NSAIDs; (Non Steroidal Anti-Inflammatory Drugs); Types, Uses

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NSAIDs (Nonsteroidal anti-inflammatory agents) are a group of medicines that relieve pain and fever and reduce inflammation. There are nearly two dozen different NSAIDs available, but they all work in the same way, and that is by blocking a specific group of enzymes called cyclo-oxygenase enzymes. Analgesics and adjunct pain medications share their mechanism of action. They all deliver analgesic effect by interfering with the pain signaling cascade.

Types of NSAIDs

Non-Narcotic Analgesics

GenericBrand Name

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

GenericBrand Name
BromfenacProlensa, Bromday
DiclofenacCataflam, Voltaren, Zipsor
EtodolacLodine, Lodine XL
IbuprofenAdvil, Cramp End, Dolgesic, Excedrin IB, Genpril, Haltran, Ibren, Ibu, Ibuprin, Ibuprohm, Ibu-Tab, Medipren, Midol IB, Motrin, Nuprin, Pamprin-IB, Q-Profen, Rufen, Trendar
IndomethacinIndocin, Indocin SR, Tivorbex
KetoprofenActron, Orudis, Oruvail
KetorolacToradol, Sprix
Mefenamic AcidPonstel
MeloxicamMobic, Vivlodex
NaproxenAleve, Anaprox,
Anaprox DS, EC-Naprosyn, Naprelan, Naprosyn
TolmetinTolectin, Tolectin DS

Acetic acid derivatives & Oxicams

N-Arylanthranilic acids (fenamates)  & Propionic acid derivatives

Narcotic Pain Medications (Painkillers)

GenericBrand Name
BuprenorphineBuprenex, Butrans transdermal patch
HydromorphoneDilaudid, Dilaudid-5, Dilaudid-HP, Hydrostat IR, Exalgo ER
MethadoneDolophine, Methadose
MorphineAstramorph PF, AVINZA, Duramorph, Kadian,
M S Contin, MSIR, Oramorph SR, Rescudose, Roxanol
OxycodoneOxyContin, Roxicodone, Oxecta
PropoxypheneCotanal-65, Darvon

Central Analgesics

GenericBrand Name
Tramadol and AcetaminophenUltracet


GenericBrand Name
Butalbital, Acetaminophen, and CaffeineFemcet, Fioricet, Esgic, Esgic-Plus
Butalbital, Aspirin, and CaffeineFiorinal
Butalbital, acetaminophen, caffeine, and codeineFioricet with Codeine
Hydrocodone and IbuprofenHydrostal IR, Vicoprofen
Oxycodone/NaltrexoneTroxyca ER
Pentazocine/NaloxoneTalwin NX
Narcotic Analgesics and Acetaminophen
Acetaminophen and CodeineCapital with Codeine, Margesic #3, Phenaphen with Codeine, Tylenol with Codeine
Dihydrocodeine, Acetaminophen, and CaffeineDHCplus
Hydrocodone and AcetaminophenAllay, Anexsia 5/500, Anexsia 7.5/650, Dolacet, Dolagesic, Duocet, Hycomed, Hydrocet, Hydrogesic, HY-PHEN, Lorcet 10/650, Lorcet-HD, Lortab, Panacet 5/500, Panlor, Stagesic, T-Gesic, Ugesic, Vicodin, Zydone
Oxycodone and AcetaminophenEndocet, Percocet, Roxicet, Roxilox, Tylox; Xartemis XR
Pentazocine and AcetaminophenTalacen
Propoxyphene and AcetaminophenDarvocet-N 50,
Darvocet-N 100, E-Lor, Propacet 100
Narcotic Analgesics and Aspirin
Aspirin, Caffeine, and DihydrocodeineSynalgos-DC
Aspirin and CodeineEmpirin with Codeine
Hydrocodone and AspirinDamason-P, Lortab ASA, Panasal 5/500
Oxycodone and AspirinEndodan, Percodan, Percodan-Demi, Roxiprin
Pentazocine and AspirinTalwin Compound
Propoxyphene, Aspirin, and CaffeineDarvon Compound-65, PC-Cap, Propoxyphene Compound-65
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Topical Analgesics

GenericBrand Name
CapsaicinArthriCare, ARTH-RX, Axsain, Capsagel, Dura-Patch, Methacin, Qutenza, Zotrix, Zotrix-HP

Mechanism of Action of NSAIDs

Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition. COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation.

