By E. Raid. The McGregor School of Antioch University.

Finally purchase 80mg diovan mastercard, the bound radioactivity (due to Cortisol-H3) is measured which is then employed to calculate exactly the amount of cortisol present in the sample by the help of a Standard Curve (or Calibration Curve) buy diovan 80mg on-line. Procedure : The various steps to be followed sequentially for the assay of cortisol in plasma are as follows : (1) The cortisol is usually extracted from the samples drawn from the patients, as follows : Place 100µl of plasma in each of two tubes and add 2. Set tubes 1 and 2 aside until Step-13, Step-6 From this point onwards the various tubes are treated as follows : Step-7 Incubate tubes 3 through 18 and all patient sample tubes in a pre-set constant temperature water-bath at 45°C for exactly 5 minutes, Step-8 Immediately after Step-7 incubate tubes 3 through 18 and all patient tubes in an ice-water bath (0 to 4°C) for 30 minutes. Shake the rack several times at short-intervals to ensure that the tubes attain 0-4°C rapidly, Step-9 Quickly add 0. Shake each vial to solubilize the contents: An emulsion should form, and Step-15 Count the radioactivity in the vials in sequence for 1 to 10 minutes. Now, subtract the blank from all other counts per minute to obtain the actual counts per minute and average the counts per minute for vials 1 to 2 to find the total count per minute. The percent bound may be calculated using the following expression : Counts per minute % Bound = × 100 Total counts per minute Finally, plot the percent bound Vs nanograms (ng) per tube of cortisol standard either on linear or on semilog paper and make use of this Standard Curve to calculate the amount of cortisol present in the unkown samples. The basic principles underlying both automated and unautomated methods of analysis are more or less the same. Out of the broad-spectrum of biological samples blood analysis is the most common one. There exists a number of parameters which may be assayed, and spectrophotometry is ideally suited for nearly all of them, a few typical examples are cited in Table 2. Glucose Glucose reduces Cu2+ to Cu+ ; & Cu+ reduces 420 phosphomolybdic acid (Folin-Wu) 4. To the resulting solution phosphomolybdic acid is added, which is subsequently reduced by Cu2O to give rise to an intensely coloured ‘molybdenum blue’ that is measured at 420 nm accurately. The major component parts com- prise of the various important sections namely : the preparation section, the reaction section and the analysis section which will be discussed briefly here. Preparation section Reaction section Analysis section Flame photo Dialyzer meter Recorder Proportioning heat Sampler or pumps bath Colori computer phaser meter Programmer Figure 2. Preparation Section This particular section of the Auto Analyzer consists mainly of the sampler, proportioning pumps, and programmer. First, the sampler introduces a fixed quantity of serum sample into the ‘analysis train’, which varies from one instrument to another instrument supplied by different manufacturers. The proportioning pump controls the rate of advancement,viz 10 inch/minute, of each sample through the analysis stream. Each analysis stream is made of transparent plastic flexible tubing, and each patient-sample is separated from one another by an air- bubble. Reaction Section The reaction section essentially comprises of the dialyzer, heat bath and phaser, and obviously the reaction takes place in this zone. Evidently, B is added always in excess to ensure : (a) rapid reaction, and (b) complete reaction by forcing the reaction to the right in accordance to the Le Chatelier’s principle. Therefore, in actual experimental operations temperature is increased by the aid of a heat-bath so as to accelerate the reaction which in turn allows the reaction to attain equilibrium state as rapidly as possible. Naturally at a very high temperature there is every possibility for decomposition of either the products or the reactants. Analysis Section The recent advancement in the field ofcomputer technology and anlytical instrumentation it has become very easy and convenient to have the analyical data from a series of biological samples processed at high speed as digital readouts or on computerized recorders. Many hospitals round the globe make extensive use of advanced computer softwares for data processing as stated beiow : • Uptodate listing of various laboratory tests, • Listing of drugs and metabolites that cause interference both biochemically and analytically, • Storing of levels of biologically important compounds for various disease states, and • A tentative diagnosis for a patient based on his serum sample under investiation together with the drugs and dosages being administered and the levels of biologically important compounds. Caution : Nevertheless, the concerned physician or pharmacist must exercise his or her own expertise and knowledge while prescribing drug(s) to a patient along with these computerized data informations. How would you carry out the assay of ‘bilirubin’ or ‘cholesterol’ by colorimetric method? Describe ‘enzymatic assays’ based on colorimetric method of analysis under the following two situations : (i) When ‘substrate’ is in large excess, (ii) When ‘enzyme concentration’ is in large excess. Give a comprehensive account on the various ‘automated methods of clinical analysis’ with an appropriate example. Sawicki, E, Photometric Organic Analysis, Part I, Wiley-Interscience, New York, 1970. In fact, the quantitative pharmaceutical analysis is not merely confined to just taking a random sample, performing a single assay quickly, and finally making a loud claim that the result so obtained cannot be challenged. Truly speaking an ideal analyst must have a total in-depth knowledge of the chemistry involved along with the pros and cons of interferences that may be caused due to the host of compounds, elements and ions besides adequate exposure and hands-on experience of the statistical distribution of values. The terminology ‘error’ invariably refers to the difference in the numerical values between a measured value and the true value. Consequently, the differences thus obtained between the standard values and those by the new analytical methods are then treated as ‘errors’ in the latest procedure. It is pertinent to mention here that it becomes rather difficult at times to place a particular ‘error’ into one of the above mentioned categories ; however, the classification may prove to be beneficial with regard to study of the various analytical errors that crop up in the course of routine analysis. The most important errors belonging to this particular class are : (a) Personal Errors : They are exclusively caused due to ‘personal equation’ of an analyst and have no bearing whatsoever either on the prescribed procedure or methodology involved.

