Antiarthritics

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An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

Contents

A dorsal view of the hand, revealed swelling of the finger joints, indicative of an underlying inflammatory process at the proximal interphalangeal joints Arthritis on the Right Hand.jpg
A dorsal view of the hand, revealed swelling of the finger joints, indicative of an underlying inflammatory process at the proximal interphalangeal joints

Common antiarthritic drug classes include the following: disease-modifying antirheumatic drugs, biologic response modifiers, analgesics, non-steroidal anti-inflammatory drugs, and corticosteroids. [1]

Signs of Arthritis. Swelling of the ankle joints which is indicative of an underlying inflammatory process. Swelling of the ankle joints.jpg
Signs of Arthritis. Swelling of the ankle joints which is indicative of an underlying inflammatory process.

Types of arthritis

Osteoarthritis

Osteoarthritis (OA) is caused by the wear and tear damage to the joint's cartilage.

The compelling pharmacological recommendations for the treatment of OA 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. [2]

Rheumatoid arthritis

Illustration of a Hand affected by Rheumatoid arthritis Rheumatoid arthritis -- Smart-Servier (cropped).jpg
Illustration of a Hand affected by Rheumatoid arthritis

Rheumatoid Arthritis (RA) is an inflammatory disease that's caused by an autoimmune condition. The condition occurs when bodily cells begin to attack and target their own healthy joint tissues resulting in redness, inflammation, and pain. Patients with RA may be given antiarthritics that are used to block inflammation and help prevent joint damage.

The typical first-line pharmacological recommendation for patients with symptomatic rheumatoid arthritis is DMARD monotherapy (Methotrexate preferred). In moderate or severe disease activity, it is recommended to combine conventional DMARDs, add a TNF-α Inhibitors or a non-TNF biologic or Tofacitinib. [3]

Gout

Gout swelling of the big toe Gout Signs and Symptoms.jpg
Gout swelling of the big toe

Gout is another common type of inflammatory arthritis that typically affects one joint at a time. Pharmacological treatment of gout typically relies on the management of flare-ups. Flare-ups are treated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, steroids, and/or the anti-inflammatory medication colchicine. [4]

Juvenile rheumatoid arthritis

Juvenile rheumatoid arthritis, the most common type of childhood (under age of 16) arthritis, can cause permanent physical damage to joints. [5] Pharmacological interventions include NSAIDs (naproxen, ibuprofen, and indomethacin), intra-articular corticosteroid (IAC) injections like triamcinolone hexacetonide (TH), conventional DMARDs (Methotrexate), and TNF inhibitors such as Etanercept. [6]

Medical use

Antiarthritic drugs are used to treat or prevent joint pain and joint diseases. These medications also provide symptomatic relief to common arthritic joint symptoms including swelling, tenderness, pain, stiffness, and decreased range of motion. [7] These symptoms may persist or occur periodically and if symptoms are not managed, major complications may develop including permanent joint changes, chronic pain, and functional disabilities. [7] Ultimately, antiarthritic treatments aim to achieve disease remission or low disease activity if remission cannot be achieved and thereby improving quality of life. [8]

The pharmacological effects of antiarthritic medications are typically exerted through the reduction of inflammation, suppression of the immune system and/or aid in easing pain.

Disease-modifying antirheumatic drugs (DMARDs)

Disease-modifying antirheumatic drugs (DMARDs) are often used to decrease inflammation at the site of injury for RA. DMARDs also act to relieve pain and decrease progression and worsening of RA. It mainly functions by slowing or stopping the immune system from attacking the joints. [9]

Conventional DMARDs are known to be the first-line treatment for rheumatoid arthritis. [9] Treatment can be a monotherapy or in combination with other anti-arthritic medications. Common DMARDs include oral methotrexate, leflunomide, or sulfasalazine.

Conventional DMARDs have a slow onset of action and can take 2–3 months to exhibit effect. [9] Short-term bridging treatment with a corticosteroid is often considered when introducing a treatment with a new conventional DMARD. The use of short-term corticosteroids will help with a rapid symptomatic relief while waiting for the DMARD to exert effect.

