Nonsteroidal Antiinflammatory Drugs And Antipyretic Analgesics Question And Answers

Nonsteroidal Antiinflammatory Drugs And Antipyretic Analgesics

Question 1. What Are Analgesics? Classify Them. Describe the Pharmacological Action, Therapeutic Uses, And Side Effects Of Acetylsalicylic Acid.
Or
Classify NSAIDs. Write Indication And Adverse Effects Of Aspirin.
Or
Classify Non­Steroidal Anti­Inflammatory Drugs. Describe the Therapeutic Uses And Adverse Affects Of Aspirin.
Or
Classify NSAIDs. Write Adverse Effects Of Aspirin.
Or
Classify NSAIDs. Describe the Uses Of Aspirin.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Analgesics Classifiation 

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Read And Learn More: Pharmacology Question And Answers

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:

• • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone

• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Pharmacological Actions Of Acetylsalicylic Acid Or Aspirin

• Analgesic action: Acetylsalicylic acid is effective against pain with inflammation such as dental pain and rheumatic pain.
  Mechanism: NSAIDs inhibit the COX enzyme thus preventing the synthesis of prostaglandins.
  Prostaglandins are mediators of inflammatory processes and bring about effects like pain and fever. They also sensitize free nerve endings to pain stimuli, aspirin causes irreversible acetylation of COX.
• Antiinflammatory action: It is due to the inhibition of prostaglandin synthesis at the site of injury.
  Aspirin also inhibits the migration of neutrophils and other WBC to the site of action. It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
• Antipyretic action: Aspirin blocks the action of pyrogen due to which prostaglandin synthesis in the hypothalamus is inhibited and hence depression in the temperature set point in the hypothalamus.
  It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
  It set the hypothalamic thermostat and reduces elevated body temperature during fever. These drugs also promote heat loss and lead to cutaneous vasodilatation and sweating.
• Blood: Aspirin irreversibly inhibits the synthesis of thromboxane A2 by acetylating COX enzyme irreversibly in platelets. Thus, platelet aggregation is prevented and bleeding time is prolonged.
• GIT: In GIT aspirin is unionized at gastric pH and is absorbed in mucosal cells and ionizes and cannot diffuse back, this causes gastric mucosal damage.
• Aspirin also inhibits COX-1 causing a decrease in PGE2 and PGI2-synthesis decreasing mucus barrier and causing gastric mucosal damage.
• Respiration: At anti-inflammatory doses, salicylates increase oxygen consumption by a skeletal muscle release which causes an increase in CO2 production there is hyperventilation due to which CO2 is washed out and hence results in respiratory alkalosis, and at higher doses metabolic acidosis is caused.
• CVS: Aspirin at large doses increases oxygen demand and increases cardiac output.
• Urate excretion: Aspirin at a small dose inhibits uric acid secretion by DCT due to which plasma urate level is increased. It also blocks the action of uricosuric drugs and hence it is avoided in gout patients.

Therapeutic Uses Or Indication Of Aspirin/Acetyl Salicylic Acid

• As analgesic: It is used for headaches, toothache, joint pain, dysmenorrhea, and myalgia. (Dosage 0.3 to 0.6 gm per day)
• As antipyretic: It is used in a fever of any origin
• In acute rheumatic fever, it is the first drug to be used.
• It is used in rheumatoid arthritis and osteoarthritis.
• In myocardial infarction and stroke: Aspirin inhibits platelet aggregation by blocking COX enzymes in platelets thus it prevents clot formation and lowers the incidence of reinfarction.
• In patent ductus arteriosus aspirin can bring about closure and prevent surgery.
• Aspirin is used in pregnant women to delay labor.
• Aspirin is useful in pregnancy-induced hypertension.

Side Effects/Adverse Effect Of Acetylsalicylic Acid Or Aspirin

• Analgesic doses, i.e. 0.3 to 1.5 gm per day. Aspirin causes nausea, vomiting, hypersensitivity reaction, epigastric distress, gastritis, peptic ulcer, and precipitation of asthma.
• Anti-inflammatory doses: A syndrome called salicylism is produced, salicylism dizziness, vertigo, tinnitus, reversible impairment of hearing and of vision hyperventilation, and electrolytic imbalance.
• Aspirin causes acute salicylate poisoning in adults.
• In patients with G6PD deficiency if aspirin is given it can lead to hemolytic anemia.
• Chronic use of aspirin interferes with vitamin K in the liver which decreases the synthesis of clotting factors which predispose to bleeding.
• Reye’s syndrome: Usage of salicylate in children having viral infection can lead to hepatic damage along with fatty infiltration and encephalopathy
• In pregnancy: Salicylates inhibit prostaglandin synthesis and delay the onset of labor, it also increases the tendency of postpartum hemorrhage. It can also lead to premature ductus arteriosus in newborns.
• Analgesic nephropathy: On chronic use of aspirin there is slow progressive renal failure which can occur on chronic use of salicylates.
• In very high doses acute salicylate poisoning occurs in adults.

Question 2. Classify Anti­Inflmmatory, Analgesic Agents. Discuss the Mode Of Action, Toxicities, And Contraindications Of Aspirin.
Answer:

Classification of Anti­inflmmatory Analgesic Agents

• Non-selective COX inhibitors:
  • Salicylates: Aspirin
  • Propionic acid derivatives: Ibuprofen, ketoprofen, naproxin
  • Anthranilic acid derivative: Mephenamic acid
  • Arylacetic acid derivative: Diclofenac, aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolopyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenyl butanone, oxyphen butanone.
• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, profit-endzone
  • Benzoxazocine derivative: Nefopam.

For a mode of action of aspirin refer to Ans. 1 of the same chapter.

Toxicities Of Aspirin

• The toxicity of aspirin is mild and severe.
• Mild toxicity is known as salicylism. Symptoms associated with salicylism are headache, tinnitus, vertigo, confusion, nausea, vomiting, diarrhea, sweating, hyperpnea, electrolyte imbalance, etc.
• Severe toxicity is known as acute salicylate poisoning. It occurs in both adults and children. It is more common in children. The fatal dose in adults is 15 to 30 gm and is lower in children. The signs of acute salicylate poisoning are vomiting, dehydration, hyperpyrexia, electrolyte imbalance, hyperglycemia, GI hemorrhages, delirium, convulsions, coma, and death due to respiratory failure + circulatory failure.

Contraindications Of Aspirin

• Aspirin is contraindicated in hypertensive patients, asthmatic, peptic ulcer patients, and patients with bleeding disorders.
• Aspirin is contraindicated in children suffering from the viral syndrome, i.e. Reye’s syndrome.
• Aspirin is contraindicated in hepatic necrosis.
• During pregnancy, it should not be given near or at term because it causes delayed labor and greater postpartum blood loss.
• It causes premature closure of ductus arteriosus.
• It should be avoided by breastfeeding mothers.

