Category: Pharmacy

Introduction

Six Sigma has been known as the main quality-control program that manufacturing businesses use for preserving the high standards of their products. On the one hand, the program is extremely beneficial for its orientation to customers and meeting their expectations (Pavel & Sarbu, 2014). On the other hand, some companies may find following the program too strict and impractical in specific situations. Thus, it is the disadvantages that should be considered in order to understand the full extent of Six Sigma use.

Main body

The first disadvantage is associated with the system contributing to bureaucracy and rigidity because of its application to all components of planning and production. It stifles the creativity of workers because all they should think about is customer expectations and preferences (DeMerceau, 2018). Many measures of quality control that may align with the expectations of a company may not be considered because of the overarching objective of achieving a high level of customer satisfaction. In the context of pharmaceutical businesses, a choice of inexpensive, simple packaging may be rejected in favor of expensive to attract customers.

Conclusion

For small businesses, Six Sigma is extremely costly to implement, and companies that are only starting up may find it challenging to comply with the high standards that may do nothing for their profitability (What is six sigma & how can it help my business?, 2018). In the sphere of pharmaceuticals, expectations are particularly high because of strict competition and the monopoly-like prevalence of giants such as Pfizer or Johnson & Johnson. Implementing Six Sigma in these organizations is easier because they possess enough financial and talent resources to adapt their processes to the needs and requirements of customers. Overall, Six Sigma is a widely popular quality control system but is significantly limiting to companies that do not have enough experience.

References

DeMerceau, J. (2018). Advantages & disadvantages of six sigma. Web.

Pavel, A-P., & Sarbu, R. (2014). Integrating six sigma with quality management systems for the development and continuous improvement of higher education institutions. Procedia  Social and Behavioral Sciences, 143, 643-648.

What is six sigma & how can it help my business? (2018). Web.

Introduction

Restatement of a company is the correction of a previously issued statement due to either some irregularity or some mistake in the accounting process. There are different types of errors; they include errors of omission, commission, and principal. The discussion involves a pharmaceutical company by the name of Cyclacel pharmaceuticals that produce drugs that provide treatment of cancer and other diseases.

Discussion

Its restatement was due to an error of commission, which was some miscalculation of the net loss per share that related to payment of 6% preferred stock. The error had resulted in the payment of dividends to the preferred shares even though the company had made losses. The payment was to be accrued to the wrong dividend account. Though the company accrued the unpaid dividend, it didnt include the amount when calculating diluted loss per common share for the year ended December 31, 2009. The net loss per common share was thus revised from $0.88 to $0.94 per share. This was later amended to the annual report to help in the consolidation of statements of cash flows related to dividends of preferred stock, though it did not affect the timing or the amount of the net cash flows. The errors would affect the price per share and the giving of shares, but it would not affect the profit and loss account and the balance sheet (Gauthier, 2002).

The accounting principle is guidelines used in financial accounting for given jurisdiction known as accounting standards, which include the standards and convection rule of accountancy (Arens & Loebbecke,2003). For this case, the miscalculation brings about the principle of permanence of the method as the required is not attained due to the errors. (Gauthier,2002). The errors had increased the amount of debt of money the stockholders were demanding from the company. It is also clear that the price per share would decrease from the original $1.23 to $1.21. This would lead to stockholders incurring some loss in a time of sale. It would discourage the stockholders and they would lose trust with the company and some would opt to sell them when the price went up. This was because the company was making only losses and they still had not yet been paid their outstanding balance. The time of price decrease would also be considered as the time to buy the shares and in this case, most investors buy more of these shares. But this would not apply for this case as many investors like a company that gives dividends and yet have high returns.

Conclusion

The restatement of the company has helped in reducing some risks that would not only be detrimental to the company but also the investors at large. It can be found out that; the accruing of more money to the dividend account would have minimized the return of the company, the reduction of the price per share, and thus this would have discouraged the stockholders. The failure to pay a dividend to stockholders would affect the outlook of the company to investors. The restatement also helped in restoring the faith with the company as the stockholders see the dedication of the company and its faithfulness in correcting and taking responsibility for errors. Lastly, restatement helped the company from making a miscalculation that would have been carried all long and would be very detrimental in the long term.

Reference List

Arens, A., & Loebbecke, J., (2003). Auditing, an integrated approach: New York: Prentice-Hall.

Gauthier, S., (2002). Governmental Accounting, Auditing, and Financial Reporting. New York: Oxford University Press.

It can be stated that differences in compensation plans stem from differences in the scale of the two businesses. Parkleigh Pharmacy is a small department store that sells expensive accessories and home decoration for high-income customers, whereas Kaufmanns is a large department store chain that offers a broad range of products for middle-income customers. It can be seen that Parkleigh Pharmacy and Kaufmanns are two different target markets.

One could assume that Kaufmanns pays commission to salespeople because it has a greater internal labor market as compared to those of Parkleigh Pharmacy. Employees who work in a company with a large internal labor market are expected to spend there much of their career (Brickley, Smith, & Zimmerman, 2016). Kaufmanns is thus interested in motivating its employees to stay loyal to the firm and continue their work there. If incentivized, it is more likely that salespeople will not perform dysfunctional activities at the cost of losing future benefits. Considering the large size of Kaufmanns, the organization may offer a commission for its workers without impacting the marginal revenue in a negative way.

At the same time, a small department store that sells a product to a restricted group of clients may be unable to offer a wide range of promotion opportunities and fringe benefits. The establishment of sales commissions for salespeople of Parkeligh Pharmacy may have a negative impact on marginal revenue products and be not economically feasible (Froeb, McCann, Shor, & Ward, 2015). Also, even though this information has not been given in the scenario, it should be mentioned that market wage rates may be different for Rochester and Pennsylvania. Nevertheless, the hourly wage is determined by the labor market, and the fact that there is a demand for a position of a salesperson at Parkleigh Pharmacy means that the company is paying at a competitive level.

Salespeople who work at Parkleigh Pharmacy and do not get commission may attain the appropriate level of job satisfaction so as not to consider more financially beneficial alternatives. Apart from that, since the customer base of Parkleigh Pharmacy consists of niche clients, the company may want to avoid salespeople pushing to make a sale to collect a commission, knowing that the customer will not be happy with the product. Parkleigh may offer its employees discounts on purchases in order to prevent stealing and increase sales. Also, the company may benefit from the discount being invisible to taxing agencies. In such a case, the firm will pay less amount of money as a revenue tax.

