NSAID class generic chemical scaffolds (arylpropionic and diarylheterocycle/coxib), 2D skeletal formulas

NSAID (Class) Chemical Structure

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1. Identification

Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX-1/COX-2) to reduce prostaglandin and thromboxane synthesis, producing analgesic, antipyretic, and anti-inflammatory effects; aspirin uniquely irreversibly acetylates COX.

Brand Names

Not applicable at class level (examples span multiple brands and generics).

Name

NSAIDs (Nonsteroidal Anti-inflammatory Drugs)

Background

Subclasses:
• Salicylates (e.g., aspirin) — irreversible acetylation
• Arylpropionic acids (e.g., ibuprofen, naproxen) — reversible, COX-1/2
• Arylacetic acids (e.g., diclofenac, indomethacin, ketorolac)
• Enolic acids/oxicams (e.g., piroxicam, meloxicam)
• Fenamates (e.g., mefenamic acid)
• Selective COX-2 inhibitors (coxibs) (e.g., celecoxib, etoricoxib)

Modality

Small molecules

Groups

Approved; prescription/OTC (jurisdiction and product dependent)

Structure

NSAID class overview with representative 2D structures (arylpropionic acid and coxib motifs); weakly acidic, highly albumin-bound COX inhibitors.
NSAID class generic chemical scaffolds (arylpropionic and diarylheterocycle/coxib), 2D skeletal formulas

Weight

Varies by agent

Chemical Formula

Varies by agent

Synonyms

Nonsteroidal anti-inflammatory agents; COX inhibitors

External IDs

ATC family: M01A (subgroups per subclass)

2. Pharmacology

Indication

Symptomatic treatment of pain, fever, and inflammation (musculoskeletal disorders, dysmenorrhea, dental pain); migraine (some agents); gout flares; PDA closure in neonates (indomethacin/ibuprofen IV); cardiovascular prevention at low-dose aspirin (antiplatelet).

Associated Conditions

Osteoarthritis, rheumatoid arthritis, spondyloarthritides, peri-operative pain (short-course ketorolac), headache disorders, soft-tissue injury.

Associated Therapies

With gastroprotection (PPI) in GI-risk patients; with acetaminophen in multimodal analgesia; low-dose aspirin often continued for cardioprotection (manage timing with other NSAIDs).

Contraindications & Blackbox Warnings

Class boxed warnings (non-aspirin NSAIDs and COX-2 selective): ↑ risk of serious cardiovascular thrombotic events (MI, stroke); ↑ risk of serious GI bleeding, ulceration, perforation.
Contraindications: peri-operative pain in CABG, active GI bleeding/ulcer, prior NSAID-induced asthma/urticaria, severe renal failure without monitoring. Pregnancy: avoid from 20 weeks (fetal renal dysfunction/oligohydramnios) and especially after 30 weeks (ductus arteriosus closure).

Pharmacodynamics

COX inhibition → ↓ PGE₂/PGI₂ (analgesia, antipyresis, ↓ inflammation); COX-1 gastric/platelet inhibition explains GI bleeding and antiplatelet effects. Aspirin irreversibly blocks platelet COX-1 for lifespan; others are reversible.

Mechanism of action

Competitive (reversible) blockade of COX-1/COX-2 active sites (all non-aspirin NSAIDs); acetylation of a serine residue by aspirin (irreversible) → prevents arachidonic-acid conversion to prostanoids.

Absorption

Rapid oral absorption for most; peak 0.5–3 h; food may delay tₘₐₓ without major AUC change.

Volume of distribution

Moderate; highly albumin-bound (often >95%) with acidic scaffolds.

Protein binding

High for most arylacetic/arylpropionic members; celecoxib moderately high.

Metabolism

Predominantly hepatic (CYP2C9 for many; glucuronidation common). Aspirin → salicylate by esterases.

Route of elimination

Renal (metabolites ± unchanged) ± biliary; half-life ranges: short (ibuprofen 2–4 h) to long (piroxicam ~45–50 h).

Half-life

Agent-specific; sustained-release and long-t½ oxicams permit once-daily dosing.

Clearance

Hepatic metabolism; renal impairment chiefly affects metabolites/salicylate; dose adjust where labeled.

Adverse Effects

GI: dyspepsia, ulcer, bleeding; renal: AKI, sodium/water retention, ↑ BP; CV: MI/stroke risk (non-aspirin); hematologic: platelet inhibition (aspirin); hypersensitivity/bronchospasm (AERD); hepatic: transaminitis (diclofenac signal); CNS: headache, dizziness.

Toxicity

Overdose: tinnitus (salicylates), metabolic derangements, CNS symptoms; treat supportively (alkalinize urine for salicylate). Non-aspirin NSAIDs: mainly GI/renal/CNS toxicity.

Pathways

Arachidonic-acid cascade blockade at COX; downstream ↓ prostaglandins/thromboxanes.

Pharmacogenomic Effects/ADRs

CYP2C9 poor metabolizers: ↑ exposure to several NSAIDs (e.g., celecoxib); clinical impact drug-specific.

3. Interactions

Drug Interactions

  • Anticoagulants/antiplatelets/SSRIs/SNRIs → ↑ bleeding risk
  • ACEI/ARB + diuretic (“triple whammy”) → ↑ AKI risk
  • Lithium → ↓ renal clearance (↑ levels)
  • Methotrexate → ↓ renal clearance (↑ toxicity), especially high doses
  • CYP2C9 inhibitors/inducers → exposure changes (celecoxib, diclofenac, ibuprofen, naproxen)
  • Low-dose aspirin: ibuprofen taken first may block aspirin’s irreversible platelet access—separate dosing (aspirin first; delay ibuprofen)

Food Interactions

Food may delay absorption; some labels prefer dosing with food to reduce GI upset.

4. Categories

ATC Codes

M01A (anti-inflammatory and antirheumatic products, non-steroids); specific subgroups per subclass (e.g., M01AE propionic acids, M01AB acetic acids, M01AC oxicams, M01AH COX-2 inhibitors).

Drug Categories

Analgesic; Antipyretic; Anti-inflammatory; Antiplatelet (aspirin, low dose)

Chemical Taxonomy

Predominant arylpropionic and arylacetic carboxylic acids, enolic acids (oxicams), and diarylheterocycles (coxibs); weak acids with high albumin binding.

Affected organisms

Humans (therapeutic use)

5. Chemical Identifiers

UNII / CAS / InChI / SMILES

Not applicable at class level (agent-specific).
Representative scaffolds: arylpropionic acid (Ar–CH(CH₃)–CO₂H); diaryl-pyrazole/pyrazoline (coxibs).

6. References

Goodman & Gilman’s The Pharmacological Basis of Therapeutics — NSAIDs and coxibs chapter.
Katzung & Trevor’s Basic & Clinical Pharmacology — Nonopioid analgesics, antipyretics, NSAIDs.
Hochberg et al., rheumatology and osteoarthritis guidelines (GI/CV risk stratification).
FDA class labeling for non-aspirin NSAIDs and aspirin (boxed warnings; pregnancy precautions).
Up-to-date pharmaceutics reviews on COX biology, platelet effects, and drug–drug interactions.

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