Question 3. Classify NSAIDs. Discuss Pharmacological Actions, Indication, And Contraindications Of Aspirin.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:
  • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone
• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Pharmacological Actions Of Acetylsalicylic Acid Or Aspirin

• Analgesic action: Acetylsalicylic acid is effective against pain with inflammation such as dental pain and rheumatic pain.
  Mechanism: NSAIDs inhibit the COX enzyme thus preventing the synthesis of prostaglandins.
  Prostaglandins are mediators of inflammatory processes and bring about effects like pain and fever. They also sensitize free nerve endings to pain stimuli, aspirin causes irreversible acetylation of COX.
• Antiinflammatory action: It is due to the inhibition of prostaglandin synthesis at the site of injury.
  Aspirin also inhibits the migration of neutrophils and other WBC to the site of action. It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
• Antipyretic action: Aspirin blocks the action of pyrogen due to which prostaglandin synthesis in the hypothalamus is inhibited and hence depression in the temperature set point in the hypothalamus.
  It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
  It set the hypothalamic thermostat and reduces elevated body temperature during fever. These drugs also promote heat loss and lead to cutaneous vasodilatation and sweating.
• Blood: Aspirin irreversibly inhibits the synthesis of thromboxane A2 by acetylating COX enzyme irreversibly in platelets. Thus, platelet aggregation is prevented and bleeding time is prolonged.
• GIT: In GIT aspirin is unionized at gastric pH and is absorbed in mucosal cells and ionizes and cannot diffuse back, this causes gastric mucosal damage.
• Aspirin also inhibits COX-1 causing a decrease in PGE2 and PGI2-synthesis decreasing mucus barrier and causing gastric mucosal damage.
• Respiration: At anti-inflammatory doses, salicylates increase oxygen consumption by a skeletal muscle release which causes an increase in CO2 production there is hyperventilation due to which CO2 is washed out and hence results in respiratory alkalosis, and at higher doses metabolic acidosis is caused.
• CVS: Aspirin at large doses increases oxygen demand and increases cardiac output.
• Urate excretion: Aspirin at a small dose inhibits uric acid secretion by DCT due to which plasma urate level is increased. It also blocks the action of uricosuric drugs and hence it is avoided in gout patients.

Contraindications Of Aspirin

• Aspirin is contraindicated in hypertensive patients, asthmatic, peptic ulcer patients, and patients with bleeding disorders.
• Aspirin is contraindicated in children suffering from the viral syndrome, i.e. Reye’s syndrome.
• Aspirin is contraindicated in hepatic necrosis.
• During pregnancy, it should not be given near or at term because it causes delayed labor and greater postpartum blood loss.
• It causes premature closure of ductus arteriosus.
• It should be avoided by breastfeeding mothers.

Question 4. Write A Short Note On Non­Steroidal Anti­Inflmmatory Drugs.
Or
Write Short Note On NSAIDs.
Or
Write Short Note On Anti­Inflmmatory Drugs.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:
  • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone
• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Various NSAIDs Along With Their Features

 

 

Question 5. List At least Two Drugs From NSAIDs. Describe Pharmacological Action And Therapeutic Uses Of This Class Of Drug.
Answer:

The two drugs from NSAIDs are as follows:

1. Salicylates, i.e. aspirin.
2. Paracetamol.

Salicylates

Pharmacological Actions Of Acetylsalicylic Acid Or Aspirin

• Analgesic action: Acetylsalicylic acid is effective against pain with inflammation such as dental pain and rheumatic pain.
  Mechanism: NSAIDs inhibit the COX enzyme thus preventing the synthesis of prostaglandins.
  Prostaglandins are mediators of inflammatory processes and bring about effects like pain and fever. They also sensitize free nerve endings to pain stimuli, aspirin causes irreversible acetylation of COX.
• Antiinflammatory action: It is due to the inhibition of prostaglandin synthesis at the site of injury.
  Aspirin also inhibits the migration of neutrophils and other WBC to the site of action. It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
• Antipyretic action: Aspirin blocks the action of pyrogen due to which prostaglandin synthesis in the hypothalamus is inhibited and hence depression in the temperature set point in the hypothalamus.
  It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
  It set the hypothalamic thermostat and reduces elevated body temperature during fever. These drugs also promote heat loss and lead to cutaneous vasodilatation and sweating.
• Blood: Aspirin irreversibly inhibits the synthesis of thromboxane A2 by acetylating COX enzyme irreversibly in platelets. Thus, platelet aggregation is prevented and bleeding time is prolonged.
• GIT: In GIT aspirin is unionized at gastric pH and is absorbed in mucosal cells and ionizes and cannot diffuse back, this causes gastric mucosal damage.
• Aspirin also inhibits COX-1 causing a decrease in PGE2 and PGI2-synthesis decreasing mucus barrier and causing gastric mucosal damage.
• Respiration: At anti-inflammatory doses, salicylates increase oxygen consumption by a skeletal muscle release which causes an increase in CO2 production there is hyperventilation due to which CO2 is washed out and hence results in respiratory alkalosis, and at higher doses metabolic acidosis is caused.
• CVS: Aspirin at large doses increases oxygen demand and increases cardiac output.
• Urate excretion: Aspirin at a small dose inhibits uric acid secretion by DCT due to which plasma urate level is increased. It also blocks the action of uricosuric drugs and hence it is avoided in gout patients.

Therapeutic Uses Or Indication Of Aspirin/Acetyl Salicylic Acid

• As analgesic: It is used for headaches, toothache, joint pain, dysmenorrhea, and myalgia. (Dosage 0.3 to 0.6 gm per day)
• As antipyretic: It is used in a fever of any origin
• In acute rheumatic fever, it is the first drug to be used.
• It is used in rheumatoid arthritis and osteoarthritis.
• In myocardial infarction and stroke: Aspirin inhibits platelet aggregation by blocking COX enzymes in platelets thus it prevents clot formation and lowers the incidence of reinfarction.
• In patent ductus arteriosus aspirin can bring about closure and prevent surgery.
• Aspirin is used in pregnant women to delay labor.
• Aspirin is useful in pregnancy-induced hypertension.

Paracetamol (Pharmacological Action)

• Analgesic: Paracetamol inhibits COX in the brain and it also raises pain thrust.
• Antipyretic: It decreases fever of any origin due to inhibition of the COX enzyme.
• Urate excretion: Paracetamol does not affect urate excretion and is given in gout patients.

Therapeutic Uses Of Nsaids

• It is used as an antipyretic drug for fever to decrease body temperature. It is the best antipyretic.
• It is used as an analgesic for toothache, myalgia, headache, dysmenorrhea, etc.
• It is the choice of analgesic and antipyretic drug in pregnancy, peptic ulcer, bronchial asthma, in children, and in hemophiliacs.
• It has very negligible anti-inflammatory action as it poorly inhibits COX.

