By L. Rocko. College of Mount Saint Joseph. 2019.
Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease purchase online amoxil. Milrinone: systemic and pulmonary hemody- namic effects in neonates after cardiac surgery cheap amoxil on line. Predictors of clinical outcome in advanced heart failure patients on continuous intravenous milrinone therapy 500 mg amoxil mastercard. Outpatient continuous parenteral inotropic therapy as bridge to transplantation in children with advanced heart failure. Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates. Pharmacokinetics and side-effects of milrinone in infants and children after open heart surgery. Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled interventional study. Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Intravenous arginine-vasopressin in children with vasodilatory shock after cardiac surgery. Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock. Use of alpha-agonists for management of anaphylaxis occurring under anaesthesia: case studies and review. Supraventricular tachycardia in children: clinical features, response to treatment, and long-term follow-up in 217 patients. Continuous intravenous phenylephrine infusion for treatment of hypoxemic spells in tetralogy of Fallot. Phenylephrine increases pulmonary blood flow in children with tetralogy of Fallot. Vasopressors and intestinal mucosal perfusion after cardiac surgery: Norepinephrine vs. Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Use of alpha-agonists for management of anaphylaxis occur- ring under anaesthesia: case studies and review. Norepine- phrine and metaraminol in septic shock: a comparison of the hemodynamic effects. Perioperative haemodynamic effects of an intravenous infusion of calcium chloride in children following cardiac surgery. The effect of calcium on pulmonary vascular resistance and right ventricular function. Cardiovascular effects of intrave- nous triiodothyronine in patients undergoing coronary artery bypass graft surgery. Thyroid hormone supplementation for the prevention of morbidity and mortality in infants undergoing cardiac surgery. Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease. Comparison between dobutamine and levosi- mendan for management of postresuscitation myocardial dysfunction. Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress. Duration of haemodynamic action of a 24-h infusion in patients with congestive heart failure. Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neuro- hormonal and immune activation in patients with advanced heart failure. Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction. Levosimendan for the treatment of acute heart failure syndromes: time to identify subpopulations of responding patients. Preconditioning effects of levosimendan in coronary artery bypass-grafting—a pilot study. Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate. Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery. Specifically, the principal groups of pediatric patients with cardiovascular disease who may benefit from afterload reduction therapies include the following: 1. Patients with normal cardiac anatomy and myocardial function who have sys- temic hypertension. Patients with normal cardiac anatomy but impaired myocardial function, either caused by primary myocardial disease (e. The vasodilators are pharmacological agents that produce relaxation of smooth muscle in the wall of blood vessels, leading to reduced vascular resistance and the potential for increased blood flow. Some vasodilators act on arterial vessels, others on venous vessels, and a third group on both arteries and veins. The vasodilators can be classified according to their predominant site of action or by their mechanism of action. In this chapter, these agents are classified by their mechanism of action (see Table 4-1). Vasodilators 79 therefore, reducing its blood level leads to less vasoconstriction. Dose every 8 to 12 hours and titrate dose for response Neonates: Oral: initial or “test” dose 0. Titrate dose to maximum of 6 mg/kg/day in two to four divided doses Adults: Oral: initial dose 12. Titrate dose upward by 25 mg/dose at 1- to 2-week intervals to a maxi- mum dose of 450 mg/day. Usual dose range is 25 to 100 mg/day in two divided doses Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response should be cho- sen. Lower doses are appropriate for patients who are also being treated with diuretics and are water and sodium depleted. Dosing adjustment for renal impairment: Creatinine clearance (Cl ) 10 to 50mL/min/1. Monitoring for blood pressure effect should focus on the period 1 to 3 hours after dosing. Adverse Effects Cardiovascular: hypotension, tachycardia Respiratory: cough, dyspnea. The risk of neutropenia is increased by approximately 15-fold in patients with renal dysfunction Cutaneous/peripheral: rash, angioedema Other: fever, anaphylactoid reaction Precautions Dosing should be adjusted downward in patients with renal impairment, col- lagen vascular disease, or obstruction to systemic arterial flow (e. Monitor renal function closely in patients with known renal impairment, low cardiac output, or volume depletion (e. Drug-Drug Interactions In patients who are also receiving potassium supplements or a potassium-sparing diuretic (e.
