Nonsteroidal Antiinflammatory Drugs NSAIDS Q What are nonsteroidal

Non-steroidal & Anti-inflammatory Drugs [NSAID’S]

Q. What are non-steroidal & non-inflammatory drugs? Ans: The term non steroidal distinguishes these drugs from steroids, which, among a broad range of other effects, have a similar depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic and thus are used as a nonaddictive alternative to narcotics anti-inflammatory refers to the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids which affect the central nervous system. Q. What are analgesics? Ans: the drugs which relive or suppress the sensation of pain by acting on central nervous system but without producing any degree of loss of conciousness. the analgesic may either decrease the pain sensation or may make the patient unaware of the existing PAIN. Q. What is PAIN ? ANS. Pain is an unpleasant sensory and emotional experience associated ANS with actual or potential tissue damage, or described in terms of such damage.

Q. What is pharmacokinetics of NSAID’S ? ANS: 1) Most non-steroidal anti-inflammatory drugs are weak acids. 2)They are absorbed well from the stomach and intestinal mucosa. 3)They are highly protein-bound in plasma usually to albumin, so that their volume of distribution typically approximates to plasma volume. 4) Most NSAIDs are metabolized in the liver by oxidation and conjugation to inactive metabolites that typically are excreted in the urine though some drugs are partially excreted in bile. 5) Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage. 6) Ibuprofen and diclofenac have short half-lives (2– 3 hours).

Classification of NSAID’S Non selective NSAID’s Diclofenac Ibuprofen Ketoprofen Aspirine Naproxen Piroxlcam Indomethacil SELECTIVE NSAID’s Celecoxib Rofecoxib Etoricoxib Meloxicam

CHEMICAL CLASSIFICATION OF NSAID’S 1) Alicylates Aspirin Diflunisal Salicylic acid 4)Selective COX-2 inhibitors Celecoxib Rofecoxib Valdecoxib Parecoxib Lumiracoxib 2)Propionic acid derivatives Ibuprofen Naproxen Ketoprofen Oxaprozin 5)Sulfonanilides Nimesulide 3)Acetic acid derivatives indomethacin Tolmetin Diclofenac Aceclofenac

MECHANISM OF ACTION : 1)Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase(COX) , inhibiting both the cyclooxygenase-1 and cyclooxygenase 2 (COX-2) isoenzymes. 2)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. 3)Prostaglandins act (among other things) as messenger molecules in the process of inflammation 4) This mechanism of action was discovered by John Vane (1927– 2004), who received a Nobel Prize for his work 5)COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. 6)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. 7)COX-2 is an enzyme facultative expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.

8)When nonselective inhibitors (such as aspirin, ibuprofen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result 9)NSAIDs are also used in the acute pain caused by gout because they inhibit urate crystal phagocytosis besides inhibition of prostaglandin syntheses.

Q. What are the adverse effect of NSAID’S ? ANS: Adverse effect of NSAID’S are as follows: 1) Combinational risk : • If a COX-2 inhibitor is taken, a traditional NSAID ( over-the-counter) should not be taken at the same time. In addition, people on daily aspirin therapy (e. g. , for reducing cardiovascular risk) must be careful if they also use other NSAIDs, as these may inhibit the cardio protective effects of aspirin. • Use of methotrexate together with NSAIDS in rheumatoid arthritis is safe, if adequate monitoring is done. 2)Cardiovascula: • NSAIDs aside from aspirin, both newer selective COX-2 inhibitors and traditional antiinflammatory, increase the risk of myocardial infarction and stroke. • They are not recommended in those who have had a previous heart attack as they increase the risk of death and / or recurrent MI. • Evidence indicates that may be the least harmful out of these.

• NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of heart failure in people without a history of cardiac disease. • In people with such a history, use of NSAIDs was associated with a more than 10 -fold increase in heart failure. 3)Gastrointestinal: • The main adverse drug reactions associated with NSAID use relate to direct and indirect irritation of the gastrointestinal (GI) tract. • NSAIDs cause a dual assault on the GI tract: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of protective prostaglandins. • Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucus secretion and diminished tropic effects on epithelial mucosa. • Common gastrointestinal ADRs include: 1. Nausea/Vomiting 2. Dyspepsia 3. Gastric ulceration/bleeding. 4. Diarrhea

