Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are medications used to reduce inflammation, pain, and fever.
Disease-modifying Antirheumatic Drugs (DMARDs) are drugs used to slow the progression of rheumatoid arthritis and other inflammatory diseases.
NSAIDs work by inhibiting enzymes involved in the production of prostaglandins, which are compounds that promote inflammation.
Other NSAIDs reversibly inhibit COX.
Aspirin is highly bound to plasma proteins.
NSAIDs provide analgesic effects by decreasing prostaglandins peripherally at the site of inflammation, which reduces nerve ending sensitization to histamine and bradykinin.
At high doses, aspirin's elimination follows zero order kinetics.
Aspirin irreversibly inhibits COX1, leading to decreased TXA2 production, which results in no platelet aggregation.
Traditional DMARDs include Methotrexate, Leflunomide, Hydroxychloroquine, and Sulfasalazine.
No PGs = No inflammation.
Aspirin is absorbed in the stomach and upper small intestine.
NSAIDs are used for their anti-inflammatory, analgesic, and antipyretic properties.
Sulfasalazine has a slow onset of action, ranging from 6 weeks to 6 months.
Adverse effects include leukopenia, gastrointestinal issues, hemolysis in patients with G6PD deficiency, and potential hypersensitivity.
When secreted by synovial macrophages, IL-1 and TNF-α stimulate synovial cells to proliferate and synthesize collagenase, leading to cartilage degradation and increased bone resorption.
Examples include aspirin, indomethacin, ibuprofen, ketoprofen, piroxicam, and diclofenac.
PGE2 and PGI2 normally maintain Glomerular Filtration Rate (GFR) and Renal Blood Flow (RBF).
Yes, selective COX2 inhibitors carry the same renal risk as non-selective COX inhibitors.
Sulfonylurea antidiabetic agents.
NSAIDs exert an antipyretic effect by decreasing PGE2 in the hypothalamic thermoregulatory center, which resets the thermostat.
Pregnancy category X.
COX-1 is involved in renal homeostasis and the production of endothelial PGI2.
NSAIDs decrease PGE2 and PGI2-mediated vasodilation, edema, and leukocyte infiltration.
Ibuprofen has the lowest GI bleeding risk among non-selective NSAIDs.
Folinic acid (leucovorin) supplementation.
The duration shouldn’t exceed 5 days due to severe adverse effects.
Other biologic therapies such as abatacept and rituximab can be considered.
Methotrexate inhibits DHFR, which leads to the inhibition of DNA synthesis in T cells (S phase specific).
Respiratory acidosis.
They inhibit COX-2-mediated prostacyclin synthesis in the vascular endothelium, increasing the risk for serious cardiovascular thrombotic events.
Yes, aspirin crosses the blood-brain barrier and the placenta.
They may induce premature closure of fetal ductus arteriosus, which is maintained by PGE1 & PGE2.
Ketorolac is the most potent analgesic among NSAIDs, comparable to opioids.
NSAIDs have an antiplatelet effect by inhibiting platelet aggregation.
Toxic doses inhibit the respiratory center.
A trial with a different TNF-α inhibitor or a non-TNF biologic therapy is appropriate.
Adverse effects include nausea, stomatitis, alopecia, and bone marrow suppression.
COX-2
Tocilizumab and sarilumab are monoclonal antibodies against IL-6.
Aspirin covalently binds and acetylates COX causing irreversible inhibition.
NSAIDs can produce GI adverse effects ranging from heartburn to gastric and duodenal ulcers.
These effects can be prevented by taking NSAIDs with food, using Misoprostol, proton pump inhibitors like omeprazole, or opting for selective COX-2 inhibitors or paracetamol.
Suppression (leukopenia), pulmonary fibrosis, hepatotoxicity, nephrotoxicity.
The primary use of DMARDs is to manage autoimmune diseases like rheumatoid arthritis by modifying the disease process.
It can cause hepatotoxicity via NAPQI metabolite.
Reye’s syndrome
Lipocortin inhibits phospholipase A2, reducing the release of arachidonic acid and subsequently decreasing the formation of eicosanoids.
Vomiting, tinnitus, vertigo, decreased hearing
Patients are at increased risk for infections such as tuberculosis and sepsis, as well as fungal opportunistic infections.
Methyl salicylate, known as 'oil of wintergreen', is used externally as a cutaneous counterirritant in liniments, such as arthritis creams and sports rubs.
COX-1 is constitutive and present in the GIT, kidneys, and platelets, while COX-2 is inducible and produced in response to inflammatory stimuli in virtually any tissue.
It leads to metabolic acidosis.
Analgesic and antipyretic, with no anti-inflammatory activity.
No, it has no antiplatelet or ulcerogenic activity.
At low doses (<2g/day), aspirin decreases uric acid secretion.
Abatacept is a biologic T-cell co-stimulation modulator that binds CD80 & CD86 on APCs, preventing interaction with CD28 on T cells.
They are used for conditions such as tendinitis, rheumatoid arthritis, and osteoarthritis. Examples include Aspirin (high dose 3-6 g/day), ketoprofen (200 mg/day), and piroxicam (20 mg/day).
JAK inhibitors influence the transcription of genes responsible for the differentiation, proliferation, and function of NK cells, T-cells, and B-cells.
Yes, they can be used in other autoimmune diseases such as ankylosing spondylitis.
Adverse effects include gastrointestinal issues, cardiovascular risks, and renal impairment. Precautions should be taken in patients with certain pre-existing conditions.
