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There are also cases where parenteral nanoparticulate drug administration is targeted for drug delivery to the lung symptoms hypoglycemia cheap kemadrin 5 mg amex. Therefore medicine numbers buy kemadrin now, this chapter provides an integrated discussion of various organs and tissues utilized either as alternate routes for drug delivery to the systemic circulation or as organ or tissue drug targets, either by local or after systemic administration. The need for alternate routes of drug delivery into the systemic circulation originates with the challenges involved in the systemic delivery of drugs administered orally. Enteric-coated products featuring pH-sensitive polymers include tablets, capsules, and pellets and are designed to keep an active substance intact in the stomach and tend to release it to the upper intestine. Small intestine has a large epithelial Organ-specific drug delivery 339 surface area, which consists of mucosa, villi, and microvilli. Drug must first diffuse through the unstirred aqueous layer, the mucus layer, and the glycocalyx (which is the coating of the mucus layer) to reach the microvilli, which is the apical cell membrane. The tight junction between the cell membranes of adjacent epithelial cells acts as a major barrier to the intercellular passage of drug molecules from the intestinal lumen to the lamina propria. Most protein and peptide drugs are susceptible to rapid degradation by digestive enzymes. Various delivery systems have been proposed to increase drug absorption from the colon and ileum and minimize exposure of the drug to proteolytic enzymes. Enteric coatings that delay drug release for a sufficient period of time have been used to target both the ileum and colon. Coadministration of enzyme inhibitors and absorption enhancers have shown some promise. Encapsulation into erodible or biodegradable nanoparticles have been explained as a way of protecting drugs from enzymatic degradation. Submicron size particles are absorbed through transcytosis by both enterocytes and M cells, which are epithelial cells of the mucosa-associated lymphoid tissues. For systemic action of drugs, the oral route has been the preferred route of administration. Several nonoral routes of drug delivery have been utilized to provide adequate drug concentrations in the systemic circulation, in addition to localized drug treatment. These include the rectal, vaginal, and the transdermal routes of drug administration. More importantly, rectal drug administration has the advantage of minimizing or avoiding hepatic first-pass metabolism. The rectal bioavailability of lidocaine in human is 65%, as compared to an oral bioavailability of 30%. Rectal route is used to administer diazepam to children who are suffering from epilepsy and in whom it is difficult to establish intravenous access. Moreover, rectal administration should 340 Pharmaceutical Dosage Forms and Drug Delivery be avoided in immunosuppressed patients in whom even minimal trauma could lead to the formation of an abscess. Most steroids are readily absorbed by vaginal epithelium, leading to their higher bioavailability compared to their oral administration because of a reduced first-pass metabolism. For drugs with high membrane permeability, vaginal absorption is determined by permeability of the aqueous diffusion layer, whereas for drugs with low membrane permeability, such as testosterone and hydrocortisone, vaginal absorption is determined by membrane permeability. Contraceptive creams contain spermicidal agents and are used just prior to sexual intercourse. Among the factors influencing percutaneous absorption are the physicochemical properties of the drug, including its molecular weight, solubility, partition coefficient, nature of the vehicle, and condition of the skin. In general, patches are composed of three key compartments: (1) a protective seal that forms the external surface and protects it from damage, (2) a compartment that holds the medication itself and has an adhesive backing to hold the entire patch on the skin surface, and (3) a release liner that protects the adhesive layer during storage and is removed just prior to application. Most patches belong to one of two general types-the reservoir system and the matrix system. Drug transport from the patch to the skin is channelized and controlled through a rate-limiting surface layer. The matrix system, on the other hand, incorporates the drug uniformly across the patch in a polymer matrix. Diffusion of the drug through the polymer matrix and the bioadhesive properties of the polymer determines the rate of drug absorption. Marketed transdermal patches are exemplified by Estraderm (estradiol), Testoderm (testosterone), Alora (estradiol), Androderm (testosterone), Organ-specific drug delivery 341 and Transderm-Scop (scopolamine). In addition, occlusive dressings are available, which have low water vapor permeability. These dressings help prevent water loss from the skin surface, resulting in increased hydration of the stratum corneum.

