Summary PHARMACOLO NURS 251 Pharmacology Module 9

Module 9 9.1: Introduction to Specialty Medications In general, specialty medicatons are high cost medicatons used for treatng complex disease states. They can be challenging to both manufacture and administer, and they ofen require signifcant patent educaton and close monitoring to ensure their safe and appropriate use. Although specialty medicatons were once a very small piece of the pharmaceutcal industry, there has been a signifcant change over the last 20 years and especially within the last decade. Specialty medicatons are now the fastest growing segment of the pharmaceutcal industry. Common characteristcs associated with specialty medicatons are listed in Table 9.1. Table 9.1 Specialty Medicaton Characteristcs High Cost Potental for limited or exclusive availability for distributon Complex treatment regimen that require ongoing monitoring and patent educaton Treat rare diseases Special handling, storage, or delivery requirements Treat diseases known to have long term or severe side effects or increased fatality Biologically derived and available in injecton, infusion, or oral form Payers may defne what they consider to be a specialty medicaton for reimbursement and contractng purposes. With the increase in specialty medicatons over the last two decades, a whole new approach to dispensing these medicatons emerged called specialty pharmacies. Generally, specialty medicatons are not available at typical community pharmacies, so patents must obtain them through specialty pharmacies. There are many reasons for this: some practcal, some fnancial, and some clinical. Traditonal retail pharmacy is not designed to handle these complex, costly medicatons. First, the high cost alone, in many cases, would prohibit retail pharmacies from stocking the medicaton. Second, the ofen-busy nature of a retail pharmacy does not align itself well with being able to appropriately manage and support the needs of patents with complex disease states. For these reasons, the frst specialty pharmacies began in the early 2000s. Specialty pharmacies are typically required, through their contract with health insurance companies, to meet unique requirements that are not part of their contracts with retail pharmacies. Examples of these requirements are listng in Table 9.2. Table 9.2 Examples of Specialty Pharmacy Services Coordinatng care and facilitatng the drug access Case management- disease state management Facilitatng mail order delivery logistcs Product device training when applicable Working with health insurance to determine coverage and help coordinate any requirements of the insurance company Data management of technical and clinical patent care services. Investgatng patent assistance programs for patents without insurance or lack of coverage Call center development Patent Experience A patent receiving a prescripton for a specialty medicaton should be aware that the process for getng the medicaton is going to look different than the normal retail pharmacy experience. However, the system is designed so that the patent has the best chance of successfully obtaining and using the medicaton safely and appropriately. The prescripton would frst be sent to the specialty pharmacy. The specialty pharmacy then takes responsibility for making sure the patent gets the medicaton, understands the risks and benefts, is able to afford it, able to take it appropriately, and will follow through with any necessary monitoring. The patent may be connected with a case manager that will call them on a monthly basis to make sure there are no issues with the medicatons, check to see if they had any required monitoringcompleted, provide any necessary educaton, and/or answer patent questons. Patent follow-up ofen happens every month prior to sending out the next months’ worth of medicatons in order to minimize waste, ensure safety, and assess for efcacy. As specialty pharmacies are generally not local to the patent they are caring for, care and coordinaton are ofen provided telephonically. The process is centralized, and the medicatons are shipped to the patent’s house or, in some cases, to the facility that will be administering the medicatons. Brief Overview of Common Disease States Treated with Specialty Medications Common disease states managed by specialty pharmacies include (1) oncology, (2) multple sclerosis, (3) rheumatoid arthrits, (4) Crohn’s disease, (5) hepatts C, and (6) HIV/AIDs. This module with introduce some of the most commonly used specialty medicatons that most health care professionals would come into contact with, regardless of their specialty. Many of these conditons represent an entre