Pharmacology of NSAIDs and COX Inhibitors
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Questions and Answers

Which of the following drugs is classified as a propionic acid derivative?

  • Diclofenac
  • Ibuprofen (correct)
  • Phenylbutazone
  • Piroxicam

    • What is a key characteristic of selective COX-2 inhibitors compared to non-selective COX inhibitors?

  • They have stronger analgesic effects.
  • They do not affect platelet function. (correct)
  • They are more effective at treating headaches.
  • They cause more gastrointestinal side effects.

    • Which substance among the following is a consequence of using phenylbutazone?

  • Increased diuretic effect
  • Enhanced platelet aggregation
  • Failure to induce liver enzymes
  • Gastrointestinal bleeding (correct)

    • What is the half-life of piroxicam?

    <p>45 hours</p> Signup and view all the answers

    Which of the following drugs is known for being a prodrug?

    <p>Nabumetone</p> Signup and view all the answers

    What adverse effect is commonly associated with dipyrone (novalgin)?

    <p>Bone marrow depression</p> Signup and view all the answers

    Which specific COX-2 inhibitor is mentioned as being used for osteoarthritis?

    <p>Etoricoxib</p> Signup and view all the answers

    Among the following, which drug is primarily characterized by its effect on leukocyte migration?

    <p>Piroxicam</p> Signup and view all the answers

    What is the primary mechanism by which NSAIDs exert their analgesic effects?

    <p>Inhibition of prostaglandin synthesis</p> Signup and view all the answers

    Which of the following statements about COX isoenzymes is true?

    <p>Salicylates block both COX-1 and COX-2.</p> Signup and view all the answers

    What is a key adverse effect associated with high doses of salicylic acid?

    <p>Hyperthermia due to uncoupling of oxidative phosphorylation</p> Signup and view all the answers

    Which of the following is classified as a selective COX-2 inhibitor?

    <p>Celecoxib</p> Signup and view all the answers

    Which of the following is NOT a derivative of salicylic acid?

    <p>Indomethacin</p> Signup and view all the answers

    What effect does aspirin have on platelet aggregation?

    <p>It irreversibly inhibits platelet aggregation</p> Signup and view all the answers

    Which of the following correctly states the systemic actions of salicylates?

    <p>They have both analgesic and antipyretic actions.</p> Signup and view all the answers

    What type of drugs does phenylbutazone belong to?

    <p>Pyrazolone derivatives</p> Signup and view all the answers

    What is the primary mechanism by which acetaminophen exerts its analgesic effects?

    <p>Inhibition of COX enzyme centrally and weakly peripherally</p> Signup and view all the answers

    Which of the following describes the metabolism of acetaminophen?

    <p>Conjugated with glucuronic acid and sulphate into inactive forms</p> Signup and view all the answers

    Which side effect is most likely to occur with an acute overdose of acetaminophen?

    <p>Hepatic necrosis</p> Signup and view all the answers

    What distinguishes GABAA receptors from GABAB receptors in terms of their function?

    <p>GABAA receptors mediate postsynaptic neuronal inhibition</p> Signup and view all the answers

    Which of the following substances is classified as an agonist to the 5-HT1A receptor?

    <p>Buspirone</p> Signup and view all the answers

    What is a significant characteristic of the toxic metabolite N-acetyl-p-benzoquinone?

    <p>It is detoxified by glutathione</p> Signup and view all the answers

    Which condition is a contraindication for the use of acetaminophen?

    <p>Severe renal impairment</p> Signup and view all the answers

    What is the primary action of benzodiazepines in the central nervous system?

    <p>Enhancing GABA action</p> Signup and view all the answers

    What is a consequence of excessive CO2 loss due to large doses of a specific medication?

    <p>Respiratory alkalosis</p> Signup and view all the answers

    What is the primary effect of GABA binding to its receptor on the α and β subunits?

    <p>Hyperpolarization and inhibition of neuronal firing</p> Signup and view all the answers

    How does salicylate in large doses affect uric acid levels?

    <p>Increases uric acid excretion</p> Signup and view all the answers

    What effect does a small dose of aspirin have on platelet aggregation?

    <p>Inhibits aggregation of platelets</p> Signup and view all the answers

    What is the primary mechanism of action for benzodiazepines on GABAA receptors?

    <p>They enhance the effect of GABA and increase the frequency of Cl- channel opening.</p> Signup and view all the answers

    Which type of benzodiazepine is classified as short-acting based on its half-life?

    <p>Triazolam</p> Signup and view all the answers

    What is a primary result of the inhibition of prostaglandin synthesis by aspirin?

    <p>Gastric ulceration and bleeding</p> Signup and view all the answers

    What happens to bicarbonate levels in compensated respiratory alkalosis?

