PharmaMedical Trend Analysis - PMTA

01/01/2024

Happy New Year 2024!!! Have Your New Year Healthy, Prosperous and Blissful!!!
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09/07/2023

Know the Proper Use of Antibiotics

Strategies to Preserve the Efficacy of Antibiotics and Avoid Superbugs

The irrational and random use of antibiotics can create superbugs. Therefore, for the decades, WHO (World Health Organization) has been advising the government and people of every country for the rational use of antibiotics to preserve the efficacy of antibiotics for future generations.
Dr Hanan Balkhy, Assistant Director-General of WHO, Division of Antimicrobial resistance explained the risks and reasons behind these risks if people practise the irrational use of antibiotics. People use these antibiotics to kill bacteria causing disease to humans. But these bacteria also try to survive and adopt different strategies to escape the effect of the antibiotics. Therefore, it is very vital to preserve the efficacy of antibiotics. Otherwise, these antibiotics will not protect us even from common injuries. Dr Hanan Balkhy indicated three points to follow when taking antibiotics.
1. Take antibiotics only when your doctor or health care provider prescribe it for you.
2. Complete the antibiotic course based on the advice provided by your doctor. If you do not complete the course, bacteria will develop mechanisms to become irresponsive to these antibiotics.
3. You must not share your antibiotic with family or friends because physician or health care provider should prescribe it for the person based on specific signs and symptoms. Some certain viral infections really do not require antibiotics.
Dr Hanan Balkhy reported that WHO is working with three other critical organizations, such as animal health, environmental health and agriculture to identify the best hygiene methods to avoid exposure to infection.
Source: WHO, 2023. URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/science-in-5/episode-99-three-things-to-keep-in-mind-when-taking-antibiotics.

09/07/2023

Strategies to Preserve the Efficacy of Antibiotics and Avoid Superbugs

The irrational and random use of antibiotics can create superbugs. Therefore, for the decades, WHO (World Health Organization) has been advising the government and people of every country for the rational use of antibiotics to preserve the efficacy of antibiotics for future generations.
Dr Hanan Balkhy, Assistant Director-General of WHO, Division of Antimicrobial resistance explained the risks and reasons behind these risks if people practise the irrational use of antibiotics. People use these antibiotics to kill bacteria causing disease to humans. But these bacteria also try to survive and adopt different strategies to escape the effect of the antibiotics. Therefore, it is very vital to preserve the efficacy of antibiotics. Otherwise, these antibiotics will not protect us even from common injuries. Dr Hanan Balkhy indicated three points to follow when taking antibiotics.
1. Take antibiotics only when your doctor or health care provider prescribe it for you.
2. Complete the antibiotic course based on the advice provided by your doctor. If you do not complete the course, bacteria will develop mechanisms to become irresponsive to these antibiotics.
3. You must not share your antibiotic with family or friends because physician or health care provider should prescribe it for the person based on specific signs and symptoms. Some certain viral infections really do not require antibiotics.
Dr Hanan Balkhy reported that WHO is working with three other critical organizations, such as animal health, environmental health and agriculture to identify the best hygiene methods to avoid exposure to infection.
Source: WHO, 2023. URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/media-resources/science-in-5/episode-99-three-things-to-keep-in-mind-when-taking-antibiotics.

09/07/2023

Be Aware of Artificial Sweeteners and their Health Problems

09/07/2023

Artificial Sweeteners May Be More Dangerous for Health

People avoid sugars due to the fear of weight gain and some other health related problems. They take artificial sweeteners instead of sugar. But according to the World Health Organization (WHO), artificial sweeteners may not help people to lose weight in the long-run, but they have some dangerous health effects. Artificial sweeteners may increase the risk of diabetes, heart disease and death. People consume some common artificial sweeteners or sugar substitutes such as stevia, aspartame and sucralose.
WHO conducted a systematic review of the available evidence. The summary of review indicate that the uptake of non-sugar sweeteners doesn’t provide any long-term benefit to lower the body fat in adults and children. But the long-term use of these non-sugar sweeteners may augment the risk of type 2 diabetes, cardiovascular diseases, and mortality in adults.
Dr Francesco Branca, WHO director for nutrition and food safety, also emphasized that the consumption of artificial sweeteners instead of sugar doesn’t provide benefit of weight loss in the long-term. Therefore, he recommended the uptake of food with naturally occurring sugars, like fruit, or unsweetened food and beverages. He said that artificial sweeteners are not essential dietary factors and have no nutritional value.

