# Antiarthritics

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{{Short description|Drug class}}
An '''antiarthritic''' is any drug used to relieve or prevent arthritic symptoms, such as [joint pain](/source/joint_pain) or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing [inflammation](/source/inflammation) or acting as an [immunosuppressant](/source/immunosuppressant). These drugs are typically given orally, topically or through administration by [injection](/source/Injection_(medicine)). The choice of antiarthritic medication is often determined by the nature of [arthritis](/source/arthritis), the severity of symptoms as well as other factors, such as the [tolerability](/source/tolerability) of side effects.

thumb|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 drug](/source/disease-modifying_antirheumatic_drug)s, [biologic response modifiers](/source/Biological_response_modifier), [analgesic](/source/analgesic)s, [non-steroidal anti-inflammatory drugs](/source/Nonsteroidal_anti-inflammatory_drug), and [corticosteroid](/source/corticosteroid)s.<ref>{{Cite web|title=Rheumatoid Arthritis Drug Guide: Types of Drugs, Uses, Side Effects|url=https://www.webmd.com/rheumatoid-arthritis/rheumatoid-arthritis-medications|access-date=2021-04-01|website=WebMD|language=en}}</ref>

thumb|Signs of arthritis. Swelling of the ankle joints which is indicative of an underlying inflammatory process.

== Types of arthritis ==

=== Osteoarthritis ===
[Osteoarthritis](/source/Osteoarthritis) (OA) is caused by the wear and tear damage to the joint's [cartilage](/source/cartilage).

The compelling pharmacological recommendations for the treatment of OA are oral [NSAIDs](/source/Nonsteroidal_anti-inflammatory_drug), topical NSAIDs (for hands and knees), and intra-articular steroids. Other conditionally recommended therapies include [acetaminophen](/source/Paracetamol), [tramadol](/source/tramadol), [duloxetine](/source/duloxetine), [chondroitin](/source/chondroitin), and topical [capsaicin](/source/capsaicin).<ref>{{Cite journal|title=2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee|url=https://www.rheumatology.org/Portals/0/Files/Osteoarthritis-Guideline-Early-View-2019.pdf|journal=American College of Rheumatology}}</ref>

=== Rheumatoid arthritis ===
thumb|Illustration of a hand affected by rheumatoid arthritis
[Rheumatoid arthritis](/source/Rheumatoid_arthritis) (RA) is an [inflammatory disease](/source/Inflammation) that's caused by an [autoimmune](/source/Autoimmunity) 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](/source/inflammation) and help prevent joint damage.

The typical first-line pharmacological recommendation for patients with symptomatic rheumatoid arthritis is DMARD monotherapy ([methotrexate](/source/methotrexate) preferred). In moderate or severe disease activity, it is recommended to combine conventional DMARDs, add a [TNF-α inhibitors](/source/TNF_inhibitor) or a non-TNF biologic or [tofacitinib](/source/tofacitinib).<ref>{{Cite journal|title=2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis|url=https://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf|journal=American College of Rheumatology}}</ref>

=== Gout ===
thumb|Gout swelling of the big toe.

[Gout](/source/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 drug](/source/nonsteroidal_anti-inflammatory_drug)s (NSAIDs) like [ibuprofen](/source/ibuprofen), [steroid](/source/steroid)s, and/or the anti-inflammatory medication [colchicine](/source/colchicine).<ref>{{Cite web|date=2020-07-27|title=Gout, Arthritis, CDC|url=https://www.cdc.gov/arthritis/basics/gout.html|access-date=2021-03-15|website=www.cdc.gov|language=en-us}}</ref>