If neither store pays sales commissions, an hourly wage offered by Parkleigh Pharmacy is expected to be higher than that of Kaufmanns. This may be explained by the sizes of both companies and the benefits they guarantee employees. Considering its great internal labor market, Kaufmanns may be a good choice for people who can bear low payment at the entry-level but expect to get paid more in the future.

Moreover, despite the low hourly wage rate, the total package of Kaufmanns may appear to be more beneficial than employee discounts and include insurance coverage, medical benefits, and a retirement plan. In turn, Parkleigh Pharmacy may not have such a great internal labor market and benefits package. Therefore, a high hourly rate and employee discount may be the only ways in which the company can meet the individuals reservation utility.

References

Brickley, J. A., Smith, C. W., & Zimmerman, J. L. (2016). Managerial economics and organizational architecture (6th ed.). New York, NY: McGraw-Hill.

Froeb, L. M., McCann, B. T., Shor, M., & Ward, M. R. (2015). Managerial economics: A problem solving approach (4th ed.). Boston, MA: Cengage Learning.

Introduction

The signing of the Patient Protection and Affordable Care Act, Public Law 111-148 (H.R. 3590) (PPACA) into law by President Obama on March 23, 2010, had implications on the entire medical fraternity. According to King (2010), The Patient Protection and Affordable Care Act (PPACA), commonly known as the health care reform law, will likely have a more far-reaching effect on health care in America than even the passage of Medicare. This law will impact the pharmaceutical industry in several ways. The two mechanisms in PPACA that seek to control and that will greatly impact the health pharmaceutical industry is value-based purchasing and shared savings program. In fact, much of the controversy surrounding PPACA has arisen from its impact on private health insurance and the laws intention to expand coverage of the uninsured (King, 2010).

Impact of PPACA on Pharmaceutical Industry

The impact of this legislation on the pharmaceutical industry will be Section 3022 of PPACA. This will demand accountability for quality, cost, and efforts in the overall care of Medicare beneficiaries, have a formal legal structure and shift their leadership and management structure in line with the demands of the new regulations. In addition to the above, the Public Law defines processes for pharmaceutical companies to promote evidence-based medicine and patient engagement, report on quality and cost measures, and coordinate care and meet criteria for patient-centeredness (King, 2010).

In addition to the above, the discount program will impact this health care industry. Traynor (2010) illustrates that the discount program calls for 50% discounts on the total cost of brand-name drugs for beneficiaries within the coverage gap. On becoming effective, this discount will be effected at the point of sale. This means that pharmaceutical will be required to be more accountable in their practices. In addition to the above, the Patient Protection and Affordable Care Act seek to promote the production of brand name drugs in that as the coinsurance coverage for brand names will be rising from 7% in 2011 to 75% in 2020, the coinsurance for a gap for generic drugs will come down from 100% to 25% in the same period. The pharmaceutical industry will therefore lean more to towards the manufacture of brand-name drugs as opposed to generic drugs.

Time for Financial Responsibility and Accountability

It is my opinion that the Pharmaceutical industry is not targeted by any section of this law. The underlying factor is that there is a need to provide access to quality access medical services to individuals who cannot afford them. The value-based purchasing and shared programs, along with other sections of the Law are geared at changing the sect of the curve. A time has come for greater responsibility and accountability of the critical departments of our health care system. According to McGuireWoods (2010), bringing the ceiling of the coverage gap lower, the Healthcare Reform Bill seeks to allow the beneficiaries with the greatest prescription drug expenses to take advantage of catastrophic coverage and its 5% coinsurance rate.

Conclusion

It can be discerned from the above discussion that the signing of the Patient Protection and Affordable Care Act, Public Law 111-148 (H.R. 3590) (PPACA) into law will demand that the Pharmaceutical industry align their practices within the guidelines of this legislation. In addition to the above, the purpose of this Law is purely to provide an increase in coinsurance for the Medicare beneficiaries that are aimed at the provision of universal health care.

References

McGuireWoods (2010). Healthcare reform bill tries to address Medicare part D coverage gap crisis. Web.

Traynor, K. (2010). Health reform law offers relief in Medicare Part D coverage gap. American Journal of Health-System Pharmacy, 67(13), 1049. Web.

King, P. (2010). Turning the Battleship: Can PPACA Change the Trajectory of Medicare Costs? Web.

Working in the healthcare industry as a pharmacy technician has different requirements for candidates for this position. In particular, an employee is to provide confirmed training in this profile, have the necessary documents allowing him or her to do this type of activity, and be registered in the state database. At the same time, the procedures for obtaining confirmations and their purpose differ from one another, even though each of the stages is essential for applying for this position. The rules for certification, licensure and registration of pharmacy technicians will be discussed in terms of the differences among these procedures with a focus on Texas laws.

Certification Requirements

The first stage that marks the path to work as a pharmacy technician is to undergo special training. According to Mattingly (2018), after completing all the necessary stages of education, an individual is obliged to pass the Pharmacy Technician Certification Exam (PTCE) offered by the Pharmacy Technician Certification Board (PTCB) (p. 1057). This exam is a screening test that determines whether a specialist meets the expected qualifications and can perform intermediate duties by the state-regulated norms. The successful completion of this exam means obtaining a certificate confirming the availability of professional training and the ability to work as a pharmacy technician. Today, this test is available online, which simplifies the procedure (How to register as a pharmacy technician in Texas, 2020). Thus, certification is the initial stage that gives the right to continue professional activities in the industry.

Employment conditions may differ from state to state, which, however, is not a prerequisite for differences in the grading of pharmacy technicians by their individual classifications. As Mattingly (2018) notes, in Texas, training is optional as an entry-

level requirement, but certification is required. Moreover, according to the Texas State Board of Pharmacy (2014), when submitting the documents for registration, a candidate should ensure that his or her certification is current (future expiration date) (para. 2). Therefore, the key difference between certification and other procedures is that this is the initial stage to confirm the professional qualifications of a candidate for the position of a pharmacy technician.