COX-1 is a constitutively expressed enzyme with a “house-keeping” role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result.

NSAIDs have been studied in various assays to understand how they affect each of these enzymes. While the assays reveal differences, unfortunately, different assays provide differing ratios. The discovery of COX-2 led to research to the development of selective COX-2 inhibiting drugs that do not cause gastric problems characteristic of older NSAIDs.

Paracetamol (acetaminophen) is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body. However, many aspects of the mechanism of action of NSAIDs remain unexplained, and for this reason, further COX pathways are hypothesized. The COX-3pathway was believed to fill some of this gap but recent findings make it appear unlikely that it plays any significant role in humans and alternative explanation models are proposed.

NSAIDs interact with the endocannabinoid system and its endocannabinoids, as COX2 have been shown to utilize endocannabinoids as substrates, and may have a key role in both the therapeutic and adverse effects of NSAIDs, as well as in NSAIDs-induced placebo responses.NSAIDs are also used in the acute pain caused by gout because they inhibit urate crystal phagocytosis besides inhibition of prostaglandin synthase.

Indications/Uses of NSAIDs

NSAIDs are usually used for the treatment of acute or chronic conditions where pain and inflammation are present.

NSAIDs are generally used for the symptomatic relief of the following conditions.

  • Osteoarthritis
  • Rheumatoid arthritis
  • Mild-to-moderate pain due to inflammation and tissue injury
  • Low back pain
  • Inflammatory arthropathies (e.g., ankylosing spondylitis, psoriatic arthritis, reactive arthritis)
  • Tennis elbow
  • A headache
  • A migraine
  • Acute gout
  • Dysmenorrhoea (menstrual pain)
  • Metastatic bone pain
  • Postoperative pain
  • Muscle stiffness and pain due to Parkinson’s disease
  • Pyrexia (fever)
  • Ileus
  • Renal colic
  • Macular edema

Contra-Indications of NSAIDs

NSAIDs may be used with caution by people with the following conditions

  • Irritable bowel syndrome
  • Persons who are over age 50, and who have a family history of GI (gastrointestinal) problems
  • Persons who have had past GI problems from NSAID use

NSAIDs should usually be avoided by people with the following conditions

  • Peptic ulcer or stomach bleeding
  • Uncontrolled hypertension
  • Kidney disease
  • People that suffer from inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
  • Past transient ischemic attack (excluding aspirin)
  • Past stroke (excluding aspirin)
  • Past myocardial infarction (excluding aspirin)
  • Coronary artery disease (excluding aspirin)
  • Undergoing coronary artery bypass surgery
  • Congestive heart failure (excluding low-dose aspirin)
  • In the third trimester of pregnancy
  • Persons who have undergone gastric bypass surgery
  • Persons who have a history of allergic or allergic-type NSAID hypersensitivity reactions, e.g. aspirin-induced asthma
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The Side Effect of NSAIDs

NSAIDs’ common adverse effect profile.

Gastrointestinal toxicity•Dyspepsia
•Gastroduodenal ulcers
•GI bleeding and perforation
Cardiovascular adverse effects•Edema
•Congestive heart failure
•Myocardial infarction
•Stroke and other Thrombotic events
Nephrotoxicity•Electrolyte imbalance
•Sodium retention
•Reduce glomerular filtration rate
•Nephrotic syndrome
•Acute interstitial nephritis
•Renal papillary necrosis
•Chronic kidney disease [3]