Source: WHO

29/01/2023

Association of Rheumatoid Arthritis with Coronary Artery Disease and Stroke Risk

What is rheumatoid arthritis?
Rheumatoid arthritis is the most common autoimmune and inflammatory disease with a prevalence of 1%-2% worldwide, which causes inflammation, joint pain, swelling and damage in the wrist and small joints of the hand, knee and feet. It can also impact the shoulders and knees. This disease can affect other parts of the body systems, including the skin, eyes, lungs, heart and blood vessels.

How does rheumatoid arthritis occur?
The disorder of the body’s autoimmune system mistakenly attacks human’s own body's tissues, especially the lining of the joints, called the synovium resulting in rheumatoid arthritis (Arthritis foundation, 2021), which causes a painful swelling in the joints and eventually result in bone erosion and joint deformity. The autoimmune system fights their body’s cells as invaders, such as bacteria and viruses, and releases inflammatory chemicals that attack those cells. After inflammation, the synovium gets thicker making the joint area painful, tender, red and swollen. Therefore, it becomes difficult and painful to move the joint of hands, knee, ankle and shoulders (Arthritis foundation, 2021).

Symptoms
• Joint pain, warmth, tenderness, swelling or stiffness.
• Joint stiffness that is usually worse in the mornings and after inactivity
• Fatigue, fever and loss of appetite
• More than one joint is affected.

Association of rheumatoid arthritis with coronary disease and stroke risk
Cardiovascular disease (CVD) is one of the most common diseases that causes the death of significant number of people worldwide. People with rheumatoid arthritis have more probability of having cardiovascular disease and diabetes with the rate of 1.5 times higher than the general population. The low mobility, movement and exercise are presumed to be one of the main factors for high prevalence of cardiovascular disease and diabetes mellitus. There are some more probable factors, such as shared risk factors (e.g., obesity and smoking), and side effects of antirheumatic therapies. However, the traditional risk factors do not fully support the reasons of increased rate of cardiovascular disease risk in rheumatoid arthritis. Therefore, medical research presumed that rheumatoid arthritis may be a novel and independent risk factor for coronary disease. The studies reported that cardiovascular disease and rheumatoid arthritis have overlapping pathophysiologic mechanisms which may contribute, such as systemic inflammation, with cytokines raised in rheumatoid arthritis may cause atherosclerotic diseases and cardiovascular risk in rheumatoid arthritis (Yuan et al., 2022). But there were some confusions or limitations to fully support this finding or hypothesis.
Therefore, Yuan et al. (2022) conducted a mendelian randomization analysis by using genetic variants. They concluded that genetic liability to rheumatoid arthritis was associated with elevated risk of cardiovascular disease and Intracerebral hemorrhage (ICH), but not ischemic stroke or subarachnoid hemorrhage, because genetic liability to rheumatoid arthritis was associated with elevated levels of tumor necrosis factor [TNF], and C-reactive protein [CRP], which appeared to mediate the association with cardiovascular disease. Thus, they provided important genetic evidence supporting the link between rheumatoid arthritis and some cardiovascular diseases and underscored the role of inflammation in driving cardiovascular disease specifically.

