Malegra DXT

F. Rathgar. Siena Heights University.

The above two modifications have been duly incorporated in a double-beam spectrophotometer purchase 130mg malegra dxt with mastercard. In fact, the source beam is usually split in two different manners, namely : (a) Separated in Space : In this instance, the source beam is split between the sample cell-path and the reference cell-path, and finally detected by two diode detectors. Here, the two detectors should be adequately matched so that no changes occur relative to each other during the measurements, (b) Separated in Time : In this case, the source beam is split with the help of an optical chopper which permits the source beam to alternate between the sample cell-path and the reference cell- path. Here, the source should be stable enough so that no changes take place in the radiant energy during the chopping time. Keeping in view, this specific, rigid and stringent requirement, the separation-in-space method is found to be normally of lower precision and accuracy than the separation-in time-method. Evidently, the optical choppers are quite expensive, and therefore, the instrument manufacturers very often utilize the separation-in-space method for the routine measurement spectrophotometers. However, the most sophisticated double-beam spectrophotometer is usually pretty expensive by vir- tue of the following facts, namely : (i) Greater operating stability, (ii) Rapid speed compared to single-beam instruments, (iii) Complicated optical system involved, and (iv) Recording device for recording absorbance Vs wavelength. These instruments are mostly based on microcomputer-controlled devices with built-in recorder to accom- plish faster speed and greater operating stability. Extinction is solely dependent upon the following two factors, namely : (a) Concentration of the absorbing substance present in the solution, and (b) Thickness of the absorbing layer taken for measurement. Bearing in mind the ease in calculations and also the convenience of reference, the extinction of a 1-cm layer of a 1% w/v solution is usually recommended in most of the official compendia (i. This particular property is the basis for most assay methods included in pharmacopoeia that are absolutely free from interfering materials, besides being utilized for identifying substances. In actual practice, where a test or an assay recommends the usage of a Reference Substance, the spectrophotometric measurements are always performed first with the solution prepared from the Reference Substance by the directions provided in the specific monograph and then with the corresponding solution prepared from the substance under examination. Nevertheless, the second measurement must be done immediately after the first, by employing the same cell and the same instrumental parameters. Importantly, when a double bond recording instrument is being employed the solvent cell is always placed in the reference beam. Particular care must be taken to employ solvents free from contaminants absorbing in the specific spectral region being used. In measuring the extinction of a solution at a given wavelength, the extinction of the solvent cell and its contents must not exceed 0. Particularly, the solvent in the solvent cell should always be of the same purity, grade and batch as that employed to prepare the respective solution and above all it must be free from fluorescence at the wavelength of measurement. All the measure- ments are normally performed with reference to the solvent used to prepare the solution being examined, unless otherwise indicated in the individual monograph. In tests for identification, a recording instrument is always preferred ; besides, the concentration of the solution and the path-length are specifically monitored. In case, the laid down conditions are not suitable for a particular instrument, the thickness of the solution (i. Now, transfer 10 ml of this solution into a 100 ml volumetric flask, add 10 ml of buffer solution pH 9. To tube 1 add 10 ml of imidazole-mercury reagent, mix, stopper the tube and immerse it in a water-bath previously maintained at 60 °C for exactly 25 minutes, with occasional swirling. Calculations : The content of C16H19N3O5S may be calculated from the difference between the extinctions of Solution-1 and that of Solution-2 and from the difference obtained by repeating the operation using 0. Cognate Assays : Ampicillin can also be assayed by employing the above method using 0. The primary aromatic amino group present in the latter is subsequently diazotized in the usual manner and coupled in acidic solution with N-(1-naphthyl)-ethylenediamine hydro- chloride in the absence of light (caution). To an aliquot of the resulting acetic acid solution an excess of phenoldisulphonic acid is added to produce a yellow colour which is subsequently intensified by adding an excess of ammonia. Materials Required : Glyceryl trinitrate tablets : 20 ; glacial acetic acid (90% v/v) : 5 ml ; phenoldisulphonic acid solution (heat 3 g of phenol with 20 ml of sulphuric acid on a water-bath for 6 hours, and transfer the resulting liquid to a stoppered vessel) : 2 ml ; strong ammonia solution ; 20 ml ; potassium nitrate (previously dried at 105 °C) : 1 g ; Procedure : Weigh and powder 20 tablets. To 2 ml of the supernatant liquid add 2 ml of phenoldisulphonic acid solution and allow to stand for 15 minutes. Finally, measure the extinction of a 1-cm layer of the filtrate at 405 nm, as described earlier, employing as blank 2 ml of glacial acetic acid, treated exactly in a similar fashion, begin- ning at ‘‘add 2 ml of phenoldisulphonic acid solution......... Taking 2 ml of this solution, just repeat the assay beginning the procedure at ‘‘add 2 ml of phenoldisulphonic acid solution...... Cognate Assays : The following two pharmaceutical products, namely : Pentaerythritol tetranitrate Tablets and Diluted Isosorbide dinitrate are assayed by using a solution of phenoldisulphonic acid as detailed below : S. Now, measure the extinction of the irradiated solution at the maximum at about 418 nm as described earlier. Give a brief and comprehensive account of the following terminologies : (a) Electromagnetic spectrum, (b) Molar absorptivity, (c) Absorption spectra, (d) Structural features, and (e) Absorption bands. Discuss the theory, procedure and calculations for the assay of the following medicinal compounds : (i) Folic acid, (ii) Glyceryl trinitrate tablets, and (iii) Trans-Diethylstilbesterol. It also serves as a powerful ‘analytical tool’ for the extensive and intensive study of molecular structure. In fact, infrared absorption spectra are due to changes in vibrational energy accompanied by changes in rotational energy.