Registration Procedure

Before obtaining a license to work as a pharmacy technician, the registration procedure need to be completed. With a focus on Texas, one can highlight that this requirement is mandatory in all the state pharmacies. Therefore, one must have an active registration with the Texas State Board of Pharmacy to start professional activities (How to register as a pharmacy technician in Texas, 2020, para. 11). The difference between registration and certification is that the latter confirms an individuals qualifications and ability to work in the given industry, while the first procedure is essential as a tool of access to direct responsibilities. These steps cannot be reversed or substituted for each other, although Texas, as Mattingly (2018) remarks, is one of five states that do not require training confirmation to gain access to the pharmacy technician position. However, there are conventions for each of these procedures, which explains the uniqueness of the working access system.

The Texas rules of pharmacy technician registration allow obtaining the required documents online. According to the Texas State Board of Pharmacy (2014), certification is sufficient to apply for the registration in the state registry. Apart from paying tax and depositing funds for the fingerprint procedure, there are no additional costs, and an applicant receives registration documents in four-six weeks (How to register as a pharmacy technician in Texas, 2020). Thus, the whole procedure is easy and, at the same time, individual.

Licensure Features

The key difference between licensure and certificate and registration is the level of regulation. Mattingly (2018) argues that access to work as a pharmacy technician is regulated not only at the federal but also at the state level, and the main procedure governing this permit is licensure. At the same time, depending on the legislation, this condition is optional. The author notes that in Texas, the key document that determines an opportunity to start working as a pharmacy technician is the confirmation of registration, and no additional licenses are required. In case registration has expired, an employee has a chance to renew this permission by following the aforementioned scheme and indicating that the application is resubmitted (Texas State Board of Pharmacy, 2014). Thus, for Texas, certification and registration are the key procedures that validate an individuals eligibility to apply for professional practice as a pharmacy technician.

Conclusion

The procedures of the certification, licensure, and registration of pharmacy technicians have a general focus on regulating access to professional activities but reflect distinctive stages. Certification is the initial step that implies confirming an individuals qualifications, and registration and licensure differ in their degree of regulation  federal and state, respectively. For Texas, the procedure of licensure is irrelevant since certification and registration are required to start working as a pharmacy technician. In addition, Texas is one of the states where an applicant does not need to prove ones training, which speeds up the receipt of the relevant documents.

References

How to register as a pharmacy technician in Texas. (2020). Southern Careers Institute. 

Mattingly, A. N. (2018). Entry-level practice requirements of pharmacy technicians across the United States: A review. The Bulletin of the American Society of Hospital Pharmacists, 75(14), 1057-1063. 

Texas State Board of Pharmacy. (2014). Pharmacy technician registration. 

Hundreds of pharmacies operating in the country have clearly regulated conditions for the provision of services to the population and comply with specific standards dictated by the relevant legislation. With consumers free to access most drugs, control over pharmacy operations is an essential aspect of policies that are developed to maintain the national healthcare safety. As specific measures to address the issue, individual rules and laws are intended to coordinate the operation of pharmacies and promote a service delivery regime based on the existing regulations. This paper aims to compare two laws related to the operation of pharmacies  the Drug Supply Chain Security Act (DSCSA) and the Texas Pharmacy Act. These regulations are federal and state laws, respectively, and are intended to coordinate the activities of pharmacies, but some of their provisions differ, in particular, the scope.

Scope of the Laws

When comparing the scope that both laws under consideration cover, one can note that each of them aims to implement specific rules at different levels. According to the U.S. Food and Drug Administration (2019), the DSCSA is a federal law, and within its scope, pharmacies are included in the national context. This act was ratified in 2013, and its key purpose is to monitor the safety of drugs sold to the public, which explains the involvement of pharmacies as the main intermediaries (U.S. Food and Drug Administration, 2019). As one of the requirements for the operation of pharmacies, the DSCSA puts forward the rules according to which every outlet is to have an appropriate registration or license. Consequently, the law prohibits selling pharmaceuticals without an officially confirmed seller status. Similar conditions apply to the receipt and storage of drugs of different pharmacological groups. In addition, according to the U.S. Food and Drug Administration (2019), pharmacies must monitor the expiration date of drugs. In case of detecting counterfeit medications, investigations should be carried out by the official representatives to identify and fix the source of the problem.

The Texas Pharmacy Act has similar goals, but its key difference is the scope that applies only to Texas. The interest in the professional activities of pharmaceutical outlets is due to the need to ensure the safety of the population at the state level and monitor citizens welfare (Texas State Board of Pharmacy, 2014). At the same time, unlike the DSCSA, the Texas Act is more detailed as a regulatory project that defines the range of stakeholders responsibilities. In particular, this scope includes the duties of administrators and employees, the work of insurance authorities, and other aspects (Texas State Board of Pharmacy, 2014). Licensing principles are also mentioned, and the nuances of obtaining the official permission to sell pharmaceuticals are considered. In addition, according to the Texas State Board of Pharmacy (2014), the terms of professional responsibilities for the employees of different categories are provided, and specific penalties for violations are stated. While comparing the two laws in question, one, however, can find some similar features, in particular, the conditions of mediation imposed on pharmacies both at the federal and state levels.

Mediation Features

Both the DSCSA and the Texas Pharmacy Act provide for assessing the role of pharmacies as intermediaries in the sale of pharmaceuticals to the public. According to the U.S. Food and Drug Administration (2019), pharmacies are to follow the terms of safe trade, which is to control the quality of drugs and the conditions for their storage. The Texas Act also includes this clause, and individual administrative inspections are referred to as monitoring measures (Texas State Board of Pharmacy, 2014). One of the main features in both laws is the definition of licensing standards for pharmacies. Nevertheless, in these rules, there are some distinctive features to mention. For instance, in Texas, registration is a sufficient procedure for the legalization of pharmacy employees activities, while in many other states, licensure coordinated by the federal authorities is required (Texas State Board of Pharmacy, 2014). However, this aspect influences the work of pharmacies insignificantly and can be presented as a minor difference.

Given the similarity of the two laws in the context of the mediating role of pharmacies, one can assume that both acts perform similar functions. At the same time, the DSCSA is a broader regulatory act in which the oversight of pharmacy operations is one of the topics. The Texas Pharmacy Act, in turn, focuses only on this aspect of the healthcare system and citizens well-being. As a result, the federal code of laws proposes general provisions, and the state act is aimed at specific conditions for organizing the work of pharmacies and related nuances  stakeholder liability, employment, and other topics. Thus, the scope is the most evident criterion that distinguishes the laws in question.