Question 6. Describe The Action And Uses Of Aspirin. How Paracetamol Diffrs From It?
Answer:

Pharmacological Actions Of Acetylsalicylic Acid Or Aspirin

• Analgesic action: Acetylsalicylic acid is effective against pain with inflammation such as dental pain and rheumatic pain.
  Mechanism: NSAIDs inhibit the COX enzyme thus preventing the synthesis of prostaglandins.
  Prostaglandins are mediators of inflammatory processes and bring about effects like pain and fever. They also sensitize free nerve endings to pain stimuli, aspirin causes irreversible acetylation of COX.
• Antiinflammatory action: It is due to the inhibition of prostaglandin synthesis at the site of injury.
  Aspirin also inhibits the migration of neutrophils and other WBC to the site of action. It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
• Antipyretic action: Aspirin blocks the action of pyrogen due to which prostaglandin synthesis in the hypothalamus is inhibited and hence depression in the temperature set point in the hypothalamus.
  It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
  It set the hypothalamic thermostat and reduces elevated body temperature during fever. These drugs also promote heat loss and lead to cutaneous vasodilatation and sweating.
• Blood: Aspirin irreversibly inhibits the synthesis of thromboxane A2 by acetylating COX enzyme irreversibly in platelets. Thus, platelet aggregation is prevented and bleeding time is prolonged.
• GIT: In GIT aspirin is unionized at gastric pH and is absorbed in mucosal cells and ionizes and cannot diffuse back, this causes gastric mucosal damage.
• Aspirin also inhibits COX-1 causing a decrease in PGE2 and PGI2-synthesis decreasing mucus barrier and causing gastric mucosal damage.
• Respiration: At anti-inflammatory doses, salicylates increase oxygen consumption by a skeletal muscle release which causes an increase in CO2 production there is hyperventilation due to which CO2 is washed out and hence results in respiratory alkalosis, and at higher doses metabolic acidosis is caused.
• CVS: Aspirin at large doses increases oxygen demand and increases cardiac output.
• Urate excretion: Aspirin at a small dose inhibits uric acid secretion by DCT due to which plasma urate level is increased. It also blocks the action of uricosuric drugs and hence it is avoided in gout patients.

Therapeutic Uses Or Indication Of Aspirin/Acetyl Salicylic Acid

• As analgesic: It is used for headaches, toothache, joint pain, dysmenorrhea, and myalgia. (Dosage 0.3 to 0.6 gm per day)
• As antipyretic: It is used in a fever of any origin
• In acute rheumatic fever, it is the first drug to be used.
• It is used in rheumatoid arthritis and osteoarthritis.
• In myocardial infarction and stroke: Aspirin inhibits platelet aggregation by blocking COX enzymes in platelets thus it prevents clot formation and lowers the incidence of reinfarction.
• In patent ductus arteriosus aspirin can bring about closure and prevent surgery.
• Aspirin is used in pregnant women to delay labor.
• Aspirin is useful in pregnancy-induced hypertension.

 

 

Question 7. Compare The Action And Uses Of Morphine And Aspirin.
Answer:

 

 

Question 8. Write A Brief Account On Drugs In Dental Pain.
Answer:

NSAIDs are the main drugs for the management of acute dental pain. The nature of pain, risk factors, and individual preferences are to be considered while prescribing an NSAID.

• For mild to moderate pain with litte inflmmation: Paracetamol or low dose ibuprofen.
• Postextraction or acute short-lasting pain: Ketorolac, Diclofenac, and nimesulide.
• Gastric intolerance or peptic ulcer patients: Paracetamol or selective COX2 inhibitor.
• During dental analgesia if the patient is with history of asthma or anaphylactic reaction to aspirin/other
  NSAID: Nimesulide is given.
• If dental analgesia is present in the pediatric patient: Paracetamol, ibuprofen, and naproxen are given.
• If dental analgesia is given during pregnancy paracetamol is the safest drug to be given.
• Hypertensive, diabetic, ischemic heart disease, epileptic, and other patients receiving long-term regular medication: The possibility of drug interaction with NSAIDs should be considered and the physician should be consulted.
• Patient with risk factors for cardiovascular diseases,
  or stroke: Avoid etoricoxib/celecoxib; Ibuprofen or low-dose aspirin can be used.

Question 9. Describe Analgesic And Anti­Inflmmatory Action In Toothache.
Answer:

Analgesic action in toothache: Prostaglandins induce hyperalgesia by affecting the transducing property of free nerve-ending stimuli that do not normally elicit pain.

NSAIDs do not affect the tenderness induced by the application of prostaglandins, but block pain-sensitizing mechanisms induced by bradykinin, TNF–α.

Interleukins and other algesic substances primarily by inhibiting COX–2. This constitutes a peripheral component of the analgesic action of NSAIDs.

They are more effective against inflammation associated with toothache, including acute dental or postextraction pain.

Anti­inflmmatory action in toothache: Anti-inflame-tory action of NSAIDs is due to inhibition of prostaglandin synthesis at the site of injury.

They also affect other mediators of inflammation and so inhibit granulocyte adherence to damaged vasculature.

NSAIDs also lead to the modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.

Question 10. Explain Why Nimesulide Is Preferred Over Aspirin As Anti­Inflmmatory Agent?
Answer:

Nimesulide is a newer NSAID. It is a relatively weaker inhibitor of prostaglandin synthesis. Its anti-inflammatory action is exerted by mainly reducing the generation of superoxide by neutrophils.

• Nimesulide is completely absorbed orally and is 99% plasma bounded.
• Inhibition of platelet-activated factor synthesis so acts as an anti-inflammatory agent.
• It acts as a free radical scavenger.
• It inhibits metalloproteinase activity in cartilage.
• The anti-inflammatory activity of nimesulide is superior to other NSAIDs.
• It is useful for short-lasting painful inflammatory conditions, for Example. dental surgery, ear, nose, and throat.

While

• While aspirin as an anti-inflammatory produces a syndrome called salicylism.
• Aspirin therapy in children with rheumatoid arthritis has been found to raise serum levels indicating liver damage.
• In adults, long-term therapy with high dosage can cause hepatic injury.
• Aspirin is contraindicated in patients with peptic ulcer, and bleeding tendencies and in children suffering from chickenpox or influenza.
• It is also indicated in chronic liver diseases and is avoided in diabetes and in breastfeeding mothers.

Question 11. Classify Non­Narcotic Analgesics. Give The Pharmacological Actions, Therapeutic Uses, And Adverse Effects Of Aspirin.
Answer:

NSAIDs are non-narcotic analgesics.

Analgesics is a drug that relieves pain without affecting consciousness.

