How Do NSAIDs Work?

NSAIDs are non-steroidal anti-inflammatory drugs prescribed to treat inflammation and associated symptoms. NSAIDs reduce inflammation, bring down fever, and relieve pain. NSAIDs also reduce blood clotting time, and some NSAIDs such as aspirin are protective against heart disease.

NSAIDs control inflammation by inhibiting the activity of enzymes known as cyclooxygenases (COX-1 and COX-2), essential for the biosynthesis of prostaglandin. Prostaglandin is a fatty compound that promotes inflammation, which results in pain, fever, and other symptoms.

COX-1 produces prostaglandins which have many functions that include initiating inflammation, protecting the stomach lining from stomach acids, maintaining kidney function, and regulating blood clotting. COX-2 produces prostaglandins when joints are injured.

Traditional NSAIDs inhibit both COX-1 and COX-2, but COX-2 inhibitors are a category of NSAIDs that inhibit only COX-2 activity. Both types of COX inhibitors provide pain relief (analgesia), but COX-2 inhibitors do not usually cause NSAID side effects such as stomach upset or bleeding issues. COX-2 inhibitors also do not protect against heart disease.

NSAIDs are available in several formulations, strengths, and forms which include the following:

• Oral formulations such as tablets, capsules, and solutions
• Periarticular installation in which NSAID is injected in combination with a local anesthetic for pain relief after certain surgical procedures
• Rectal suppository inserted into the rectum
• Intravenous (IV) injection
• Intramuscular (IM) injection
• An oral film that is applied inside the mouth
• Intranasal medication that is sprayed into the nostrils

NSAIDs may be prescribed to treat acute or chronic pain, fever, and inflammation. NSAIDs are used to treat inflammation and pain in the following conditions:

• Postoperative pain after surgical procedures such as:
  • Bunionectomy (removal of bunions)
  • Inguinal hernia repair
  • Total knee replacement
• Headaches
• Shoulder pain
• Rheumatoid arthritis (RA): An autoimmune inflammatory joint condition.
• Juvenile rheumatoid arthritis: Childhood RA.
• Osteoarthritis: An age-related degenerative joint disease.
• Dysmenorrhea: Painful menstrual periods.
• Ankylosing spondylitis: An autoimmune inflammatory disease that causes the vertebrae to fuse over time.
• Migraine: A severe type of headache often with nausea and sensitivity to light and sound.
• Gout: A painful joint condition caused by uric acid buildup.
• Inflammatory conditions:
  • Bursitis: Inflammation of the fluid-filled sacs (bursae) in joints 
  • Tendonitis: Inflammation of tendons
  • Synovitis: Inflammation of connective tissue (synovium) in joints
  • Tenosynovitis: Inflammation of tendon and synovium

Other conditions some of the NSAIDs are used to treat include:

• Patent ductus arteriosus (PDA): A normal fetal connection between the aorta and pulmonary artery that persists abnormally in newborn babies. Intravenous NSAID closes the PDA by blocking the prostaglandins that keep the ductus arteriosus open and enable normal blood circulation. NSAIDs typically used include ibuprofen and indomethacin.
• Familial adenomatous polyposis: An inherited genetic disorder that causes the growth of multiple polyps in the colon raising the risk for colorectal cancer. NSAIDs such as celecoxib, sulindac, and aspirin have been found to reduce the size and number of polyps.
• Nephrogenic diabetes insipidus: An inherited genetic kidney disorder that causes excessive water loss due to the inability of the kidneys to reabsorb fluid. Indomethacin is used as an antidiuretic to reduce urine output.
• Malignant glioma: Glioma is a type of brain or spinal tumor. Clinical trials show that etodolac may slow down tumor growth and has orphan designation to treat malignant glioma.
• Cardiovascular conditions: Aspirin is commonly used to reduce the clotting action and improve blood flow in conditions with reduced blood flow to the heart. Low-dose aspirin may be prescribed as prophylaxis for people at high risk for cardiovascular diseases.
• Ischemic stroke/transient ischemic stroke (TIA): Aspirin is used to improve blood flow after strokes caused by the reduced blood supply to the brain.