specialty in medicine and are very complex. Therefore, for the purposes of this module, these conditons will be introduced briefly. Oncology is the study and treatment of cancer. Cancer is a disease process that involves the development and proliferaton of abnormal calls. Cancer cells are marked by both a structural change and a loss of functon from the original healthy cell. They are ofen characterized by multplying at a faster than normal rate. As this collecton of abnormal cells, called a tumor, grows it can become life threatening as it deprives normal body cells of the nutrients they need to functon. Multple Sclerosis (MS) is an ofen unpredictable, disabling disease of the central nervous system. It disrupts the flow of informaton both within the brain as well as between the brain and the body. Damage to the myelin coatng around the nerve fbers in the CNS causes the nerve signals to be disrupted. This damage ultmately leads to the symptoms of MS that can vary between individuals with the disease. Some of the more common symptoms include fatgue, difculty walking, numbness or tngling, stffness in the limbs, weakness, vision problems, cognitve changes, pain, depression, and emotonal changes. Rheumatoid Arthrits (RA) is a chronic autoimmune disorder that causes inflammaton and tssue damage in the joints. It is a very painful and (ofen) disabling disease. The common symptoms of RA include pain, stffness, and reduced range of moton. Generally, the treatment would not start with a specialty medicaton. The inital medicatons fall under the class disease modifying antrheumatc drug (DMARD). However, these are not always effectve or in some instances, patents may no longer respond as they once did. In either case, a patent would be then switched to one of the specialty medicatons reviewed below. Crohn’s Disease is an inflammatory bowel disease caused by inflammaton in the digestve tract which can lead to symptoms such as abdominal pain, severe diarrhea, fatgue, weight loss, and malnutriton. The inflammaton can spread deep into the layers of the affected bowel tssues making the symptoms extremely painful and ofen hard to control. Hepatts C is a viral infecton that causes liver inflammaton which can sometmes lead to serious liver damage. The virus is spread through infected blood. There are ofen no symptoms associated with chronic hepatts C untl the virus damages the liver signifcantly enough. Symptoms of hepatts C then include bleeding and bruising easily, fatgue, poor appette, dark urine, swelling, weight loss, and confusion. Interestngly, acute hepatts C ofen goes undiagnosed because of the lack of or self-limitng nature of the symptoms. Additonally, some people that contract hepatts C never go on to develop chronic hepatts C because their body is able to clear the virus on its own. However, those that do progress to chronic hepatts C, will likely develop liver failure and need a liver transplant should they live long enough if the disease is lef untreated. Recent treatments have made the possibility of a cure very likely with only three months of treatment. HIV/AIDS is a notorious virus with incredible advancements in treatment over the last 30 years. HIV stands for human immunodefciency virus and is the causatve agent of acquired immunodefciency syndrome (AIDS). The virus is spread through sexual contact, perinatally from an infected mother, or by injecton into the blood. The typical course of the infecton is characterized by an acute clinical illness that varies in presentaton followed by a longer clinical latency.People may go years without any symptoms. However, during this asymptomatc tme, the virus is working in the body to destroy the immune system, specifcally the CD4 Cells (T-cells). With the destructon of immune cells, the person is eventually no longer able to fght off pathogens (disease causing agents), a state referred to as being immunocompromised. When a pathogen is able to take advantage of the lowered immunity, it is called an opportunistc infecton. At this point, the patent is generally considered to have AIDS. HIV/AIDS cannot be cured, but it can be controlled with antretroviral therapy (ART). 