Allow to not more intense than that pro- stand for 2 minutes discount amoxil 500 mg, decant the liquid into a test- duced by treating 4 ml of a tube containing 0 purchase amoxil 250 mg overnight delivery. Sodium Acid Citrate -do- Any red colour produced is not more intense than that pro- duced by treating in the same manner 4 ml of a 0 order amoxil american express. Com- bine the ethereal layers, evaporate the filtrate to 5 ml and add 1 ml of 2 M acetic acid and l. Limit Test for Phosphate The limit test for phosphate is based upon the formation of a yellow colour reaction with molybdovanadic reagent (combination of ammonium vanadate and ammonium molybdate) in an acidic medium. However, the exact composition of the molybdovanadophosphoric acid complex is yet to be established. Calculate the content of Phosphate from a calibration curve prepared by treating suitable vols. A few typical examples are described below which essentially contains the above cited nonmetallic impurities : 1. The estimation depends upon the conversion of boron to borate and the organic matter is subsequently destroyed by ignition with anhydrous sodium carbonate. Ignite the residue rapidly until the organic matter has been destroyed, allow to cool and add 0. Add sufficient ethanol (96%) to produce 100 ml, filter and measure the absorbance of the filtrate at the maximum of 555 nm. Calculate the content of boron from a reference curve prepared from the absorbance obtained by treating suit- able aliquots of a solution of boric acid in the same manner. Free Halogens A few typical examples of pharmaceutical chemicals in which free halogens like Iodine, Bromine, Fluo- rine and Chlorine are present as non-metallic impurities are given below. Prescribed Limits : Any colour in the chloroform layer is discharged on the addition of 0. Doxycycline Hydrochloride : (Free Fluorine) Materials Required : Doxycyline Hydrochloride : 0. Prescribed Limit : The colour of the resulting solution is greater than that obtained by repeating the operation with no substance enclosed in the successive portions of filter paper burnt in the method for oxygen flask combustion, but adding 3. Tetrachloroethylene (Free Chlorine) Perform the limit test as stated under chloroform. Selenium Sulphide Theory : Selenium is very toxic and its contamination is usually controlled by an absorptiometric method after destruction of the organic compound with fuming nitric acid. The latter converts selenium (Se) as selenous acid (H2SeO3), which on subsequent treatment with 3,3′-diaminobenzidine under controlled experimental pa- rameters, results into the formation of a highly coloured compound known as 3,4-diaminophenylpiazselenol. The latter is consequently extracted with toluene after making the aqueous solution alkaline, and the colour compared with a standard prepared likewise from a known amount of selenium. Prescribed Limit : The measured absorbance at 420 nm is not greater than that of a solution prepared by treating 5 ml of selenium standard solution (1 ppm Se) in the same manner (5 ppm, calculated as Se). What is the importance of ‘Purity’ in pharmaceutical chemicals for manufacturing drugs? Give a comprehensive account on the following aspects : (a) Biological response Vs chemical purity. Elaborate with specific examples the various sampling procedures and errors commonly encountered in a quality control laboratory. Why do the chemical purity and bioavailability of a ‘drug’ equally important to determine the efficiency of a ‘dosage form’? What are the various ‘physical parameters’ that ultimately establish the purity of a drug substance? Discuss the ‘miscellaneous characteristic features’ included in ‘official compendia’ to establish the purity, authenticity and identification of drugs. Give a detailed account on the ‘Limit Tests’ Vs ‘Quantitative Determinations’ by providing suitable examples. Describe the theory, apparatus and procedure involved in the ‘limit tests’ for metallic impurities e. Elaborate the various ‘limit tests’ recommended for the ‘Non-metallic Impurities’ in official compendia e. How will you determine the limit test for ‘Iron’ in Calcium Lactate and Zinc Oxide? Volumetric analysis essentially comprises of the most precise and accurate measurement of interacting solutions or reagents. It makes use of a number of graduated apparatus, such as : graduated (volumetric) flasks, burettes, pipettes and measuring cylinder of different capacities (volumes). However, it is pertinent to mention here that quite a few techniques related to measurement of pharmaceutical substances and reagents involved is more or less common to both gravimetric and volumetric analysis. Besides, in gravimetric analysis, some more additional techniques play a vital role, namely : precipitation, filtration, washing of the precipitate and ignition of the precipitate. Biomedical analytical chemistry happens to be one of the latest disciplines which essentially embraces the principles and techniques of both analytical chemistry and biochemistry. This particular aspect of analytical chemistry has gained significant cognizance in the recent past by virtue of certain important techniques being included very much within its scope of analysis, namely : colorimetric assays, enzymic assays, radioimmunoassays and automated methods of clinical analysis. It is, however, important to mention here that certain