Arthritis Patient's hands; Picture source: Pexels

01/01/2023

Dual benefits of cardiovascular therapeutics for cardiovascular disease and anxiety treatment

The cardiovascular disorders, hypertension, coronary artery disease, and mental disturbances, such as anxiety and depressive disorders are the most common problems among the people, which are causing the high rate of morbidity and death. Anxiety and depression deteriorate the cardiovascular disease and pathologies. On the other hand, the cardiovascular diseases may cause the mental and emotional disturbances. There is bidirectional relationship between the psychological disturbances and cardiovascular diseases. Therefore, the patients with cardiovascular diseases should be examined and treated for their disturbances of emotions, cognition, and behavior (Repova et al., 2022).
When patients with heart or vasculature disturbances take principal cardiovascular drugs, the medicines can interact with the mental state of the patient and optimize their therapeutic benefit. The beta-blockers, central sympatholytics, ACE inhibitors, ARBs, aldosterone receptor blockers, sacubitril/valsartan, and fibrates are presumed to have anxiolytic effect in animal experiments and clinical settings. Therefore, when the patients with cardiovascular diseases are treated, their mental condition, cognition and behavior should be taken into account to select the cardiovascular drugs, which can provide them with benefit for both mental disturbances and cardiovascular disorders.

Relationship between mental disturbances and cardiovascular diseases
Depressive disorders are one of the reasons of disability. The cardiovascular diseases have close relationship with mental disorders, such as anxiety and depression (Repova et al., 2022).
The psychosocial disorders such as anxiety, hostility, stress, or conflict situations stimulate and activate autonomic nervous system and neurohumoral cascade resulting in development of endothelial dysfunction, hypertension, diabetes mellitus, and target organ damage. On the other hand, the cardiovascular pathologies associated with neurohumoral imbalance result in the formation of anxiety and mental disorders. The patients with anxiety have high risk of cardiovascular diseases, such as coronary artery disease, stroke, heart failure, and cardiovascular death, whilst cardiovascular diseases coincide with anxiety development. The above phenomena indicate the bidirectional relationship between (1) the negative emotions and mental disturbances in the form of distress, anxiety, or depression and (2) increased risk of cardiovascular diseases. Cardiac patients and patients with anxiety demonstrate the similar symptoms, such as nervousness, palpitations, apprehension, fatigue, breathlessness, headache, sweating, dizziness, or insomnia. A diagnosis of anxiety can even indicate the future adverse cardiovascular disease (Repova et al., 2022).

Impact of cardiovascular drugs on mental disorders
Cardiovascular drugs which are used to treat the patients with cardiovascular diseases may also affect the development and severity of anxiety or depression. A considerable number of experimental and clinical studies have been conducted to determine the impact of different cardiovascular drug groups on anxiety or depression. Repova et al. (2022) made a review to focus on the impact of currently used, well-established cardiovascular treatment for mental disturbances including anxiety and depression, which will indicate the future clinical and research directions.
Beta-blockers and drugs interfering with the renin-angiotensin-aldosterone system are considered to be important. Selective beta-blockers might be more effective in alleviating mental stress and anxiety disorders. Actually, selective beta-blockers decreased symptoms of anxiety in patients with chronic heart failure (metoprolol), mitral valve prolapse syndrome (celiprolol) and anxiety-related mental health problems (atenolol). There are different types of cardiovascular drugs. Out of them, beta-blockers, ACE inhibitors, ARBs, aldosterone receptor blockers, and sacubitril/valsartan are presumed to have an anxiolytic effect in animal experiments and clinical settings.
The mutual interactions between cardiovascular diseases and mental disorders including anxiety can improve health-related quality of life. Anxiety coming from cardiovascular pathology or developed independently from heart disorder can deteriorate cardiovascular prognosis. The impact of cardiovascular drugs on the mental state of the patient will open a new door of optimal treatment providing mutual benefit for the cardiovascular patients. The cardiovascular patients should be monitored whether they are showing any changes in their mood, cognition, and behavior in terms of distress and anxiety, because this will help to prevent worsening of their conditions. Finally, we should explore further to enhance our understanding about therapeutics regarding their possible interference with mood, mind, and behavior, which could help manage both the cardiovascular diseases and mental disturbances of the population with cardiovascular pathologies.

Reference
Repova K., Aziriova S., Krajcirovicova K., Simko F., 2022. Cardiovascular therapeutics: A new potential for anxiety treatment? Med Res Rev. 42(3):1202-1245.

