NSAIDS 2024 Part I 2 PDF

Nonsteroidal Antiinflammatory Drugs and Antipyretic - Analgesics Dr. Anuroop Singhai Oral Surgery Division Non Steroidal Antiinflammatory Drugs and Antipyretic-Analgesics Introduction Analgesic is a drug that selec-vely relieves pain by ac-ng in the CNS or on peripheral pain mechanisms, without sign...

Nonsteroidal Antiinflammatory Drugs and Antipyretic - Analgesics Dr. Anuroop Singhai Oral Surgery Division Non Steroidal Antiinflammatory Drugs and Antipyretic-Analgesics Introduction Analgesic is a drug that selec-vely relieves pain by ac-ng in the CNS or on peripheral pain mechanisms, without significantly altering consciousness. Analgesics relieve pain as a symptom without affec-ng its cause. They are used when the noxious s-mulus (evoking pain) cannot be removed, or as an adjuvant to more e-ologic approach to pain, such as an-bio-c treatment of apical tooth abscess. Analgesics are divided into two groups: A. Opioid / narco-c / morphine like analgesics. B. Nonopioid / non-narco-c / an-pyre-c / aspirin-like analgesics or nonsteroidal an-inflammatory drugs (NSAIDs). Classification NSAID Antiinflammatory Drugs / Antipyretic-Analgesics Nonselec9ve COX inhibitors Preferential Salicylates Enolic acid derivatives COX-2 inhibitors Nimesulide Diclofenac Propionic acid derivatives Acetic acid derivatives Aceclofenac Meloxicam Etodolac Fenamate Pyrazolone derivatives Selec9ve COX-2 inhibitor Celecoxib Etoricoxib Parecoxib Analgesic-antipyretics with poor anti-inflammatory action Para aminophenol derivative Paracetamol (Acetoaminofen) Benzoxazocine deriva9ve Nefopam Slow-reacting substance of anaphylaxis (SRS-A) is an important mediator of anaphylactic and other immediate allergic reactions. SRS-A can be found in most tissues, especially in the lung, after appropriate antigenic challenge. It is released along with histamine and other Mechanism of Action that either one or both play a role in the bronchial constriction and mucosal edema of asthma. Leukotriene B4 can enhance chemotactic and chemokinetic responses in human neutrophils, monocytes, and eosinophils. These findings suggest that leukotrienes are involved Cell membrane phospholipids Phospholipases Steroids inhibit Other Arachidonic acid COX-1 and COX-2 inhibitors, aspirin, ibuprofen, naproxen and celecoxib inhibit lipoxygenases Cyclooxygenase 5-Lipoxygenase Prostaglandin G2 (PGG2) 5-HPETE 12-Lipoxygenase Leukotriene A4 (LTA4) Platelets Prostacyclin (PGI2) Thromboxane A2 (TXA2) Vasodilation, inhibits platelet aggregation Vasoconstriction, promotes platelet aggregation PGD2 PGE2 PGF2 Smooth muscle Leukotriene C4 (LTC4) Leukotriene D4 (LTD4) Leukotriene E4 (LTE4) Lipoxin A4 (LXA4) 5-HETE Chemotaxis Prostaglandin H2 (PGH2) Endothelium HETEs HPETEs Leukotriene B4 (LTB4) Vasoconstriction Bronchospasm Increased vascular permeability Lipoxin B4 (LXB4) Vasodilation, Inhibit neutrophil adhesion and chemotaxis Vasodilation, Increased vascular permeability-edema FIG 17-1 Pathways of arachidonic acid metabolism to prostaglandins and leukotrienes and their subsequent PG Synthesis Inhibition Beneficial Actions: 1. 2. 3. 4. 5. Analgesia: prevention of pain nerve ending sensitization Antipyresis Antiinflammatory Antithrombotic Closure of ductus arteriosus in newborn Shared Toxicities: 1. 2. 3. 4. 5. Gastric mucosal damage Bleeding: inhibition of platelet function Limitation of renal blood flow : Na+ and water retention Delay/prolongation of labour Asthma and anaphylactoid reactions in susceptible individuals Features of nonselective COX inhibitors and selective COX-2 inhibitors Nonselective COX inhibitors COX-2 inhibitors 1. Analgesic + + 2. Antipyretic + + 3. Antiinflammatory + + 4. Antiplatelet aggregatory + – 5. Gastric mucosal damage + – 6. Renal salt/water retention + + 7. Delay/prolongation of labour + + 8. Ductus arteriosus closure + ? 