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:
  • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone
• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Pharmacological Actions Of Acetylsalicylic Acid Or Aspirin

• Analgesic action: Acetylsalicylic acid is effective against pain with inflammation such as dental pain and rheumatic pain.
  Mechanism: NSAIDs inhibit the COX enzyme thus preventing the synthesis of prostaglandins.
  Prostaglandins are mediators of inflammatory processes and bring about effects like pain and fever. They also sensitize free nerve endings to pain stimuli, aspirin causes irreversible acetylation of COX.
• Antiinflammatory action: It is due to the inhibition of prostaglandin synthesis at the site of injury.
  Aspirin also inhibits the migration of neutrophils and other WBC to the site of action. It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
• Antipyretic action: Aspirin blocks the action of pyrogen due to which prostaglandin synthesis in the hypothalamus is inhibited and hence depression in the temperature set point in the hypothalamus.
  It also causes modulation of T cell function, stabilization of lysosomal membrane, and inhibition of chemotaxis.
  It set the hypothalamic thermostat and reduces elevated body temperature during fever. These drugs also promote heat loss and lead to cutaneous vasodilatation and sweating.
• Blood: Aspirin irreversibly inhibits the synthesis of thromboxane A2 by acetylating COX enzyme irreversibly in platelets. Thus, platelet aggregation is prevented and bleeding time is prolonged.
• GIT: In GIT aspirin is unionized at gastric pH and is absorbed in mucosal cells and ionizes and cannot diffuse back, this causes gastric mucosal damage.
• Aspirin also inhibits COX-1 causing a decrease in PGE2 and PGI2-synthesis decreasing mucus barrier and causing gastric mucosal damage.
• Respiration: At anti-inflammatory doses, salicylates increase oxygen consumption by a skeletal muscle release which causes an increase in CO2 production there is hyperventilation due to which CO2 is washed out and hence results in respiratory alkalosis, and at higher doses metabolic acidosis is caused.
• CVS: Aspirin at large doses increases oxygen demand and increases cardiac output.
• Urate excretion: Aspirin at a small dose inhibits uric acid secretion by DCT due to which plasma urate level is increased. It also blocks the action of uricosuric drugs and hence it is avoided in gout patients.

Therapeutic Uses Or Indication Of Aspirin/Acetyl Salicylic Acid

• As analgesic: It is used for headaches, toothache, joint pain, dysmenorrhea, and myalgia. (Dosage 0.3 to 0.6 gm per day)
• As antipyretic: It is used in a fever of any origin
• In acute rheumatic fever, it is the first drug to be used.
• It is used in rheumatoid arthritis and osteoarthritis.
• In myocardial infarction and stroke: Aspirin inhibits platelet aggregation by blocking COX enzymes in platelets thus it prevents clot formation and lowers the incidence of reinfarction.
• In patent ductus arteriosus aspirin can bring about closure and prevent surgery.
• Aspirin is used in pregnant women to delay labor.
• Aspirin is useful in pregnancy-induced hypertension.

Side Effects/Adverse Effect Of Acetylsalicylic Acid Or Aspirin

• Analgesic doses, i.e. 0.3 to 1.5 gm per day. Aspirin causes nausea, vomiting, hypersensitivity reaction, epigastric distress, gastritis, peptic ulcer, and precipitation of asthma.
• Anti-inflammatory doses: A syndrome called salicylism is produced, salicylism dizziness, vertigo, tinnitus, reversible impairment of hearing and of vision hyperventilation, and electrolytic imbalance.
• Aspirin causes acute salicylate poisoning in adults.
• In patients with G6PD deficiency if aspirin is given it can lead to hemolytic anemia.
• Chronic use of aspirin interferes with vitamin K in the liver which decreases the synthesis of clotting factors which predispose to bleeding.
• Reye’s syndrome: Usage of salicylate in children having viral infection can lead to hepatic damage along with fatty infiltration and encephalopathy
• In pregnancy: Salicylates inhibit prostaglandin synthesis and delay the onset of labor, it also increases the tendency of postpartum hemorrhage. It can also lead to premature ductus arteriosus in newborns.
• Analgesic nephropathy: On chronic use of aspirin there is slow progressive renal failure which can occur on chronic use of salicylates.
• In very high doses acute salicylate poisoning occurs in adults.

Question 12. Write On Analgesic, Anti­Inflmmatory Drugs. Names, Uses In Dentistry, Common Adverse Effects.
Answer:

NSAIDs

• Non-Selective Cox Inhibitors:
  • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone
• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

NSAIDs are the main drugs for the management of acute dental pain. The nature of pain, risk factors, and individual preferences are to be considered while prescribing an NSAID.

• For mild to moderate pain with litte inflmmation: Paracetamol or low dose ibuprofen.
• Postextraction or acute short-lasting pain: Ketorolac, Diclofenac, and nimesulide.
• Gastric intolerance or peptic ulcer patients: Paracetamol or selective COX2 inhibitor.
• During dental analgesia if the patient is with history of asthma or anaphylactic reaction to aspirin/other
  NSAID: Nimesulide is given.
• If dental analgesia is present in the pediatric patient: Paracetamol, ibuprofen, and naproxen are given.
• If dental analgesia is given during pregnancy paracetamol is the safest drug to be given.
• Hypertensive, diabetic, ischemic heart disease, epileptic, and other patients receiving long-term regular medication: The possibility of drug interaction with NSAIDs should be considered and the physician should be consulted.
• Patient with risk factors for cardiovascular diseases,
  or stroke: Avoid etoricoxib/celecoxib; Ibuprofen or low-dose aspirin can be used.

Side Effects/Adverse Effect Of Acetylsalicylic Acid Or Aspirin

• Analgesic doses, i.e. 0.3 to 1.5 gm per day. Aspirin causes nausea, vomiting, hypersensitivity reaction, epigastric distress, gastritis, peptic ulcer, and precipitation of asthma.
• Anti-inflammatory doses: A syndrome called salicylism is produced, salicylism dizziness, vertigo, tinnitus, reversible impairment of hearing and of vision hyperventilation, and electrolytic imbalance.
• Aspirin causes acute salicylate poisoning in adults.
• In patients with G6PD deficiency if aspirin is given it can lead to hemolytic anemia.
• Chronic use of aspirin interferes with vitamin K in the liver which decreases the synthesis of clotting factors which predispose to bleeding.
• Reye’s syndrome: Usage of salicylate in children having viral infection can lead to hepatic damage along with fatty infiltration and encephalopathy
• In pregnancy: Salicylates inhibit prostaglandin synthesis and delay the onset of labor, it also increases the tendency of postpartum hemorrhage. It can also lead to premature ductus arteriosus in newborns.
• Analgesic nephropathy: On chronic use of aspirin there is slow progressive renal failure which can occur on chronic use of salicylates.
• In very high doses acute salicylate poisoning occurs in adults.

Question 13. Mention Classification And Uses And Drug Action Of Analgesic Drugs.
Answer:

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:
  • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone
• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Question 14. Write A Short Note On Paracetamol.
Answer:

• Paracetamol is a para-aminophenol derivative.
• It has a poor anti-inflammatory effect.
• Paracetamol is given by both oral and parenteral routes.
• Paracetamol should be well disturbed all over the body and is metabolized in the liver by sulfate and glucuronide conjugation. Metabolites get excreted in the urine.