Conclusion

As the reviewed pharmacy laws for comparison, the DSCSA and the Texas Pharmacy Act are presented, and despite the similarities in the topic they address, the scope is an essential criterion that distinguishes both acts. In terms of defining the mediating role of pharmacies, these regulations are similar as they emphasize responsibilities to the public and inspection boards. At the same time, the DSCSA is a broader law covering different areas, while the Texas Act addresses only the activities of pharmacies at the state level.

References

Texas State Board of Pharmacy. (2014). Texas Pharmacy Act. Web.

U.S. Food and Drug Administration. (2019). Pharmacists: Utilize DSCSA requirements to protect your patients. Web.

Arthritis is a medical condition that affects the joints, causing inflammation and, to some extent, tenderness. In the U.S., close to 54.4 million individuals have been diagnosed with at least one form of arthritis, of which approximately 23.7 million persons have low work productivity as a result of the condition (Center for Disease Control and Prevention [CDC], 2018). The major symptoms of the disease include such conditions as joint pain, stiffness, itching, and inflammation. Notably, the indications progress gradually or abruptly and worsen with age. Arthritis is more regular among aging adults, though it can be diagnosed in any other person irrespective of age, including children.

The main common type of arthritis is osteoarthritis, though other common forms include such diseases as gout, fibromyalgia, lupus, and rheumatoid arthritis. Osteoarthritis causes cartilage to break down, whereas RA is an autoimmune disorder where the immune system of an individual attacks its organs, in this case, the joints. It is marked by symmetric, erosive synovitis and, in most cases, extraarticular connection. Patients with RA experience a chronic variation of the disease, and regardless of therapy, it may lead to advanced joint obliteration, distortion, disability, and even premature cell apoptosis (Zhang et al., 2018). In gout, arthritis results from uric acid crystals accumulation in the blood (Macfarlane, Seibel and Zhou, 2020). In other forms of arthritis, underlying diseases condition such as psoriasis or lupus can cause the development of arthritis. Based on this analysis, individuals suffering from a rare form of arthritis might manifest significant and various symptoms, thus requiring the application of different treatment modalities.

Treatment of arthritis varies and depends on the various kinds of arthritis and their underlying disease conditions. However, the main objectives of arthritis treatments are to lower the symptoms of the disease condition and to promote quality of life and well-being (Gale et al., 2018). The prescribed drug for the patient in the case study is prednisone. Therefore, to comprehend the need for alternative drugs for the case of a patient with arthritis, the mechanism of action of prednisone is necessary.

Prednisone is a glucocorticoid drug whose main action is to lower inflammation, yet it suppresses the immune systems. The mechanism of action involves the prednisone stimulating the glucocorticoid receptors in the body cells, which results in the suppression of the harmful cytokines (Berardicurti et al., 2020). Prednisone reduces the swelling through the inhibition of the relocation of polymorphonuclear white blood corpuscle and retreating amplified blood vessel absorbency (Zheng, Guo and Wu, 2018). It also stifles the immune system by decreasing the action and capacity of the defense system.

In this case, the antineoplastic properties may relate to the hindrance of glucose conveyance. Furthermore, such obstruction includes phosphorylation and stimulation of cell apoptosis in undeveloped white blood cells (Rice et al., 2017). Furthermore, it may have antiemetic capacities by obstructing the brain excitation of the emetic center through suppression of prostaglandin (Chilkoti et al., 2019). Prednisone is a pro-drug to prednisolone, and with its immunomodulating properties, it can enter a cell upon surface receptor binding (Berardicurti et al., 2020). Once inside a cell and into the nucleus, prednisone attaches and stimulates certain nuclear receptors, which lead to transformed gene expression and suppression of pro-inflammatory cytokine excretion (Rice et al., 2017). Therefore, the drug lowers the number of lymphocytes circulating in the blood, thus promoting cell differentiation and inducing cell death in subtle tumor cells.

Through the inhibited cytokines, there is a reduction in inflammation, pain, and associated stiffness. Furthermore, prednisone acts as Cyclooxygenase-2 (COX-2) inhibitors, which are nonsteroidal anti-inflammatory drugs (NSAIDs) that mark and binds to the active sites of COX-2, an enzyme accountable for the pain and swelling in somatic cells (Verhoeven et al., 2019). Based on the illustrations above, with regards to underlying health conditions of an individual with arthritis and the mechanism of action of prednisone, other alternative treatments are necessary to reduce or lower the adverse effects of prednisone, a glucocorticoids molecule.

Some of the alternative therapeutic drugs for arthritis are fast-acting NSAIDs, which play a role in relieving pain and lowering swelling in arthritis. For example, Aspirin acts as an inhibitor of prostaglandins when used at high doses, thus reducing the sensation of pain and inflammation in arthritis, especially RA (Zhang et al., 2018). The disadvantages of using Aspirin include such side effects as tinnitus, loss of hearing, and gastrointestinal intolerance. Another newer drug in the market that acts the same way as Aspirin is celecoxib (Celebrex), a COX-2 inhibitor that has GI bowel effects (Krasselt and Baerwald, 2019). Celebrexs mechanism of action involves the suppression of the enzyme COX-2, which further hampers the metabolism of prostaglandins, prostacyclin, and thromboxane (Krasselt and Baerwald, 2019). Other regular side effects include vomiting, nausea, abdominal pain, ulceration, and bleeding of the stomach walls. The adverse effects can be managed by taking antacids, proton pump inhibitors (PPI), or misoprostol (Cytotec) to reduce gastrointestinal bleeding or ulcers.

Other substitute drugs for prednisone are Disease-modifying antirheumatic drugs (DMARDs). DMARDs are used to encourage remission by hindering the advancement of joint destruction or malformation as symptomatic conditions of arthritis (Kelly et al., 2018). Moreover, the drugs are used to lessen the progressive risk of lymphoma, a condition associated with RA (Kelly et al., 2018). A good example is Methotrexate (MTX), a drug agent that reversely competes with dihydrofolic acid (FH2) for the binding site on the enzyme Dihydrofolate reductase, thus preventing the binding of dihydrofolic acid (FH2) to the enzyme that converts FH2 to folinic acid (FH4) (Chabner and Longo, 2019). Short of FH4, the breakdown of purine and pyrimidine are hampered, and the formation of amino acids and polyamines is repressed.

