Leflunomide

MONDAY, April 17, 2023 -- Arthritis is a common disease that causes pain and inflammation in different body joints, making it difficult to enjoy everyday tasks and physical activity. Fortunately, there are many different medications for arthritis. Depending on what type of arthritis you have and its severity, an arthritis medication may help you manage pain and other symptoms. Here is a breakdown of the most common arthritis medications, how they work and their potential side effects. The Arthritis Foundation lists the following as the medications used to treat arthritis: Analgesics including acetaminophen (Tylenol) and opioids Nonsteroidal anti-inflammatory drugs (NSAIDs) Corticosteroids Disease-modifying antirheumatic drugs (DMARDs) including biologics and targeted DMARDs Analgesics The Arthritis Foundation reports that analgesics may help with mild to moderate pain, but they will not help with the inflammation associated with arthritis. Analgesics work in the nervous system and alter how your brain perceives pain. They can be used to treat the pain associated with any type of arthritis, although more effective options are available. Analgesics can be opioid, non-opioid or a combination. Common analgesics are: Acetaminophen (Tylenol) Codeine Oxycodone Fentanyl Hydrocodone Potential side effects: Kidney damage Liver damage Addiction Constipation Gastrointestinal bleeding Use caution when taking these medications; take only as prescribed. NSAIDs NSAIDs work by blocking prostaglandin. According to the Cleveland Clinic , one role prostaglandins play is forming clots and causing inflammation at the site of an injury. NSAIDs are used to treat the pain and inflammation associated with rheumatoid arthritis and osteoarthritis . Common over-the-counter (OTC) NSAIDs are: Aspirin (Bayer, St. Joseph, Anacin, Excedrin and more) Ibuprofen (Motrin, Advil) Naproxen sodium (Aleve) Prescription NSAIDs are: Celecoxib (Celebrex) Diclofenac (Voltaren, available by brand name in topical form) Fenoprofen (Nalfon) Indomethacin (Indocin, available by brand name in liquid form) Ketorolac tromethamine (Toradol) Meclofenamate sodium (Meclomen) Diflunisal (Dolobid) Tolmetin (Tolectin) Ketoprofen (Orudis) Flurbiprofen (Ansaid) Potential side effects of NSAIDs are: Increased risk of stomach and bowel issues like ulcers and bleeding Increased risk of stroke Heart problems Stomach pain Nausea Diarrhea/constipation Corticosteroids According to the Arthritis Foundation , corticosteroids mimic cortisol, a hormone your body produces naturally. They are used to treat inflammatory types of arthritis, including rheumatoid arthritis and psoriatic arthritis. They are great for short-term relief of inflammation but are not recommended for long-term use because of their side effects. Your doctor may prescribe a lower dose if you require them for long-term use. Common corticosteroids: Prednisone (Deltasone, Prednicot, Cotolone) Prednisolone (Orapred, Omnipred) Cortisone (Cortone) Hydrocortisone (Cortef, Hydrocort) Triamcinolone (Aristocort) Dexamethasone (Decadron) Common side effects of corticosteroids: Blood sugar spikes Weight gain Bone loss Risk of cataracts High blood pressure Infections Mood changes DMARDs The Arthritis Foundation says that DMARDs work with the body to “stop or slow the disease process in inflammatory forms of arthritis.” They work by blocking inflammation. There are many different DMARDs on the market, and they all have different ways of working in the body. Conventional DMARDs work by broadly suppressing the immune system. Often they are used in combination with other therapies. Targeted DMARDs block specific pathways inside immune cells. Biologic DMARDs are produced by live cells and work on specific immune proteins called cytokines. Common DMARDs: Apremilast (Otezla) Baricitinib (Olumiant) Cyclophosphamide (Cytoxan) Cyclosporine (Gengraf, Neoral) Hydroxychloroquine (Plaquenil) Leflunomide (Arava) Methotrexate (Otrexup, Rasuvo, RediTrex) Mycophenolate mofetil (CellCept) Sulfasalazine (Azulfidine) Tofacitinib (Xeljanz, Xeljanz XR) According to the Cleveland Clinic , common side effects of traditional DMARDs include: Loss of appetite Nausea Diarrhea Abdominal pain Rash, allergic reaction Liver problem Increased risk of infection Low blood cell counts Common side effects of biologic DMARDs include: Increased risk of common and serious infections Reactivation of tuberculosis, herpes zoster, and hepatitis