=== Juvenile rheumatoid arthritis ===
[Juvenile rheumatoid arthritis](/source/Juvenile_idiopathic_arthritis), the most common type of childhood (under age of 16) arthritis, can cause permanent physical damage to joints.<ref>{{Cite web|date=2020-07-27|title=Childhood Arthritis, CDC|url=https://www.cdc.gov/arthritis/basics/childhood.htm|access-date=2021-03-31|website=www.cdc.gov|language=en-us}}</ref> Pharmacological interventions include NSAIDs ([naproxen](/source/naproxen), [ibuprofen](/source/ibuprofen), and [indometacin](/source/indometacin)), intra-articular corticosteroid (IAC) injections like [triamcinolone](/source/triamcinolone) [hexacetonide](/source/Acetonide) (TH), conventional DMARDs ([methotrexate](/source/methotrexate)), and TNF inhibitors such as [etanercept](/source/etanercept).<ref>{{Cite journal|last1=Giancane|first1=Gabriella|last2=Consolaro|first2=Alessandro|last3=Lanni|first3=Stefano|last4=Davì|first4=Sergio|last5=Schiappapietra|first5=Benedetta|last6=Ravelli|first6=Angelo|date=2016-08-12|title=Juvenile Idiopathic Arthritis: Diagnosis and Treatment|journal=Rheumatology and Therapy|volume=3|issue=2|pages=187–207|doi=10.1007/s40744-016-0040-4|issn=2198-6576|pmc=5127964|pmid=27747582}}</ref>

== 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.<ref name=":3" /> 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.<ref name=":3">{{Cite web|title=What Is Arthritis?|url=https://www.arthritis.org/health-wellness/about-arthritis/understanding-arthritis/what-is-arthritis|access-date=2021-03-31|website=www.arthritis.org|language=en}}</ref> Ultimately, antiarthritic treatments aim to achieve disease remission or low disease activity if remission cannot be achieved and thereby improving [quality of life](/source/quality_of_life).<ref>{{Cite web|date=2020-12-14|title=Rheumatoid Arthritis|url=https://www-new-medicinescomplete-com.eproxy.lib.hku.hk/#/content/bnf/_527458681?hspl=rheumatoid&hspl=arthritis|access-date=2021-03-31|website=British National Formulary}}</ref>

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) ==
{{main|Disease-modifying antirheumatic drug}}
Disease-modifying antirheumatic drugs (DMARDs) are often used to decrease [inflammation](/source/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](/source/immune_system) from attacking the joints.<ref name=":4" />

Conventional DMARDs are known to be the first-line treatment for rheumatoid arthritis.<ref name=":4">{{Cite journal|title=Rheumatoid arthritis in adults: management|url=https://www.nice.org.uk/guidance/ng100/resources/rheumatoid-arthritis-in-adults-management-pdf-66141531233989|journal=National Institute for Health and Care Excellence}}</ref> Treatment can be a monotherapy or in combination with other anti-arthritic medications. Common DMARDs include oral [methotrexate](/source/methotrexate), [leflunomide](/source/leflunomide), or [sulfasalazine](/source/sulfasalazine).

Conventional DMARDs have a slow onset of action and can take 2–3 months to exhibit effect.<ref name=":4" /> Short-term [bridging](/source/Bridge_therapy) treatment with a [corticosteroid](/source/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](/source/Methotrexate) is considered to be the preferred conventional DMARD to treat RA.<ref name=":5">{{Cite web|date=2020-03-30|title=Methotrexate – an immunosuppressant used to treat inflammatory conditions|url=https://www.nhs.uk/medicines/methotrexate/|access-date=2021-03-31|website=nhs.uk|language=en}}</ref> Route of administration includes oral [tablet](/source/tablet_(pharmacy))s and liquids as well as intravenous and subcutaneous injections.<ref name=":5" /><ref>{{Citation|last1=Benjamin|first1=Onecia|title=Disease Modifying Anti-Rheumatic Drugs (DMARD)|date=2021|url=https://www.ncbi.nlm.nih.gov/books/NBK507863/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29939640|access-date=2021-04-01|last2=Bansal|first2=Pankaj|last3=Goyal|first3=Amandeep|last4=Lappin|first4=Sarah L.}}</ref>

==== Mechanism of action ====
Methotrexate is a DMARD that acts as a competitive inhibitor on the enzyme [dihydrofolate reductase](/source/dihydrofolate_reductase) and hinders the formation of [tetrahydrofolate](/source/Tetrahydrofolic_acid).<ref name=":0">{{Cite web|date=2021-01-26|title=Methotrexate|url=https://www-new-medicinescomplete-com.eproxy.lib.hku.hk/#/content/martindale/9550-n?hspl=Methotrexate#content%2Fmartindale%2F9550-n%239550-n|access-date=2021-03-14|website=Martindale: The Complete Drug Reference}}</ref> Tetrahydrofolate is essential for the synthesis of [purine](/source/purine) and [pyrimidine](/source/pyrimidine) which consequently controls the formation of [DNA](/source/DNA) and [RNA](/source/RNA) that are responsible for the immune response and inflammation.<ref name=":0" /> By preventing the formation of tetrahydrofolate and the subsequent proteins, DMARDs suppress the immune response and reduce arthritis inflammation.