The disadvantages of using MTX for the management of arthritis pose significant adverse side effects. For instance, the treatment of arthritis using MTX requires occasional testing of blood for serious complications such as liver issues and bone marrow weakening (Chabner and Longo, 2019). This can be reversed by administering a folic acid supplement, which reduces the side effects of MTX. MTX provides dosage flexibility because of its ability to be adjusted as required by the patient (Chabner and Longo, 2019). Apart from biologics which are efficient in impeding the progress of joint injury triggered by RA, leflunomide is the newest medicine in the market for oral administrations used to control arthritis conditions. Once the agent is transformed to malononitrilamide, it impedes the formation of ribonucleotide uridine monophosphate pyrimidine, thus relieving pain and retards the advanced development of RA (Chabner and Longo, 2019). However, its side effects include high blood pressure, gastrointestinal bowel movements, liver damage, and bone marrow damage.

The interaction of drugs for both pharmacodynamics and pharmacokinetics has anticipated undesirable impacts. The increased chances of drug-to-drug interactions taking place in the human body are amplified by the administration of various medicines for different therapeutic purposes. For instance, in the aging adult population, the persons prone to the usage of many drugs, the high rate of prescribed medicines results in increased drug interactions, thereby causing several hospitalizations. The interactions among drugs often result in adverse effects, hence lowering the therapeutic segments of each particular drug (Ryu, Kim and Lee, 2018). Possible interactions can ascend at any age in an individuals life, but the rate of polypharmacy in the aging populations life escalates the risk considerably.

Clinical symptoms of drug-to-drug interactions often vary greatly and depend on the interacting molecules forming the medicines. For example, the interactions may result in the insufficient lowering of hypertension, where such drops in pressure may lead to conditions such as hypovolemic shock (Onakpoya, Heneghan and Aronson, 2018). Concerning this case scenario, drug interactions in the context of ADME (absorption, distribution, metabolism, and excretion) are considered pharmacokinetic interactions.

Pharmacokinetic interaction of drugs influenced by the ADME can affect the efficiency of the molecules concentrations at their sites of action. Such impacts of the interactions can lead to the synthesis of complexes, direct or indirect antagonism for uptake carriers, or stimulation of processing enzymes and efflux carriers (Yilancioglu, 2019; Piazza et al., 2018; Kou, He and Sun, 2020). Interactions of drugs taking place at the absorption level often result in the synthesis of complexes. The formed complexes significantly lower the bioavailability of drugs, a condition related to incomplete absorption or first-pass elimination, or both. For instance, the bisphosphonates used in bone brittleness, such as alendronate, have a remarkably low bioavailability of 0.6% (Hosny and Rizg, 2018). Alendronate, sold under the brand name Fosamax, is used to treat osteoporosis, yet there are considerable chances that its protective properties are lowered when used with PPI at the same time (Hosny and Rizg, 2018). Moreover, calcium ions found in most antacids can lower bioavailability further. Therefore, the subsequent intake of foods containing calcium or other antacids comprising of such compounds as aluminum or magnesium should considerably be avoided.

A multidrug efflux carrier, which causes chemotherapy resistance in tumour developments, is expressed in tissue barriers such as the blood-brain barrier (BBB), lymphocytes, and other tissues such as the placenta. For example, P-glycoprotein (P-gp, ABCB1) may be expressed in the kidney or liver and is excreted principally via lipophilic attachments within the cell facilitated by the apical membranes of epithelial or endothelial cells (Hu et al., 2020). As such, the inhibition of the P-glycoprotein can be used to subdue the chemotherapy resistance in tumor treatments (Riganti et al., 2018). In this case, P-gp-mediated efflux transport can mediate the lowering of the receptiveness of the lymphocytes to the HIV protease inhibitors (Riganti et al., 2018). For instance, Ritonavir, with an adverse effect at high dosages, necessitates the impediment of the P-gp.

Moreover, Ritonavir may hamper the actions of drug-metabolizing cytochrome P450 3A4 (CYP3A4). According to Satoh et al. (2017), the combination of ciclosporin with tuberculostatic rifampicin results in drug interactions at the P-gp level (Satoh et al., 2017). The combination of the drugs can lead to subtherapeutic meditations, where the rifampicin attaches within the inside of the cell at the nuclear receptor level of the PXR, controller of the transcriptional regulator of P-gp expression.

Drug interactions can also lead to the inhibition of drug metabolism. In most cases, drugs that are metabolically interacting are mediated by the stiff completion for the binding sites of the cytochrome P450 enzyme (CYP). This enzyme is often expressed in the liver and stimulates the phase I oxidation of almost all drugs (Storelli et al., 2018). The interaction of the use of PPIs and cytochrome P450 2C19 (CYP2C19) can be used to explain the metabolically interacting drugs (Kuzin et al., 2018). For instance, drugs such as omeprazole or any other PPI are considered to repress the action of CYP2C19 (Kuzin et al., 2018). Omeprazole is both an enzyme substrate and an inhibitor of CYP2C19.

Conversely, PPIs such as Omeprazole can impede the metabolism of other drugs during drug-to-drug interactions. For instance, citalopram has its rate of breakdown lowered by the action of omeprazole, causing increased unwanted risk effects, which include elevated QT prolongation (Wu et al., 2019). In other cases, omeprazole with drugs such as diazepam causes hampered demethylation of the benzodiazepine in the molecule benzodiazepine diazepam, hence causing a reduction in its elimination, yet with a slight increase in half-life at a dose of 20mg omeprazole (Çelebi and Y1lmaz, 2017). In other cases, the interaction of omeprazole with human immunodeficiency virus (HIV) protease inhibitors such as atazanavir influences the bioavailability of the latter.

Though the interaction is not facilitated by cytochrome P450, the bioavailability is influenced by a rise in pH. For example, research on patients receiving 300mg of atazanavir or 100mg of ritonavir for half a month in combination with 40mg of omeprazole resulted in the therapeutic outcome reduction of atazanavir (Cmax) by 48% and ritonavir by 62%. (Pontelo et al., 2020). Based on the safety guidelines on the use of atazanavir, an increase of the molecule by a dose of 400mg does not have a therapeutic impact on the effects of omeprazole exposure. Therefore, based on this analysis, it is recommended not to use PPIs or the H2-receptor blockers in combination with atazanavir.