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Drug delivery systems available for targeted oral delivery include those that use enteric coatings generic 40 mg diovan visa, prodrugs purchase 80mg diovan free shipping, osmotic pumps, colloidal carriers and hydrogels; these technologies are discussed in Chapter 6. Technologies for targeted drug delivery are most advanced for parenteral administration. Such technologies are concerned with delivering drugs to specific targets in the body and also to protect drugs from degradation and premature elimination. They include the use of: • soluble carriers, such as monoclonal antibodies, dextrans, soluble synthetic polymers; • particulate carriers, such as liposomes, micro- and nano-particles, microspheres; • target-specific recognition moieties, such as monoclonal antibodies, carbohydrates and lectins. These technologies, and the various anatomical, physiological and pathological issues that pertain to their use, are discussed in detail in Chapter 5. Recent advances in biological and chemical sciences have led to the development of various “Smart” technologies to ensure more effective drug delivery and targeting of drugs to specific sites within the body. The advantages and limitations of these systems are discussed in detail in Chapter 16. Such systems are used to achieve site-specific drug delivery following parenteral administration. Release of the attached drug molecules at the target site can be achieved by enzymatic or hydrolytic cleavage. Larger complexes, some undergoing clinical trials, include drug conjugates with soluble natural, or synthetic, polymers. Nano- and microparticles Nanoparticles are solid colloidal particles, generally less than 200 nm. Such systems include poly (alky1- cyanoacrylate) nanoparticles used for parenteral drug delivery and targeting. Microparticles are colloidal particles in the micrometer scale, typically in the size range 0. Synthetic polymers, such as poly(lactide-co-glycolide), are widely used in the preparation of microparticulate drug delivery systems and also as biodegradable implantable devices. Natural polymers, such as albumin, gelatin and starch, are also used as microparticulate drug carriers. Liposomes, vesicular structures based on one or more lipid bilayer(s) encapsulating an aqueous core, represent highly versatile carriers. Liposomes can be prepared using a variety of techniques to give a wide range of sizes (approximately 30 nm–10 µm), structures and physicochemical properties, to facilitate the encapsulation of both water-soluble and lipid-soluble drugs (see Section 5. Commercial products based on liposome technology are available and many more products are in clinical trials, for a variety of indications. Macrodevices Macrodevices are widely used in many applications, including: • parenteral drug delivery, mechanical pumps, implantable devices; • oral drug delivery: solid dosage forms such as tablets and capsules which incorporate controlled release/ targeting technologies; • buccal drug delivery: buccal adhesive patches and films; • transdermal drug delivery: transdermal patches, iontophoretic devices; • nasal drug delivery: nasal sprays and drops; • pulmonary drug delivery: metered-dose inhalers, dry-powder inhalers, nebulizers; • vaginal drug delivery: vaginal rings, creams, sponges; • ophthalmic drug delivery: ophthalmic drops and sprays. This is painful for the patient, as well as generally requiring the intervention of medical professionals. The oral route, which involves merely swallowing a tablet, liquid or capsule, thus represents a much more convenient and attractive route for drug delivery. Some other dosage forms, for example nebulizers, pessaries and suppositories, may meet with more limited patient compliance. Ease of termination The dosage form should be easily removed either at the end of an application period, or in the case where continued drug delivery is contra-indicated. A transdermal adhesive system is easily removed if necessary, as is a buccal patch. However, non-biodegradable polymeric implants and osmotic pumps must be surgically retrieved at the end of treatment. Although a biodegradable polymeric implant does not require surgical retrieval, its continuing biodegradation makes it difficult to terminate drug delivery, or to maintain the correct dose at the end of its lifetime. Biocompatibility and absence of adverse effects The drug delivery system should be non-toxic and non-immunogenic. For example, concerns over the body’s responses to a foreign material often raise the issues of biocompatibility and safety of implantable devices. The use of dosage forms containing penetration enhancers, which potentiate drug absorption via a variety of mechanisms and are used in oral, buccal, transdermal, nasal, ophthalmic, pulmonary and vaginal drug delivery, has raised serious questions about the potential deleterious effects they exert on epithelial tissue. As well as the possibility of direct damage to the epithelium, the increased epithelial permeability may allow the ingress of potentially toxic agents. Large effective area of contact For drugs absorbed via passive mechanisms (see Section 1. The dosage form can influence the size of the area over which the drug is deposited. For example, the use of nasal drops offers a larger solution/ membrane surface area for immediate absorption than if the drug solution is delivered in the form of a nasal spray (see Section 9.