==== Side effects ====
Methotrexate is commonly associated with dose-related [toxic effects](/source/Toxicity) involving the [bone marrow](/source/bone_marrow) and [gastrointestinal tract](/source/gastrointestinal_tract).<ref name=":0" /> [Folic acid](/source/Folate) may be given weekly to help diminish the frequency of [side-effects](/source/Side_effect).<ref name=":0" /> Methotrexate is also associated with acute and chronic [liver damage](/source/Liver_disease).

Other adverse effects include:<ref name=":0" />

* Life-threatening [interstitial lung disease](/source/interstitial_lung_disease) 
* [Tubular necrosis](/source/Acute_tubular_necrosis)
* [Renal failure](/source/Kidney_failure) 
* [Skin reactions](/source/Skin_condition)
* [Alopecia](/source/Hair_loss)
* Ocular irritation.

[Folic acid](/source/Folate) (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.<ref name=":5" /> As such, it will help to reduce the side effects of methotrexate.<ref name=":5" />

==== Contraindications ====
Contraindications of methotrexate include:<ref name=":1">{{Cite web|date=2020-10-20|title=Methotrexate|url=https://www-new-medicinescomplete-com.eproxy.lib.hku.hk/#/content/bnf/_680195013?hspl=Methotrexate#content%2Fbnf%2F_680195013%23pot-contraindications|access-date=2021-03-14|website=British National Formulary}}</ref>

* Patient with active infection 
* [Ascites](/source/Ascites) 
* [Immunodeficiency syndromes](/source/Immunodeficiency) 
* [Pleural effusion](/source/Pleural_effusion).

In addition, methotrexate is [teratogenic](/source/Teratology) and has been associated with [fetal deaths](/source/Perinatal_mortality).<ref name=":1" /> As a consequence, it is avoided during [pregnancy](/source/pregnancy).

=== Biologic response modifiers ===
[Biologic response modifiers](/source/Biological_response_modifier) (biological therapies) are drugs classified as a special type of DMARDs. It is typically administered when conventional DMARDs do not work.<ref name=":6">{{Cite web|title=Biologics, Arthritis Foundation|url=https://www.arthritis.org/drug-guide/biologics/biologics|access-date=2021-03-31|website=www.arthritis.org|language=en}}</ref> It is genetically engineered to target various [protein](/source/protein)s that are involved in the immune response. The route of administration is available through [intravenous](/source/Intravenous_therapy) or [subcutaneous](/source/subcutaneous_injection) injection.<ref name=":14">{{Citation|last1=Sapkota|first1=Binita|title=Biologic Response Modifiers (BRMs)|date=2021|url=https://www.ncbi.nlm.nih.gov/books/NBK542200/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=31194357|access-date=2021-03-31|last2=Makandar|first2=Shah N.|last3=Acharya|first3=Saurav}}</ref>

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.<ref name=":6" />

[Biologic response modifiers](/source/Biological_response_modifier) can be divided into classes based on protein molecules that it inhibits such as [tumor necrosis factor](/source/tumor_necrosis_factor) (TNF), [interleukin-1](/source/Interleukin-1_family) (IL-1), [interleukin-6](/source/Interleukin_6) (IL-6), and [white blood cell](/source/white_blood_cell)s like [B cell](/source/B_cell)s or [T cell](/source/T_cell)s.<ref name=":7">{{Cite journal|last1=Tank|first1=Nitishkumar D.|last2=Karelia|first2=Bharti N.|last3=Vegada|first3=Bhavisha N.|date=2017|title=Biological Response Modifiers in Rheumatoid Arthritis: Systematic Review and Meta-analysis of Safety|journal=Journal of Pharmacology & Pharmacotherapeutics|volume=8|issue=3|pages=92–105|doi=10.4103/jpp.JPP_155_16|doi-broken-date=11 July 2025|doi-access=free|issn=0976-500X|pmc=5642138|pmid=29081616}}</ref>

