NSAIDS(NON-STEROIDAL ANTI INFLAMMATORY DRUGS)

MEDICINAL CHEMISTRY-1

1. INDIRA GANDHI NATIONAL TRIBAL UNIVERSITY ,AMARKANTAK(M.P) ASSIGNMENT ON NON-STEROIDAL ANTI-INFLAMMATORY DRUGS SUBMITTED BY: SUBMITTED TO: MARY MELNA PROF. N.S. HARI NARAYAN ENROLL NO: MOORTY SIR 1801024022

2. OVERVIEW: What’s Inflammation-Importance and sign of inflammation NSAIDS- Introduction,Mechanism,Physiology of pain,Classification Salicylate (Aspirin)-Introduction, Synthesis, Pharmacology, Adverse Effects,Uses,Interaction,Precaution & Contraindication Propinoic Acid Derivatives(Ibuprofen)-Introduction, Pharmacology, Uses, Side Effects.

3. NSAIDs It produces anti-inflammatory action means it acts against the inflammation. What’s Inflammation ? Inflammation is derived from latin word inflammatio which means to set on fire. It’s a complex biological responses of body tissues to harmful stimuli,such as pathogens,damaged cells or irritants. This complex process involves several immune cells,blood vessels and molecular mediators.

4. Importance of Inflammation Inflammation occurs in the body to eliminate the initial causes of cell injury ,clear out necrotic cells and tissue damage. 5 Signs of Inflammation

5. Introduction of NSAIDs The drugs which comes under NSAIDs category have analgesic ,antipyretic and anti-inflammatory action. These are the drugs without steroidal ring. NSAIDs don’t depress CNS,don’t produce physical dependence,have no abuse liability and are weaker analgesic instead morphine shows all characteristics. It’s also known as Non-narcotic ,Non- opoids or aspirin like analgesics. Mainly NSAIDs act on peripheral pain mechanisms,but also in the CNS to raise pain threshold.

6. Mechanism of action of NSAIDs:

7. PHYSIOLOGY OF PAIN

8. Trick:-SOAAPP-F NON SELECTIVE COX INHIBITOR:

9. SELECTIVE COX-II INHIBITOR PREFERENTIAL COX-II INHIBITORS ANALGESIC & ANTIPYRETICS Celecoxib,Valdecoxib,Etoricoxib,Parecoxib Nimesulide,Meloxicam,Nabumetone 1.Para-aminophenol Derivatives- Paracetamol 2.Pyrazolone Derivatives- Metamizol,Propiphenazone 3.Benzoxazocine Derivatives- Nefopam

10. SALICYLATE(ASPIRIN) INTRODUCTION: Aspirin is a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs are a class of drugs. Other NSAIDs include ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn ). They work in a similar way to reduce the amount of prostaglandin your body makes. Prostaglandin is a natural substance that most cells in your body make. Your cells release prostaglandins when you’re injured. They contribute to your body’s inflammation, which causes a variety of effects, including swelling, fever, and increased sensitivity to pain. By blocking your body’s production of prostaglandins, NSAIDs such as aspirin can help prevent and relieve these symptoms of injury.

11. SALICYLATE(ASPIRIN) SYNTHESIS OF ASPIRIN:

12. SALICYLATE(ASPIRIN) PHARMACOLOGY : Aspirin (acetylsalicylic acid) is the best-known salicylate and belongs to the non steroid anti-inflammatory drug class. Despite wide use being made since more than 100 years, knowledge about mechanism of action and therapeutic issues continually evolves. The main mechanism of action is prostaglandin synthesis inhibition. This is achieved through inhibition of prostaglandin endoperoxide synthase (PGHS) or cyclooxygenase (COX) synthesis. Most of the therapeutic uses of aspirin are explained by this mechanism. Nevertheless aspirin uses change as time goes by: if the main one during the first fifty years was an analgesic, anti-pyretic and anti-inflammatory one, the last fifty years saw aspirin being used mainly as an anti-thrombotic agent, in primary and secondary thrombo -embolic prevention. Better knowledge of mechanism of action points today at, on one hand, more selective and therefore better tolerated molecules, and, on the other hand, at new therapeutic applications, such as anti-cancer and neurodegenerative diseases prevention.