NSAIDs must be used with caution in people with kidney/liver impairment or gastrointestinal issues. Some NSAID formulations are combined with other drugs for specific reasons. The NSAID combinations include:

• Amlodipine/celecoxib: NSAID combo with calcium channel blocker, a medication used to treat hypertension.
• Bupivacaine/meloxicam: NSAID combo with a local anesthetic administered as periarticular injections for postoperative pain.
• Diphenhydramine/ibuprofen: NSAID combo with a mild sedative to improve sleep.
• Ibuprofen/famotidine: NSAID combo with medication to inhibit stomach acid production and reduce the risk of ulcers.
• Naproxen/sumatriptan: NSAID combo with a medication that constricts swollen blood vessels and stops pain signal transmission to the brain, used to treat migraines.

Side effects of NSAIDs may include the following:

• Dizziness
• Drowsiness
• Abdominal pain and cramps
• Heartburn
• Constipation
• Tinnitus (ringing in ears)
• Hearing disturbances
• Hearing loss
• Nausea
• Vomiting
• Increased stomach acid secretion
• Gastrointestinal
  • Perforation
  • Hemorrhage
  • Ulcers
• Diarrhea
• Steatorrhea (excessive fat in stools)
• Bloody stools
• Melena (tarry stool)
• Gastritis
• Diverticulitis
• Anorexia (loss of appetite)
• Flatulence
• Dyspepsia (indigestion)
• Heartburn
• Gastroesophageal reflux disease (GERD)
• Weight changes
• Inflammatory disorder of the digestive tract
• Non-necrotizing enterocolitis (damage to intestinal tissue)
• Rectal discomfort with rectal suppositories
• Headache
• Chills/fever
• Lightheadedness
• Vertigo
• Asthenia (abnormal physical weakness)
• Malaise
• Fatigue
• Fluid retention
• Peripheral edema
• Stomatitis (sore mouth)
• Xerostomia (dry mouth)
• Dysgeusia (taste disorder)
• Glossitis (inflammation of the tongue)
• Esophagitis (inflammation of the esophagus)
• Pancreatitis (inflammation of the pancreas)
• Hematemesis (blood in vomit)
• Angioedema (swelling in the tissue under the skin or mucous membranes)
• Bronchospasm
• Serum sickness (drug reaction similar to an allergy), rare
• Immune hypersensitivity reaction
• Anaphylaxis
• Dermatologic reactions such as:
  • Rash and irritation
  • Hives (urticaria)
  • Pruritus (itching)
  • Scaling eczema
  • Erythema multiforme (round lesions like a bullseye)
  • Erythematous macular rashes (red flat rashes)
  • Exfoliative dermatitis (redness and peeling of the skin)
  • Stevens-Johnson syndrome (a rare medical emergency with flu-like symptoms and a painful rash)
  • Toxic epidermal necrolysis (a severe skin condition with widespread redness, skin cell death, and exfoliation which can lead to sepsis)
  • Photosensitivity
• Effects on the central nervous system
• Electrolyte imbalance and dehydration
• Urinary tract infection
• Kidney damage
• Decreased urine output
• Hematuria (blood in urine)
• Dysuria (pain with urination)
• Increased urination frequency
• Urinary retention
• Increased blood creatinine
• Interstitial nephritis (inflammation in the spaces between kidney tubules)
• Nephrotic syndrome (excessive protein passed in urine due to kidney damage)
• Kidney failure
• Amnesia (memory loss)
• Mood changes
• Depression
• Anxiety
• Insomnia
• Abnormal dreams
• Abnormal thinking
• Hallucinations
• Mood changes
• Euphoria
• Irritability
• Nervousness
• Restlessness
• Confusion
• Difficulty in concentration
• Tremor
• Paresthesia (prickling sensation)
• Vasodilation
• Flushing
• Sweating
• Pallor
• Blurred vision
• Diplopia (double vision)
• Amblyopia (lazy eye)
• Conjunctivitis (inflammation of the conjunctiva, the membrane over the whites of the eye and inner eyelid surfaces)
• Nasal discomfort (with intranasal sprays)
• Rhinalgia (pain in the nose)
• Increased lacrimation (tearing)
• Throat irritation
• Rhinitis (inflammation of the nasal passage)
• Sinusitis (inflammation of the sinus)
• Pharyngitis (inflammation of the pharynx)
• Tachycardia (increased heart rate)
• Hypertension (high blood pressure)
• Exacerbation of angina (chest pain)
• Arrhythmia (irregular heartbeat)
• Congestive heart failure (CHF)
• Myocardial infarction (heart attack)
• Hypotension (low blood pressure)
• Bradycardia (slow heartbeat)
• Vasculitis (inflammation of blood vessels)
• Palpitations
• Syncope (fainting)
• Inhibition of platelet aggregation
• Increased clotting time
• Ecchymosis (skin discoloration due to bleeding under the skin)
• Epistaxis (nasal bleeding)
• Hemorrhage
• Premature hemolysis (red cell death)
• Reduced blood cell counts causing conditions such as:
  • Neutropenia (low levels of neutrophil, a type of immune cell)
  • Agranulocytosis (low granulocytes, immune cells with granules)
  • Aplastic anemia (anemia due to reduced red cell production)
  • Hemolytic anemia (anemia from rapid destruction of red cells)
  • Eosinophilia (high level of eosinophils, a type of immune cell)
  • Thrombocytopenia (decrease in platelet count)
  • Thrombocytopenic purpura (easy bruising and bleeding due to thrombocytopenia)
• Bone marrow depression
• Reye syndrome (a rare but serious condition that causes swelling in the liver and brain)
• Intraventricular hemorrhage (bleeding in and around the brain ventricles)
• Cerebrovascular accident
• Hypoproteinemia (abnormally low level of proteins in the blood)
• Bacteremia (bacteria in the blood)
• Sepsis
• Dyspnea (shortness of breath)
• Apnea (cessation of breathing)
• Asthma
• Pulmonary edema
• Pulmonary hypertension
• Upper respiratory tract infection
• Respiratory depression or failure
• Atelectasis (partial or complete collapse of a lung or section of a lung)
• Bacterial pneumonia
• Adrenal insufficiency
• Hypoglycemia (low glucose level in blood)
• Hypernatremia (high sodium level in blood)
• Elevated blood urea nitrogen (BUN) levels
• Hypoalbuminemia (low albumin level in blood)
• Elevated lactate dehydrogenase (LDH) level in blood
• Thrombocytosis (excessive platelets in the blood)
• Thrombotic tendency (increased tendency to develop clots in blood vessels)
• Hypokalemia (low potassium in the blood)
• Decreased hemoglobin and/or hematocrit
• Wound hemorrhage
• Cough
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• Hepatotoxicity (liver toxicity)
• Elevated levels of liver enzymes ALT and AST
• Hepatitis
• Jaundice
• Liver failure
• Arthralgia (joint pain)
• Back pain