Pharmacological Action

• Analgesic: Paracetamol inhibits COX in the brain and it also raises pain thrust.
• Antipyretic: It decreases fever of any origin due to inhibition of the COX enzyme.
• Urate excretion: Paracetamol does not affect urate excretion and is given in gout patients.

Therapeutic Uses of Paracetamol

• It is used as an analgesic for headaches, musculoskeletal pain, toothache, dysmenorrhea, and in pregnancy.
• As antipyretic to decrease the body temperature in fever.
• It is used as an analgesic and antipyretic in cases having peptic ulcer, hemophilia, and bronchial asthma.
• It is also used as an antipyretic in children.

Adverse Effects of Paracetamol

• Nausea and rashes occur occasionally.
• Hepatotoxicity and nephrotoxicity are seen during chronic use.
• In high doses acute paracetamol poisoning will occur.

Question 15. Explain The Pharmacological Basis Of Nimesulide Is Often Preferred Over Aspirin In Peptic Ulcer Patients.
Answer:

Aspirin-related side effects like gastric mucosal damage and peptic ulcer formation are not associated with nimesulide.

Effect Of Aspirin On Peptic Ulcer Patient

Aspirin is the most common NSAID associated with gastric bleeding. This is attributed to the following reasons:

• Aspirin is a nonselective and irreversible inhibitor of the cyclo-oxygenase (COX) enzyme.
  It inhibits the COX 1 enzyme present in the gastric mucosa and thus reduces the formation of cytoprotective prostaglandins (like PGE2 and PGI2).
  These eicosanoids protect the stomach by three mechanisms:

1. By inhibiting the acid secretion via blockade of the proton pump
2. By increasing the secretion of mucus and bicarbonate which is cytoprotective
3. Enhancing the mucosal blood flow Due to a lack of prostaglandins, there is a risk of peptic ulcer and gastric mucosal damage that may lead to bleeding.

 

 

• Aspirin is a weak acid that is present in the unionized (lipid soluble) form in the acidic medium of the gastric lumen.
  It diffuses inside the gastric mucosal cells and inside the cell; it gets ionized as the intracellular pH is alkaline (pH 7.1).
  This ionized (lipid-insoluble) form of the drug is not able to diffuse back into the lumen. This results in the ‘ion trapping’ of the drug thereby enhancing its toxicity.
• By irreversible inhibition of the COX enzyme, aspirin has anti-platelet action. It interferes with hemostasis and increases the risk of gastric bleeding.
• Aspirin may also cause ulceration by local irritation from contact with the orally administered drug with the gastric mucosa. This local irritation allows back diffusion of the acid into the gastric mucosa and induces tissue damage.
• Finally, it is possible that the enhanced generation of LOX products (i.e. Leukotrienes) may also contribute to gastric mucosal damage in individuals on NSAID therapy.
• So nimesulide is preferred over aspirin because the above-mentioned effects are not produced by nimesulide.

 

 

Question 16. Enumerate And Write the Mode Of Action Of Cox­2 Inhibitors As NSAIDs.
Answer:

The COX-2 inhibitors are:

1. Preferential COX-2 inhibitors: Nimesulide, Meloxicam, Nabumetone
2. Selective COX-2 Inhibitor: Celecoxib, Rafecoxib, Valdecoxib.

Mode Of Action

• Preferential COX­2 inhibitor: The COX-2 inhibitors reduce the generation of superoxide by neutrophils → Inhibition of platelet-activating factor synthesis and tumor necrosis factor α → free radical scavenging → Inhibitor of metalloproteinase activity in cartilage.
  In this way, it acts as NSAID.
• Selective COX­2 inhibitor: These drugs cause inhibition of COX-2 without affecting the function of COX-l and hence act as NSAID.

Question 17. Classify Non­Steroidal Anti­Inflammatory Drugs. Describe the Pharmacological Actions And Adverse Effects Of Aspirin. How Does It Differ From Paracetamol?
Answer:

Therapeutic Uses Or Indication Of Aspirin/Acetyl Salicylic Acid

• As analgesic: It is used for headaches, toothache, joint pain, dysmenorrhea, and myalgia. (Dosage 0.3 to 0.6 gm per day)
• As antipyretic: It is used in a fever of any origin
• In acute rheumatic fever, it is the first drug to be used.
• It is used in rheumatoid arthritis and osteoarthritis.
• In myocardial infarction and stroke: Aspirin inhibits platelet aggregation by blocking COX enzymes in platelets thus it prevents clot formation and lowers the incidence of reinfarction.
• In patent ductus arteriosus aspirin can bring about closure and prevent surgery.
• Aspirin is used in pregnant women to delay labor.
• Aspirin is useful in pregnancy-induced hypertension.

Side Effects/Adverse Effect Of Acetylsalicylic Acid Or Aspirin

• Analgesic doses, i.e. 0.3 to 1.5 gm per day. Aspirin causes nausea, vomiting, hypersensitivity reaction, epigastric distress, gastritis, peptic ulcer, and precipitation of asthma.
• Anti-inflammatory doses: A syndrome called salicylism is produced, salicylism dizziness, vertigo, tinnitus, reversible impairment of hearing and of vision hyperventilation, and electrolytic imbalance.
• Aspirin causes acute salicylate poisoning in adults.
• In patients with G6PD deficiency if aspirin is given it can lead to hemolytic anemia.
• Chronic use of aspirin interferes with vitamin K in the liver which decreases the synthesis of clotting factors which predispose to bleeding.
• Reye’s syndrome: Usage of salicylate in children having viral infection can lead to hepatic damage along with fatty infiltration and encephalopathy
• In pregnancy: Salicylates inhibit prostaglandin synthesis and delay the onset of labor, it also increases the tendency of postpartum hemorrhage. It can also lead to premature ductus arteriosus in newborns.
• Analgesic nephropathy: On chronic use of aspirin there is slow progressive renal failure which can occur on chronic use of salicylates.
• In very high doses acute salicylate poisoning occurs in adults.

 

 

Question 18. Write A Short Note On Selective Cox­2 Inhibitors
Answer:

Selective COX-2 inhibitors are celecoxib, rofecoxib, valdecoxib, etoricoxib, and parecoxib

Currently, 3 selective COX-2 inhibitors i.e. celecoxib, etoricoxib, and parecoxib are available and valdecoxib
and rofecoxib have been withdrawn for an increase in cardiovascular risk.

Celecoxib

• Celecoxib exerts anti-inflammatory, analgesic, and antipyretic actions with low ulcerogenic potential.
• Platelet aggregation in response to collagen exposure remains intact in celecoxib recipients and serum thromboxane B2 levels were not reduced.
• Sideeffctsareabdominalpain, dyspepsia, and mild diarrhea.
• Rashes, edema, and a small rise in blood pressure are also noted.
• It is used mainly in osteoarthritis and rheumatoid arthritis.