    <p>Decrease due to renal excretion</p> Signup and view all the answers

    What distinguishing feature do non-benzodiazepines like Zolpidem and Zaleplon primarily exhibit?

    <p>They primarily agonize BZ1 receptors with minimal muscle relaxant effects.</p> Signup and view all the answers

    How do barbiturates enhance their effects compared to benzodiazepines?

    <p>They prolong the duration of GABA-gated chloride channel opening.</p> Signup and view all the answers

    What physiological process is affected by the delays in childbirth under the influence of certain medications?

    <p>Uterine contractions</p> Signup and view all the answers

    What action do benzodiazepines exhibit that can lead to anterograde amnesia?

    <p>They cause sedation and hypnosis.</p> Signup and view all the answers

    How does a large dose of aspirin affect vitamin K?

    <p>Competes for its action, leading to hypoprothrombinaemia</p> Signup and view all the answers

    Which benzodiazepine is known for its anticonvulsant effects in raising seizure thresholds?

    <p>Nitrazepam</p> Signup and view all the answers

    What type of acid-base imbalance can larger doses of aspirin lead to in children?

    <p>Metabolic acidosis</p> Signup and view all the answers

    What is the primary action of flumazenil in relation to benzodiazepines?

    <p>It blocks the effects of benzodiazepines.</p> Signup and view all the answers

    What can be considered an advantage of using benzodiazepines over barbiturates?

    <p>Lower risk of tolerance development</p> Signup and view all the answers

    Which of the following side effects is specifically associated with zolpidem at high doses?

    <p>Amnestic effect</p> Signup and view all the answers

    Which statement about buspirone is true?

    <p>It has no muscle relaxant properties.</p> Signup and view all the answers

    What class of drugs does phenobarbitone belong to?

    <p>Long acting barbiturates</p> Signup and view all the answers

    What is a common side effect of benzodiazepines?

    <p>Tolerance</p> Signup and view all the answers

    Which of the following is a use of short acting barbiturates like pentobarbitone?

    <p>Preanaesthetic medication</p> Signup and view all the answers

    What effect do zolpidem and zaleplon primarily target?

    <p>Short-term insomnia treatment</p> Signup and view all the answers

    Which type of benzodiazepine receptor do zolpidem and zaleplon bind to?

    <p>BZ1 receptor</p> Signup and view all the answers

    Study Notes

    Non Steroidal Anti-inflammatory Drugs (NSAIDs)

    • NSAIDs are analgesic, antipyretic, and anti-inflammatory
    • Their effects are from inhibiting prostaglandin synthesis by blocking the cyclo-oxygenase (COX) enzyme.
    • Two COX isoenzymes exist: COX-1 (constitutive in cells) and COX-2 (induced during inflammation).
    • Corticosteroids are powerful anti-inflammatory agents but have chronic toxicity limitations.

    Classification of Analgesic Antipyretic Drugs

    • Non-selective COX inhibitors:
      • Salicylates (aspirin, sodium salicylate, diflunisal)
      • Indol derivatives (indomethacin)
      • Anthranilic acid derivatives (mefenamic acid)
      • Propionic acid derivatives (ibuprofen, ketoprofen, naproxen)
      • Aryl acetic acid derivatives (diclofenac, ketorolac)
      • Oxicams (piroxicam)
      • Alkanones (nabumetone)
      • Pyrazolone derivatives (phenylbutazone, oxyphenylbutazone, azapropazone)
      • Aniline derivatives (phenacetin, paracetamol)
    • Selective COX-2 inhibitors:
      • Celecoxib
      • Meloxicam

    Salicylates (1)

    • Derived from salicylic acid (highly irritant)
    • Include aspirin, sodium salicylate, diflunisal
    • Local actions: antifungal, antiseptic, and counter-irritant (methyl salicylate)
    • Systemic actions:
      • CNS: inhibits prostaglandin synthesis, increases pain threshold, increases heat loss through cutaneous vasodilation and sweating
      • High doses can lead to hyperthermia through oxidative phosphorylation uncoupling

    Anti-inflammatory, Anti-rheumatic Action (2)

    • Inhibit cyclooxygenase enzyme, preventing prostaglandin synthesis (important for inflammation)
    • Aspirin irreversibly inhibits the enzyme.
    • Inhibit platelet aggregation
    • Inhibit kallikrein system (reducing pain, redness, and edema)
    • Stabilize lysosomal membranes (reducing tissue damage)
    • Inhibit leukocyte and macrophage migration (inhibiting chemotaxis)

    Respiration and Acid/Base Balance (3)

    • Ordinary dose: little effect
    • Large dose: increased respiratory rate, CO2 loss, respiratory alkalosis, reduced plasma bicarbonate
    • High doses: produce metabolic acidosis and respiratory acidosis (in children)
    • Cardiovascular System (CVS): little effect. Large doses can lead to peripheral vasodilation (VD) and reduced vascular resistance (VMC).
    • Uric Acid: filtered through glomeruli, reabsorbed and secreted in tubules. Salicylates in large doses increase uric acid excretion (uricosuric), and in small doses reduce uric acid secretion causing retention in the blood.