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of NSAID drugs include:

• acetylsalicylic acid
• Advil
• Advil PM
• Aleve
• amlodipine/celecoxib
• Anaprox
• Anaprox DS
• Anjeso
• Ansaid
• ASA
• aspirin
• aspirin rectal
• Bayer Advanced Aspirin
• Bayer Buffered Aspirin
• Bayer Children's Aspirin
• Bayer Extra Strength
• Bayer Extra Strength Plus
• Bayer Low Adult Strength
• Bayer Women's Low Dose
• Bufferin
• Bufferin Extra Strength
• bupivacaine/meloxicam
• Caldolor
• Cambia
• Cataflam
• Celebrex
• celecoxib
• choline magnesium trisalicylate
• Consensi
• Daypro
• diclofenac
• diflunisal
• diphenhydramine/ibuprofen
• Duexis
• Durlaza
• Dyloject
• EC Naprosyn
• Ecotrin
• Ecotrin Maximum Strength
• etodolac
• Extended Release Bayer 8-Hour Caplets
• Extra Strength Bayer Plus Caplets
• Feldene
• fenoprofen
• flurbiprofen
• Genuine Bayer Aspirin
• Halfprin DSC
• ibuprofen
• ibuprofen IV
• ibuprofen/famotidine
• Indocin
• Indocin SR
• indomethacin
• ketoprofen
• ketorolac
• ketorolac intranasal
• Maximum Bayer Aspirin
• meclofenamate
• mefenamic acid
• meloxicam
• Menstridol
• Mobic
• Motrin
• nabumetone
• Nalfon
• Naprelan
• Naprosyn
• Naprox Sodium
• naproxen
• Naproxen EC
• Naproxen SR
• naproxen/sumatriptan
• NeoProfen
• oxaprozin
• PediaCare Children's Pain Reliever/Fever Reducer IB
• PediaCare Infant's Pain Reliever/Fever Reducer IB
• piroxicam
• salsalate
• Sprix
• St. Joseph Adult Chewable Aspirin
• St. Joseph Regular Strength
• sulindac
• tolmetin
• Treximet
• Trilisate ASA combination
• Vazalore
• Vivlodex
• Voltaren-XR
• Zipsor
• Zorvolex