Dissolution rate constant can be calculated using dissolution data collected from a well-defined system medications while breastfeeding discount kemadrin line. For example treatment varicose veins quality kemadrin 5 mg, a preparation of drug particles weighing 550 mg and having a total surface area of 0. Assuming that analysis of bulk dissolution sample showed that 262 g had dissolved after 10 min, if the saturation solubility of the drug in water is 1. The solubility and dissolution rates of acidic drugs are low in acidic gastric fluids, whereas the solubility and dissolution rates of basic drugs are high. Similarly, the solubility and dissolution rates of basic drugs are low in basic intestinal fluids, whereas those of acidic drugs is high. Viscosity (of the dissolving medium): the greater the viscosity of the dissolving liquid, the lower the diffusion coefficient of the drug and hence the lower the dissolution rate. Viscosity of the dissolving bulk medium and/or the unstirred layer on the surface of the dissolving formulation can be affected by the presence of hydrophilic polymers in the formulation, which dissolve to form a viscous solution. The thickness of the diffusion layer is influenced by the degree of agitation of the dissolving medium, both in vitro and in vivo. Hence, an increase in gastric and/or intestinal motility may increase the dissolution rate of poorly soluble drugs. The pH of the diffusion layer has a significant effect on the solubility of a weak electrolyte drug and its subsequent dissolution rate. However, particle size reduction may not always be helpful in increasing the dissolution rate of a drug and hence its oral bioavailability. Thus, smaller particles with lower porosity may have lower surface area compared with larger particles with greater porosity. The dissolution rate depends on the effective surface area, which includes the influence of particle porosity. For such drugs, particle size reduction may increase not only the rate of drug dissolution in gastric fluids but also the extent of drug degradation. Crystalline structure: Amorphous (noncrystalline) forms of a drug may have faster dissolution rate compared with the crystalline forms. These different forms may have significantly different drug solubility and dissolution rates. Intrinsic dissolution rate reflects the dissolution rate of a drug crystal or powder normalized for its surface area. Drug forms that have higher intrinsic dissolution rate are expected to have higher dissolution rates. The greater strength of a crystalline polymorph, sometimes evident by its high melting point and sometimes by the rank order, correlates with its lower intrinsic dissolution rate. Similarly, amorphous solids, which lack a long-range order that defines crystalline structure, tend to have higher intrinsic dissolution rates. Temperature: An increase in temperature leads to greater solubility of a solid, with positive heat of the solution. Surfactants: Surface-active agents increase the dissolution rate by (a) lowering the interfacial tension, which lowers the contact angle of the solvent on the solid surface and increases wetting of the drug particle and penetration of the solvent inside the dosage form, and (b) increasing the saturation solubility of the drug in the dissolution medium. Bioequivalence, on the other hand, is a comparison of relative bioavailability of two dosage forms in terms of the rate and extent of the drug levels achieved in the systemic circulation and the maximum drug 84 Pharmaceutical Dosage Forms and Drug Delivery concentration reached. Generic drugs are required to satisfy statistical criteria of bioequivalence to the branded version before they can be considered equivalent. Drug absorption is affected not only by the properties of drug and its dosage forms but also by the nature of the biological membranes. Active transport Passive diffusion can also be classified as paracellular or transcellular, depending on the route of drug absorption across the epithelial cell barrier. Drug transport across the tight junctions between cells is known as paracellular transport.

Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial schedule 8 medicines order 5mg kemadrin. Comparison of a polymerbased paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial medicine while pregnant purchase 5 mg kemadrin. Strut position, blood flow, and drug deposition: implications for single and overlapping drugeluting stents. Periprocedural and late consequences of overlapping Cypher sirolimus eluting stents: pooled analysis of five clinical trials. Restenosis rates following bifurcation stenting with sirolimus-eluting stents for de novo narrowings. Clinical and angiographic outcome after implantation of drug-eluting stents in bifurcation lesions with the crush stent technique: importance of final kissing balloon postdilation. Incidence and predictors of restenosis after sirolimus-eluting stent implantation in high-risk patients. Predictive factors of restenosis after coronary implantation of sirolimusor paclitaxel-eluting stents. Predictors of restenosis after placement of drug-eluting stents in one or more coronary arteries. Clinical correlates of restenosis following coronary implantation of drug-eluting stents. Clinical, angiographic and procedural predictors of angiographic restenosis after drug-eluting stent implantation. Beyond restenosis: fiveyear clinical outcomes from second generation coronary stent trials. Quantitative assessment of angiographic restenosis after sirolimus eluting stent implantation in native coronary arteries. Preliminary observations regarding angiographic pattern of restenosis after rapamycin-eluting stent implantation. Isolation of Chinese hamster ovary cell mutants requiring the continuous presence of taxol for cell division. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious Allergic reactions after the implantation of drug-eluting stents: is it the pill or the polymer Impact of final stent dimensions on long-term results following sirolimus eluting stent implantation: serial intravascular ultrasound analysis from the sirius trial. Nonuniform strut distribution correlates with more neointimal hyperplasia after sirolimus-eluting stent implantation. Volumetric intravascular ultrasound assessment of neointimal hyperplasia and nonuniform stent strut distribution in sirolimus-eluting stent restenosis. Frequency, predictors and outcome of stent fracture after sirolimus-eluting stent implantation. Stent fracture, an incidental finding or a significant marker of clinical in-stent restenosis Serial angiographic and intravascular ultrasound analysis of late stent strut fracture of sirolimus-eluting stents in native coronary arteries. Clinical and angiographic outcomes after overdilatation of undersized sirolimus-eluting stents 59. Serial assessment of tissue growth inside and outside the stent after implantation of drug-eluting stent in clinical trials. Evaluation of four-year coronary artery response after sirolimus-eluting stent implantation using serial quantitative intravascular ultrasound and computerassisted grayscale value analysis for plaque composition in event-free patients. Pathology of secondgeneration everolimus-eluting stents versus first-generation sirolimusand paclitaxel-eluting stents in humans. Durability of antirestenotic efficacy in drug-eluting stents with and without permanent polymer. Optical coherence tomography characteristics of in-stent restenosis are different between first and second generation drug eluting stents. Postsirolimus-eluting stent restenosis treated with repeat percutaneous intervention: late angiographic and clinical outcomes.