Methotrexate

Methotrexate is considered to be the preferred conventional DMARD to treat RA. [10] Route of administration includes oral tablets and liquids as well as intravenous and subcutaneous injections into the skin. [10] [11]

Mechanism of action

Methotrexate is a DMARDs that acts as a competitive inhibitor on the enzyme dihydrofolate reductase and hinders the formation of tetrahydrofolate. [12] Tetrahydrofolate is essential for the synthesis of purine and pyrimidine which consequently controls the formation of DNA and RNA that are responsible for the immune response and inflammation. [12] By preventing the formation of tetrahydrofolate and the subsequent proteins, DMARDs suppresses the immune response and reduces arthritis inflammation.

Side effects

Methotrexate is commonly associated with dose-related toxic effects involving the bone marrow and gastrointestinal tract. [12] Folic acid may be given weekly to help diminish the frequency of side-effects. [12] Methotrexate is also associated with acute and chronic liver damage.

Other adverse effects include: [12]

Folic acid (vitamin B9) may be given by medical practitioners during the drug therapy using methotrexate. Folic acid acts to provide protection for the healthy cells in the human body. [10] As such, it will help to reduce the side effects of methotrexate. [10]

Contraindications

Contraindications of methotrexate include: [13]

In addition, methotrexate is teratogenic and has been associated with fetal deaths. [13] As a consequence, it is avoided during pregnancy.

Biologic response modifiers

Biologic response modifiers (biological therapies) are drugs classified as a special type of DMARDs. It is typically administered when conventional DMARDs do not work. [14] It is genetically engineered to target various proteins that are involved in the immune response. The route of administration is available through intravenous or subcutaneous injection. [15]

Biologic response modifiers are commonly used as a monotherapy or in combination with non-biologics, such as methotrexate. Combination of biologics is not advised due to limited additional benefit accompanied with a substantial increase in risks. [14]

Biologic response modifiers can be divided into classes based on protein molecules that it inhibits such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), and white blood cells like B cells or T cells. [16]

Mechanism of action

Biologic response modifiers act by altering the immune response of the human body. The mechanism of action is either through interfering with the effect of cytokines, inhibiting the costimulation of T cell activation, or inhibiting B cells. [15] Cytokines are proinflammatory and are responsible for regulating the human immune response. [17]

TNF-α inhibitors

TNF-α Inhibitors are the most commonly prescribed medication among biologic response modifiers used to treat arthritis. Patients with rheumatic conditions may have higher levels of TNF in the systemic circulation. [18] As a result of increased levels of TNF, there would be more inflammation and persistent symptoms of arthritis. [18] Certolizumab is the only TNF-α Inhibitor that can be administered during pregnancy. [14]

Examples: [14]

Interleukin inhibitors

IL-1 and IL-6 are particularly involved as proinflammatory cytokines contributing to arthritic symptoms. [19] The inhibition of these cytokines is effective in reducing inflammation and consequently reducing the severity of arthritis. [17]

Examples: [14]

Selective costimulation modulator of T cells

Selective Costimulation Modulator of T Cells is a type of biologic that targets the inhibition of T cell activation as well as the selective blocking of the interaction between CD80 and CD86 receptors to CD28. [20] To prevent CD28 interaction with the CD80/CD86 receptors, these drugs modulate by binding to these receptors on antigen presenting cells (APC). [20] As a result, this type of biologic inhibits T cell proliferation and B cell immunological response. [20]

Abatacept is available as an antiarthritic medication for moderate to severe RA. This biologic can also be used to treat patients with juvenile rheumatoid arthritis. [14]

Examples: [16]

B Cells inhibitor

B Cells, or B lymphocytes are a type of white blood cells that contribute to the pathogenesis of RA. [21] B cells have a variety of functions including being an efficient APC, contribute to T cell activation, produce cytokines that promote the permeation of leukocytes into the joints and more. [21] The therapeutic effect of B cells inhibitor is dependent on the disruption of these diverse functions.

Examples: [16]

Side effects

The adverse reactions of biologic response modifier therapies are associated with their mechanism of action that disrupts the immune homeostasis of the human body. [15] These inhibitory biologics cause suppression of the immune response resulting in an increase in risk and susceptibility to infection. [14] [15]

Common infections include: [14]

It may also cause mild side effects such as headache and nausea. [14]

Janus kinase inhibitors

Janus kinase (JAK) inhibitors are used to treat RA. Similar to biologic response modifiers, these drugs act to reduce immune response. [22] However, these medications are available in tablet formulations, unlike biologics. [23]

Examples: [22]

Mechanism of action

JAK inhibitors act by inhibiting Janus Kinases which consequently affect a cascade of enzymes responsible for signaling a variety of cytokine and haematopoietic growth factor receptors. [24] As a consequence, inhibiting these enzymes leads to the control and suppression of immune pathways.