Photograph Source: Pixabay

01/01/2023

Cardiovascular Disease and Mental Anxiety

Dual benefits of cardiovascular therapeutics for cardiovascular disease and anxiety treatment

The cardiovascular disorders, hypertension, coronary artery disease, and mental disturbances, such as anxiety and depressive disorders are the most common problems among the people, which are causing the high rate of morbidity and death. Anxiety and depression deteriorate the cardiovascular disease and pathologies. On the other hand, the cardiovascular diseases may cause the mental and emotional disturbances. There is bidirectional relationship between the psychological disturbances and cardiovascular diseases. Therefore, the patients with cardiovascular diseases should be examined and treated for their disturbances of emotions, cognition, and behavior (Repova et al., 2022).
When patients with heart or vasculature disturbances take principal cardiovascular drugs, the medicines can interact with the mental state of the patient and optimize their therapeutic benefit. The beta-blockers, central sympatholytics, ACE inhibitors, ARBs, aldosterone receptor blockers, sacubitril/valsartan, and fibrates are presumed to have anxiolytic effect in animal experiments and clinical settings. Therefore, when the patients with cardiovascular diseases are treated, their mental condition, cognition and behavior should be taken into account to select the cardiovascular drugs, which can provide them with benefit for both mental disturbances and cardiovascular disorders.

Relationship between mental disturbances and cardiovascular diseases
Depressive disorders are one of the reasons of disability. The cardiovascular diseases have close relationship with mental disorders, such as anxiety and depression (Repova et al., 2022).
The psychosocial disorders such as anxiety, hostility, stress, or conflict situations stimulate and activate autonomic nervous system and neurohumoral cascade resulting in development of endothelial dysfunction, hypertension, diabetes mellitus, and target organ damage. On the other hand, the cardiovascular pathologies associated with neurohumoral imbalance result in the formation of anxiety and mental disorders. The patients with anxiety have high risk of cardiovascular diseases, such as coronary artery disease, stroke, heart failure, and cardiovascular death, whilst cardiovascular diseases coincide with anxiety development. The above phenomena indicate the bidirectional relationship between (1) the negative emotions and mental disturbances in the form of distress, anxiety, or depression and (2) increased risk of cardiovascular diseases. Cardiac patients and patients with anxiety demonstrate the similar symptoms, such as nervousness, palpitations, apprehension, fatigue, breathlessness, headache, sweating, dizziness, or insomnia. A diagnosis of anxiety can even indicate the future adverse cardiovascular disease (Repova et al., 2022).

Impact of cardiovascular drugs on mental disorders
Cardiovascular drugs which are used to treat the patients with cardiovascular diseases may also affect the development and severity of anxiety or depression. A considerable number of experimental and clinical studies have been conducted to determine the impact of different cardiovascular drug groups on anxiety or depression. Repova et al. (2022) made a review to focus on the impact of currently used, well-established cardiovascular treatment for mental disturbances including anxiety and depression, which will indicate the future clinical and research directions.
Beta-blockers and drugs interfering with the renin-angiotensin-aldosterone system are considered to be important. Selective beta-blockers might be more effective in alleviating mental stress and anxiety disorders. Actually, selective beta-blockers decreased symptoms of anxiety in patients with chronic heart failure (metoprolol), mitral valve prolapse syndrome (celiprolol) and anxiety-related mental health problems (atenolol). There are different types of cardiovascular drugs. Out of them, beta-blockers, ACE inhibitors, ARBs, aldosterone receptor blockers, and sacubitril/valsartan are presumed to have an anxiolytic effect in animal experiments and clinical settings.
The mutual interactions between cardiovascular diseases and mental disorders including anxiety can improve health-related quality of life. Anxiety coming from cardiovascular pathology or developed independently from heart disorder can deteriorate cardiovascular prognosis. The impact of cardiovascular drugs on the mental state of the patient will open a new door of optimal treatment providing mutual benefit for the cardiovascular patients. The cardiovascular patients should be monitored whether they are showing any changes in their mood, cognition, and behavior in terms of distress and anxiety, because this will help to prevent worsening of their conditions. Finally, we should explore further to enhance our understanding about therapeutics regarding their possible interference with mood, mind, and behavior, which could help manage both the cardiovascular diseases and mental disturbances of the population with cardiovascular pathologies.