==== 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 [cytokine](/source/cytokine)s, inhibiting the costimulation of [T cell](/source/T_cell) activation, or inhibiting [B cell](/source/B_cell)s.<ref name=":14" /> Cytokines are proinflammatory and are responsible for regulating the human immune response.<ref name=":15">{{Cite journal|last1=Arango Duque|first1=Guillermo|last2=Descoteaux|first2=Albert|date=2014|title=Macrophage Cytokines: Involvement in Immunity and Infectious Diseases|journal=Frontiers in Immunology|language=English|volume=5|page=491|doi=10.3389/fimmu.2014.00491|pmid=25339958|pmc=4188125|issn=1664-3224|doi-access=free}}</ref>

==== TNF-α inhibitors ====
[TNF-α Inhibitors](/source/TNF_inhibitor) are the most commonly prescribed medication among biologic response modifiers used to treat [arthritis](/source/arthritis). Patients with rheumatic conditions may have higher levels of TNF in the systemic circulation.<ref name=":18">{{Cite web|title=TNF Inhibitors|url=https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/TNF-Inhibitors|access-date=2021-04-01|website=www.rheumatology.org}}</ref> As a result of increased levels of TNF, there would be more [inflammation](/source/inflammation) and persistent symptoms of arthritis.<ref name=":18" /> [Certolizumab](/source/Certolizumab_pegol) is the only TNF-α Inhibitor that can be administered during [pregnancy](/source/pregnancy).<ref name=":6" />

Examples:<ref name=":6" />

* [Adalimumab](/source/Adalimumab)
* [Certolizumab](/source/Certolizumab_pegol)
* [Etanercept](/source/Etanercept)
* [Golimumab](/source/Golimumab)
* [Infliximab](/source/Infliximab)

==== Interleukin inhibitors ====
[IL-1](/source/Interleukin-1_family) and [IL-6](/source/Interleukin_6) are particularly involved as proinflammatory [cytokine](/source/cytokine)s contributing to arthritic symptoms.<ref>{{Cite journal|last1=Ogata|first1=Atsushi|last2=Kato|first2=Yasuhiro|last3=Higa|first3=Shinji|last4=Yoshizaki|first4=Kazuyuki|date=2019-03-04|title=IL-6 inhibitor for the treatment of rheumatoid arthritis: A comprehensive review|journal=Modern Rheumatology|volume=29|issue=2|pages=258–267|doi=10.1080/14397595.2018.1546357|issn=1439-7595|pmid=30427250|s2cid=53307275|doi-access=free}}</ref> The inhibition of these cytokines is effective in reducing inflammation and consequently reducing the severity of arthritis.<ref name=":15" />

Examples:<ref name=":6" />

* [Anakinra](/source/Anakinra)
* [Tocilizumab](/source/Tocilizumab)
* [Canakinumab](/source/Canakinumab)
* [Secukinumab](/source/Secukinumab)
* [Ustekinumab](/source/Ustekinumab)
* [Ixekizumab](/source/Ixekizumab)
* [Sarilumab](/source/Sarilumab)

==== 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](/source/CD80) and [CD86](/source/CD86) receptors to [CD28](/source/CD28).<ref name=":16">{{Cite journal|last1=Herrero-Beaumont|first1=Gabriel|last2=Martínez Calatrava|first2=María José|last3=Castañeda|first3=Santos|date=2012-03-01|title=Abatacept Mechanism of Action: Concordance With Its Clinical Profile|url=http://www.reumatologiaclinica.org/en-abatacept-mechanism-action-concordance-with-articulo-S2173574312000081|journal=Reumatología Clínica (English Edition)|language=en|volume=8|issue=2|pages=78–83|doi=10.1016/j.reumae.2011.08.004|pmid=22104048|s2cid=3331466 |issn=2173-5743|url-access=subscription}}</ref> To prevent [CD28](/source/CD28) interaction with the CD80/CD86 receptors, these drugs modulate by binding to these receptors on [antigen presenting cells](/source/Antigen-presenting_cell) (APC).<ref name=":16" /> As a result, this type of biologic inhibits [T cell](/source/T_cell) proliferation and [B cell](/source/B_cell) immunological response.<ref name=":16" />