9.2: Introduction to Immunomodulating Drugs Over the last twenty years, medical technology has developed a new group of drugs that affect the immune system. Many of these drugs are synthesized through recombinant DNA technology, which is the process of joining DNA molecules from two different sources and insertng them into a host organism which then generates specifc products for human use. These drugs are ofen referred to as biologics and are almost always considered specialty medicatons. They are in a large part responsible for the growth of the specialty pharmacy industry. Such drugs work by altering the body’s response to diseases such as cancer, autoimmune, inflammatory and infectous diseases. Biologics can work either by enhancing or restrictng the patent’s natural immune response. To beter understand how such medicatons work within the body, we will briefly cover the physiology of the immune system. Immune Response Overview One of the main functons of the immune system is to identfy substances as being either foreign or of self. When bacteria or viruses enter the body, the immune system should recognize both as foreign and initate an immune response to eliminate it from the body. More specifcally, there is humoral immunity and cell-mediated immunity. Humoral immunity is defned as the immune response mediated by B-cells and the producton of antbodies targeted against specifc antgens. B-cells are leukocytes that develop into plasma cells and then produce antbodies that bind to and inactvate antgens. Antbodies are molecules that have the ability to bind to and inactvate antgen molecules through the formaton of an antgen-antbody complex. Cell-mediated immunity which works in collaboraton with humoral immunity, is the immune response mediated by Tcells. T-cells (T lymphocytes) are not involved in the producton of antbodies but instead act through either direct cellto-cell contact or through the producton of cytokines. Cytokines are a generic term for non-antbody proteins released by specifc cell populatons (actvated T-cells) upon contact with antgens. They act as intercellular mediators of an immune response. Of note, there are various subtypes of T-cells: (1) helper, (2) suppressor and (3) cytotoxic. T helper cells are cells that promote the direct actons of numerous other cells associated with the immune system. T suppressor cells regulate and limit the immune response, balancing the effect of T helper cells. Cytotoxic T cells (natural killer cells) are differentated T-cells that can recognize foreign antgens being presented on the surface of another cell. Once recognized, the cytotoxic T-cell then atacks and destroys the partcular target cell. The main types of biologics covered in this module are classifed as immunomodulatng drugs. Immunomodulatng drugs are defned as a subclass of biologics that specifcally or nonspecifcally enhance or reduce the immune response. The subclasses of immunomodulatng drugs include (1) interferons, (2) monoclonal antbodies, (3) interleukin receptor antagonists and agonists and (4) other miscellaneous drugs. Since these drugs alter a patent’s immune response, they are ofen used in cancer treatments because they are able to specifcally target the cancer cells while leaving healthy cells alone. They are also commonly used to treat autoimmune and inflammatory conditons by interfering with a patent’s overactve immune response in diseases like rheumatoid arthrits.Select Immunomodulating Drugs Interferons are proteins that have anttumor, antviral, and immunomodulatng propertes. They are most commonly used in the treatment of certain cancers and viral infectons. Interferons have three different effects on the immune system. (1) They can restore functon if it is not working properly, (2) they can augment its functon, or (3) they can inhibit its functon. Inhibitng its functon becomes important in autoimmune diseases because the immune system is not working properly. Note: Due to the fact that most of these drugs are only available in a brand name opton, clinicians generally refer to them by their brand name. It is recommended that the student be familiar with both the brand and generic name of the drugs covered in this module. Example Interferon Interferon beta-1a (Avonex or Rebif) is indicated to treat relapsing multple sclerosis. It interacts with the specifc cell receptors found on the surface of human cells. They have been shown to slow the progression of physical disability and decrease the frequency of clinical exacerbatons. Avonex is a once weekly intramuscular injecton while Rebif is a three tmes per week subcutaneous injecton. The most common adverse effects with interferons are flu-like symptoms such as fever, chills, malaise, myalgia, and fatgue. Monoclonal Antbodies are becoming the drugs of choice for many diseases such as cancer, rheumatoid arthrits, Crohn’s disease, multple sclerosis, and organ transplant. In the treatment of cancer, they have an advantage over traditonal chemotherapy medicatons in that they can specifcally target cancer cells and leave healthy cells alone. These drugs are made using recombinant DNA technology making them extremely costly. Despite being more