Reference
Repova K., Aziriova S., Krajcirovicova K., Simko F., 2022. Cardiovascular therapeutics: A new potential for anxiety treatment? Med Res Rev. 42(3):1202-1245.

Photograph Source: Pixabay

01/01/2023

How do cancers and tumours evade the immunity? Current therapeutic options and future research

Cancer is one of the deadliest diseases causing very high death toll every day in the world. Frequently, cancer has a poor prognosis. Multiple therapeutic strategies and treatment options have been developed for various cancers and tumours. The chemotherapy, radiotherapy, targeted therapy, and immunotherapy are applied over the past several decades. However, resistance to these therapies is a major issue that impedes the clinical outcomes and effectiveness of cancer treatments and impacts patient survival. The patients with early stage positively respond to the treatments, but they poorly respond and show dire clinical outcomes at a later stage (Wu et al., 2021 and references therein).

Tumours and Immunity Evasion
Tumours develop immunity resistance through several mechanisms (Wu et al., 2021 and references therein):
·Some tumours have been demonstrated to lose expression of MHC molecules making them unable to present tumour antigens, thus evading T cell recognition.
·Some tumours secrete immunosuppressive cytokines, e.g., IL-10.
· Some tumours generate physical barriers, e.g., collagen and fibrin, thus making them invisible to the immune system.
·Tumours can also evade the immune response by up-regulating inhibitory molecules and inducing a form of self-tolerance.
·An immune response can be produced by T cells depending on co-stimulatory signals. However, inhibition of co-stimulatory signals creates immune tolerance. Cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1(PD1) are both inhibitory receptors involved in down-regulation of immune responses.

Multiple Strategies to Prevent Immune Resistance
Multiple strategies targeting the TME have been investigated to prevent resistance to radiotherapy, chemotherapy, and immunotherapy (Wu et al., 2021 and references therein).
·Cancer-Associated Fibroblasts (CAFs) is the most abundant cell type in the TME that have the critical role in therapeutic resistance of tumour cells. Therefore, targeting CAF functions is a promising approach for tumour therapy.It has been shown to be an efficient tumour therapy strategy to stop the communication between tumour cells and their environment by targeting adhesion molecules, proteolytic enzymes, and ECM components.
·Different strategies can be used to target the immune system in TME and tackle cancers, because the immune system in TME influences the response of tumours to various clinical therapies.
·The low oxygen pressure and acidosis conditions in the TME affect a tumour’s response to treatment. Therefore, manipulating hypoxia and acidosis conditions in the TME can stop tumour progression.
·Capturing and leading the TME to increase drug delivery can significantly increase the efficacy of chemotherapeutic drugs.
Photograph source: Xu et al. (2022)
Wu P, Gao W, Su M, Nice EC, Zhang W, Lin J, Xie N, 2021. Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment. Front. Cell Dev. Biol. 9:641469.

Xu, L., Zou, C., Zhang, S. et al., 2022. Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors. J Hematol Oncol 15, 87.

01/01/2023

Pharmaceutical Workplace Safety

Technologist is using protective uniform, wearing hairnet, mask, goggles, and gloves, and then closing industrial tank reservoir.
Photograph source: Freepik

16/12/2022

Quality and price of active ingredients and their impact on effectiveness and potency of medicine

Dr Md Anawar Hossain

• The good quality of active pharmaceutical ingredients (APIs) can ensure the manufacturing of the high quality, effective and safe essential drugs, while the use of low quality APIs can produce less effective and unsafe drugs.
• The price volatility of APIs can affect the small pharmaceutical companies.
• One potential way to address the above problems would be to broaden the WHO prequalification system and include APIs for drugs that are on the WHO model list for essential medicines.