13. SALICYLATE(ASPIRIN) SIDE EFFECTS : Common side effects of aspirin can include: Nausea,vomiting,stomach pain,heartburn Serious side effects of aspirin are rare, but can include: Allergic reactions. Symptoms can include: Hives,rash,swelling of your eyes, face, lips, tongue, or throat,wheezing or difficulty breathing Changes in your acid-base balance, which affects how systems in your body work. Symptoms can include: Hoarseness,fast heartbeat,fast breathing,cold and clammy skin Salicylate toxicity. Early symptoms can include: ringing in your ears,hearing loss Stomach bleeding. Symptoms can include: bloody vomit,vomit that looks like coffee grounds,bright red blood in your stools,black or tarry stools

14. SALICYLATE(ASPIRIN) USES: Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever , and inflammatory conditions, such as rheumatoid arthritis , pericarditis , and Kawasaki disease . Lower doses of aspirin have also been shown to reduce the risk of death from a heart attack , or the risk of stroke in people who are at high risk or who have cardiovascular disease, but not in elderly people who are otherwise healthy.There is some evidence that aspirin is effective at preventing colorectal cancer , though the mechanisms of this effect are unclear.In the United States, low-dose aspirin is deemed reasonable in those between 50 and 70 years old who have a risk of cardiovascular disease over 10%, are not at an increased risk of bleeding, and are otherwise healthy.

15. SALICYLATE(ASPIRIN) INTERACTION: Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride are known to enhance the intoxicating effect of salicylates , and alcohol also increases the gastrointestinal bleeding associated with these types of drugs. Aspirin is known to displace a number of drugs from protein-binding sites in the blood, including the antidiabetic drugs tolbutamide and chlorpropamide , warfarin , methotrexate , phenytoin , probenecid , valproic acid (as well as interfering with beta oxidation , an important part of valproate metabolism), and other NSAIDs. Corticosteroids may also reduce the concentration of aspirin. Ibuprofen can negate the antiplatelet effect of aspirin used for cardioprotection and stroke prevention.The pharmacological activity of spironolactone may be reduced by taking aspirin, and it is known to compete with penicillin G for renal tubular secretion.Aspirin may also inhibit the absorption of vitamin C.

16. SALICYLATE(ASPIRIN) PRECAUTIONS: Use an immediate-release aspirin in such an event. Make sure your doctor knows if you are pregnant or breastfeeding. Do not use this medicine during the later part of a pregnancy unless your doctor tells you to. This medicine may increase risk for bleeding problems, including stomach ulcers or bleeding. CONTRAINDICATION: Many medicines should not be used together by the same person. For instance, a person who takes warfarin to thin the blood should not take aspirin , which is a blood thinner . This is an example of a relative contraindication.

17. PROPIONIC ACID DERIVATIVES (IBUFROFEN) INTRODUCTION: Ibuprofen is a medication in the nonsteroidal anti-inflammatory drug (NSAID) class that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used by mouth or intravenously. It typically begins working within an hour.

18. PROPIONIC ACID DERIVATIVES (IBUFROFEN) PHARMACODYNAMICS :Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that possesses anti-inflammatory, analgesic and antipyretic activity. Its mode of action, like that of other NSAIDs, is not completely understood, but may be related to prostaglandin synthetase inhibition. PHARMACOKINETICS :Ibuprofen pharmacokinetics are only minimally influenced by advanced age, the presence of alcoholic liver disease, or rheumatoid arthritis . Levels of ibuprofen in breast milk are negligible. In addition, ibuprofen can be combined with acetaminophen without altering the pharmacokinetic profile.

19. PROPIONIC ACID DERIVATIVES (IBUFROFEN) USES : Ibuprofen is used primarily to treat fever (including post-vaccination fever), mild to moderate pain (including pain relief after surgery ), painful menstruation , osteoarthritis , dental pain, headaches , and pain from kidney stones . About 60% of people respond to any NSAID; those who do not respond well to a particular one may respond to another. It is used for inflammatory diseases such as juvenile idiopathic arthritis and rheumatoid arthritis . It is also used for pericarditis and patent ductus arteriosus .

20. PROPIONIC ACID DERIVATIVES (IBUFROFEN) SIDE EFFECTS: Adverse effects include nausea , dyspepsia , diarrhea , constipation , gastrointestinal ulceration/bleeding, headache , dizziness , rash, salt and fluid retention, and high blood pressure . Infrequent adverse effects include esophageal ulceration, heart failure , high blood levels of potassium , kidney impairment , confusion, and bronchospasm . Ibuprofen can exacerbate asthma, sometimes fatally. Ibuprofen may be quantified in blood, plasma, or serum to demonstrate the presence of the drug in a person having experienced an anaphylactic reaction, confirm a diagnosis of poisoning in people who are hospitalized, or assist in a medicolegal death investigation. A monograph relating ibuprofen plasma concentration, time since ingestion, and risk of developing renal toxicity in people who have overdosed has been published.

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