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions shinee symptoms mp3 generic kemadrin 5 mg with visa. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects treatment urinary incontinence generic kemadrin 5mg without a prescription. Intravascular ultrasound comparison of the retrograde versus antegrade approach to percutaneous intervention for chronic total coronary occlusions. Subintimal guidewire tracking during successful percutaneous therapy for chronic coronary total occlusions: insights from an intravascular ultrasound analysis. Sub-intimal tracking and re-entry technique with contrast guidance: a safer approach. Dissection and reentry techniques and longer-term outcomes following successful percutaneous coronary intervention of chronic total occlusion. Tuchikane E, Yamane M, Mutoh M, Japanese Multicenter Registry Evaluating the Retrograde Approach for Chronic Coronary Total Occlusion. Angiographic success and procedural complications in patients undergoing percutaneous coronary chronic total occlusion interventions: a weighted metaanalysis of 18,061 patients from 65 studies. Interventricular septal hematoma and ventricular septal defect after retrograde intervention for a chronic total occlusion of a left anterior descending coronary artery. The retrograde technique for recanalization of chronic total occlusions: a step-by-step approach. Cardiovascular events are responsible for 75% of all hospitalizations and 80% of all deaths in diabetic patients (12). Diabetic patients have smaller luminal diameters in segments adjacent to obstructive coronary lesions and more completely occluded segments (20). In addition to a greater atherosclerotic burden, diabetic patients have a larger amount of lipid-rich plaques, which may be more prone to rupture (21). Diabetic patients also have an impaired ability to develop coronary collaterals (23). Finally, intravascular ultrasound has shown that the coronary arteries of diabetic patients are less likely to undergo advantageous remodelling, which is an early compensatory enlargement at atherosclerotic sites to maintain luminal area and flow (24, 25). Approximately 25% occur in diabetic patients, who fare worse after either type of revascularization compared with those without diabetes (33, 34). Diabetic nephropathy, including reduced creatinine clearance and proteinuria, identifies patients with markedly decreased survival after coronary revascularization (41). The subgroup analysis according to diabetes status was prespecified in the trial protocol, although no formal statistical hypothesis was defined a priori. Prespecified subgroup analyses of diabetic versus non-diabetic patients have also been reported at 1and 3-year intervals (57, 58). There were no differences in the rates of cerebrovascular events between treatment groups at 5 years. The duration of diabetes before randomization for each group was 10 years, and the baseline glycosylated haemoglobin was 7. It was a protocol requirement that all patients in both groups had aggressive diabetic control post-randomization with a target glycosylated haemoglobin of <7%. Sixtyfive per cent of patients had three-vessel disease, of whom 88% had complete revascularization and only 2. Because the study was underpowered because of early termination, no differences were found in either the composite endpoint or its components for the predefined subgroups on the basis of HbA1c or insulin use, with the exception of all-cause mortality (3. However, the use of other evidence-based therapies such as statins, beta-blockers, and angiotensin converting enzyme inhibitors and angiotensin receptor blockers was similar in the two study groups (69). Conventional analysis does not show a statistical difference in primary outcome, but the study was underpowered for this comparison. Early termination of this study shortened follow-up to a mean of only 2 years, compared with the planned 3. The outcome of death was significantly more likely with higher degrees of incomplete revascularization when analysed as a continuous variable but not by categorical analysis. In each era and overall, incomplete revascularization had an adverse impact on the adjusted rate of long-term survival. Jeopardized myocardium is defined as the total territory of myocardium supplied by arteries with at least one 50% stenosis. The amount of jeopardized myocardium decreases initially following revascularization but subsequently increases due to restenosis, graft failure, or formation of new vessel lesions. Smaller vessels with more diffuse disease make revascularization more challenging in patients with diabetes.