targeted than traditonal cancer therapies, severe allergic inflammatory type infusion reactons can occur. Patents ofen need to be pre-medicated to reduce the incidence. Example Monoclonal Antbodies Adalimumab (Humira) acts on tumor necrosis factor (TNF), which is a naturally occurring cytokine involved in the normal inflammatory and immune response. Adalimumab works by preventng TNF molecules from binding to the TNF cell surface. It also works by impactng the typical inflammatory responses regulated by TNF. Although originally indicated for rheumatoid arthrits, it can also be used in Crohn’s disease, ulceratve colits, plaque psoriasis, and psoriatc arthrits. The most common adverse reactons are infectons, injecton site reactons, headache, and rash. Infliximab (Remicade) works very similarly to adalimumab, although it does carry a unique contraindicaton. Due to being shown to worsen heart failure, it should not be used in patents with class III or IV on the New York Heart Associaton Scale. Bevacizumab (Avastn) works by binding to and inhibitng vascular endothelial growth factor, which is a protein that promotes the development of new blood vessels in both tumor and normal body tssues. It is indicated to treat metastatc colon cancer, rectal cancer, non-small-cell lung cancer, and malignant glioblastoma (type of brain cancer). Adverse effects include blood clots, GI issues, headache, dizziness, and weight loss. Natalizumab (Tysabri) is a humanized monoclonal antbody derived from murine myeloma cells. It works by binding to the alpha4 subunit of integrins, which are proteins found on the surface of leukocytes. These proteins have been associated with the disease process of multple sclerosis, although the exact mechanism is not completely understood. It is known that natalizumab inhibits the leukocyte adhesion that the alpha4 protein subunits are involved. It is indicated to be used to treat multple sclerosis (MS). There is a risk of a rare viral infecton in the brain for patents on this medicaton. Therefore, in 2006 the FDA limited its distributon and patents must enroll in a specifc program prior to being able to receive the drug. Less severe adverse effects include depression, fatgue, headache, GI issues, and lower respiratory tract infectons. Interleukins are a natural part of the immune system. They are actually classifed as lymphokines because they are cytokines produced at least in part by lymphocytes. They are soluble proteins released from actvated lymphocytes suchas natural killer cells. There are several different interleukins that have been identfed, and each has different specifc actons within the body. For example, interleukin-2 (IL-2) specifcally is known to have ant-tumor actons. Example Interleukins Aldesleukin (IL-2) (Proleukin) is an interleukin-2 derivatve and works indirectly to restore the immune response by binding to receptor sites on T-cells, stmulatng them to multply. One type of cell that results is called the lymphokineactvated killer (LAK) cell. LAK cells can recognize and destroy cancer cells while leaving other healthy cells alone. For this reason, Aldesleukin is specifcally indicated for metastatc renal cell carcinoma (kidney cancer that has spread) and melanoma (skin cancer). Adverse events include severe toxicites, specifcally capillary leak syndrome—the body’s capillaries are no longer able to retain the substances that make up blood causing them to “leak” into the surrounding tssue. This results in severe fluid retenton that can be life-threatening if not treated. The syndrome is reversible with the discontnuaton of the drug. Other more typical adverse events include fever, chills, rash, fatgue, liver toxicity, muscle pain, and headache. Anakinra (Kineret) is a recombinant form of human interleukin -1 (IL-1) receptor antagonist. It acts by inhibitng the binding of IL-1 to its many receptor sites throughout the body. Because this drug serves to block an immune process, it is effectve in treatng rheumatoid arthrits, which is a conditon where the immune system is not functoning properly. Adverse events most commonly include injecton site reactons, respiratory tract infectons, and headache. Miscellaneous There are several immunomodulatng drugs that work by various mechanisms but do not fall into one of the previous categories. Two of the more commonly used miscellaneous immunomodulators are covered below. Example Drugs Abatacept (Orencia) is a selectve co-stmulaton modulator indicated for the treatment of rheumatoid arthrits. It works by inhibitng T-cell actvaton. Common adverse effects include headaches, upper respiratory tract infectons, and hypertension. It should not be combined