Side effects

The common side effect of using JAK inhibitors is the increased susceptibility to infections. For example: [22]

Analgesics

Analgesics or painkillers are defined as medications that help to manage and reduce pain. It is often used in treatments of arthritis to provide relief on the site of injury. Acetaminophen, opioids and counterirritants are common analgesics used in the therapy of arthritis. However, these drugs have no control over inflammation. [25]

Acetaminophen

Acetaminophen (Paracetamol) is a common over-the-counter option to manage pain. It is commonly used to relieve mild to moderate severity of pain. [26] There are various routes of administration including oral, rectal and intravenous. [26] [27] Acetaminophen is often recommended in treating osteoarthritic patients.

Mechanism of action

Despite the mechanism of action of acetaminophen is not completely understood, it appears to act on the COX pathway. It reduces COX activity by inhibiting the synthesis of prostaglandins in the central nervous system. [27] The reduction of COX activity contributes to its analgesic effects. [27]

Side effects

Hepatotoxicity is often associated with the overdose of acetaminophen causing acute liver failure. The maximum recommended daily dosage for an adult is 4000 mg. [26]

Opioids

In more severe cases of arthritic pain, opioids may be prescribed by the general practitioner. For example, tramadol, oxycodone or hydrocodone.

Mechanism of action

Opioids function on the central nervous system to provide pain relief. The long term use of opioids has been associated with mental and physical side effects including drug dependence. [28]

Side effects

Common side effects of opioids include: [29]

Counterirritants

Counterirritant is a drug that belongs to the analgesic class. Typically, these agents are in topical formulations such as ointments and creams that contain menthol or capsaicin. It only provides modest pain relief and is not effective for managing severe pain. [30]

Mechanism of action

Counterirritants act by exciting and subsequently desensitizing epidermal nociceptive sensory neurons. [31] [32] When applied to the site of injury, it produces a heating sensation and consequently surface irritation of the skin. This sensation interferes with the transmission of pain signals from the joints to the brain. Thereby distracting the brain from pain. [30]

Side effects

Topical therapies minimize systemic exposure and reduce the risks of patients developing adverse events that are common with orally administered pain management medications such as NSAIDs. [32] However, counterirritants are associated with undesirable reactions at the site of application. Typical side effects include dryness, erythema, burning, and discoloration. [32]

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) belongs to a drug class that has both analgesic and anti-inflammatory effects. [25] 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 may cause discomfort to the stomach and may also increase the 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.

Mechanism of action

NSAIDs exhibit their pharmacological effects through the inhibition of the cyclooxygenase (COX) enzyme. COX is a necessary protein that facilitates the conversion of arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. When the COX activity is inhibited, the synthesis of the subsequent eicosanoids is reduced. As a result, NSAIDs produce analgesic and anti-inflammatory effects. [33]

Side effects

Similar to corticosteroids, NSAIDs should be used for short periods of time due to the risk of side effects. Common side effects of NSAIDs include

Rarer side effects consist of complications affecting the liver, kidneys or heart and circulation, potentiating the cause of heart failure, heart attacks and strokes. [34]

Corticosteroids

Corticosteroid is a class of drugs that features the reduction of inflammation and suppression of the immune system. [35] Common medication includes prednisone and cortisone. These corticosteroids can be taken orally or can be injected directly into the painful joints.

Due to the extensive risk of side effects associated with the use of corticosteroids, it is generally recommended for short term therapy. For example, during a flare-up or an episode of arthritic symptoms, short-term corticosteroids are administered to rapidly decrease inflammation of the joints.

