NSAID Uses and Classes Quiz

NSAID Uses and Classes

• NSAIDs are used for muscle pain, dysmenorrhea, arthritis, fever, gout, migraines
• Can be used as an opioid-sparing agent in acute trauma cases
• NSAIDs are divided into groups based on chemical structure and selectivity:
  • Acetylated salicylates (aspirin)
  • Non-acetylated salicylates (diflunisal, salsalate)
  • Propionic acids (naproxen, ibuprofen)
  • Acetic acids (diclofenac, indomethacin)
  • Enolic acids (meloxicam, piroxicam)
  • Anthranilic acids (meclofenamate, mefenamic acid)
  • Naphthylalanine (nabumetone)
  • Selective COX-2 inhibitors (celecoxib, etoricoxib)
• Non-selective NSAIDs include diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin
• COX-2 selective NSAIDs include celecoxib, rofecoxib, valdecoxib

NSAID Mechanism

• NSAIDs primarily work by inhibiting cyclooxygenase (COX)
• COX is responsible for converting arachidonic acid into thromboxanes, prostaglandins, and prostacyclins
• This inhibition prevents the production of these eicosanoids, which contribute to inflammation, pain, and fever
• Thromboxanes play a role in platelet adhesion
• Prostaglandins cause vasodilation, increase temperature, and contribute to pain relief
• There are two COX isoenzymes: COX-1 and COX-2
• COX-1 is constitutively expressed in the body and is involved in maintaining gastrointestinal lining, kidney function, and platelet aggregation
• COX-2 is not constitutively expressed but is inducibly expressed during an inflammatory response
• Most NSAIDs are nonselective and inhibit both COX-1 and COX-2
• COX-2 selective NSAIDs only target COX-2, leading to a different side effect profile
• COX-2 selective NSAIDs are thought to provide anti-inflammatory benefit without harming the stomach lining

Nifedipine Pharmacokinetics

• Nifedipine is readily absorbed from the GI tract after sublingual, oral, and rectal administration
• Bioavailability is approximately 56% to 77% due to presystemic metabolism
• Peak plasma concentration after oral administration of 10mg occurs between 30-60 minutes
• After intravenous administration, elimination is biphasic with a short alpha-phase half-life of 13 minutes and a longer beta-phase half-life of 1.26 hours
• A third phase with a half-life of 8 hours is observed after higher oral doses or continuous infusion
• Nifedipine undergoes hepatic metabolism into two main metabolites: 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3-carboxylic acid (M I) and 2-hydroxymethyl-pyridinecarboxylic acid (M II)

Aspirin Development

• Aspirin’s history dates back thousands of years with the use of willow bark and plants containing salicylates
• Synthetic salicylate was developed by Felix Hoffman at Bayer Company in Germany in 1897
• Aspirin became the most widely used medication globally
• In 1971, Vane discovered the mechanism of aspirin’s actions, proving that it inhibits cyclooxygenase (COX) leading to the formation of prostaglandins (PGs) which mediate inflammation, swelling, pain, and fever

Drug Elimination

• Medical absorption is the movement of a drug from its site of administration into the blood.
• Oral medications enter the stomach, where they are either dissolved and pass through epithelial cells or travel undissolved to the small intestine for absorption.
• Drugs pass through the intestinal wall and enter the portal venous system, leading to the first-pass effect in the liver.
• The liver metabolizes the drug, potentially inactivating it or excreting it into bile.
• The remaining active drug leaves the liver and enters the general circulation, reaching its target organs.
• Intravenous injection bypasses the first-pass effect in the liver.
• Drugs administered into muscle or subcutaneous tissue pass through gap junctions into capillaries and then into the bloodstream.
• Bioavailability refers to the fraction of a drug dose absorbed into the bloodstream.
• Bioavailability is less than 100% due to the first-pass effect but is 100% for intravenous administration.
• Different drugs have varying bioavailability because they are absorbed at different rates.

Ibuprofen

• Ibuprofen is sold under trade names like Nurofen and Advil.
• It’s a non-steroidal anti-inflammatory drug (NSAID) and a COX inhibitor.
• It is effective for headaches, fever, and pain.
• Ibuprofen has analgesic, antipyretic (fever-reducing), and anti-inflammatory properties.
• NSAIDs are FDA-approved for antipyretic, anti-inflammatory, and analgesic uses.