An example of a selective COX-2 inhibitor is celecoxib.
It leads to anti-inflammatory actions, analgesic effect, and antipyretic effect.
They may reduce the effectiveness of certain medications through displacement from plasma proteins.
It has a slow onset of action, taking 1-3 months.
At high doses (>5 g/day), aspirin decreases tubular reabsorption of uric acid, increasing uric acid excretion.
Cyclooxygenase (COX) is an enzyme that converts arachidonic acid into prostaglandins and thromboxanes, which are involved in inflammation and other physiological processes.
TNF-α blockers decrease the signs and symptoms of rheumatoid arthritis.
Yes, Sulfasalazine is the drug of choice in pregnancy.
Live vaccinations should not be administered while on TNF α inhibitor therapy.
The FDA issued a black box warning due to increased risk of cardiovascular events such as heart attacks or stroke.
Aspirin can cause gastrointestinal irritation or bleeding.
DMARDs slow the course of RA, induce remission, and prevent further destruction of the joints.
Headache, diarrhea, nausea, and hepatotoxicity.
NSAIDs or corticosteroids may also be used for relief of symptoms if needed.
Pregnancy Category X medication.
Aspirin-induced asthma
They are effective for low to moderate intensity pain such as headache, dysmenorrhea, and dental pain.
Biological DMARDs include TNF inhibitors like Etanercept, Infliximab, Adalimumab, and Certolizumab, as well as Non-TNF inhibitors like Anakinra, Tocilizumab, Sarilumab, Abatacept, and Rituximab.
COX-2 is produced in virtually any tissue in response to inflammatory stimuli.
Chronic use may cause nephritis, nephrotic syndrome, and renal impairment.
Yes, it can be given safely in pregnancy.
Periodic liver and kidney function tests, CBC & monitoring for signs of infection.
Adverse effects include ocular toxicity, hemolysis in patients with G6PD deficiency, CNS disturbances, GI upset, and skin discoloration.
Sulfasalazine is classified as pregnancy category C.
Sulfasalazine is used for early, mild rheumatoid arthritis (RA) in combination with methotrexate and/or hydroxychloroquine, and mainly in inflammatory bowel disease (IBD).
There is an increased risk of infection, particularly with non-TNF biologic therapies.
Aspirin is used in low doses of 75-325 mg/day for post-MI prophylaxis and stroke prevention in high-risk patients.
These agents should be used very cautiously in those with heart failure, as they can cause and/or worsen preexisting heart failure.
The lack of thromboxane (TXA2) persists for the lifetime of the platelet, which is approximately 3 to 7 days.
Aspirin enhances the activity of warfarin by displacing it from plasma protein binding sites.
It is a prodrug metabolized by colonic flora to sulfapyridine and 5-ASA, with sulfapyridine being the active moiety in RA treatment.
It can cause respiratory alkalosis due to increased respiratory center activity leading to hyperventilation and decreased pCO2.
They reduce the progression of structural damage and improve physical function.
Monotherapy may be initiated with any of the traditional DMARDs for patients with low disease activity.
It is used for mild RA, often combined with methotrexate; also used in malaria, SLE, and off-label for COVID.
Thromboxane A2 (TXA2) is a potent vasoconstrictor and promoter of platelet aggregation, playing a crucial role in hemostasis.
Infliximab, adalimumab, and certolizumab are monoclonal antibodies against TNF-α; certolizumab is a pegylated TNF-α blocker.
It inhibits PGs synthesis in the brain but not at sites of inflammation.
All NSAIDs are category C during the 1st and 2nd trimester.
Rituximab is a monoclonal antibody against CD20 on the surface of B lymphocytes.
It is not recommended in patients with liver disease.
Monitoring signs of infection, CBC, and liver enzymes.
Active metabolite (teriflunomide) inhibits dihydroorotate dehydrogenase (DHODH), leading to decreased pyrimidine synthesis and decreased T lymphocyte proliferation (G1 arrest).
Leukotrienes (LTs) are inflammatory mediators formed from arachidonic acid by the enzyme 5-lipoxygenase.
Anakinra is a monoclonal antibody against the IL-1 receptor.
GI toxicity
Combination DMARD therapy (usually methotrexate based) or the use of anti-TNF drugs (adalimumab, certolizumab, etanercept, and infliximab) may be needed.
Eicosanoids are derived from phospholipids through the action of phospholipase A2, leading to the release of arachidonic acid.
Janus Kinase (JAK) inhibitors are oral medications that disrupt JAK/STAT signaling; examples include Tofacitinib, Baricitinib, and Upadacitinib.
The onset is typically 3-6 weeks of treatment.
Increased bleeding tendency
Alteration of renal function in susceptible individuals
Indomethacin is used to close patent ductus arteriosus.
DMARDs should be started within 3 months of diagnosis to help stop the progression of the disease.
Gout
Naproxen has the lowest risk of cardiovascular events.
Meloxicam has higher COX-2 selectivity, low risk for GI complications, and high risk for CV events.
Clinical response can be seen within 2 weeks of therapy.
Other NSAIDs than aspirin have no effect on uric acid or acid-base balance.
It inhibits the processing of peptide.
Salicylic acid is used topically to treat acne, corns, calluses, and warts.
They are used to reduce fever in febrile states.
The major types of prostaglandins include PGI2 (prostacyclin), PGE2, and PGF2α.
Etanercept is a recombinant human TNF-α receptor that binds & neutralizes TNF-α.