with TNF blocking drugs like adalimumab and infliximab or with anakinra due to the increased risk of serious infecton. Etanercept (Enbrel) is a recombinant DNA-derived TNF-blocking drug. It works by binding to TNF and blocking its ability to bind to its target receptors on the cell surface. It is indicated to treat rheumatoid arthrits and plaque psoriasis. Common adverse effects include headache, injecton site reactons, upper respiratory tract infectons, dizziness, and weakness. In general, these drugs are administered by injecton although the exact route varies. See the summary chart (Table 9.3) of the immunomodulatng drugs covered in this module for specifcs on the route of administraton.9.3: Antivirals & Antiretroviral Therapy Antivirals for the Treatment of Hepatitis C There have been major advancements in the treatment of hepatts C in the last 5 years. Prior to these new medicatons, the treatment for hepatts C included interferon and a drug called ribavirin. Ribavirin did not target the virus itself but rather helped to enhance the immune system with the hope that the body would then be able to fght off the virus. The cure rates were low while the side effects were high; so many people did not even atempt treatment. Over tme, the likely outcome for these patents (if they lived long enough) was the need for a liver transplant. With the development of a new class of antviral medicaton that targets the hepatts C virus specifcally, the likelihood of a cure is now close to 96%. One of the best aspects of the new treatments is the short duraton. In fact, patents may only need to be treated for 8-12 weeks. This represents a signifcant improvement from traditonal treatment that lasted anywhere from 24-48 weeks and had a 50% success rate at best. The new treatments available are considered “direct actng” antviral medicatons. In simple terms, they interfere with the proteins that help the virus grow and spread. Two of the more common optons are introduced below. Ledipasvir/sofosbuvir (Harvoni) was the pill that launched this radical change in the treatment of Hepatts C. In general, the side effects are mild, and the cure rate is high. The price tag is also high at about $95,000 for a 12-week treatment course. Ombitasvir/paritaprevir/ritonavir with dasabuvir (Viekira Pak) has two separate pills. In general, the side effects are mild with the excepton of some cases of serious liver injury, mostly seen in patents with underlying advanced liver disease. Of note, ritonavir is a protease inhibitor (see secton below on HIV) with no actvity against hepatts C. It is a potent inhibitor of CYP 3A4 enzymes within the liver and is used to increase the concentratons of paritaprevir. The cost is also high at about $84,000 for a 12-week treatment course.Antiretroviral Therapy (ART) A full review of ART is beyond the scope of this course. This module will simply introduce the main classes of antretrovirals and provide a basic understanding of the pharmacologic treatment of HIV. There have been many great advancements in the treatment of HIV since it was frst identfed in the early 1980s. Due to the high cost of most HIV medicatons and the importance of compliance, HIV medicatons are almost always considered specialty medicatons. HIV is unique from other viruses because it mutates rapidly which leads to drug resistance. When this happens, the drugs are no longer effectve against the virus. In order to beter understand the different classes of antretrovirals, HIV as a virus needs to be reviewed in a bit more detail. HIV HIV is a retrovirus. As such, HIV contains the enzyme reverse transcriptase which coverts its RNA genome into DNA. The viral DNA can then be integrated into the host cell’s DNA where it will be replicated alongside the host DNA. Thus, the virus ‘tricks’ the host into replicatng its viral genome which then leads to the producton of the viral proteins required to assemble new viruses. HIV specifcally targets macrophages and helper T-cells, effectvely compromising the immune system of the host. Once HIV has control of the cell, it ofen begins producing more HIV that can go out and infect more host cells. Over tme, the patent becomes more and more immunosuppressed, meaning that the body’s ability to fght infecton has been compromised. Once the patent begins developing multple opportunistc infectons because of the depleton in lymphocytes (T-cells), they are said to have AIDS. Importantly, once a patent is infected with HIV, they have it for life. There is no cure. The medicatons are simply used to help control the virus and prevent it from propagatng further to hopefully delay the onset of AIDS. HIV treatment should always