other routine procedures also carried out in a clinical laboratory fall beyond the scope of biomedical analytical chemistry, narnely : microbiological assays, heamatological assays, serum analysis, urine analysis and assays of other body fluids. Titrant is the solution of known strength (or concentration) employed in the assay e. Titration is the process of adding and then actually measuring the volume of titrant consumed in the assay. Indicator is a chemical substance sensitive enough to display an apparent change in colour very close to the point in the ongoing titration process at which equivalent quantities of analyte and titrant have almost virtually reacted with each other. Equivalence Point (or Stoichiometric Point) is the point at which there appears an abrupt change in certain characteristic of the prevailing reaction mixture—a change that is either ascertained electrometrically or is visibly spotted by the use of indicators. In usual practice, the volumetric titrations may be accomplished either by direct titration method e. In other words, 1 g of H, acting as a reducing agent, loses electrons equivalent to 96,500 C. Thus, most calculations in volumetric determinations (titrimetry) are enormously facilitated by using titer values, which may be seen in the following chapters related to various categories of volumetric titrations. For instance, in the offcial procedure for the assay of tartaric acid, it is stated that ‘Each millilitre of 1 N sodium hydroxide is equivalent to 75. However, the weights are measured upto the fourth place of decimal by using a manually operated good analytical balance or a single-pan electrical balance that need to be calibrated periodically with the help of a standard weight box. In the broader sense, volumetric apparatus may be divided into two categories, namely : (a) To deliver a definite volume of liquid, and (b) To contain a definite volume of liquid. A burette is a graduated glass tube of uniform bore throughout the entire length, used for the accurate delivery and measurement of variable volumes of liquids. They are usually closed at the bottom either by a Teflon or glass stopcock to monitor and control the outflow of liquid. The tolerances on capacity for burettes, as speci- fied in the relevant Indian Standards Institution, specifications are given in Table 2. All Class ‘A’ and a few of Class ‘B’ burettes have graduations that extend right round the barrel (or stem) of the burette to minimise errors due to parallax while taking the exact burette reading.
As described above buy amoxil 250mg free shipping, a greater understanding of the molecular specificity of this carrier could provide important leads for the delivery of peptides order discount amoxil line. Proteins and large peptides may be transported across cells via endocytic processes amoxil 500 mg otc. Transcytosis is achieved if the endocytic vesicles can reach the basal membrane without fusion with lysosomes. However, various studies have shown that in the majority of cases the internalized protein is degraded, indicating that the transcytotic pathway is a minor one and most of the endocytosed protein is subject to lysosomal degradation. Unwanted distribution may also cause toxic side-effects resulting from drug action at non-target sites. Premature excretion may arise if small, highly potent, therapeutic peptides are cleared rapidly through the kidneys, before reaching the target site. For optimal drug therapy, drug delivery systems must tailor drug input in response to such factors as: 37 • circadian and other rhythms of predictable period; • modulations on a minute-to-minute basis, in response to such factors as nutrient delivery, physical activity and metabolic stress; • the pulsatile release patterns of many endogenous peptides and proteins; • the complex feedback control mechanisms which affect the release and biological effects of many endogenous peptides and proteins 1. However, nucleic acid-based biopharmaceuticals are now becoming increasingly important therapeutic entities. Research into nucleic acid-based therapeutics is currently focused in two main areas: • gene therapy; • oligonucleotide therapy. This whole field is still at a largely experimental stage, but holds great potential to revolutionize the treatment and prevention of disease if safe and effective delivery vectors can be found. The delivery of nucleic acid based-therapeutics is the subject of Chapter 14; the following discussion comprises a brief introduction to gene therapy. Many of these are caused by the lack of production of a single gene product, or are due to the production of a mutated gene product incapable of carrying out its natural function. Some of the genetic conditions for which the defective gene has been pinpointed are summarized in Table 1. Gene therapy represents a seemingly straightforward therapeutic strategy to correct such diseases, which would be achieved by simply inserting a “healthy” copy of the gene in question into appropriate cells of the patient. Cancer To date, the majority of gene therapy trials have been directed towards cancer therapy rather than correcting inherited genetic defects. Various strategies have been investigated in an attempt to treat cancer using a gene therapy approach, including: • modifying lymphocytes in order to enhance their antitumor activity; • modifying tumor cells to enhance their