(2019) Pain: NSAIDs and Analgesic Ladder

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Questions and Answers

What was the major mechanism of action of all NSAIDs demonstrated by Vane and co-workers?

Inhibition of leukotriene synthesis

Inhibition of prostaglandin synthesis (correct)

Enhancement of lipoxygenase activity

Promotion of prostaglandin production

Which compound obtained from willow bark led to the discovery of aspirin in 1899?

Acetyl salicylate

Bitter glycoside

Salicylic acid (correct)

Sodium salicylate

What strategy was proposed by WHO to provide adequate pain relief for cancer patients?

Intermittent pain relief

Around-the-clock pain relief (correct)

On-demand pain relief

Opioid-based pain relief only

What is the main difference between NSAIDs and opioids in terms of analgesic strength?

Opioids are stronger analgesics compared to NSAIDs Signup and view all the answers

Which enzyme is responsible for the synthesis of leukotrienes in the prostaglandin synthesis pathway?

Lipoxygenase (LOX) Signup and view all the answers

What is the IASP definition of pain based on the provided text?

An unpleasant sensory and emotional experience associated with or resembling tissue damage Signup and view all the answers

Which enzymes are inhibited by NSAIDs to reduce prostaglandin synthesis?

COX-1 Signup and view all the answers

According to the WHO Analgesic Ladder Strategy, what is the recommended step for moderate to severe pain?

Combining NSAIDs with opioids from the beginning Signup and view all the answers

How do weaker analgesics differ from opioids in terms of pain management effectiveness?

Opioids are more potent in managing severe pain than weaker analgesics Signup and view all the answers

Which class of analgesics primarily target COX-2 to reduce inflammation and pain?

Selective COX-2 inhibitors Signup and view all the answers

What is a key difference between the mechanism of action of NSAIDs and opioids in pain management?

Opioids act directly on central nervous system receptors, while NSAIDs reduce inflammation by inhibiting COX enzymes Signup and view all the answers

What is the mechanism by which NSAIDs exert their anti-inflammatory effect?

Blocking COX enzymes selectively Signup and view all the answers

Which prostaglandin is primarily responsible for vascular endothelium vasodilation and inhibition of platelet aggregation?

PGI2 Signup and view all the answers

Which class of NSAIDs includes aspirin, ibuprofen, and naproxen?

Non-selective COX inhibitors Signup and view all the answers

What is the primary effect of NSAIDs on platelet function?

Inhibiting platelet aggregation Signup and view all the answers

Which event is a common consequence of NSAID-induced deficiency of prostaglandins (PGs)?

Prolongation of bleeding time Signup and view all the answers

Which prostaglandin is primarily responsible for smooth muscle contraction throughout the body and inhibition of gastric acid secretion?

PGE2 Signup and view all the answers

What is the main difference between non-selective and selective COX-2 inhibitors in terms of COX enzyme inhibition?

Non-selective inhibitors block both COX enzymes, while selective inhibitors block COX-1 only. Signup and view all the answers

Study Notes

Pain and NSAIDs

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, influenced by biological, psychological, and social factors.

History of NSAIDs

Willow bark was used for centuries as an analgesic.
Salicylic acid was obtained by hydrolysis of the bitter glycoside extracted from willow bark in 1838.
Sodium salicylate was developed in 1875, and acetyl salicylate (Aspirin) was introduced in 1899.
Vane and co-workers demonstrated that aspirin inhibits prostaglandin production in guinea-pig isolated lungs in 1971, earning a Nobel Prize in Medicine in 1982.

Mechanism of Action of NSAIDs

NSAIDs inhibit prostaglandin synthesis by blocking the action of cyclooxygenase (COX) enzymes.
There are two isoforms of COX enzyme: COX-1 and COX-2.
NSAIDs can block both COX enzymes or selectively block COX-2 enzyme.

Classification of NSAIDs

Classification based on chemical structure:
- Salicylates (Aspirin)
- Arylalkanoic acids (Indomethacin, Sulindac)
- Heteroarylalkanoic acids (Tolmetin, Diclofenac)
- Oxicams (Piroxicam, Tenoxicam)
Classification based on COX affinity:
- Non-selective COX inhibitors (Aspirin, Ibuprofen, Diclofenac)
- Selective COX-2 inhibitors (Celecoxib, Etoricoxib)

Effects of NSAIDs

Beneficial actions:
- Analgesia: prevention of nerve ending sensitization
- Antipyresis: reduction of body temperature
- Anti-inflammatory: reduction in signs of inflammation
- Antithrombotic: inhibition of platelet aggregation
Adverse effects:
- Gastric mucosal damage
- Prolonged bleeding time
- Limitation of renal blood flow
- Delay/prolongation of labor
- Asthma, hypersensitivity, and anaphylactic reactions

Specific NSAIDs

Aspirin:
- Non-selective and irreversibly inhibits both COX enzymes
- Classic actions: analgesic, antipyretic, and anti-inflammatory
- Inhibits platelet aggregation
- ADR: salicylism (mild intoxication) and acute salicylate poisoning (severe intoxication)

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Description

Learn about the ascending pain pathway, NSAIDs introduction, weaker analgesics, WHO Analgesic Ladder Strategy, and the history of NSAIDs from willow bark to sodium salicylate. Explore the use of non-steroidal anti-inflammatory drugs in pain management.