include more than one mechanism of acton. Monotherapy cannot counter the development of drug resistance, and a missed dose can quickly lead to a poor outcome. The current treatment strategy is referred to as HAART (highly actve antretroviral therapy). HAART consists of three antretrovirals taken in combinaton. This increases the effectveness of the regimen by presentng the virus with multple obstacles to try and overcome. Note: The effects of the HIV virus and the counter effects of the antretrovirals can get very technical very quickly and again is really beyond the scope of this course. Basic concepts of virus propagaton will be introduced in order to have a working understanding of these drugs. As mentoned above, in order to multply, viruses must be able to enter the cell nucleus and integrate with the host DNA. They frst enter the cell by ataching to the outer cell membrane. Thus, this inital atachment is a potental site of acton for drug therapy. The second thing that must happen is the virus needs to be able to take over the process of DNA transcripton so that the host cell is now ultmately producing progeny virus to be sent out to infect more cells. This is another site of acton for drug therapy—the drugs target the process of transcripton. When the host cell is successfully producing the virus, it also must be able to expel the virus out of the cell (egress) and into circulaton in order to fnd another host cell to infect. Inhibitng egress is another potental site of acton for drug therapy. The most common combinaton therapy to start with is a triple cocktail that combines two nucleoside-analogue reverse transcriptase (NRTIs) and one nonnucleoside reverse transcriptase inhibitor (NNRTI), or one protease inhibitor. Fortunately, there are now combinaton tablets that have all three of these medicatons in a single dose. New advancements are contnually being made in the area of HIV research. This module will introduce fve primary drug classes used in the treatment of HIV. Fusion Inhibitors work by preventng the complete fusion of HIV to the host cell. Therefore, penetraton of the virus into the host cell is blocked as are any subsequent steps. However, fusion inhibitors are not 100% effectve. For this reason, additonal strategies are used to combat the virus. Nucleoside-analogue reverse transcriptase inhibitors (NRTIs) are part of the recommended HAART regimen. Nucleosides are the fundamental building blocks of RNA and DNA. The NRTIs work by incorporatng themselves into theDNA and inhibitng the reverse transcriptase and synthesis of new viruses. This, in turn, decreases viral replicaton and the infecton is reduced. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are also part of the recommended HAART regimen. NNRTIs work by directly binding to the enzyme reverse transcriptase found within HIV, thus blocking its ability to take over the transcripton process of the host cell. Integrase Inhibitors work by blocking the enzyme integrase which is essental for the virus to be able to enter the host cell nucleus and begin incorporatng its viral DNA into the host cells’ DNA. Protease Inhibitors are the third opton for the recommended HAART regimen. As their name indicates they work by inhibitng protease, an enzyme essental for the fnal assembly of the new virus. The new virus is thus unable to be released into circulaton to fnd a new host cell. Table 9.4 below provides an overview of specifc select antretroviral medicatons. Table 9.4 Examples of Antretrovirals Drug Class Example Drug(s) NRTI Zidovudine (Retrovir) Tenofovir (Viread) Emtricitbine (Emtriva) Lamivudine (Epivir) NNRTI Efavirenz (Sustva) Rilpivirine (Edurant) Nevirapine (Viramune) Protease Inhibitor Atazanavir (Reyataz) Darunavir (Prezista) Ritonavir (Norvir) Integrase Inhibitor Dolutegravir (Tivicay) Raltegravir (Isentress) Fusion Inhibitors Enfuvirtde (Fuzeon) HAART requires multple medicatons in order for the best chance of controlling the virus. Many of the above medicatons are available in combinaton pills in order to make the dosing regimen simpler. Adherence to these medicatons is critcal to increase effectveness and avoid or at least delay the development of drug resistance. Some of the common combinaton tablets are listed below in Table 9.5. Table 9.5 Examples of Combinaton Tablets for the Treatment of HIV Drug name and components Drug classes Atripla (efavirenz/lamivudine/tenofovir) NNRTI/NRTI/NRTI Truvada (emtricitabine and tenofovir) NRTI/NRTI Complera (emtricitabine/rilpivirine/tenofovir) NRTI/NNRTI/NRTI The adverse effects associated with HIV medicatons are generally very drug-specifc and beyond the scope of this module. However, most drugs tend