Mechanism of action

Corticosteroids mediates multiple steps in the inflammatory pathway. To exert an effect, the steroid compound binds to glucocorticoid receptors. As a result, the receptors changes their conformation and influences glucocorticoid response elements. These elements are connected with either suppression or stimulating transcription of genes responsible for ribonucleic acid and protein synthesis. Corticosteroids are responsible for inhibiting transcription factors that control the synthesis of proinflammatory molecules, including macrophages, eosinophils, lymphocytes, mast cells, and dendritic cells. Corticosteroids also exert their effect by inhibiting phospholipase A2. Phospholipase A2 controls the production of various inflammatory mediators. [35]

Side effects

Injected corticosteroids may cause:

Patients taking short term oral corticosteroids may experience:

Long term usage may lead to more severe complications including:

In case of facing severe side effects, the drug should not be stopped suddenly. If corticosteroids are stopped abruptly, the patient may experience fatigue, nausea, vomiting, diarrhoea, and abdominal pain. [36]

See also

Related Research Articles

<span class="mw-page-title-main">Arthritis</span> Type of joint disorder

Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Rheumatoid arthritis</span> Type of autoimmune arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.

<span class="mw-page-title-main">Methotrexate</span> Chemotherapy and immunosuppressant medication

Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection.

<span class="mw-page-title-main">Infliximab</span> Biopharmaceutical drug for autoimmune disorders

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis of the spine

Ankylosing spondylitis (AS) is a type of arthritis from the disease spectrum of axial spondyloarthritis. It is characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bowel problems—as well as back pain—may occur. Joint mobility in the affected areas sometimes worsens over time. Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors. More than 90% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is based on symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.

<span class="mw-page-title-main">Disease-modifying antirheumatic drug</span> Category of drugs

Disease-modifying antirheumatic drugs (DMARDs) comprise a category of otherwise unrelated disease-modifying drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to nonsteroidal anti-inflammatory drugs and steroids.

Spondyloarthritis (SpA), also known as spondyloarthropathy, is a collection of clinical syndromes that are connected by genetic predisposition and clinical manifestations. The best-known clinical subtypes are enteropathic arthritis (EA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and reactive arthritis (ReA). Spondyloarthritis typically presents with inflammatory back pain and asymmetrical arthritis, primarily affecting the lower limbs, and enthesitis, inflammation at bone-adhering ligaments, tendons, or joint capsules.

<span class="mw-page-title-main">Psoriatic arthritis</span> Long-term inflammatory arthritis

Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

Anti-inflammatory or antiphlogistic is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

<span class="mw-page-title-main">Uveitis</span> Inflammation of the uvea of the eye

Uveitis is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is described anatomically, by the part of the eye affected, as anterior, intermediate or posterior, or panuveitic if all parts are involved. Anterior uveitis (iridocyclitis) is the most common, with the incidence of uveitis overall affecting approximately 1:4500, most commonly those between the ages of 20–60. Symptoms include eye pain, eye redness, floaters and blurred vision, and ophthalmic examination may show dilated ciliary blood vessels and the presence of cells in the anterior chamber. Uveitis may arise spontaneously, have a genetic component, or be associated with an autoimmune disease or infection. While the eye is a relatively protected environment, its immune mechanisms may be overcome resulting in inflammation and tissue destruction associated with T-cell activation.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous or exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.

<span class="mw-page-title-main">Tenoxicam</span> Non-steroidal anti-inflammatory drug

Tenoxicam, sold under the brand name Mobiflex among others, is a nonsteroidal anti-inflammatory drug (NSAID). It is used to relieve inflammation, swelling, stiffness, and pain associated with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and periarthritis of the shoulders or hips.

<span class="mw-page-title-main">Acemetacin</span> NSAID analgesic medication

Acemetacin is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis, rheumatoid arthritis, lower back pain, and relieving post-operative pain. It is manufactured by Merck KGaA under the tradename Emflex. It is no longer available in the UK, however is available in other countries as a prescription-only drug.

<span class="mw-page-title-main">Fostamatinib</span> Chemical compound

Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth.

<span class="mw-page-title-main">Upadacitinib</span> Biopharmaceutical drug

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

Autoimmunity refers to a pathological immune response of the body's immune system against itself. Autoimmune disease is widely recognized to be significantly more common in women than in men, and often presents differently between the sexes. The reasons for these disparities are still under investigation, but may in part involve the presence of an additional X chromosome in women, as well as the higher presence of female sex hormones such as estrogen. The risk, incidence, and character of autoimmune disease in women may also be associated with female-specific physiological changes, such as hormonal shifts during menses, pregnancy, and menopause.

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