The analysis of the current study also looks into the possible interactions of drugs of the molecule anticoagulants. The significant interactions highlighted in anticoagulant-related drugs are those medicines with a narrow therapy. Vitamin K antagonist has a life-threatening hemorrhage effect, to an elevated prevalence of drug-to-drug interactions related to increased hospitalization (Pengo and Denas, 2018). With an interaction with the older molecules of macrolides such as erythromycin, which are molecules related to the inhibition of the cytochrome P450 3A4, the metabolism of phenprocoumon is adversely lowered (Chen et al., 2018). The use of fluconazole, a non-potent CYP3A4 inhibitor, has resulted in such complications as bleeding in patients using the drug in combination with warfarin anticoagulant therapy (Pengo and Denas, 2018). As such, warfarin indicates elevated bioavailability, which is associated with the presence of fluconazole, necessitating the inhibition of the CYP2C9. Therefore gaining knowledge on systematic pharmacokinetic interactions is important. The information is relevant, especially on the enzymatic-related metabolic pathway because they affect the breakdown or synthesis of drugs and complexes, respectively. The knowledge is also important in predicting whether the formed protein complexes are a substrate of a drug carrier or inhibitor or stimulant of such proteins.

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Introduction

Pharmaceuticals are an industry that is doing well financially due to the patents and exclusive rights they enjoy due to their developments. They are a part of the economy that has grown technologically. Thus, joining up with other sectors ensures that their investment gets back to them. For example, the use of insurances PBMS (Getzen and Allen, 245).

Prescription

A prescription for a drug is a plan of care or a document containing the exact drugs required by the patient. The drugs are usually taken to a pharmacy from where one gets to purchase the prescribed drug. A prescription indicates the amounts to be taken, how, and when the drug should be taken, and possibly the side effects of the drug. When the drugs are restricted to the prescription status, the funds are shared among the retailer 20-25%, the pharmaceutical company 70-80% and the wholesaler gets 2-3% (Getzen and Allen, 246).

Patents

Patent rights granted to pharmaceutical companies protect their brand name. Patents allow the pharmaceutical company that comes up with the drug to be the only company selling it exclusively for a given period. This greatly benefits the pharmaceutical industries that have them. The industries can earn from patents since, for the period they are patented, they have no competitors. The patients who cannot afford the drug get to be oppressed while the wholesalers and retailers earn less (Getzen and Allen, 249).

Fixed costs

Fixed costs are important to pharmaceuticals since they do not change and they are very minimal. They allow these industries to gain huge profit margins as they easily influence their selling prices to earn great profits. The production costs do not change thus the pharmaceuticals can invest a considerable amount as this is fixed and it is guaranteed that they earn from it. Pharmaceutical companies need to invest a lot into marketing due to the high competition in this industry. With production costs being fixed, they can channel the other funds into marketing and attract customers for their products (Getzen and Allen, 254).

Insurance costs

Insurance companies handle the prescription costs through the use of Pharmacy Benefit Managers (PBMs). They are subcontractors chosen by the insurance companies to administer claims, develop benefit plans, and manage relationships with the pharmaceutical companies. They have no direct influence on what health professionals prescribe to their patients. However, they can indirectly influence through creating lists of preferred drugs, as well as making co-payments and pocketbooks (Getzen and Allen, 257).

Pharmaceutical research & Factors of Drug prescription

Most pharmaceutical research is done so that new development can be developed. The most costly aspect of pharmaceutical research is that the success or failure of a single product will mean the success or failure of the corporation. Pharmaceutical companies compete through intensive awareness creation of the drug, and the generic drugs have paved the way for incentives. They invest in the marketing of the drug, and the size of expenditure on marketing indicates the power and influence of physicians. Price is not an important factor when it comes to drugs or what doctors see. What matters is the quality, effectiveness, and detailing of the drug or doctor (Getzen and Allen, 259).

Change in Length of patent

If a change was enacted in the length of patents held by pharmaceutical companies, it will be positive for the patents to be made valid for a longer duration. In this case, it will be unprofitable if the duration is shortened. A long period will mean they exploit the market hence increasing their profit margins (Getzen and Allen, 261).

Conclusion

Pharmaceutical companies have long-term benefits from their association with insurance companies. They also benefit from the patents that protect them from the unnecessary competition. They ought to carry out fruitful research and developments to meet their consumers objectives. In this case, consumers want to get good quality, and effective drugs to either prevent or cure diseases.

Works Cited

Getzen, Thomas E, and Bruce Allen. Health Care Economics. Hoboken, NJ: Wiley, 2007. Print.

Introduction

Noradrenaline is a hormone produced as a catecholamine by the sympathetic neurons from the heart; it is mainly used as a neurotransmitter. An increase in the levels of this hormone leads to contractions. The adrenal medulla is responsible in the production of this catecholamine that is further released by the synapses.

Noradrenaline lacks the methyl group present in adrenaline (Bailey, Schwieger & Hug 1993). It functions mainly in stress conditions whereby it suppresses the adrenoreceptors within the walls of blood vessels causing the muscles to contract. When the blood vessels narrow, the blood gets redirected to essential organs like the brain and heart. In this practical, the effects of noradrenaline towards vascular rings with and without endothelium will be studied and enable us to find out the difference (Aldasoro, Martínez, Vila, Flor & Lluch1993, p.106).

Principle

Isolated arterial rings were obtained based on the presence and absence of endothelial cells show different vascular dilation and constriction. When the arterial rings are incubated into the bath chambers containing different drugs, enzyme reactions occur to lead to an endothelium dependent reaction to noradrenaline. Acetylcholine is a vasoconstrictor (Aldasoro, Martínez, Vila, Flor & Lluch1993, p.105). Acetylcholine and prazosin accelerates the release of a certain factors that causes vasodilation such as nitric oxide. Prazosin relaxes both artery and vein. Noradrenaline reduces the output of acetylcholine. Higher concentration of acetylcholine produces a relaxation effect on the arteries (Edvinsson, Emson, McCulloch, Tatemoto & Uddman 1984).