Prequalification of Active Pharmaceutical Ingredients
Prequalification of active pharmaceutical ingredients (APIs) is an important step to ensure the production of good quality APIs. These products should be manufactured in compliance with WHO (World Health Organization) Good Manufacturing Practices (GMP). The pharmaceutical companies should use the prequalified APIs to manufacture their finished pharmaceutical product (FPP).
The API manufacturers must submit their API master file procedure (APIMF) to get their application approved for prequalification of an FPP (WHO, 2022). The APIMF includes the manufacturing details, quality controls procedure, accepted active ingredient specifications, and the assay and related substances test methods for assessment and any changes, before or after prequalification, is included in the updated APIMF version, which, therefore, clearly identify an API with a specific APIMF version. Active pharmaceutical ingredient manufacturers should apply to receive a WHO Confirmation of API Prequalification and obtain successful prequalification, before their APIs are included in the WHO List of Prequalified Active Pharmaceutical Ingredients (WHO, 2022).

API Manufacturer’s Site Inspection
The site of the API manufacturer should be inspected by WHO and verified whether it complies with WHO GMP requirements (WHO, 2022). The API manufacturing companies should apply along with a site master file (SMF) for each manufacturing site of each API and intermediate involved in the preparation of the API related to prequalification sought. An SMF contains the information about the production and/or quality control of pharmaceutical manufacturing operations conducted at a site, and any related integrated operations conducted at adjacent site or buildings.

Source, Quality and Price of Active Pharmaceutical Ingredients
The good quality of active pharmaceutical ingredients can ensure the manufacturing of the high quality, effective and safe essential drugs. The manufacturing cost of the final finished medicine product depends on the purchase price or manufacturing cost of APIs. In the developing countries, most of the pharmaceutical companies purchase APIs from other manufacturers. Only a limited number of large manufacturers of finished pharmaceutical products have their own API manufacturing capabilities in the developed countries, but none of them can make all required APIs in-house. The small manufacturers in developing countries face difficulties to source the global API market and ensure that they get a quality product at a fair price. Besides these, there is possibility that the greedy manufacturers or traders can control or monopolize parts of the API market for essential medicines with low commercial attractiveness. Given the limited sources of APIs, the manufacturers can increase the price of APIs to make more profit (Bumpas and Betsch, 2009).
One potential way to address this problem would be to broaden the WHO prequalification system and include APIs for drugs that are on the WHO model list for essential medicines.

Quality of APIs and Their Effect on Effectiveness of Medicine
The high quality of active pharmaceutical ingredients has a great effect on the effectiveness and safety of medicines. Active pharmaceutical ingredient is the central component of medicine. Sometimes, more than one API is used in one medicine. The quality requirements of an API help the manufacturer to determine the use of ingredients and the permissible limit of usage.

Properties and Purity of APIs
The active pharmaceutical ingredient has three main properties such as physical, chemical and biological properties, which can be used in the treatment of diseases. Active pharmaceutical ingredients may have chemical impurities. In addition, the impurities may come from the solvent used in mixing of ingredients. Therefore, the manufacturers should test the potency of the medicines. The physical properties of APIs, such as particle size/proportion and polymorphism are critical factors for suitability of an API for drug use, which control the flow properties of the API, rate of absorption and the bioavailability of the medicine. The particle size of the ingredient controls the solubility of the medicine in human body. The manufacturing process must ensure that the APIs are clean enough for use in non-sterile dosage formula, free from biological threat and toxins (Mankind Pharma, 2022).

References

Bumpas J, Betsch E, 2009. Exploratory study on active pharmaceutical ingredient manufacturing for essential medicines. Health, Nutrition and Population (HNP) discussion paper; World Bank, Washington, DC. © World Bank. https://openknowledge.worldbank.org/handle/10986/13682 License: CC BY 3.0 IGO.

Mankind Pharma, 2022. Quality factors for active pharmaceutical ingredients. Link: https://www.mankindpharma.com/blog/quality-factors-for-active-pharmaceutical-ingredients. Accessed on 13/06/2022.

WHO, 2022. Active Pharmaceutical Ingredients. Prequalification Procedures and Fees: FPPs, APIs & QCLs.