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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.
References List
Berardicurti, O. et al. (2020) Glucocorticoids in rheumatoid arthritis: the silent companion in the therapeutic strategy, Expert Review of Clinical Pharmacology, 13(6), pp. 593-604.
CDC. (2018) National Statistics. Web.
Çelebi, A. and Y1lmaz, H. (2017) When proton pump inhibitors are compared, are there specific cases in which a certain proton pump inhibitors should be particularly preferred?, Turkish Journal of Gastroenterology, 28(1), S68-S70.
Chabner, B. A. and Longo, D. L. (2019) Cancer chemotherapy, immunotherapy, and biotherapy: principle and practice, in Bruce, A. C. and Carmen, J. A. (eds.) Antifolates. 6th edn. Philadelphia: Wolters Kluwer, pp. 159-194.
Chen, X. et al. (2018) Evaluation of oral anticoagulants with vitamin K epoxide reductase in its native milieu, Blood, The Journal of the American Society of Hematology, 132(18), 1974-1984.
Chilkoti, G. T. et al. (2019) Perioperative stress dose of corticosteroid: pharmacological and clinical perspective, Journal of Anesthesiology, Clinical Pharmacology, 35(2), pp. 147-152.
Gale, S. et al. (2018) Risk associated with cumulative oral glucocorticoid use in patients with giant cell arteritis in real-world databases from the USA and UK, Rheumatology and Therapy, 5(2), pp. 327-340.
Hosny, K. M. and Rizg, W. Y. (2018) Quality by design approach to optimize the formulation variables influencing the characteristics of biodegradable intramuscular in-situ gel loaded with alendronate sodium for osteoporosis, Plos One, 13(6), pp. 1-11.
Hu, C. et al. (2020) The solute carrier transporters and the brain: physiological and pharmacological implications, Asian Journal of Pharmaceutical Sciences, 15(2), pp. 131-144.
Kelly, A. et al. (2018) Patients attitudes and experiences of diseasemodifying antirheumatic drugs in rheumatoid arthritis and spondyloarthritis: a qualitative synthesis, Arthritis Care & Research, 70(4), pp. 525-532.
Kou, L., He, Z. and Sun, J. (2020) Special topic: the emerging role of transporters in drug interaction and delivery, Asian Journal of Pharmaceutical Sciences, 15(2), pp.129-130.
Krasselt, M. and Baerwald, C. (2019) Celecoxib for the treatment of musculoskeletal arthritis, Expert Opinion on Pharmacotherapy, 20(14), 1689-1702.
Kuzin, M. et al. (2018) Effects of the proton pump inhibitors omeprazole and pantoprazole on the cytochrome P450-mediated metabolism of venlafaxine, Clinical Pharmacokinetics, 57(6), 729-737.
Macfarlane, E., Seibel, M. J. and Zhou, H. (2020) Arthritis and the role of endogenous glucocorticoids, Bone Research, 8(1), 1-17.
Onakpoya, I.J., Heneghan, C.J. and Aronson, J.K. (2018) Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review, Expert Opinion on Drug Safety, 17(1), pp. 63-72.
Pengo, V. and Denas, G. (2018) Optimizing quality care for the oral vitamin K antagonists (VKAs), Hematology 2014, the American Society of Hematology Education Program Book, 2018(1), pp. 332-338.
Piazza, I. et al. (2018) A map of protein-metabolite interactions reveals principles of chemical communication, Cell, 172(2), pp. 358-372.
Pontelo, B. M. et al. (2020) Profile of drug-drug interactions and impact on the effectiveness of antiretroviral therapy among patients living with HIV followed at an Infectious Diseases Referral Center in Belo Horizonte, Brazil, Brazilian Journal of Infectious Diseases, 24(2), 104-109.
Rice, J. B. et al. (2017) Long-term systemic corticosteroid exposure: a systematic literature review, Clinical therapeutics, 39(11), pp. 2216-2229.
Riganti, C. et al. (2018) Design, biological evaluation, and molecular modeling of tetrahydroisoquinoline derivatives: discovery of a potent P-Glycoprotein ligand overcoming multidrug resistance in Cancer stem cells, Journal of Medicinal Chemistry, 62(2), pp. 974-986.
Ryu, J. Y., Kim, H. U. and Lee, S. Y. (2018) Deep learning improves prediction of drugdrug and drugfood interactions, Proceedings of the National Academy of Sciences, 115(18), pp. 1-8.
Satoh, D., I. et al. (2017) Establishment of a novel hepatocyte model that expresses four cytochrome P450 genes stably via mammalian-derived artificial chromosome for pharmacokinetics and toxicity studies, PloS One, 12(10), pp. 1-18.
Storelli, F. et al. (2018) Complex drug-drug-gene-disease interactions involving cytochromes P450: a systematic review of published case reports and clinical perspectives, Clinical Pharmacokinetics, 57(10), pp. 1267-1293.
Verhoeven, F. et al. (2019) Structural efficacy of NSAIDs, COX-2 inhibitor and glucocorticoid compared with TNF± blocker: a study in adjuvant-induced arthritis rats, Rheumatology, 58(6), pp. 1099-1103.
Wu, W. T. et al. (2019) Cardiovascular outcomes associated with clinical use of citalopram and omeprazole: a nationwide populationbased cohort study, Journal of the American Heart Association, 8(20), pp. 1-7.
Yilancioglu, K. (2019) Antimicrobial drug interactions: a systematic evaluation of protein and nucleic acid synthesis inhibitors, Antibiotics, 8(3), pp. 1-8.
Zhang, X. et al. (2018) Aspirin promotes apoptosis and inhibits proliferation by blocking G0/G1 into S phase in rheumatoid arthritis fibroblast-like synoviocytes via downregulation of JAK/STAT3 and NF-ºB signaling pathway, International Journal of Molecular Medicine, 42(6), pp. 3135-3148.
Zheng, N., Guo, C. and Wu, R. (2018) Iguratimod is effective in refractory rheumatoid arthritis patients with inadequate response to methotrexatecyclosporin Ahydroxychloroquineprednisone, Scandinavian Journal of Rheumatology, 47(5), pp. 422-424.
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