Aims

1. To obtain a cumulative concentration response curve to noradrenaline on arterial rings with intact endothelium.
2. To obtain a cumulative concentration response curve to noradrenaline to arterial ring with endothelium removed.
3. To obtain a cumulative concentration response curve to noradrenaline to arterial ring with prior endotoxin treatment to remove endothelium.
4. To examine the effects of acetylcholine (1×10^-6 mol.l^-1) on the tissue
5. To examine the effects of acetylcholine (at 2 concentrations, e.g. 1×10^-9 and 1×10^-6 mol.l^-1) in the 3 arterial rings.
6. To test the effect of acetylcholine when the tissues response to noradrenaline is at its maximum.

Materials

1. A Computer programme that is developed to simulate the effects of drugs on isolated tissue preparations such as vascular rings. This program will investigate the effects of drugs and look at the pharmacological properties of vasodilator and vasoconstrictor agents.
2. An arterial ring with either an intact endothelium or denuded of endothelium
3. An endothelium denuded arterial ring removed from an animal treated four hours previously with E. coli endotoxin had been simulated.
4. Noradrenaline (Concentrations of 1 x 10^-9 to 1 x 10^-6 mol.l^-1)
5. Acetylcholine (Concentrations of 1 x 10^-9 to 1 x 10^-6 mol.l^-1)
6. Prazosin (Concentration of 1 x 10^-6 and 1 x 10^-8 mol.l^-1 )

Method

The simulation used in this practical was provided by a computer program known as vascular rings resource package. The programme has every option for the procedure to attain results on the effects of noradrenaline on vascular rings.

Noradrenaline was added to the vascular rings that were divided into three (arterial rings with intact endothelium, arterial ring with endothelium removed and arterial ring with prior endotoxin treatment to remove endothelium).A cumulative curve was then obtained on the different arterial rings.More noradrenaline was added progressively doubling the concentration of drug each time, i.e. add 5×10^-9 mol.l^-1, then 8×10^-9 mol.l^-1, 2×10^-8mol.l^-1, 5×10^-8 mol.l^-1, 1×10^-7 mol.l^-1, 5×10^-7mol.l^-1, 1×10^-6 mol.l^-1.This was done until adding more noradrenaline caused no further change or increase in the size of the response.

When trying to obtain the cumulative concentration response curve the wash out bath command was not selected. Effects of acetylcholine (1×10^-6 mol.l^-1) were observed on each preparation. The effect of acetylcholine was tested when the tissues response to noradrenaline was at its maximum (i.e. after pre-contraction of the arterial ring with noradrenaline). The effects of acetylcholine at two concentrations (1×10^-9 and 1×10^-6 mol.l^-1) was investigated on the three arterial rings and the responses recorded. The data obtained was then tabulated on an assessment sheet and a semi log graph plotted to produce a log concentration /response curve.

Results

Using a concentration of 1×10^-9 mol.l^-1 (0.001 µmol.l^-1) it was found out that a very small response is produced in some preparations (e.g. using a concentration of 1×10^-9 mol.l^-1 (0.001 µmol.l^-1) may only produce a small response). In any event this response was similar in size and shape to the kind of response you would produce if you had a real piece of arterial ring set up in an organ bath.

Statistics

The data obtained from the experiment was calculated as mean + standard error of the mean (S.E.M.).P < 0-050 was taken as the level of significance and the Students t test was then used to compare results.

The half-maximal effective concentration (EC50) was calculated by linear interpolation between two points on either side of the 500% of the maximal on each concentration-response curve and by reading the corresponding concentration on the logarithmic scale (Edvinsson, Emson, McCulloch, Tatemoto & Uddman 1984, p.160). Calculation of the mean of the readings was the obtained (Pepine 1998, 795).

The contractile response produced to each artery according to their vasoconstriction in the presence of noradrenaline was compared with the antagonist k2, where k2 is the mean of contractions before and after the contraction in the presence of the drug. The values obtained were of standard deviation (González & Estrada 1991, 370).

It was noted that there was no significant difference between arterial ring with endothelium removed and arterial ring with prior endotoxin treatment to remove endothelium (Chen, Suzuki & Weston 1988, 1172).

Definition of the EC₅₀

The half maximal effective concentration (EC₅₀) denotes the amount of a substance be it a drug, or a toxicant which brings about an effect that is refers to the concentration of a drug, antibody or toxicant which induces a response intermediate between the utmost and baseline observable effect after a particular period of exposure. It is commonly used as a measure of drugs potency. The EC₅₀ usually produces a curve as an expression of the response. This response signifies the amount of a substance at which 50% of the utmost response is obtained (Bredt, Hwang &Snyder 1990, p. 770).

Questions

EC₅₀ for noradrenaline in the presence

• EC₅₀ for noradrenaline in the presence of Prazosin 1 x 10^-6
• 3 x 10^-8
• EC₅₀ for noradrenaline in the presence of Prazosin 1 x 10^-8
• 1 x 10^-7
• EC₅₀ for noradrenaline in the presence of Prazosin 1 x 10^-8
• 1 x 10^-8

Emax for noradrenaline in the presence and Absence of Antagonist

• Emax for noradrenaline in the presence of Prazosin 1 x 10^-6
• 1x 10^-6
• Emax for noradrenaline in the presence of Prazosin 1 x 10^-8
• 1 x 10^-6
• Emax for noradrenaline in the presence of Prazosin 1 x 10^-8
• 1 x 10^-6

Arterial ring with endothelium: Presence of the endothelium on the artery regulated the contracting effect of acetylcholine and noradrenaline. The artery contracted to a lower dimension.

Arterial ring with endothelium removed: Absence of the endothelium allowed the artery to contract easily. An increase in the levels of noradrenaline also caused an increase in the rate of contraction of the artery.

Arterial ring with prior endotoxin treatment to remove endothelium: The endotoxin increased the constrictor effect of noradrenaline. Thus the diameter of the artery was smaller.

Briefly explain the differences in response to noradrenaline in the 3 preparations: The arterial ring with an endothelium showed minimum contraction due to the presence of the muscles on the artery. When the endothelium was removed the artery was smooth enough for to relax. Addition of E.coli strain on the artery led to an attenuation of the endothelium, thus the constriction observed was minimal (González, Fernandez, Martín, Moncada & Estrada 1992, p.155).