4) inflammatory bowel disease: • NSAIDs should be used with caution in individuals with inflammatory bowel disease due to their tendency to cause gastric bleeding and form ulceration in the gastric lining. Pain relievers such as paracetamo; (also known as acetaminophen) or drugs containing codeine (which slows down bowel activity) are safer medications for pain relief in IBD 5) Renal: • NSAIDs are also associated with a relatively high incidence of renal adverse drug reactions. • The mechanism of these renal ADRs is due to changes in renal hemodynamic (kidney blood flow), ordinarily mediated by prostaglandins, which are affected by NSAIDs. • Common ADRs associated with altered renal function include 1. Salt (Sodium) and fluid retention 2. Hypertension (high blood pressure) • In rarer instances NSAIDs may also cause more severe renal conditions 1. Interstitial nephritis 2. Nephritic syndrome 3. Acute renal failure 4. Acute tubular necrosis

6) During pregnancy: • NSAIDs are not recommended during pregnancy, particularly during the third trimester. • While NSAIDs as a class are not direct teratogens they may cause premature closure of the fetal ductu arteriosus and renal ADRs in the fetus. • Additionally, they are linked with premature birth and miscarriage. Aspirin, however, is used together with heparin in pregnant women with antiphospholipid antibodies. • Additionally, Indomethacin is used in pregnancy to treat polyhydramnios by reducing fetal urine production via inhibiting fetal renal blood flow. • In contrast, paracetamol is regarded as being safe and well-tolerated during pregnancy, but Lifers et al. released a study in 2010 indicating that there may be associated male infertility in the unborn. Doses should be taken as prescribed, due to risk of hepatotoxicity with overdoses

Uses: • 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 : 1. Osteoarthritis 2. Rheumatoid arthritis 3. Low back pain 4. Inflammatory arthropathies (e. g. , reactive arthritis) 5. Tennis elbow 6. Headache 7. migraine 8. Acute gout 9. Metastatic bone pain 10. Postoperative pain 11. Pyrexia (fever) 12. Ileus 13. Renal colic

• They are also given to neonate infants whose ducts arteriosus is not closed within 24 hours of birth. • Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation. • This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. • Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A 2.

Q. What are the prominent(important) members of NSAID’S ? ANS: 1)The most prominent members of this group of drugs, Aspirin, ibuprofen are all available over the counter in most countries. 2)Paracetamol is generally not considered an 2) NSAID because it has only little anti-inflammatory activity. 3)It 3) treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.

1)ASPIRINE: 1. Aspirin is a salicylate (sa-LIS-il-ate). It works by reducing substances in the body that cause pain, fever, and inflammation. 2. Aspirin is used to treat pain, and reduce fever or inflammation. 3. It is sometimes used to treat or prevent heart attacks, strokes, and chest pain (angina). Aspirin should be used for cardiovascular conditions only under the supervision of a doctor. 4. Aspirin may also be used for purposes not listed in this medication guide. Aspirin side effects : • • • ringing in your ears, confusion, hallucinations, rapid breathing, seizure (convulsions); Severe nausea, vomiting, or stomach pain bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds fever lasting longer than 3 days swelling, or pain lasting longer than 10 days Common aspirin side effects may include • upset stomach, heartburn • drowsiness • mild headache.

2) Paracetamol: 1. Paracetamol is a pain reliever and a fever reducer. The exact mechanism of action of is not known. 2. Paracetamol is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers. 3. It relieves pain in mild arthritis but has no effect on the underlying inflammation and swelling of the joint. 4. Paracetamol may also be used for other purposes not listed in this medication guide Paracetamol side effects: 1. low fever with nausea, stomach pain, and loss of appetite; 2. dark urine, clay-colored stools 3. jaundice (yellowing of the skin or eyes).

Paracetamol dose information: 1. Adult Paracetamol Dose for Fever: General Dosing Guidelines: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours orally or rectally. Paracetamol 500 mg tablets: Two 500 mg tablets orally every 4 to 6 hours 2. Adult Paracetamol Dose for Pain: General Dosing Guidelines: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours orally or rectally. Paracetamol 500 mg tablets: Two 500 mg tablets orally every 4 to 6 hours 3. Pediatric Dose for Fever: Oral or Rectal: 1 month: 10 to 15 mg/kg/dose every 6 to 8 hours as needed. 1 month to 12 years: 10 to 15 mg/kg/dose every 4 to 6 hours as needed. 12 years: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours.

3)Ibuprofen: 1. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body. 2. Ibuprofen is used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injury. 3. Ibuprofen is used in adults and children who are at least 6 months old. Ibuprofen side effects: 1. 2. 3. 4. 5. swelling or rapid weight gain little or no urinating fever, sore throat, and headache with a severe blistering, peeling, and red skin rash bruising, severe tingling, numbness, pain, muscle weakness severe headache, neck stiffness, chills, increased sensitivity to light, and/or seizure (convulsions) 6. nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)

Prepared by: A. Masarrat khan(76) B. Pathan Saleem (77) C. Jagnnath Phalke (78) D. Qazi Shazama (79) E. Quazi Adel (80)