Some success has also been attained in the transbuccal delivery of peptides and proteins order malegra dxt 130 mg online. Thus it can be expected that a more exponential growth phase will develop in the coming years. Name 3 differences between the buccal mucosa and the mucosa of the gastrointestinal tract. What advantages does the buccal route offer for the systemic delivery of peptides? What is the main structural difference between the gingival and the cheek epithelium? Rank the permeability of the gastrointestinal mucosa, the skin and the buccal mucosa in the order lowest to highest. Evolution has provided the mammalian organism with an external covering, the principal function of which is to act as a barrier, specifically to the loss of tissue water. Think about it: the concentration of water inside the human body is 190 on the order of 50 M, while that in the atmosphere is clearly very much less. Thus, there is a strong driving force for water to be lost from the body and, to prevent desiccation, an efficient barrier at the interface is therefore required. The skin, and more specifically skin’s outermost layer, the stratum corneum, provides this shield. Of course, in so doing, the skin also presents a formidable resistance to the absorption, either deliberate or accidental, of chemicals which contact the external surface. Nevertheless, the challenge of transdermal drug delivery has been accepted by pharmaceutical scientists and, over the past 25 years, considerable progress and achievement have been recorded. So, what led to the investigation of the skin as a potential route for systemic drug input in light of the formidable challenges posed by the stratum corneum? First, the skin offers a large (1–2 m ) and very accessible surface for drug2 delivery. Second, transdermal applications, relative to other routes, are quite noninvasive, requiring the simple adhesion of a “patch” much like the application of a Band-Aid. As a result, thirdly, patient compliance is generally very good—that is, in general, people are quite comfortable with the use of a simple-looking patch (no matter how complex the interior machinery). And, fourth, with again a positive aspect for the patient, a transdermal system is easily removed either at the end of an application period, or in the case that continued delivery is contra-indicated—with the exception of intravenous infusions, no other delivery modality offers this advantage. Although transdermal administration is limited at present to relatively few drugs, it has proven to be a considerable commercial success when compared to other “controlled release” technologies. The current worldwide market for transdermal systems is about $2 billion annually. Macroscopically, skin comprises two main layers: the epidermis and the dermis (~0. The dermal-epidermal junction is highly convoluted ensuring a maximal contact area. Other anatomical features of the skin of interest are the appendageal structures: the hair follicles, nails and sweat glands. The keratinocytes comprise the major cellular component (>90%) and are responsible for the evolution of barrier function. The epidermis per se can be divided into five distinct strata which correspond to the consecutive steps of keratinocyte differentiation. The ultimate result of this differentiation process is formation of the functional barrier layer, the stratum corneum (~0. The stratum basale or basal layer is responsible for the continual renewal of the epidermis (a process occurring every 20–30 days). Proliferation of the stem cells in the stratum basale creates new keratinocytes which then push existing cells towards the surface. The next layer of the epidermis is the stratum spinosum, named for the numerous spiny projections (desmosomes) on the cell surface. The keratinocytes maintain a complete set of organelles and also include membrane-coating granules (or lamellar bodies) which originate in the Golgi. Subsequently, we encounter the stratum granulosum or granular layer, characterized by numerous keratohyalin granules present in the cytoplasm of the more flattened, yet still viable, keratinocytes. More lamellar bodies are also apparent and concentrate in the upper part of the granular cells. The transition layer, the stratum lucidum, comprises flattened cells which are not easy to visualize microscopically. The cellular organelles are broken down leaving only keratin filaments in the stratum granulosum an interfilament matrix material in the intracellular compartment. The membrane coating granules fuse with the cell membrane and release their contents into the intercellular space. Finally, in the stratum corneum, the outermost layer, protein is added to the inner surface of the cell membrane to form a cornified envelope that further strengthens the resistance of the cell. A layer of lipid covalently bound to the cornified envelope of the corneocyte contributes to this exquisite organization. The intercellular lipids of the stratum corneum include no phospholipids, comprising an approximately equimolar mixture of ceramides, cholesterol and free fatty acids.