    Blood (4)

    • Small doses (75-150 mg/day) of aspirin inhibit platelet aggregation (acetylation of cyclooxygenase).
    • Larger doses compete with vitamin K, inhibiting prothrombin formation (leading to hypoprothrombinemia).
    • G6PD deficiency can cause hemolytic anemia

    Gastrointestinal Tract (GIT) (5)

    • Inhibition of prostaglandins (PGs) can lead to gastric ulceration and bleeding, inhibiting acid secretion, and impacting gastric blood flow.
    • Reduced mucus secretion.
    • Nausea and vomiting (central and peripheral effects).

    Metabolic Actions (6)

    • Uncoupling of oxidative phosphorylation and increased cellular metabolism leads to increased oxygen and CO2 consumption.
    • High doses cause hyperglycemia from increased cortisone and adrenaline levels

    Other Actions (7)

    • Inhibiting antigen-antibody reaction
    • Release of adrenaline with larger doses
    • Displacement of thyroxine from protein binding sites.
    • Delay in labor onset (in larger doses)

    Administration (8)

    • Taken after meals to minimize gastric irritation
    • Sodium salicylate should be administered in an enteric-coated tablet.

    Therapeutic Uses (9)

    • Local: salicylic acid as an antifungal and antiseptic; methyl salicylate as a counter-irritant
    • Systemic:
      • Analgesic/antipyretic (0.6-0.65 g/day)
      • Anti-inflammatory (50-75 mg/kg/day)
      • Acute rheumatic fever (10 g/day)
      • Rheumatoid arthritis (8 g/day)
      • Preventing intravascular thrombosis (aspirin 75-150 mg/day)
      • Gout (>5 g/day)

    Side Effects and Toxicity (10)

    • Gastric irritation (increased occult blood in stools)
    • Hypersensitivity (asthma, rash)
    • Idiosyncratic reactions (G6PD deficiency)
    • Prolonged use: hypoprothrombinemia, salicylism (headache, mental confusion, vertigo, tinnitus, sweating, nausea, vomiting)
    • Renal irritation (albuminuria)
    • Reye's syndrome (severe hepatic damage)
    • Acute salicylate poisoning (restlessness, tremors, convulsions, vomiting, dehydration)

    Treatment (11)

    • Gastric lavage with sodium bicarbonate
    • Correction of hyperpyrexia (cold fomentation or ethyl alcohol evaporation)
    • Correction of dehydration and acid-base balance (IV fluids with electrolytes)
    • Alkalinization of urine with NaHCO3
    • Vitamin K administration

    Contraindications (12)

    • Peptic ulcer
    • Bronchial asthma
    • Idiosyncratic reactions
    • Allergies
    • Bleeding tendencies

    Indole Derivatives (Indomethacin, Sulindac) (2)

    • Indomethacin: potent prostaglandin synthesis inhibitor, oral (6hr t1/2)
      • Effective in rheumatoid arthritis, gout
      • Adverse effects: GIT disturbances, pancreatitis, headache, thrombocytopenia, aplastic anemia, hyperkalemia, skin rash, asthma. (Contraindicated in pregnancy, children, peptic ulcer)
    • Sulindac: similar to indomethacin, but less potent and has less gastric irritation (prodrug)

    Anthranilic Acid Derivatives (Mefenamic Acid) (3)

    • Mefenamic Acid inhibits COX and phospholipase A2: Less effective than aspirin as an anti-inflammatory agent
      • GI disturbances, avoid pregnancy

    Propionic Acid Derivatives (Ibuprofen, Ketoprofen, Naproxen) (4)

    • Analgesic, antipyretic, and anti-inflammatory (inhibit cyclooxygenase, prostaglandin synthesis).
    • Potent uricosuric, displace other drugs, decrease diuretic & beta-blocker effects.
    • 20 times more potent than aspirin.

    Arylacetic Acid Derivatives (Diclofenac) (5)

    • Similar actions as other NSAIDs.

    Oxicams (Piroxicam) (6)

    • Long plasma half-life (45 hours), enterohepatic cycling
    • Adverse effects: GI disturbances

    Pyrazolone Derivatives (Dipyrone, Phenylbutazone, Oxyphenbutazone, Azapropazone) (8)

    • Dipyrone: rarely used due to bone marrow depression
    • Phenylbutazone/Oxyphenbutazone/Azapropazone: strong anti-inflammatory, potent uricosuric agent, useful in acute gout attacks, absorbed quickly from GIT, high binding to plasma proteins, enzyme inducer, displaces other drugs from binding sites
    • Adverse effects: nausea, vomiting, peptic ulcer, GIT bleeding, water retention, rash, urticaria, edema, hypertension, bone marrow depression, liver and renal toxicity, and bronchospasm.