B and C Increased cholesterol levels, increased liver enzymes and low blood cell counts Increased risk of clotting When prescribed DMARDs, inform your doctor of any other medications, including over-the-counter medicines, you are taking to avoid drug interactions. Some of these medications can cause teratogenicity (defects in a developing fetus.) Writing recently in the Journal of the American Academy of Physician Assistants (JAAPA ), physician assistant Michelle DiBiase and Dr. Samantha Kohn remind people that "The mainstay of pharmacologic therapy is early intervention with use of nonbiologic and biologic DMARDs together with adjunctive medications such as NSAIDs, oral and intra-articular corticosteroids, and analgesic medications, including opioids." Your primary care provider or rheumatologist will work closely with you to determine which medications are best for your treatment. It is vital to keep them apprised of any side effects and let them know if the treatment is ineffective. They can work with you to find a treatment that helps relieve the pain and inflammation caused by arthritis. Posted April 2023

Scientists hope new findings could translate to treatments for medulloblastoma that have fewer side effects than the ones in use today. Medulloblastoma is a relatively treatable pediatric brain cancer, with survival rates of about 80% if it's treated before it spreads. But in addition to surgery, most cases require chemotherapy and radiation—treatments that can harm brain development and set the stage for complications later in life. Now, it appears that blocking a key enzyme could offer a better path to treating medulloblastoma. In a study published Nov 10. in Cancer Cell, scientists at McMaster University in Ontario described how they used a Bayer compound to curtail the cancer's spread in mouse models of its most aggressive subtype. “This potential treatment pathway will allow us to kill the weeds but save the flower of the developing brain,” William Gwynne, first author, said in a press release. The enzyme at the heart of the study is dihydroorotate dehydrogenase, or DHODH. It’s a key part of the de novo pyrimidine synthesis pathway, a pathway that ultimately leads to the creation of DNA and RNA and is known to be hijacked by cancers in their effort to grow. DHODH inhibitors like Sanofi’s Arava and Aubagio are FDA approved for the treatment of rheumatoid arthritis and multiple sclerosis, respectively, while others are under investigation against a wide breadth of conditions, including viruses and several types of cancer.   The McMaster team’s findings add one more potential indication to the list. The scientists homed in on DHODH by screening the genomes and metabolic processes of MYC-amplified medulloblastoma, a particularly deadly subtype of the brain cancer. They found alterations in the de novo pyrimidine synthesis pathway, and genetic analyses in cells and mice showed that knocking out DHODH could hinder medulloblastoma growth. The scientists then sought to find out whether an orally administered DHODH inhibitor could stop tumor growth in mice. They treated mouse models of MYC-amplified medulloblastoma with a compound called BAY2402234, which, until this past January was under investigation by Bayer for the treatment of acute myeloid leukemia and glioma. The researchers found that the compound was able to reduce tumor growth and improve survival times in the mice, increasing their life spans from about 28 days in controls to around 38 days in the ones that were treated with BAY2402234. While the team didn’t assess whether the compound had an impact on the brain development of young mice, they did find that it wasn’t harmful to cultured neural stem cells. In contrast, radiation is well known to impact neural stem cells in both children and adults and is thought to be the reason for brain damage associated with its use. Chemotherapy has been shown to kill brain cells as well, a possible explanation for the phenomenom of “chemo brain” described by patients. Given these results and the fact that BAY2402234 has already been proven safe in humans during clinical trials at the equivalent doses to the ones used in their study, the researchers called for further optimizing DHODH inhibitors preclinically in medulloblastoma both alone and in combination with other treatments. If they perform well, the drugs should be translated to clinical research, the researchers wrote in their paper.