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Pharmacodynamics When vitamin B12 is administered diovan 40 mg generic, it replaces vitamin B12 that the body would normally absorb from the diet cheap 40mg diovan amex. This vitamin is essen- tial for cell growth and replication and for the maintenance of myelin (nerve coverings) throughout the nervous system. Pharmacotherapeutics Cyanocobalamin and hydroxocobalamin are used to treat perni- cious anemia, a megaloblastic anemia characterized by decreased gastric production of hydrochloric acid and intrinsic factor defi- ciency. Intrinsic factor, a substance normally secreted by the pari- etal cells of the gastric mucosa, is essential for vitamin B12 absorp- tion. Intrinsic factor deficiencies are common in patients who have had total or partial gastrectomies or total ileal resection. Adverse reactions to vitamin B12 therapy No dose-related adverse reactions occur with vitamin B12 therapy. However, some rare reactions may occur when vitamin B12 is adminis- tered parenterally. Parenteral problems Adverse reactions to parenteral administration can include hypersensi- tivity reactions that could result in anaphylaxis and death, pulmonary edema, heart failure, peripheral vascular thrombosis, polycythemia vera, hypokalemia, itching, transient rash, hives, and mild diarrhea. Oral vitamin B12 preparations are used to supplement nutri- tional deficiencies of the vitamin. The parenteral and intranasal formulations are used to treat patients with pernicious anemia. Drug interactions Alcohol, aspirin, neomycin, chloramphenicol, and colchicine may decrease the absorption of oral cyanocobalamin. This type of anemia usually occurs in patients who have tropical or nontropical sprue, although it can also result from poor nutritional intake during pregnancy, infancy, or childhood. Pharmacokinetics Folic acid is absorbed rapidly in the first third of the small intes- tine, distributed into all body tissues, and metabolized in the liver. Excess folate is excreted unchanged in urine, and small amounts of folic acid are excreted in stool. Adverse Pharmacotherapeutics reactions to Folic acid is used to treat folic acid deficiency. Patients who are folic acid pregnant or undergoing treatment for liver disease, hemolytic ane- Adverse reactions to mia, alcohol abuse, or skin or renal disorders typically need folic folic acid include: acid supplementation. Serum folic acid levels below 5 ng/ml indi- • erythema cate folic acid deficiency. Folic drugs usually acid, iron, vitamin B12, replace one of Erythropoietin agents amino acids, copper, these missing and cobalt are all parts. After subQ administration, serum levels of epoetin alfa peak in 5 to 24 hours, while serum levels of darbepoetin alfa peak in 24 to 72 hours. The circulating half-life of epoetin alfa is also shorter at 4 to 13 hours, compared to 49 hours for darbepoetin alfa. The therapeutic effect of these agents lasts for several days after ad- ministration. Nor- mally, erythropoietin is formed in the kidneys in response to hy- poxia (reduced oxygen) and anemia. Adverse Pharmacotherapeutics reactions to Epoetin alfa is used to: erythropoietin • treat patients with anemia associated with chronic renal failure agents • treat anemia associated with zidovudine therapy in patients with human immunodeficiency virus infection Hypertension is the most • treat anemia in cancer patients receiving chemotherapy common adverse reac- • reduce the need for allogenic blood transfusions in surgical pa- tion. Major categories of anticoagulants include: • heparin and its derivatives • oral anticoagulants • antiplatelet drugs Heparin prevents • direct thrombin inhibitors clots from forming • factor Xa inhibitor drugs. Heparin Heparin, prepared commercially from animal tissue, is an anti- thrombolytic agent used to treat and prevent clot formation. Be- cause it doesn’t affect the synthesis of clotting factors, heparin can’t dissolve already-formed clots. This relationship between dose and effect is the rationale for using low-dose heparin to pre- vent clotting. Howev- er, these times may be only slightly prolonged with low or ultra- low preventive doses. Pharmacotherapeutics Heparin may be used in a number of clinical situations to prevent the formation of new clots or the extension of existing clots. Dosage adjust- ments, based on the test results, are typically necessary to ensure ther- apeutic effectiveness without increased risk of bleeding. Heparin-induced thrombocytopenia Platelet counts should be monitored in all patients receiving heparin therapy. Circulate freely Heparin can be used to prevent clotting whenever the patient’s blood must circulate outside the body through a machine, such as the cardiopulmonary bypass machine or hemodialysis machine, and during blood transfusions. Adverse reactions to heparin One advantage of heparin is that it produces relatively few adverse re- actions.