The most common

Less common


  • Abdominal or stomach cramping, burning, or tenderness
  • back or leg pains
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • bloody or black, tarry stools
  • blue lips and fingernails
  • breast enlargement and tenderness
  • burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
  • burning upper abdominal or stomach pain
  • chest pain, discomfort, or burning
  • confusion
  • continuing diarrhea
  • cough or hoarseness
  • coughing that sometimes produces a pink frothy sputum
  • cracks in the skin
  • dark urine
  • decreased appetite
  • decreased vision or any change in vision
  • depression
  • difficult or labored breathing
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
  • double vision
  • dry mouth
  • extreme fatigue
  • false sense of well-being
  • feeling of unreality
  • feeling of warmth
  • general body swelling
  • greatly decreased frequency of urination or amount of urine
  • hair loss
  • headache
  • heavier menstrual periods
  • increased hunger
  • increased sweating
  • jerky movements of the head, face, mouth, and neck
  • joint pain
  • large, flat, blue or purplish patches in the skin
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • loss of balance control
  • loss of bladder control
  • loss of consciousness
  • loss of hearing
  • loss of heat from the body
  • lower back or side pain
  • mask-like face
  • mood swings
  • muscle aches, pains, or weakness
  • muscle spasm or jerking of all extremities
  • numbness or tingling in the hands, feet, or lips
  • pain in the ankles or knees
  • pain or discomfort in the upper stomach or throat
  • pain with swallowing
  • painful or difficult urination
  • painful, red lumps under the skin, mostly on the legs
  • seeing, hearing, or feeling things that are not there
  • seizures
  • sense of detachment from self or body
  • severe constipation
  • severe mental changes
  • severe or continuing stomach pain
  • shuffling walk
  • skin rash, hives or welts, itching
  • slow, fast, irregular, pounding, or racing heartbeat or pulse
  • slowed movements
  • slurred speech
  • small red or purple spots on the skin
  • sore throat
  • unexplained weight loss
  • unpleasant breath odor
  • vaginal bleeding
  • vomiting of blood or material that looks like coffee grounds
  • weakness in the arms, hands, legs, or feet
  • weight gain
  • yellow eyes or skin

Symptoms of overdose

  • Confusion about identity, place, and time
  • severe headache
  • unusual drowsiness, dullness, or feeling of sluggishness

More common

  • Continuing ringing or buzzing or other unexplained noise in the ears
  • difficulty having a bowel movement (stool)
  • discouragement
  • feeling sad or empty
  • general feeling of discomfort or illness
  • hearing loss
  • irritability
  • loss of interest or pleasure
  • sleepiness
  • trouble with concentrating


  • Anxiety
  • bloated or full feeling
  • changes in patterns and rhythms of speech
  • excess air or gas in the stomach or intestines
  • feeling of constant movement of self or surroundings
  • involuntary muscle movements
  • lightheadedness
  • passing gas
  • sensation of spinning
  • tiredness
  • trouble sleeping
  • trouble with speaking
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Drug Interactions of NSAIDs

NSAIDs may interact with following drugs, suppliments & may change the efficasy of drugs

Drug interaction of NSAIDs and commonly used medications.

Antiplatelets (aspirin, clopidogrel)Increases risk of GI bleeding
Angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin Receptor Blockers (ARB)Increases in blood pressure by attenuating antihypertensive effects
Beta-blockersIncreases in blood pressure by attenuating antihypertensive effects
Calcium antagonistsIncreases in blood pressure by attenuating antihypertensive effects
CorticosteroidsIncreases risk of GI bleeding
Digitalis glycosidesIncrease serum digoxin level
DiureticsIncreases in blood pressure by attenuating antihypertensive effects
MethotrexateNSAIDs reduce renal excretion of methotrexate, causing methotrexate toxicity.
Selective serotonin reuptake inhibitors (SSRIs)Increases risk of GI bleeding
Warfarin and other anticoagulantsIncreases risk of GI bleeding


The Food and Drug Administration expert advisory committee recommends that:106

  • when COX-2 inhibitors and NSAIDs are to be used for the management of individual patients, they should be prescribed with the lowest effective dose and for the shortest duration.
  • they should not be prescribed for high-risk patients, e.g., patients with a history of ischemic heart disease, stroke or congestive heart failure, or in patients who have recently undergone CABG.
  • all prescription-strength NSAIDs will now display “black box” label warnings for the potential risk of cardiovascular and gastrointestinal adverse effects.
  • treatment with tNSAIDs alone in patients aged less than 65 years who do not have gastrointestinal risk factors is considered appropriate. Co-therapy with a PPI or treatment with a COX-2 inhibitor was considered unnecessary in these patients.
  • the use of a tNSAID alone was considered inappropriate in any patient with a previous gastrointestinal event and in those who concurrently receive aspirin, steroids or warfarin. These patients should receive either a tNSAID plus a PPI or a COX-2 inhibitor.
  • use of a COX-2 inhibitor with PPI co-therapy is appropriate only in patients at very high risk, such as those with a previous gastrointestinal event who are taking aspirin, and those who are taking aspirin plus steroids or warfarin.


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