Etoricoxib

• It is a newer COX-2 inhibitor and has the highest COX-2 selectivity.
• Etoricoxib is suitable for the once-a-day treatment of osteoarthritis, rheumatoid arthritis, acute
• gouty arthritis, dysmenorrhea, and acute dental surgery pain.
• It does not damage platelet function and gastric mucosa.
• Side effects are dry mouth, aphthous ulcers, taste disturbance, and paresthesia.

Parecoxib

• It is a prodrug of valdecoxib.
• It is suitable for injection, to be used in postoperative and similar short-term pain.

Question 19. Write Pharmacological Basis Of Use Of Paracetamol As Analgesic.
Answer:

It has been shown that the COX inhibition caused by paracetamol is disproportionately higher in the brain as compared to peripheral areas.

This could be attributed to the inhibition of the COX-3 enzyme in the CNS. COX–3 is involved in pain perception and fever and not in the
inflammation.

Question 20. Explain Why Paracetamol Has Weak Anti­Inflmmatory Action?
Answer:

Paracetamol has weak anti-inflammatory action because of the following mechanisms:

• Paracetamol acts by inhibiting the COX enzyme which causes less formation of inflammatory prostaglandins. It has a poor ability to inhibit COX in the presence of peroxides.
  At inflammatory sites, leucocytes generate high concentrations of peroxides, and thus, paracetamol becomes ineffective. So, paracetamol has poor anti-inflammatory activity.
• It has been shown that the COX inhibition caused by paracetamol is disproportionately higher in the brain as compared to peripheral areas. This could be attributed to the inhibition of the COX-3 enzyme in the CNS.

 

 

Question 21. Writeshortnoteonadverseeffctsandcontraindications Of Nsaids.
Answer:

Adverse Effects Of NSAIDs

• Gastrointestinal: Gastric irritation, erosion, peptic ulceration, esophagitis, nausea, anorexia.
• Renal: Sodium and water retention, chronic renal failure, intestinal nephritis, papillary necrosis
• CVS: Hypertension, risk of myocardial infarction
• Hepatic: Raised transaminases, hepatic failure
• CNS: Headache, mental confusion, vertigo, behavioral disturbance, seizure precipitation
• Hematological: Bleeding, thrombocytopenia, hemolytic anemia, agranulocytosis
• Others: Asthma exacerbation, nasal polyposis, skin rashes, pruritus, angioedema.

Contraindications of NSAIDs

• Children suffering from the viral disease should not be administered with NSAIDs because this can lead to Reye’s syndrome.
• Anticoagulant effects of aspirin and ketorolac should be considered if a patient is on anticoagulant therapy.
• NSAIDs can contradict antimicrobials and metronidazole and produce adverse effects on GIT.

Question 22. Enumerate therapeutic uses of NSAIDs.
Answer:

The following are the therapeutic uses of NSAIDs:

• Aspirin is used as an analgesic in toothache, headache, myalgia, and joint pain. Aspirin can also be used as an antipyretic in a fever of any origin.
• Aspirin is used in acute rheumatic fever, rheumatoid arthritis, osteoarthritis, postmyocardial infarction, and in post-stroke patients.
• Ibuprofen is used in soft tissue injuries, tooth extraction, and vasectomy. It also suppresses swelling and inflammation.
• Mefenamic acid is used as an analgesic in muscle, joint, and soft tissue pain.
• Diclofenac sodium is used in toothache, rheumatoid and osteoarthritis, bursitis, ankylosing spondylitis, dysmenorrhea, and in post-traumatic and postoperative inflammatory conditions.
• Piroxicam is used as a short-term analgesic and long-term anti-inflammatory drug in rheumatoid and osteoarthritis, ankylosing spondylitis, acute gout, and musculoskeletal injuries.
• Ketorolac is used in acute dental and acute musculoskeletal pain. Nimesulide is used in sports injuries, sinusitis, ENT infections, dental surgery, low backache, dysmenorrhea, osteoarthritis, and fever.
• Paracetamol is used as analgesic for headache, toothache. It is the safest NSAID drug to be given to pregnant patients during mild pain.

Question 23. Write In Brief About Ibuprofen.
Answer:

Ibuprofen is a propionic acid derivative.

Mechanism Of Action

Ibuprofen exerts its anti-inflammatory and analgesic action via inhibition of prostaglandin biosynthesis.

By inhibiting COX these agents inhibit the formation of PGE₂, PGI₂, and PGF₂ which are powerful mediators of vasodilatation, pain, and edema associated with inflammation.

Therapeutic Uses

It is used in the treatment of arthritis and osteoarthritis.

Adverse Effects

• GIT side effects: Gastric ulcer or gastric toleration may occur.
• Produce teratogenic effects if used in pregnant ladies
• It prolongs bleeding time.

Question 24. Write A Short Note On Tramadol.
Answer:

Tramadol is a synthetic opioid.

• This centrally acting analgesic relieves pain by opioids as well as additional mechanisms.
• Its affinity for µ opioid receptor is low, while that for κ and δ is very low.
• Unlike other opioids, it inhibits the reuptake of noradrenaline and 5-HT and thus activates monoaminergic spinal inhibition of pain.
• Its analgesic action is only partially reversed by the opioid antagonist naloxone.
• Tramadol causes less respiratory depression, sedation, constipation, urinary retention, and a rise in intrabiliary pressure than morphine.
• It is well tolerated; side effects are dizziness, nausea, sleepiness, dry mouth, sweating, and lowering of seizure threshold.
• Tramadol is indicated for mild to moderate short-lasting pain due to diagnostic procedures such as injury, surgery, etc, as well as for chronic pain including cancer pain, but is not effective in severe pain.

Question 25. Classify NSAIDs. Discuss Briefl The Mode Of Action, Uses, And Adverse Effects Of Diclofenac Sodium.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:

• • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone

• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Side Effects/Adverse Effect Of Acetylsalicylic Acid Or Aspirin

• Analgesic doses, i.e. 0.3 to 1.5 gm per day. Aspirin causes nausea, vomiting, hypersensitivity reaction, epigastric distress, gastritis, peptic ulcer, and precipitation of asthma.
• Anti-inflammatory doses: A syndrome called salicylism is produced, salicylism dizziness, vertigo, tinnitus, reversible impairment of hearing and of vision hyperventilation, and electrolytic imbalance.
• Aspirin causes acute salicylate poisoning in adults.
• In patients with G6PD deficiency if aspirin is given it can lead to hemolytic anemia.
• Chronic use of aspirin interferes with vitamin K in the liver which decreases the synthesis of clotting factors which predispose to bleeding.
• Reye’s syndrome: Usage of salicylate in children having viral infection can lead to hepatic damage along with fatty infiltration and encephalopathy
• In pregnancy: Salicylates inhibit prostaglandin synthesis and delay the onset of labor, it also increases the tendency of postpartum hemorrhage. It can also lead to premature ductus arteriosus in newborns.
• Analgesic nephropathy: On chronic use of aspirin there is slow progressive renal failure which can occur on chronic use of salicylates.
• In very high doses acute salicylate poisoning occurs in adults.