Beta-Lactamase

• Beta-lactamase is an enzyme produced by bacteria that breaks down the beta-lactam ring in antibiotics, rendering them ineffective.
• It is a significant factor in antibiotic resistance.

Uremic patients

• Are patients with kidney failure.
• Experience difficulty eliminating drugs from the body, leading to accumulation and potential toxicity.

Penicillin and Antibacterial Activity

• Some penicillins, such as procaine penicillin and benzathine penicillin, lack direct antibacterial activity.
• These are administered as pro-drugs.
• They require conversion to active metabolites within the body to exert their antibacterial effect.

MIC (Minimum Inhibitory Concentration)

• MIC is the lowest concentration of an antibiotic that inhibits the visible growth of a bacterium.
• It is crucial to maintain antibiotic concentrations above the MIC to effectively fight infection.

Daptomycin (Lipopeptide)

• Daptomycin shows concentration-dependent bactericidal activity.
• It is primarily excreted by the kidneys, with a longer half-life in patients receiving hemodialysis.

Broad Spectrum Antibiotics

• Broad-spectrum antibiotics are effective against a wide range of bacteria.
• They are used for infections where the specific pathogen is unknown or when the infection is caused by multiple organisms.

Time-Dependent vs Concentration-Dependent Antibiotics

• Time-dependent antibiotics: Effectiveness depends on maintaining drug concentrations above the MIC for a specific duration.
• Concentration-dependent antibiotics: Effectiveness depends on achieving high peak concentrations.
• Time>MIC is a critical factor for time-dependent antibiotics (like beta-lactams).
• Peak:MIC ratio is a critical factor for concentration-dependent antibiotics (such as aminoglycosides).

Pharmacodynamic Properties and Dose Adjustments for Kidney Disease

• Understanding an antibiotic's pharmacodynamic properties is crucial for adjusting dosages for patients with kidney disease.
• For time-dependent antibiotics (e.g., beta-lactams), it is often preferable to decrease the dose while maintaining the dosing interval.
• For concentration-dependent antibiotics, it might be better to keep the dose the same and prolong the dosing interval.

Beta-Lactam Antibiotics

• Penicillin, cephalosporin, and carbapenem antibiotics contain a beta-lactam ring.
• They inhibit the final step in bacterial cell-wall peptidoglycan synthesis, leading to bacterial cell death.

Nonlinear Pharmacokinetics

• Nonlinear pharmacokinetic models indicate that certain aspects of drug behavior, such as metabolism or absorption, can become saturated at higher doses.
• This saturation can lead to a greater than proportional increase in the area under the curve (AUC) with increasing dose.
• A common example is the saturation of metabolic pathways, resulting in decreased clearance and a higher AUC at higher doses.
• In some cases, shortening the infusion duration can also increase the AUC due to higher peak plasma concentrations and slower clearance.
• 5-Fluorouracil (5-FU) exhibits nonlinear pharmacokinetics due to saturation of its conversion to dihydrofluorouracil by dihydropyrimidine dehydrogenase.
• Doubling the dose of 5-FU can result in a 135% increase in AUC.
• Paclitaxel also demonstrates nonlinear pharmacokinetics, with shorter infusion durations (3 hours vs. 24 hours) leading to a higher AUC for a fixed dose. However, this does not result in increased toxicity.
• Alternatively, nonlinear pharmacokinetics can occur when a drug's absorption from the gastrointestinal tract or renal tubular reabsorption is saturable.
• This leads to a less than proportional increase in AUC with increasing dose.
• Drugs that resemble natural compounds and are absorbed through active transport processes often exhibit saturable absorption, such as folate analogs (methotrexate, leucovorin) and amino acid analogs (melphalan).
• Cisplatin exhibits nonlinear pharmacokinetics due to saturation of its renal tubular reabsorption.
• Continuous infusion of cisplatin leads to a 42% increase in free plasma platinum compared to a 20-minute infusion.
• Prolonged cisplatin infusion also results in a greater than threefold increase in the free platinum half-life.

Test your knowledge on Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and their various uses, classes, and mechanisms. This quiz covers the different types of NSAIDs, their chemical groups, and their therapeutic applications. Challenge yourself to see how well you understand this important class of medications.