potassium-sparing diuretics, such as amiloride, to avoid hyperkalemia. Drugs and cancer In the 1940s, antineoplastic (chemotherapeutic) drugs were de- veloped to treat cancer. A brighter future Today, many of these toxicities can be lessened so they aren’t as devastating to the patient. With modern chemotherapy, childhood malignancies, such as acute lymphoblastic leukemia, and adult cancers, such as testicular cancer, are curable in most patients. New therapeutic strategies, such as using monoclonal antibodies or targeting specific proteins, are further improving the time that a patient’s cancer can remain in remission. In addition, drugs such as interferons are being used to treat patients with cancer. Alkylating drugs Alkylating drugs, given alone or with other drugs, effectively act against various malignant neoplasms. This means that their alkylating actions may take place at any phase of the cell cycle. Nitrogen mustards I see some nitrogen mustards Nitrogen mustards represent the largest group of alkylating headed my way. First and fast Mechlorethamine hydrochloride was the first nitrogen mustard in- troduced and is rapid-acting. Pharmacokinetics (how drugs circulate) The absorption and distribution of nitrogen mustards, as with most alkylating drugs, vary widely. Metabolism and excretion Alkylating Nitrogen mustards are metabolized in the liver and excreted by drugs deactivate the kidneys. C G C G C G C G C G C G A T A T C G Drug C G T A T A G C G C may develop resistance to the cytotoxic effects of nitrogen mus- tards. The calcium in dairy products reduces the Drug interactions absorption of estramustine. Nitrogen mustards interact with a wide variety of other drugs: • Calcium-containing drugs and foods, such as antacids and dairy products, reduce absorption of estramustine. It’s also used for treatment of leukemia during bone marrow transplant procedures. Metabolism and excretion Other adverse reactions Busulfan is extensively metabolized in the liver before urinary ex- include: cretion. A backup option Busulfan is also effective in treating polycythemia vera, although Adverse other drugs are usually used to treat it because busulfan can cause severe myelosuppression (halting of bone marrow function). Concurrent use of busulfan and marrow suppression, thioguanine may cause liver toxicity, esophageal varices (en- producing severe larged, swollen veins in the esophagus), or portal hypertension leukopenia, anemia, and (increased pressure in the portal vein of the liver). Nitrosoureas This reaction is usually Nitrosoureas are alkylating agents that work by halting cancer dose-related and re- cell reproduction. Pharmacokinetics When administered topically to treat mycosis fungoides (a rare skin malignancy), carmustine is 5% to 28% systemically absorbed. Metabolism and excretion Nitrosoureas are lipophilic (attracted to fat), distributing to fatty tissues and cerebrospinal fluid.

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