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Antiarthritics are medications used to treat or prevent arthritic symptoms, such as joint pain and stiffness, which typically worsen with age.

Arthritis

Arthritis is the swelling and tenderness of one or more of your joints. The typical types of arthritis are osteoarthritis and rheumatoid arthritis.

Arthritis is also a common symptom for lupus (systemic lupus erythematosus), an autoimmune disease that attacks joints and internal organs, including the heart, lungs, brain, and kidneys.

Types of Arthritis

Osteoarthritis

Osteoarthritis (OA) is caused by the wear and tear damage to the joint’s cartilage. Cartilage usually protects the joints from damage by friction. However, accumulated damage may result in direct bone grinding on bone causing pain and restricted movements. The wear and tear may occur over many years or it can be hastened by a joint injury or infection.

Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is known as the second most common type of arthritis. It is an inflammatory disease that’s caused by autoimmune condition. The condition occurs when bodily cells begin to attack and target their own healthy joint tissues resulting in redness, inflammation and pain. Antiarthritics are used to block inflammation and help prevent joint damage.

Medical Use

The medical uses of antiarthritic drugs mainly target to relieve the arthritic symptoms, achieve disease remission or low disease activity (if remission cannot be achieved) ^bnf. Ultimately, treatment aims to improve a patient's ability to perform daily activities that may have been hindered due to the complications of arthritis.^

Drug Types

Disease-modifying antirheumatic drugs (DMARDs)

Disease-modifying antirheumatic drugs (DMARDs) are often used to decrease inflammation at the site of injury for RA. DMARDs are unlike other common medications that temporarily ease pain and reduce inflammation, it also functions to decrease progression of RA. It primarily targets the slowing or stopping of the immune system from attacking your joints.

Conventionally, DMARDs are known to be the first-line treatment for rheumatoid arthritis. It may be prescribed as monotherapy or in combination with other anti-arthritic medications. Common DMARDs include oral methotrexate, leflunomide, or sulfasalazine.

Drug Characteristics

Conventional DMARDs have a slow onset of action and can take 2–3 months to take effect. Therefore, short-term bridging treatment with a corticosteroid is often considered when introducing a treatment with a new conventional DMARD to provide rapid symptomatic control, while waiting for the new DMARD to take effect.

Methotrexate

Mechanism of Action

Methotrexate is a DMARDs that competitively inhibits the enzyme dihydrofolate reductase and prevents the formation of tetrahydrofolate which is necessary for purine and pyrimidine synthesis and consequently the formation of DNA and RNA.^

Side Effects

The most common dose-related toxic effects of methotrexate are on the bone marrow and gastrointestinal tract.^ Folic acid may be given every week to help reduce the frequency of such side-effects.^ Methotrexate is also associated with liver damage, both acute and chronic (depending on dose and duration of treatment). Other adverse effects include renal failure and tubular necrosis after high doses, pulmonary reactions including life-threatening interstitial lung disease, skin reactions (sometimes severe), alopecia, and ocular irritation.^

Contraindications:

Methotrexate is contraindicated to those with active infection; ascites; immunodeficiency syndromes; significant pleural effusion.^ In addition, it is avoided during pregnancy as like other folate inhibitors it is teratogenic, and it has been associated with fetal deaths.^

Biologic response modifiers

Biologic response modifiers (biological therapies) are typically administered in conjunction with DMARDs. This class of drug is commonly classified under the greater category of DMARDs. It is genetically engineered to target various protein molecules that are involved in the immune response. There are many subclasses of biologic response modifiers. The most commonly prescribed medication of this class to treat arthritis would be tumor necrosis factor (TNF) inhibitors. Examples include etanercept and infliximab. Other biologic agents would act on other substances that play a role in inflammation. For instance, interleukin-1 (IL-1), interleukin-6 (IL-6), Janus kinase enzymes, and certain types of white blood cells known as B cells or T cells.

However, biologic response modifiers are administered by injection and/or by IV route. Therefore, it is an expensive medication to treat arthritis.

Analgesics

Another type of medication that is often prescribed or recommended to patients with arthritis are analgesics (or painkillers). These medications help to reduce pain, but have no effect on reducing inflammation. Over-the-counter options include Acetaminophen. In more severe cases of arthritic pain, opioids may be prescribed by the general practitioner. For example, tramadol, oxycodone or hydrocodone. Opioids functions on the central nervous system to provide pain relief. The long term use of opioids have been associated with mental and physical side effects including drug dependence.^

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) is a drug class that helps reduce both pain and inflammation. NSAIDs can often be found over-the-counter including ibuprofen and naproxen. There may be exceptions to which some NSAIDs are only available by prescription. Oral NSAIDs can cause stomach irritation and may increase your risk of heart attack or stroke. Other formulation types are also available, such as creams or gels that can be applied directly to the joints.^

Side Effects

Similar to corticosteroids, NSAIDs should be used for short periods of time. This is recommended due to the potential gastrointestinal tract complications. Therefore, the type of NSAIDs prescribed would also be dependent on the patient’s past medical history including liver, kidney, heart problems or stomach ulcers.

Mechanism of Action

The mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. The therapeutic effects of NSAIDs are attributed to the lack of these eicosanoids.^

Counterirritants

Corticosteroids is a class of drugs that features the reduction of inflammation and suppression of the immune system. Common medication includes prednisone and cortisone. These corticosteroids can be taken orally or can be injected directly into the painful joints.

Side Effects

Due to the extensive risk of side effects associated with the use of corticosteroids, it is generally recommended for a short term therapy. For example, during a flare up episode of arthritic symptoms, short-term corticosteroids are administered to rapidly decrease inflammation of the joints. In case of facing severe side effects, the drug should not be stopped suddenly.

Mechanism of Action

Corticosteroids affect numerous steps in the inflammatory pathway. To exert an effect, the steroid molecule binds to glucocorticoid receptors causing a conformational change in the receptor. This receptor mediates with glucocorticoid response elements that are associated with either suppression or stimulating transcription of genes, which results in ribonucleic acid and protein synthesis. Ultimately, these agents inhibit transcription factors that control synthesis of pro-inflammatory mediators, including macrophages, eosinophils, lymphocytes, mast cells, and dendritic cells. Another important effect is inhibition of phospholipase A2, which is responsible for production of numerous inflammatory mediators.^

Non-Pharmacological Therapy

Non-pharmacological treatment includes physiotherapy, psychological interventions such as relaxation, stress management, and cognitive coping skills. The combination of both pharmacological and non-pharmacological treatment is optimal. Therefore, any treatment plan for arthritis should involve physical therapy, which will include basic stretches, exercises to ease joint stiffness, and instructions on joint protection.^

Treatment Guidelines

OA:

Based on the American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee (2019), the compelling pharmacological recommendations for treatment of osteoarthritis are oral NSAIDs, topical NSAIDs (for hands and knees), and I-A steroids. Other conditionally recommended therapies include Acetaminophen, Tramadol, Duloxetine, Chondroitin and Topical Capsaicin.^

RA:

According to the American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis (2015), the first-line pharmacological recommendation for patients with symptomatic rheumatoid arthritis would be DMARD monotherapy (Methotrexate preferred). In moderate or severe disease activity, combination traditional DMARDs or add a TNFi or a non-TNF biologic or Tofacitinib are recommended.^

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