[Abatacept](/source/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](/source/Juvenile_idiopathic_arthritis).<ref name=":6" />

Examples:<ref name=":7" />

* [Abatacept](/source/Abatacept)

==== B cells inhibitor ====
[B cell](/source/B_cell)s, or B lymphocytes are a type of white blood cells that contribute to the [pathogenesis](/source/pathogenesis) of RA.<ref name=":17">{{Cite journal|last1=Silverman|first1=Gregg J.|last2=Carson|first2=Dennis A.|date=2003-12-02|title=Roles of B cells in rheumatoid arthritis|journal=Arthritis Res Ther|volume=5|issue=4|pages=S1-6|doi=10.1186/ar1010|issn=1478-6354|pmc=2833442|pmid=15180890 |doi-access=free }}</ref> B cells have a variety of functions including being an efficient [APC](/source/Antigen-presenting_cell), contribute to T cell activation, produce [cytokine](/source/cytokine)s that promote the permeation of leukocytes into the joints and more.<ref name=":17" /> The therapeutic effect of B cells inhibitor is dependent on the disruption of these diverse functions.

Examples:<ref name=":7" />

* [Belimumab](/source/Belimumab) 
* [Rituximab](/source/Rituximab)

==== Side effects ====
The adverse reactions of biologic response modifier therapies are associated with their mechanism of action that disrupts the immune [homeostasis](/source/homeostasis) of the human body.<ref name=":14" /> These inhibitory biologics cause suppression of the immune response resulting in an increase in risk and susceptibility to [infection](/source/infection).<ref name=":6" /><ref name=":14" />

Common infections include:<ref name=":6" />

* [Colds](/source/Common_cold)
* [Upper respiratory tract infection](/source/Upper_respiratory_tract_infection)
* [Sinus infection](/source/Sinusitis)
* [Sore throat](/source/Sore_throat)
* [Bronchitis](/source/Bronchitis)
* [Urinary tract infection](/source/Urinary_tract_infection)

It may also cause mild side effects such as [headache](/source/headache) and [nausea](/source/nausea).<ref name=":6" />

== Janus kinase inhibitors ==
[Janus kinase (JAK) inhibitors](/source/Janus_kinase_inhibitor) are used to treat RA. Similar to biologic response modifiers, these drugs act to reduce immune response.<ref name=":12">{{Cite web|title=JAK inhibitors used in rheumatoid arthritis (RA)|url=https://nras.org.uk/resource/jak-inhibitors/|access-date=2021-03-31|website=NRAS|language=en-GB}}</ref> However, these medications are available in [tablet](/source/tablet_(pharmacy)) formulations, unlike biologics.<ref>{{Cite web|date=2017-11-22|title=Rheumatoid arthritis - Treatment|url=https://www.nhs.uk/conditions/rheumatoid-arthritis/treatment/|access-date=2021-03-31|website=nhs.uk|language=en}}</ref>

Examples:<ref name=":12" />

* [Tofacitinib](/source/Tofacitinib)
* [Baricitinib](/source/Baricitinib)

=== Mechanism of action ===
JAK inhibitors act by inhibiting [Janus kinase](/source/Janus_kinase)s which consequently affect a cascade of enzymes responsible for signaling a variety of [cytokine](/source/cytokine) and [haematopoietic](/source/Haematopoiesis) growth factor receptors.<ref>{{Cite journal|last1=Lin|first1=Chung MA|last2=Cooles|first2=Faye AH|last3=Isaacs|first3=John D.|date=2020-06-11|title=Basic Mechanisms of JAK Inhibition|journal=Mediterranean Journal of Rheumatology|volume=31|issue=Suppl 1|pages=100–104|doi=10.31138/mjr.31.1.100|issn=2529-198X|pmc=7361186|pmid=32676567}}</ref> 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 [infection](/source/infection)s. For example:<ref name=":12" />

* [Pneumonia](/source/Pneumonia) and [bronchitis](/source/bronchitis)
* Nose, throat or [windpipe](/source/Trachea) infections
* Urinary bladder infection ([cystitis](/source/Urinary_tract_infection))
* Other viral infections such as [shingles](/source/shingles) and [influenza](/source/influenza)