to cause nausea and vomitng. More serious adverse events that need to be monitored for include renal toxicity and neutropenia. Neutropenia is a decrease in white blood cells, specifcally neutrophils. This is especially concerning in patents that may already be immunocompromised. Patents will ofen require frequent blood counts to monitor for these more serious adverse events.Problem Set Queston 1 List characteristcs that typically describe a specialty drug. High Cost Potental for limited or exclusive availability for distributon Complex treatment regimen that require ongoing monitoring and patent educaton Treat rare diseases Special handling, storage, or delivery requirements Treat diseases known t have long term or severe side effects or increased fatality Biologically derived and available in injecton, infusion, or oral form Payers may defne what they consider to be a specialty medicaton for reimbursement and contractng purposes. Queston 2 List some common additonal requirements that the specialty pharmacy must offer to patents in order to ensure that these high cost, potentally high adverse events medicatons are used safely and appropriately. Coordinatng care and facilitatng the drug access Case management- disease state management Facilitatng mail order delivery logistcs Product device training when applicable Working with health insurance to determine coverage and help coordinate any requirements of the insurance company Data management of technical and clinical patent care services. Investgatng patent assistance programs for patents without insurance or lack of coverage Call center development Queston 3 Explain the process that a patent would need to follow in order to obtain one of these medicatons. The prescripton would frst be sent to the specialty pharmacy. The specialty pharmacy then takes responsibility for making sure the patent gets the medicaton, understands the risks and benefts, is able to afford it, take it appropriately and follows through with any necessary monitoring. The patent may be connected with a case manager that will call them on a monthly basis to make sure there are no issues with the medicatons, check to see if they are had any required monitoring, provide any necessary educaton or answer patent questons. This ofen happens every month prior to sending out the next months' worth of medicatons to minimize waste, ensure safety, and assess for efcacy. Queston 4 List the most chronic disease states that are treated with specialty medicatons. oncology, multple sclerosis, rheumatoid arthrits, Crohn’s disease, hepatts C, and HIV/AIDs Queston 5 List a descripton of the basic disease process including common symptoms of following disease states: Rheumatoid arthrits, Multple Sclerosis, Crohn’s disease, Hepatts C, and HIVRA: is a chronic autoimmune disorder that causes inflammaton and tssue damage in the joints. The common symptoms of RA include pain, stffness, and reduced range of moton. MS: It disrupts the flow of informaton within the brain and between the brain and the body. There is damage to the myelin coatng around the nerve fbers in the CNS that cause the nerve signals to be disrupted. Some of the more common symptoms include Fatgue, difculty walking, numbness or tngling, stffness in the limbs, weakness, vision problems, cognitve changes, pain, depression and emotonal changes. Crohn’s disease is an inflammatory bowel disease caused by inflammaton in the digestve tract which can lead to symptoms such as abdominal pain, severe diarrhea, fatgue, weight loss, and malnutriton. The inflammaton can spread deep into the layers of the affected bowel tssues making the symptoms extremely painful and ofen hard to control. Hepatts C: a viral infecton that caused liver inflammaton and sometmes leads to serious liver damage. The virus is spread through infected blood. There are ofen no symptoms with Chronic hepatts C untl the virus damages the liver signifcantly enough. Symptoms of hepatts C then include bleeding and bruising easily, fatgue, poor appette, dark urine, swelling, weight loss, confusion. HIV is s retrovirus that atacks the body’s immune system. The typical course of the infecton is characterized by an acute clinical illness that varies in presentaton followed by a longer clinical latency. People may go years without any symptoms. However, during this asymptomatc tme the virus is working in the body to destroy the immune system, specifcally the CD-4 Cells (T-cells). Over tme the person is no longer able to fght off bacteria that generally do not cause infecton called opportunistc infectons. Queston 6 Defne the following terms related to the immune system: Humoral immunity, cell mediated