Diclofenac Sodium Mode Of Action 

It inhibits prostaglandin synthesis reversibly and is somewhat COX-2 selective.

Diclofenac Sodium Uses

• In toothache
• Rheumatoid and osteoarthritis
• Bursitis
• Ankylosing spondylitis
• Dysmenorrhea
• Post-traumatic
• In postoperative inflammatory conditions.

Diclofenac Sodium Adverse Effects

Adverse effects are generally mild, i.e.

• Epigastric pain
• Nausea
• Headache
• Dizziness
• Rashes
• Gastric ulceration and bleeding
• Reversible elimination of serum amino transaminases.

Question 26. Explain Why Paracetamol Is Used As An Antipyretic.
Answer:

The primary mechanism of action is believed to be the inhibition of cyclooxygenase (COX), with a predominant effect on COX-2.

In the central nervous system, inhibition of COX enzymes reduces concentrations of prostaglandin E2, which lowers the hypothalamic set-point to reduce fever.

Question 27. Write Classification, Pharmacological Actions, Side Effects, And Therapeutic Uses Of Non­Steroidal Anti-inflammatory Drugs.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:

• • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone

• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Pharmacological Actions

• Analgesia: NSAIDs do not affect the tenderness induced by the direct application of prostaglandins but block the pain-sensitizing mechanism induced by bradykinin, TNF-α, interleukins, etc.
  They are more effective against inflammation-associated pain.
• Antipyresis: Fever during infection is produced through the generation of pyrogen, interleukins, TNF-α, and interferons which induce prostaglandin production in the hypothalamus and raise its temperature set point.
  NSAIDs block the action of pyrogens but not of PGE2 which is injected into the hypothalamus.
• Anti­inflammatory: NSAIDs inhibit prostaglandin synthesis at the site of injury. Anti-inflammatory of different compounds roughly corresponds with their potency to inhibit COX.
• Ductus arteriosus closure: Ductus arterioles are kept patent by local elaboration of PGE2 and PGI2.
  Unknown mechanisms switch off this synthesis and at birth ductus closes, but when this fails to occur small doses of NSAID such as aspirin or indomethacin lead to the closure of the ductus within a few hours by inhibiting prostaglandin secretion.
• Anti­platelet aggregatory: NSAIDs inhibit the synthesis of both proaggregatory (TXA2) and anti-aggregatory prostanoids (PGI2) but the effect on platelet TXA2 predominates during therapeutic doses of most NSAIDs which inhibit platelet aggregation and bleeding time is prolonged.
• Renal Effects: NSAIDs produce renal effects by three mechanisms:
  • COX-1-dependent impairment of renal blood flow and reduction of GFR can worsen renal insufficiency.
  • Juxtaglomerular COX-2 dependent sodium and water retention.
  • Ability to cause papillary necrosis on habitual intake.

Non­Steroidal Anti-inflammatory Drugs Side Effects

• Gastrointestinal: Gastric irritation, erosion, peptic ulceration, esophagitis, nausea, anorexia.
• Renal: Sodium and water retention, chronic renal failure, intestinal nephritis, papillary necrosis.
• CVS: Hypertension, risk of myocardial infarction.
• Hepatic: Raised transaminases, hepatic failure
• CNS: Headache, mental confusion, vertigo, behavioral disturbance, seizure precipitation.
• Hematological: Bleeding, thrombocytopenia, hemolytic anemia, agranulocytosis
  Others: Asthma exacerbation, nasal polyposis, skin rashes, pruritus, angioedema.

Non­Steroidal Anti-inflammatory Drugs Therapeutic Uses

• Aspirin is used as an analgesic in toothache, headache, myalgia, and joint pain. Aspirin can also be used as an antipyretic in a fever of any origin.
• Aspirin is used in acute rheumatic fever, rheumatoid arthritis, osteoarthritis, post-myocardial infarction, and in post-stroke patients.
• Ibuprofen is used in soft tissue injuries, tooth extraction, and vasectomy. It also suppresses swelling and inflammation.
• Mefenamic acid is used as an analgesic in muscle, joint, and soft tissue pain.
• Diclofenac sodium is used in toothache, rheumatoid and osteoarthritis, bursitis, ankylosing spondylitis, dysmenorrhea, and in post-traumatic and post-operative inflammatory conditions.
• Piroxicam is used as a short-term analgesic and long-term anti-inflammatory drug in rheumatoid and osteoarthritis ankylosing spondylitis, acute gout, and musculoskeletal injuries.
• Ketorolac is used in acute dental and acute musculoskeletal pain.
• Nimesulide is used in sports injuries, sinusitis, ENT infections, dental surgery, low backache, dysmenorrhea, osteoarthritis, and fever.
  • Paracetamol is used as analgesic for headache, toothache. It is the safest NSAID drug to be given to pregnant patients during mild pain.

Question 28. Explain Why Long­Term Use Of Aspirin-Like Drugs Can Produce Renal Damage.
Answer:

Aspirin can cause analgesic nephropathy characterized by chronic nephritis and renal papillary necrosis as it prevents PGE2-mediated renal vasodilatation.

Question 29. Classify Non­Steroidal Anti­Inflammatory Drugs. Enumerate Therapeutic Uses And Adverse Effects Of Paracetamol.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Classifiation Of Analgesics

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

Oploid Analgesics

• Natural opium alkaloid: Morphine and codeine
• Semisynthetic opiates: Diacetylmorphine and pholcodine
• Synthetic opioids: Pethidine, tramadol, fentanyl, methadone.

NSAIDs

• Non-Selective Cox Inhibitors:

• • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone

• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Therapeutic Uses Of Paracetamol

• It is used as an analgesic for headaches, musculoskeletal pain, toothache, dysmenorrhea, and in pregnancy.
• As antipyretic to decrease the body temperature in fever.
• It is used as an analgesic and antipyretic in cases having peptic ulcer, hemophilia, and bronchial asthma.
• It is also used as an antipyretic in children.

Adverse Effects Of Paracetamol

• Nausea and rashes occur occasionally.
• Hepatotoxicity and nephrotoxicity are seen during chronic use.
• In high doses acute paracetamol poisoning will occur.

Question 30. Explain Why Aspirin Is Not Given As An Analgesic In Tooth Extraction.
Answer:

Aspirin at low doses, i.e. from 50 to 325 mg/day irreversibly inhibits the synthesis ofthromboxaneA2 by acetylating COX enzyme irreversibly in platelets.

Thus, platelet aggregation is prevented and bleeding time is prolonged. Aspirin at high doses, i.e. 2 to 3 gm/day inhibits PGI2, i.e. prostaglandin I2 and thromboxane A2 synthesis.