When the logarithm of concentration is plotted versus effect (Figure 1-5) 130mg malegra dxt with mastercard, one can see that there is a concentration below which no effect is observed and a concentration above which no greater effect is achieved. One way of comparing drug potency is by the concentration at which 50% of the maximum effect is achieved. This means that a lesser amount of a more potent drug is needed to achieve the same effect as a less potent drug. Duration of effect is determined by a complex set of factors, including the time that a drug is engaged on the receptor as well as intracellular signaling and gene regulation. Tolerance may be caused by pharmacokinetic factors, such as increased drug metabolism, that decrease the concentrations achieved with a dose. There can also be pharmacodynamic tolerance, which occurs when the same concentration at the receptor site results in a reduced effect with repeated exposure. Tolerance can be described in terms of the dose-response curve, as shown in Figure 1-6. To assess the effect that a drug regimen is likely to have, the clinician should consider pharmacokinetic and pharmacodynamic factors. One example is the hemodynamic tolerance that occurs with continued use of organic nitrates, such as nitroglycerin. For this drug, tolerance can be reversed by interspersing drug-free intervals with chronic drug use. For some patients with diabetes mellitus there is a reduction in the number of insulin receptors on the surface of cells using glucose. These patients then become relatively insensitive to insulin and require higher doses. Therefore, the pharmacologic response for one person can be quite different from another, even with the same insulin concentrations at the receptor site. Relationship of drug concentration at the receptor site to effect (as a percentage of maximal effect). For certain drugs, studies in patients have provided information on the plasma concentration range that is safe and effective in treating specific diseasesthe therapeutic range (Figure 1-7). Below it, there is greater probability that the therapeutic benefits are not realized; above it, toxic effects may occur. No absolute boundaries divide subtherapeutic, therapeutic, and toxic drug concentrations. A gray area usually exists for most drugs in which these concentrations overlap due to variability in individual patient response. Both pharmacodynamic and pharmacokinetic factors contribute to this variability in patient response. Although this course focuses on pharmacokinetics, it is important to remember the fundamental relationship between drug pharmacokinetics and pharmacologic response. The pharmacokinetics of a drug determine the blood concentration achieved from a prescribed dosing regimen. Theophylline is an excellent example of a drug whose pharmacokinetics and pharmacodynamics are fairly well understood. When theophylline is administered at a fixed dosage to numerous patients, the blood concentrations achieved vary greatly. That is, wide interpatient variability exists in the pharmacokinetics of theophylline. This is important for theophylline because subtle changes in the blood concentration may result in significant changes in drug response. Figure 1-8 shows the relationship between theophylline concentration (x-axis, on a logarithmic scale) and its pharmacologic effect, (changes in pulmonary function [y-axis]). Figure 1-8 illustrates that as the concentration of theophylline increases, so does the intensity of the response for some patients. Theophylline concentrations below 5 mg/L are generally considered inadequate for a desired therapeutic effect, and side effects (tachycardia, nausea and vomiting, and nervousness) are more likely to occur at concentrations above 20 mg/L. Drugs like theophylline possess a narrow therapeutic index because the concentrations that may produce toxic effects are close to those required for therapeutic effects. The importance of considering both pharmacokinetics and pharmacodynamics is clear. As can be seen in this table, most drug concentrations are expressed as a unit of mass per volume (e. Many pharmacokinetic factors cause variability in the plasma drug concentration and, consequently, the pharmacologic response of a drug. For most drugs, the intersubject variability is likely to result in differing plasma drug concentrations (Figure 1-9). This variability is primarily attributed to factors influencing drug absorption, distribution, metabolism, or excretion.