9. Aspirin sensitive asthma precipitation + – Action Adverse effects of NSAIDS CNS Headache, mental confusion, ver@go, behavioural disturbances, seizure precipita@on Hepatic Raised transaminases, hepatic failure (rare) Gastrointestinal Nausea, anorexia, gastric irritation, erosions, peptic ulceration, gastric bleeding/perforation, esophagitis Haematological Bleeding, thrombocytopenia, haemolytic anaemia, agranulocytosis CVS Rise in BP, risk of myocardial infarc@on (especially with COX-2 inhibitors) Renal Na+ and water retention, chronic renal failure, nephropathy, papillary necrosis (rare) Others Asthma exacerbation, nasal polyposis, skin rashes, pruritus, angioedema Drug interactions with NSAIDS Fenamate (Anthranilic Acid Derivative) 3 Drug interactions with NSAIDs Pharmacodynamic Diuretics β blocker ACE inhibitors Anticoagulants Sulfonylureas Alcohol Cyclosporine Corticosteroids Selective serotonin reuptake inhibitors : : : : : : : : : ↓ diuresis ↓ antihypertensive effect ↓ antihypertensive effect ↑ risk of g.i. bleed ↑ risk of hypoglycaemia ↑ risk of g.i. bleed ↑ nephrotoxicity ↑ risk of g.i. bleed ↑ risk of g.i. bleed orally, highly bound to plasma proteins (90–99%), but displacement interactions Pharmacokinetic Oral anticoagulants Sulfonylureas Phenytoin Valproate Digoxin Lithium Aminoglycosides Methotrexate ] ] Metabolism inhibited; Competition for plasma protein binding ↓ Renal excretion of interacting drug adverse drug reporting system in UK. Ibuprofen (400 mg) has been found equally Salicylates Aspirin Aspirin is acetylsalicylic acid. It is rapidly converted in the body to salicylic acid which is responsible for most of the actions. Pharmacological actions 1. Aspirin has analgesic, antipyretic and antiinflammatory action. 2. Aspirin as well as the salicylic acid released from it irritate gastric mucosa → cause epigastric distress, nausea and vomiting. Aspirin – Pharmacological Actions 3. Aspirin, even in small doses, irreversibly inhibits thromboxane A2 (TXA2) synthesis by platelets. Interferes with platelet aggregation, Bleeding time is prolonged to nearly twice the normal value. This effect lasts for about a week (turnover time of platelets). Long-term intake of large doses decrease synthesis of clotting factors in liver and predisposes to bleeding. This can be prevented by prophylactic vit - K therapy. 4. The analgesic doses of aspirin (0.3–0.6 g) employed in dentistry or for headache, fever, etc. have practically no other action. Aspirin – Pharmacokinetics Absorption: Stomach and small intestines. Its poor water solubility is the limiting factor in absorption. Plasma t1⁄2: Of aspirin as such is 15–20 min, but taken together with that of released salicylic acid, it is 3–5 hours. Aspirin – Adverse effects Aspirin – Adverse effects 1. Hypersensitivity and idiosyncrasy though infrequent, these can be serious. Reactions include rashes, fixed drug eruption, urticaria, rhinorrhoea, angioedema, asthma and anaphylactoid reaction. 2. Antiinflammatory doses (3–5 g/ day) produce the syndrome called salicylism— dizziness, tinnitus, vertigo, reversible impairment of hearing and vision, excitement and mental confusion, hyperventilation and electrolyte imbalance. Salt and water retention occurs in a dose-dependent manner. 3. An association between salicylate therapy and ‘Reye’s syndrome’, a rare form of hepatic encephalopathy seen in children having viral (varicella, influenza) infection, has been noted. Long-term therapy with high dose aspirin can cause insidious onset hepatic injury. Aspirin – Adverse effects 4. Acute salicylate poisoning: It is more common in children. Coma and death due to respiratory failure + cardiovascular collapse. Treatment: a. Symptoma