immunogenicity; • inserting tumor suppressor genes into tumor cells; • inserting toxin genes into tumor cells in order to promote tumor cell destruction; 38 • inserting suicide genes into tumor cells. The gene product will subsequently interfere with pathogen survival/replication within those cells. The protein product may be retained within the cell, or it is excreted from the cell. In common with the peptide and protein-based “new biotherapeutics” described above, successful delivery is one of the major practical problems in gene therapy. These challenges in gene delivery combine to form formidable barriers to the success of gene therapy. At a practical level, two techniques are used for gene therapy delivery: • ex vivo gene therapy; 39 Figure 1. The ex vivo technique used to deliver, for example, a gene to a patient who is deficient in that gene, entails removal of target cells from the body, followed by their incubation with a nucleic acid-containing vector. After the vector delivers the nucleic acid into the human cells (assuming this is possible), they are placed back into the body, where they hopefully produce the missing gene. In order for this approach to be successful, the target cells must be relatively easy to remove from the body and reintroduce into the body. For example, vectors can be directly injected into a tumor mass; a further example involves the investigation of aerosolized vectors for the delivery of the cystic fibrosis gene to respiratory tract epithelial cells. The foreign gene is not integrated into the target cell chromosome, so expression levels are limited. Thus this technique, while adequate for vaccine strategies, appears to give insufficient protein yields for many other applications. An alternative in vivo approach is to use vectors capable of recognizing and binding only to specific cell types, so that the genetic material is delivered only to specific target cells. However to date, no such bio-specific vectors have been developed for routine therapeutic use, although intensive research in this area is ongoing. The use of appropriate viruses as vectors for therapeutic genes requires inserting the therapuetic gene into the virus. Safety issues are a large concern here as the virus must also be selectively disabled so that it cannot pursue its normal life-cycle once inside its human host and cause a viral infection. The problems associated with retroviruses as vectors, which illustrate some of the problems associated with the use of viruses as a whole, include: • Most retroviruses can only integrate into actively replicating cells, which clearly restricts their use. As the identity of most retroviral receptors remains unknown, it is difficult to predict the range of cell types the virus will infect during treatment. Physiological complications may arise if integration and transfection occur in non-target cells. The alternative approach is to use non-viral vectors, such lipid-based, peptide-based and polymer-based delivery systems, as described in detail in Chapter 14. Liposomes are relatively easy to manufacture, are generally non-toxic and are devoid of the capability to cause an infection (see Section 5. The various initial studies that have been carried out using gene therapy have highlighted the technical innovations required to achieve successful gene transfer and expression. These, in turn, should render future (“second-generation”) gene therapy protocols more successful. It should now be apparent that conventional drug delivery systems are associated with a number of limitations which can reduce drug efficacy. These limitations include an inability to: • facilitate adequate absorption of the drug; • facilitate adequate access to the target site; • prevent non-specific distribution throughout the body (resulting in possible toxic side-effects and drug wastage); • prevent premature metabolism; • prevent premature excretion; • match drug input with the required timing (zero-order or variable input) requirements Limitations of conventional drug delivery systems are particularly acute for the new biotherapeutics, such as peptide and protein drugs and nucleic acid therapies. Advanced drug delivery and targeting systems are thus being developed in order to optimize drug therapy and overcome these limitations. Further chapters will describe these new and emerging technologies, with reference to the various routes of delivery under investigation. Define the term bioavailability and describe the differences between (a) relative bioavailability and (b) absolute bioavailability. Describe the most likely pathway of drug absorption for (i) a large therapeutic peptide, (ii) a small hydrophilic molecule and (iii) a small hydrophobic molecule. The rationale for developing novel drug delivery systems therefore lies primarily in the potential commercial benefits of developing more effective means of delivering the new biotherapeutic agents. This chapter gives a market perspective to the rationale for the development of novel drug delivery systems. As introduced in the previous chapter, drug delivery technology, as a separate sector within the pharmaceutical sphere, is of quite recent origin. It had its origins in the 1950s and 1960s, when the first 44 sustained-release oral forms appeared; the best known was probably the Spansule capsule formulation developed by Smith Kline & French Laboratories.