    COX-2 Inhibitors (Selective) (15)

    • Selectively inhibit COX-2 (induced at inflammation sites)
    • Less GI disturbance than nonselective NSAIDs
    • COX-2 is active in kidney, so COX-2 inhibitors can cause renal toxicity.
    • Rofecoxib & Etoricoxib: Rheumatoid arthritis, osteoarthritis, and acute gouty arthritis.

    Aniline Derivatives (Acetaminophen/Paracetamol) (16)

    • Pharmacokinetics: Oral absorption, bound to a lesser extent to plasma proteins, metabolized by conjugation (glucuronic and sulfuric acids) in the liver
    • Minor toxic metabolite (N-acetyl-p-benzoquinoneimine): formed by cytochrome P450; detoxified by glutathione. Hepatic and kidney damage possible.

    Acetaminophen (Paracetamol) (16, 17)

    • Action: COX enzyme inhibition
    • Uses: Analgesic, antipyretic
    • Side effects: hepatotoxicity

    Aniline Derivatives (Phenacetin) (17)

    • Action: COX enzyme inhibition
    • Uses: Analgesic, antipyretic
    • Side effects: severe toxicity

    Acute Paracetamol Poisoning (18)

    • Ingestion of 15g or more.
    • Hepatotoxicity and acute renal tubular necrosis.
    • Treatment: N-acetylcysteine within 8 hours of ingestion

    Sedative, Hypnotic & Anxiolytic Drugs (19–22)

    • Used for anxiety and insomnia
    • Classification:
    • GABA-facilitating drugs (benzodiazepines, barbiturates, zolpidem)
    • 5-HT1A agonists (buspirone)
      • GABA: Ionotropic (ligand-gated ion channels) and metabotropic (G protein coupled receptors).
    • GABA bind to its receptor, opening Cl− channels causing hyperpolarization (inhibiting neuronal firing).
    • Benzodiazepines act on γ subunit receptors and enhance GABA effect
    • Zolpidem & Zaleplon bind to BZ₁ receptors.
    • Barbiturates increase GABA-gated chloride channel opening duration.

    Benzodiazepines (23)

    • Classification:
      • Long-acting (diazepam, prazepam, flurazepam, clorazepate, chlordiazepoxide)
      • Intermediate-acting (temazepam, oxazepam, lorazepam, alprazolam)
      • Short-acting (triazolam, midazolam)
    • Actions: Anti-anxiety, anterograde amnesia, sedation, hypnosis, muscle relaxant, anti-convulsant, anesthesia adjunct
    • Uses: Anxiety, insomnia, status epilepticus, pre-operative sedation
    • Side effects: Confusion, drowsiness, anterograde amnesia, ataxia, nausea, vomiting, diarrhea, dry mouth, bitter taste, allergy, and bone marrow depression, abuse & dependence

    Flumazenil (27)

    • Benzodiazepine receptor antagonist
    • Used to reverse benzodiazepine overdose and improve mental status in hepatic encephalopathy
    • Side effects: agitation, confusion, dizziness, nausea.

    Zolpidem and Zaleplon (28)

    • Non-benzodiazepine hypnotics
    • Bind to BZ₁ receptors to facilitate GABA effects
    • Minimal muscle relaxation and anticonvulsant effects
    • High doses: amnestic effect
    • Zaleplon: rebound insomnia potential

    Buspirone (29)

    • Partial agonist at 5-HT₁A presynaptic receptors
    • Affinity for dopamine D₂ receptors
    • No hypnotic, sedative, anticonvulsant, or muscle relaxant effects
    • No rebound anxiety or withdrawal if stopped suddenly
    • Side effects: tachycardia, palpitations, nervousness, paresthesia, gastrointestinal upset, miosis, and hypertension (with MAOIs)

    Barbiturates (30, 31)

    • Classification: Long-acting, intermediate-acting, short-acting, ultrashort-acting
    • Uses: Sedation, hypnosis, pre-anaesthesia, potentiate other analgesics
    • Toxicity: Tolerance, hypersensitivity, automatism, chronic use: habituation & addiction, acute overdose: hypotension, hypothermia, hyporeflexia, coma, respiratory failure
    • Treatment: gradual withdrawal

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    Description

    Test your knowledge on anti-inflammatory drugs, including their classifications and mechanisms of action. This quiz covers key characteristics of selective COX-2 inhibitors, propionic acid derivatives, and more. Understand the implications of using these medications in clinical practice.

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