So beneficial effect of PGI2 is lost, i.e. at high dosages anal- gesic action of aspirin is lost. That’s why it is not given as an analgesic in tooth extraction.

Question 31. Write Short Note On Cox­2 Inhibitor.
Answer:

COX-2 inhibitors are of two types:

• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone.
• Selective COX-2 inhibitors: Celecoxib, rafecoxib, valdecoxib, etoricoxib, parecoxib.

Mode Of Action Of Both Cox-2 Inhibitors

Preferential COX-2 inhibitor: The COX-2 inhibitors reduce the generation of superoxide by neutrophils → Inhibition of platelet-activating factor synthesis and tumor necrosis factor α → free radical scavenging → Inhibitor of metalloproteinase activity in cartilage. In this way, it acts as NSAID.
Selective COX-2 inhibitor: These drugs cause inhibition of COX-2 without affecting the function of COX-l and hence act as NSAIDs.

Preferential COX-2 Inhibitors

Nimesulide

• It is a weak inhibitor of prostaglandin synthesis.
• It is used for short-lasting painful inflammatory conditions such as dental surgeries, sports injuries, sinusitis, bursitis, etc.
• It is completely absorbed orally and is 99% plasma protein bound, metabolized, and excreted in the urine.
• Its adverse effects are nausea, loose motions, rash, pruritus, somnolence, dizziness, etc.

Meloxicam

• It is the new congener of piroxicam and has a COX-2: COX-1 Selectivity ratio of 10.
• Due to its measurable inhibition of platelet thromboxane A2 production occur at measurable doses so it is known as a preferential COX-2 inhibitor.
• It is equally efficacious as piroxicam.
• It produces fewer gastric side effects.

Nabumetone

• This is a prodrug.
• It generates an active metabolite which is a more potent COX-2 inhibitor.
• It possesses analgesic, anti-inflammatory, and antipyretic activities.
• It is very effective in the treatment of rheumatoid and osteoarthritis.

Selective COX-2 Inhibitors

Celecoxib

• Celecoxib exerts anti-inflammatory, analgesic, and antipyretic actions with low ulcerogenic potential.
• Platelet aggregation in response to collagen exposure remains intact in celecoxib recipients and serum thromboxane B2 levels were not reduced.
• Sideeffctsareabdominalpain, dyspepsia, and mild diarrhea.
• Rashes, edema, and a small rise in blood pressure are also noted.
• It is used mainly in osteoarthritis and rheumatoid arthritis.

Etoricoxib

• It is a newer COX-2 inhibitor and has the highest COX-2 selectivity.
• Etoricoxib is suitable for the once-a-day treatment of osteoarthritis, rheumatoid arthritis, acute gouty arthritis, dysmenorrhea, and acute dental surgery pain.
• It does not damage platelet function and gastric mucosa.
• Side effects are dry mouth, aphthous ulcers, taste disturbance, and paresthesia.

Parecoxib

• It is a prodrug of valdecoxib.
• It is suitable for injection, to be used in postoperative and similar short-term pain.

Question 32. Classify Nsaids And Discuss Their Adverse Effects.
Answer:

Analgesics is a drug that relieves pain without affecting consciousness.

Analgesics Classifiation 

Generally, there are two types of analgesics, i.e. opioids, and NSAIDs.

NSAIDs

• Non-Selective Cox Inhibitors:

• • Salicylates: Aspirin
  • Propionic Acid Derivatives: Ibuprofen, ketoprofen, naproxen
  • Anthranilic acid derivative: Mefenamic acid
  • Aryl-acetic acid derivative: Diclofenac, Aceclofenac
  • Oxicam derivatives: Piroxicam, tenoxicam
  • Pyrrolo-pyrrole derivative: Ketorolac
  • Indole derivative: Indomethacin
  • Pyrazolone derivative: Phenylbutazone, Oxyphenbutazone

• Preferential COX-2 inhibitors: Nimesulide, meloxicam, nabumetone
• Selective COX-2 inhibitors: Celecoxib, parecoxib, etoricoxib
• Analgesic, Antipyretic with poor anti-inflammatory action:
  • Paraaminophenol derivative: Paracetamol (Acetaminophen)
  • Pyrazolone derivatives: Metamizole, propiphenazone
  • Benzoxazocine derivative: Nefopam.

Adverse Effects Of NSAIDs

The most common side effects are:

• Vomiting
• Nausea
• Constipation
• Diarrhea
• Reduced appetite
• Headache
• Dizziness
• Rash
• Drowsiness.
• NSAIDs also may cause swelling of the arms and legs due to the retention of fluid from their renal effects.
• The most serious side effects of NSAIDs are ulcers, bleeding, kidney failure, and, rarely liver failure.
• Individuals allergic to NSAIDs may experience shortness of breath after taking an NSAID and may experience a similar reaction when other NSAIDs are taken.
• Administering aspirin to children or teenagers with chickenpox or influenza has been associated with Reye’s syndrome, a serious and potentially fatal disease of the liver.
  Therefore, aspirin and salicylates, for example, salsalate (Disalcid), should not be used in children and teenagers with suspected or confirmed chickenpox or influenza.
• NSAIDs (except aspirin) may increase the risk of heart attacks, stroke, and related conditions, which can be fatal. This risk may increase with the duration of use and in patients who have underlying risk factors for disease of the heart and blood vessels.
• NSAIDs, particularly non-selective NSAIDs, cause an increased risk of serious, even fatal, stomach and intestinal adverse reactions such as bleeding, ulcers, and perforation of the stomach or intestines.
  These events can occur at any time during treatment and without warning symptoms. Elderly patients are at greater risk for these types of reactions.

Question 33. Give Three Indications For The Use Of NSAIDs, With an Appropriate Example For Each Indication.
Answer:

Following are the three indications for the use of NSAIDs along with appropriate examples for each of the indications:

• NSAIDs are indicated in mild to moderate pain with little inflammation, For Example. paracetamol or low dose ibuprofen
• NSAIDs are indicated in postextraction or similar acute but short-lasting pain, for Example. ketorolac, diclofenac or nimesulide.
• NSAIDs are indicated in acute musculoskeletal, osteoarthritic, and injury-associated pain, for Example. paracetamol or diclofenac.

Question 34. Write A Short Note On Aspirin Allergy.
Answer:

Allergy is more common with aspirin.

• Various manifestations are skin rashes, urticaria, rhinitis, bronchospasm, angioneurotic edema, and anaphylactoid reaction.
• Bronchospasm is due to the increased production of leukotrienes.
• The chances of aspirin allergy are high in patients with asthma, nasal polyp, recurrent rhinitis, or urticaria. So aspirin should be avoided in these patients.

Question 35. Write The Basis Of Combination Of Ibuprofen With Paracetamol.
Answer:

Combination of ibuprofen with paracetamol is additive and a ceiling analgesic effct is obtained when total amount of ibuprofen + paracetamol is 1000 mg.

The combination should be used for short periods.