== Analgesics ==
[Analgesics](/source/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](/source/inflammation).<ref name="Drug Office - Oral Analgesics">{{Cite web|title=Drug Office - Oral Analgesics|url=https://www.drugoffice.gov.hk/eps/do/en/consumer/news_informations/dm_16.html|access-date=2021-03-15|website=www.drugoffice.gov.hk}}</ref>

=== Acetaminophen ===
[Acetaminophen](/source/Acetaminophen) (paracetamol) is a common [over-the-counter](/source/Over-the-counter_drug) option to manage pain. It is commonly used to relieve mild to moderate severity of pain.<ref name=":8">{{Cite web|title=Acetaminophen Monograph for Professionals|url=https://www.drugs.com/monograph/acetaminophen.html|access-date=2021-03-31|website=Drugs.com|language=en}}</ref> There are various routes of administration including [oral](/source/oral_administration), [rectal](/source/Rectal_administration) and [intravenous](/source/Intravenous_therapy).<ref name=":8" /><ref name=":9">{{Citation|last1=Gerriets|first1=Valerie|title=Acetaminophen|date=2021|url=https://www.ncbi.nlm.nih.gov/books/NBK482369/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=29493991|access-date=2021-03-31|last2=Anderson|first2=Jackie|last3=Nappe|first3=Thomas M.}}</ref> Acetaminophen is often recommended in treating [osteoarthritic](/source/Osteoarthritis) patients.

==== Mechanism of action ====
Despite the mechanism of action of acetaminophen is not completely understood, it appears to act on the [COX](/source/Cyclooxygenase) pathway. It reduces [COX](/source/Cyclooxygenase) activity by inhibiting the synthesis of [prostaglandin](/source/prostaglandin)s in the [central nervous system](/source/central_nervous_system).<ref name=":9" /> The reduction of COX activity contributes to its analgesic effects.<ref name=":9" />

==== Side effects ====
[Hepatotoxicity](/source/Hepatotoxicity) is often associated with the [overdose](/source/Drug_overdose) of acetaminophen causing acute [liver failure](/source/liver_failure). The maximum recommended daily dosage for an adult is 4000&nbsp;mg.<ref name=":8" />

=== Opioids ===
In more severe cases of arthritic pain, [opioid](/source/opioid)s may be prescribed by the general practitioner. For example, [tramadol](/source/tramadol), [oxycodone](/source/oxycodone) or [hydrocodone](/source/hydrocodone).

==== Mechanism of action ====
Opioids function on the [central nervous system](/source/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](/source/drug_dependence).<ref>{{Cite web|date=2021-01-05|title=Osteoarthritis|url=https://www-new-medicinescomplete-com.eproxy.lib.hku.hk/#/content/bnf/_121458928?hspl=analgesic|access-date=2021-03-14|website=British National Formulary}}</ref>

==== Side effects ====
Common side effects of opioids include:<ref>{{Cite web|title=Managing Pain Medication Side Effects, Memorial Sloan Kettering Cancer Center|url=https://www.mskcc.org/cancer-care/diagnosis-treatment/symptom-management/pain-management/management-side-effects|access-date=2021-03-31|website=www.mskcc.org|language=en}}</ref>

* [drowsiness](/source/drowsiness)
* [sedation](/source/sedation)
* [constipation](/source/constipation)
* [nausea](/source/nausea)
* slowed breathing.

=== Counterirritants ===
[Counterirritant](/source/Counterirritant) is a drug that belongs to the analgesic class. Typically, these agents are in [topical formulations](/source/Topical_medication) such as [ointments](/source/Topical_medication) and creams that contain [menthol](/source/menthol) or [capsaicin](/source/capsaicin). It only provides modest pain relief and is not effective for managing severe pain.<ref name=":10">{{Cite web|last=PharmD|first=Kathee de Falla|title=Over-the-Counter Topical Arthritis Pain Relief|url=https://www.arthritis-health.com/treatment/medications/over-counter-topical-arthritis-pain-relief|access-date=2021-03-31|website=Arthritis-health|language=en}}</ref>