While teaching a patient about drug therapy for diabetes effective malegra dxt 130 mg, you review the absorption, distribution, metabolism, and excretion of insulin and oral antidiabetic agents. Pharmacokinetics discusses the movement of drugs through the body and involves absorption, distribution, metabo- lism, and excretion. Which type of drug therapy is used for a patient who has a chronic condition that can’t be cured? Maintenance therapy seeks to maintain a certain lev- el of health in patients who have chronic conditions. Pharmacodynamics studies the mechanisms of ac- tion of drugs and seeks to understand how drugs work in the body. Sometimes food enhances absorption—so grab a quick snack and come back for a review. Cholinergic drugs enhance the action of acetylcholine, stimulating the parasympathetic nervous system. Cholinergic drugs Cholinergic drugs promote the action of the neurotransmitter acetylcholine. These drugs are also called parasympathomimetic drugs because they produce effects that imitate parasympathetic nerve stimulation. Mimickers and inhibitors There are two major classes of cholinergic drugs: Cholinergic agonists mimic the action of the neurotransmit- ter acetylcholine. Anticholinesterase drugs work by inhibiting the destruction of acetylcholine at the cholinergic receptor sites. How cholinergic drugs work Cholinergic drugs fall into one of two major classes: cholinergic agonists and anticholinesterase drugs. Cholinergic agonists Anticholinesterase drugs When a neuron in the parasympathetic nervous system is stim- After acetylcholine stimulates the cholinergic receptor, it’s de- ulated, the neurotransmitter acetylcholine is released. Anticholinester- choline crosses the synapse and interacts with receptors in an ase drugs inhibit acetylcholinesterase. Cholinergic agonists stimulate cholinergic re- line isn’t broken down and begins to accumulate, leading to ceptors, mimicking the action of acetylcholine. Pharmacokinetics (how drugs circulate) The action and metabolism of cholinergic agonists vary widely and depend on the affinity of the individual drug for muscarinic or nicotinic receptors. Metabolism and excretion All cholinergic agonists are metabolized by cholinesterases: • at the muscarinic and nicotinic receptor sites • in the plasma (the liquid portion of the blood) • in the liver. Pharmacodynamics (how drugs act) Cholinergic agonists work by mimicking the action of acetylcho- line on the neurons in certain organs of the body called target or- gans. Examples include the following: • Other cholinergic drugs, particularly anticholinesterase drugs (such as ambenonium, edrophonium, neostigmine, physostigmine, Adverse and pyridostigmine), boost the effects of cholinergic agonists and reactions to increase the risk of toxicity. Because they bind with • Quinidine also reduces the effectiveness of cholinergic agonists. As acetylcholine builds up, it continues to stimu- fects can include: late the cholinergic receptors. One day at a time: Recognizing a toxic response It’s difficult to predict adverse reactions to an- Enter edrophonium ticholinesterase drugs in a patient with myas- Deciding whether a patient is experiencing a thenia gravis because the therapeutic dose toxic drug response (too much drug) or a my- varies from day to day. Increased muscle asthenic crisis (extreme muscle weakness and weakness can result from: severe respiratory difficulties) can be difficult. When edrophonium is used, suction, oxygen, mechanical ventilation, and emer- gency drugs, such as atropine, must be readily available in case a cholinergic crisis occurs. Pharmacokinetics Here’s a brief rundown of how anticholinesterase drugs move through the body. Because the duration of action for an oral dose is longer, however, the pa- tient doesn’t need to take it as frequently. Distribution Physostigmine can cross the blood-brain barrier (a protective bar- rier between the capillaries and brain tissue that prevents harmful substances from entering the brain). Donepezil is highly bound to plasma proteins, tacrine is about 55% bound, rivastigmine is 40% bound, and galantamine is 18% bound. Depending on the dosage, anticholinesterase Pharmacodynamics drugs can produce a Anticholinesterase drugs promote the action of acetylcholine at stimulant or receptor sites. From minutes to weeks Reversible anticholinesterase drugs block the breakdown of acetylcholine for minutes to hours; irreversible anti- cholinesterase drugs do so for days or weeks. Drug interactions These interactions can occur with anticholinesterase drugs: • Other cholinergic drugs, particularly cholinergic agonists (such as bethanechol, carbachol, and pilocarpine), increase the risk of a toxic reaction when taken with anticholinesterase drugs. Most of the adverse re- actions caused by anti- cholinesterase drugs re- Cholinergic blocking drugs sult from increased ac- tion of acetylcholine at Cholinergic blocking drugs interrupt parasympathetic nerve im- receptor sites. These drugs Adverse reactions are also referred to as anticholinergic drugs because they prevent acetylcholine from stimulating cholinergic receptors.