immunity, Antbodies, T-cells and cytokines. Humoral immunity is defned as the immune response mediated by B cells and the producton of antbodies targeted against specifc antgens. Antbodies are molecules that have the ability to bind to and inactvate antgen molecules through the formaton of an antgen-antbody complex. Cell-mediated immunity which is the immune response mediated by T-cells. T-cells or T lymphocytes are not involved in the producton of antbodies but instead occur in different types of subtypes that act through direct cell to cell contact or through the producton of cytokines. Cytokines is a generic term for non-antbody proteins released by specifc cell populatons (actvated T cells) on contact with antgens. They act as intercellular mediators of an immune response. Queston 7 Describe the impact on the immune system of the more common immunomodulatng drugs such as: interferons, antTNF monoclonal antbodies, interleukins (specifcally IL-2). Interferons are proteins that have anttumor, antviral, and immunomodulatng propertes. Interferons have three different effects on the immune system. They can restore functon if it’s not working properly, they can augment its functon, or inhibit its functon. Interleukins are a natural part of the immune system. They are actually classifed as lymphokines because they are cytokines produces at least in part by lymphocytes. Il-2 works by indirectly to restore immune response by binding to receptor sites on T-cells stmulatng them to multply. One type of cell that results is called the lymphokine-actvated killer (LAK) cell. This LAK cell can recognize and destroy cancer cells while leaving other healthy cells aloneAnt-TNF Monoclonal antbodies acts on tumor necrosis factor (TNF), which is a naturally occurring cytokine that is involved in the normal inflammatory and immune response. they essentally work by preventng TNF molecules from binding to the TNF cell surface. Queston 8 List two of the new hepatts C treatment optons and describe how they improve previous treatment optons. Harvoni and Viekira Pak. With the development of a new class of antviral medicaton that targets the hepatts C virus specifcally, the chance for a cure, is now close to 96%. Possibly the best part of this is that the treatment is not chronic. In fact, patents may only need to be treated for 8-12 weeks. Additonally, the side effects of these new drugs are minimal in comparison to the old treatment regimen of interferon. Queston 9 Explain what the HIV virus does once it enters the body. HIV is a retrovirus. This means that it contains the enzyme reverse transcriptase. Essentally, this allows it to take over the process of DNA transcripton (how cells multply) once it enters the host cell. HIV specifcally targets macrophages and helper T-cells effectvely compromising the immune system of the host. Instead of producing cells that help fght infecton, once the HIV has control of the cell, it actually begins producing more HIV that can go out and infect more host cells. Queston 10 Explain why it is not recommended to treat HIV with only one medicaton. Monotherapy cannot counter the development of drug resistance and a missed dose can quickly lead to a poor outcome. The current treatment strategy is referred to as HAART (highly actve antretroviral therapy). HAART consists of three antretrovirals taken in combinaton. This increases the effectveness of the regimen by presentng the virus with multple obstacle to try and overcome. Queston 11 List the primary antretroviral classes covered in this module and provide a brief descripton at how they target the HIV virus. Nucleoside-analogue reverse transcriptase (NRTIs). The NRTIs work by incorporatng themselves into the DNA and inhibitng the reverse transcriptase and synthesis of new viruses. This in turn decreases viral replicaton and the infecton is reduced. Nonnucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs work by directly binding to the enzyme reverse transcriptase found within HIV virus thus blocking its ability to take over the transcripton process of the host cell. Protease Inhibitors. As their name indicates they work by inhibitng protease, an enzyme essental for the fnal assembly of the new virus. The new virus is thus unable to be released into circulaton to fnd a new host cell. Integrase Inhibitors work by blocking the enzyme integrase which is essental for the virus to be able to enter the host cell nucleus and begin incorporatng into the transcripton process. Fusion Inhibitors work by preventng the complete fusion of HIV to the host cell. Therefore, the penetraton into the host cell is blocked and it cannot take over the transcripton process.