Discussion

The arteries without the endothelium were more responsive to noradrenaline than those with the endothelium. There was a relaxation contraction response on the arteries that were already contracted with noradrenaline. The removal of the endothelium decreased the contractile response of the arteries towards noradrenaline (Caplan & Schwartz 1973, p. 719). However, contractile properties of noradrenaline were attenuated when the antagonist was added. The results presented above show that, low levels of acetylcholine induce contraction of the arterial rings. The response of the muscles on the aorta was recorded. It was noted that acetylcholine had two effects depending on the concentrations. It tends to show persistent endothelium-dependent relaxation when at low concentrations and at a higher concentration, the contraction was not dependant on the endothelium (Bredt, Hwang &Snyder 1990, p. 770).

From the results obtained, it is noted that prazosin produces a relaxation effect on the arteries depending on the content of the endothelium.

Vasodilations of the arteries are caused by the paracrine effect of the endothelial acetylcholine (Faraci 1991, p.40).

Conclusion

Acetylcholine is a vasoconstrictor. Acetylcholine and prazosin accelerates the release of a certain factor that causes vasodilation. Presence of the endothelium is plays a very important role in regulating the extent of contraction on the arteries.

Noradrenaline induced contraction, as acetylcholine had a relaxation effect on the arterial ring. The endothelium contributes independently to the mechanism of relaxation of the artery.

List of References

Aldasoro, M, Martínez, C, Vila, JM, Flor, B & Lluch, S1993, Endothelium-dependent component in the contractile responses of human omental arteries to adrenergic stimulation, European Journal of Pharmacology, vol. 250,pp.103-107.

Bailey, JM, Schwieger, IM, Hug, CC 1993, Evaluation of sufentanil anesthesia obtained by a computer-controlled infusion for cardiac surgery, Anesth Analg Journal, vol. 76,pp. 247-252.

Bredt, DS, Hwang, PM &Snyder SH 1990, Localization of nitric oxide synthase indicating a neural role for nitric oxide, Nature, vol. 347, pp.768770.

Caplan, BA & Schwartz, CJ 1973, Increased endothelial cell turnover in areas of in vivo Evans blue uptake in the pig aorta, Atherosclerosis, vol.6, pp.713-719.

Chen, G, Suzuki, H & Weston, AH 1988, Acetylcholine releases endothelium- derived hyperpolarizing factor and EDRF from rat blood vessels, Br Journal of Pharmacology, vol. 95, pp.1165-1174.

Edvinsson, L, Emson, P, McCulloch, J, Tatemoto, K & Uddman, R 1984, Neuropeptide Y: Immunocytochemical localization and effect upon feline pial arteries and veins in vitro and in situ, Acta Physiol Scand, vol. 122,pp.155-163.

Faraci, FM 1991, Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation, American Journal of Physiology, vol.261, no.1, pp.38-42.

González, C &Estrada, C 1991, Nitric oxide mediates neurogenic vasodilation of bovine cerebral arteries, Journal of Cereb Blood Flow Metab, vol.11, pp.366-370.

González, C, Fernández, A, Martín, C, Moncada, S &Estrada, C 1992, Nitric oxide from endothelium and smooth muscle modulates responses to sympathetic nerve stimulation: implications for endotoxin shock, Biochem Biophys Res Commun, vol.186,pp.150-156.

Pepine, CJ 1998, Clinical implications of endothelial dysfunction, Clinical Cardiology, vol. 21, pp.795-799.

It is a widely accepted truth that pharmaceuticals prescription in the U.S. is the most expensive aspect of the entire healthcare system. Americans tend to spend more than 1,200$ on medical drugs a year, which is multiple times more than in any other developed country (Sunrise House, 2019). Raising prices primarily affects uninsured, underinsured people, or those who own high-deductible plans. As a result, many Americans cannot afford remedies or skip doses of a prescribed drug.

In the past, the high prices of medications were attributed to innovation and improved the quality of drugs. Nonetheless, the companies are still increasing the cost of existing and available medicines even though new technologies move forward. The United States enables each drug manufacturer to set their prices and come into the market (Sunrise House, 2019). Consequently, not having strict price-setting policies, medication costs fluctuate unpredictably. Despite constant complaints and concerns about the drug prescription issue, the American government did not establish a system that would guarantee cost reduction.

Nonetheless, the state and federal governments found specific approaches for managing this problem. Such methods as increased manufacturer discounts, pre-authorization, bulk state purchases, and large retailers competition on the market were used to reduce prices. The U.S. is trying to make costs transparent for customers. Furthermore, in May 2018, Trump summoned the Administration to discuss the drug prescription problems acuteness and suggest strategies for its resolution (NCSL, 2019). As a result, he said that better negotiation, lowered list prices, increased competition, and reduced out-of-pocket spending would be efficient for solving this issue. These actions are supposed to increase the transformation of the entire healthcare system and promote a value-based approach.

Money becomes an issue when a person receives a prescription of the drugs that would cost them thousands of dollars. Consequently, the majority of the population cannot receive proper medications due to their increased prices. The government, however, attributes this problem to the manufacturers and companies that cannot negotiate costs (Sunrise House, 2019). Despite the fact the United States has been debating this issue for decades, no concrete policies were implemented to eradicate this problem.

As a result, generic drugs were introduced to substitute high-cost pharmaceuticals. Even though they are cheaper, they still undergo safety and effectiveness checkups to meet the standards as well as brand-name drugs do. Nevertheless, generic medicine cannot fully replace the original ones. Therefore, many countries have to obtain patient consent to switch to generics. For instance, in 2006, Medicaid spent $19.8 million to switch onto Simvastatin, a marketed generic form of a pharmaceutical named Zocor (Sunrise House, 2019). However, they did not receive patient consent and had to pay more.

Now both state and drug manufacturers aim to reduce medication costs and make them affordable for every American citizen. They create pricing programs such as GoodRx or 340B that help pharmacies or hospitals purchase drugs at a lowered price with a 30% discount (Emanuel, (2018). What is more, pharmaceutical companies offer coupons to decrease patients expenses. However, these measures are not as efficient as they seem to be. The quality of some drugs remains arguable; thus, the value-based approach should be utilized to evaluate if the effect corresponds with the cost. Americans must know if the medicine treats their disorders or temporarily alleviates pain to prolong their lives. Citizens deserve to live healthily without the enormous expenses of pharmaceuticals that are inutile.

References

Emanuel, E. (2018). The real cost of the US health care system. JAMA, 319(10), 983985. Web.

Sunrise House. (2019). Why are prescription drugs so expensive in the United states? Web.

NCSL. (2019). NCSL prescription drug policy resource center. Web.