==== Mechanism of action ====
[Counterirritant](/source/Counterirritant)s act by exciting and subsequently desensitizing [epidermal](/source/Epidermis) [nociceptive](/source/Nociception) [sensory neuron](/source/sensory_neuron)s.<ref name=":13">{{cite journal |last1=Barkin |first1=Robert L. |title=The Pharmacology of Topical Analgesics |journal=Postgraduate Medicine |date=2 July 2013 |volume=125 |issue=sup1 |pages=7–18 |doi=10.1080/00325481.2013.1110566911 |pmid=24547599 }}</ref> When applied to the site of injury, it produces a heating sensation and consequently surface [irritation](/source/irritation) of the skin. This sensation interferes with the transmission of pain signals from the [joint](/source/joint)s to the brain. Thereby distracting the brain from pain.<ref name=":10" />

==== 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](/source/Nonsteroidal_anti-inflammatory_drug).<ref name=":13" /> However, counterirritants are associated with undesirable reactions at the site of application. Typical side effects include [dryness](/source/Xeroderma), [erythema](/source/erythema), burning, and discoloration.<ref name=":13" />

== Nonsteroidal anti-inflammatory drugs ==
[Nonsteroidal anti-inflammatory drug](/source/Nonsteroidal_anti-inflammatory_drug)s (NSAIDs) belongs to a drug class that has both analgesic and anti-inflammatory effects.<ref name="Drug Office - Oral Analgesics"/> NSAIDs can often be found [over-the-counter](/source/Over-the-counter_drug) including [ibuprofen](/source/ibuprofen) and [naproxen](/source/naproxen). There may be exceptions to which some NSAIDs are only available by [prescription.](/source/Prescription_drug) Oral NSAIDs may cause discomfort to the stomach and may also increase the risk of [heart attack](/source/Myocardial_infarction) or [stroke](/source/stroke). Other formulation types are also available, such as [cream](/source/cream)s or [gel](/source/gel)s that can be applied directly to the joints.

=== Mechanism of action ===
NSAIDs exhibit their pharmacological effects through the inhibition of the [cyclooxygenase](/source/cyclooxygenase) (COX) enzyme. COX is a necessary protein that facilitates the conversion of [arachidonic acid](/source/arachidonic_acid) into [thromboxane](/source/thromboxane)s, [prostaglandin](/source/prostaglandin)s, and [prostacyclin](/source/prostacyclin)s. When the COX activity is inhibited, the synthesis of the subsequent [eicosanoid](/source/eicosanoid)s is reduced. As a result, NSAIDs produce analgesic and anti-inflammatory effects.<ref>{{Citation|last1=Ghlichloo|first1=Ida|title=Nonsteroidal Anti-inflammatory Drugs (NSAIDs)|date=2021|url=https://www.ncbi.nlm.nih.gov/books/NBK547742/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=31613522|access-date=2021-03-14|last2=Gerriets|first2=Valerie}}</ref>

=== Side effects ===
Similar to [corticosteroid](/source/corticosteroid)s, NSAIDs should be used for short periods of time due to the risk of side effects. Common side effects of NSAIDs include

* [stomach ulcers](/source/Peptic_ulcer_disease)
* [headache](/source/headache)s, [drowsiness](/source/Somnolence) 
* [allergic](/source/Allergy) reactions.

Rarer side effects consist of complications affecting the [liver](/source/liver), [kidney](/source/kidney)s or [heart](/source/heart) and [circulation](/source/circulatory_system), potentiating the cause of [heart failure](/source/heart_failure), [heart attacks](/source/Myocardial_infarction) and [stroke](/source/stroke)s.<ref>{{Cite web|date=2017-10-19|title=NSAIDs|url=https://www.nhs.uk/conditions/nsaids/|access-date=2021-03-31|website=nhs.uk|language=en}}</ref>

== Corticosteroids ==
[Corticosteroid](/source/Corticosteroid) is a class of drugs that features the reduction of [inflammation](/source/inflammation) and suppression of the [immune system](/source/immune_system).<ref name=":2">{{cite journal |last1=Williams |first1=Dennis M |title=Clinical Pharmacology of Corticosteroids |journal=Respiratory Care |date=June 2018 |volume=63 |issue=6 |pages=655–670 |doi=10.4187/respcare.06314 |pmid=29794202 |doi-access=free}}</ref> Common medication includes [prednisone](/source/prednisone) and [cortisone](/source/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](/source/inflammation) pathway. To exert an effect, the [steroid](/source/steroid) compound binds to [glucocorticoid receptors](/source/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](/source/transcription_(biology)) of genes responsible for [ribonucleic acid](/source/RNA) and [protein](/source/protein) synthesis. Corticosteroids are responsible for inhibiting [transcription factor](/source/transcription_factor)s that control the synthesis of proinflammatory molecules, including [macrophage](/source/macrophage)s, [eosinophil](/source/eosinophil)s, [lymphocyte](/source/lymphocyte)s, [mast cell](/source/mast_cell)s, and [dendritic cell](/source/dendritic_cell)s. Corticosteroids also exert their effect by inhibiting [phospholipase A2](/source/phospholipase_A2). Phospholipase A2 controls the production of various inflammatory mediators.<ref name=":2" />

=== Side effects ===
Injected corticosteroids may cause:

* gastrointestinal irritation
* [discomfort](/source/Comfort)
* [tachycardia](/source/tachycardia)
* [nausea](/source/nausea)
* [insomnia](/source/insomnia) 
* [metallic taste](/source/Dysgeusia) in the mouth.<ref name=":11">{{Cite web |title=Side effects of corticosteroids |url=https://www.hse.ie/eng/health/az/c/corticosteroids/effects-of-corticosteroids.html |archive-url=https://web.archive.org/web/20141016194539/https://www.hse.ie/eng/health/az/c/corticosteroids/effects-of-corticosteroids.html |archive-date=2014-10-16 |access-date=2025-01-15 |website=HSE.ie |url-status=dead}}</ref>

Patients taking short term oral corticosteroids may experience:

* mood alterations (feeling anxious or irritated)
* [insomnia](/source/insomnia)
* [fluid retention](/source/Water_retention_(medicine))
* an increase in appetite.<ref name=":11" />

Long term usage may lead to more severe complications including:

* [osteoporosis](/source/osteoporosis)
* [hypertension](/source/hypertension)
* [diabetes](/source/diabetes)
* [muscle weakness](/source/muscle_weakness)
* increased vulnerability to [infection](/source/infection)
* [glaucoma](/source/glaucoma).<ref name=":11" />

In case of facing severe side effects, the drug should not be stopped suddenly. If corticosteroids are stopped abruptly, the patient may experience [fatigue](/source/fatigue), [nausea](/source/nausea), [vomiting](/source/vomiting), [diarrhoea](/source/Diarrhea), and [abdominal pain](/source/abdominal_pain).<ref name=":11" />

== See also ==
{{cmn|
* [Arthritis](/source/Arthritis)
* [Osteoarthritis](/source/Osteoarthritis)
* [Rheumatoid Arthritis](/source/Rheumatoid_arthritis)
* [Gout](/source/Gout)
* [Juvenile rheumatoid arthritis](/source/Juvenile_idiopathic_arthritis)
* [Disease-modifying antirheumatic drug](/source/Disease-modifying_antirheumatic_drug)s
* [Biologic response modifiers](/source/Biological_response_modifier)
* [Janus Kinase Inhibitors](/source/Janus_kinase_inhibitor)
* [Analgesic](/source/Analgesic)s
* [Opioid](/source/Opioid)s
* [Counterirritant](/source/Counterirritant)s
* [Nonsteroidal anti-inflammatory drug](/source/Nonsteroidal_anti-inflammatory_drug)s
* [Corticosteroid](/source/Corticosteroid)s
* [Osteoporosis](/source/Osteoporosis)
* [Hypertension](/source/Hypertension)
* [Diabetes](/source/Diabetes)
* [Heart Failure](/source/Heart_failure)
* [Stroke](/source/Stroke)
* [Glaucoma](/source/Glaucoma)
}}

== References ==
{{reflist}}

Category:Drugs acting on the musculoskeletal system

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Adapted from the Wikipedia article [Antiarthritics](https://en.wikipedia.org/wiki/Antiarthritics) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Antiarthritics?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.