NSAIDS

Question 1

What is arachidonic acid (a.k.a.: arachidonate)?

Answer 1

A major precursor of several classes of potent biological signalling molecules that act as short-range messengers

Essential fatty acids can be converted into arachidonic acid.

Question 2

With the right COX enzyme, arachidonate can be turned into which of the following?

1. Prostaglandins
2. Inflammatory mediators
3. Thromboxanes

Answer 2

1. Prostaglandins
2. Inflammatory mediators
3. Thromboxanes

Prostaglandins include Prostaglandin H2, which has various roles in the body.

Question 3

What can Prostaglandin H2 be converted into?

Answer 3

• Prostacyclin (PGI2)
• Other prostaglandins (PGE2, PGF2α, PGD2)
• Thromboxane A2

Each of these has specific functions in the body, such as inhibiting platelet activation or facilitating platelet aggregation.

Question 4

What is the role of Prostacyclin (PGI2)?

Answer 4

• Inhibits platelet activation
• Vasodilator

It plays a crucial role in regulating blood flow and preventing blood clots.

Question 5

What are the effects of thromboxane A2?

Answer 5

• Facilitates platelet aggregation
• Vasoconstrictor
• Hypertensive agent

Thromboxane A2 is important in promoting blood clotting and increasing blood pressure.

Question 6

How do NSAIDs (such as aspirin and ibuprofen) work?

Answer 6

• Reduce inflammation by interfering with the COX1 and COX2 pathways

COX-1 inhibition can lead to side effects like stomach ulceration, while COX-2 inhibition reduces inflammation, pain, and fever.

Question 7

What is the difference in the effect of ibuprofen and aspirin on COX enzymes?

Answer 7

• Ibuprofen: reversible effect
• Aspirin: irreversible effect

Aspirin acetylates COX-1 and COX-2, affecting platelets for weeks.

Question 8

List the indications for NSAIDs.

Answer 8

• Mild pain and inflammation
• Anti-platelet action for cardiovascular and cerebrovascular disease

Aspirin is commonly prescribed for patients at risk of heart attacks or strokes.

Question 9

What are some side effects of NSAIDs?

Answer 9

• Increased leukotrienes leading to bronchoconstriction
• Impairment of gastric protection, causing inflammation, pain, bleeding

These side effects can be significant, especially in certain patient populations.

Question 10

True or false: NSAIDs should be prescribed to patients who are anticoagulated.

Answer 10

FALSE

NSAIDs can cause bleeding and are contraindicated in patients on anticoagulants.

Question 11

What happens to aspirin during metabolism?

Answer 11

• Metabolized by Phase I and Phase II reactions in the liver
• Filtered by the glomerulus unchanged

Aspirin is a weak acid that partially dissociates in solution.

Question 12

In salicylate poisoning, what does intravenous administration of bicarbonate produce?

Answer 12

Alkaline urine

This helps shift the equilibrium and enhances the excretion of salicylate.

Question 13

Fill in the blank: HSal is filtered by the glomerulus and becomes _______ in alkaline urine.

Answer 13

insoluble in fat

This change reduces its ability to diffuse back across the tubule membrane.

Question 14

Explain step-by-step how ibuprofen leads to pain relief.

Answer 14

• Inhibits COX-1 and COX-2
• ↓ conversion of arachidonic acid → PGH₂
• ↓ PGE₂ production
• ↓ sensitisation of nociceptors
• → Reduced pain perception

This process highlights the mechanism by which ibuprofen alleviates pain through its action on prostaglandins.

Question 15

What effects would you expect from a drug that selectively blocks COX-2?

Answer 15

• ↓ inflammation
• ↓ pain
• ↓ fever
• Minimal gastric side effects (COX-1 preserved)

COX-2 inhibitors are designed to reduce inflammation and pain while minimizing gastrointestinal complications.

Question 16

Explain the mechanism for epigastric pain and GI bleeding in a patient on long-term NSAIDs.

Answer 16

• COX-1 inhibition → ↓ prostaglandins
• ↓ mucus + bicarbonate + blood flow
• Loss of gastric protection
• → Ulceration + bleeding

This highlights the protective role of prostaglandins in the gastric mucosa.

Question 17

If prostaglandins reduce gastric acid, why do NSAIDs still cause ulcers?

Answer 17

• Loss of mucosal protection (mucus, bicarbonate, blood flow), not just acid levels

The main issue is the protective factors in the gastric lining being compromised.

Question 18

Explain why an asthmatic patient develops wheezing after taking aspirin.

Answer 18

• COX inhibited → arachidonic acid diverted to LOX pathway
• ↑ leukotrienes (LTC₄, LTD₄, LTE₄)
• Bronchoconstriction + mucus
• → Asthma exacerbation

This illustrates the shift in arachidonic acid metabolism leading to increased bronchoconstriction.

Question 19

Why are asthmatic patients particularly sensitive to NSAIDs?

Answer 19

• Rely more on prostaglandin balance
• Blocking COX shifts strongly toward leukotrienes → exaggerated bronchoconstriction

This sensitivity can lead to severe respiratory issues in asthmatic individuals.

Question 20

Why is low-dose aspirin prescribed after a myocardial infarction?

Answer 20

• Irreversibly inhibits COX-1 in platelets
• ↓ thromboxane A₂
• ↓ platelet aggregation
• → Reduced clot formation

This mechanism helps prevent further clotting events in patients with cardiovascular issues.

Question 21

Are patients still at risk of bleeding if they stop aspirin 2 days before surgery?

Answer 21

Yes — platelets are irreversibly inhibited and last 7–10 days

This highlights the long-lasting effects of aspirin on platelet function.

Question 22

Why does aspirin’s effect last much longer than its half-life?

Answer 22

• Irreversible COX inhibition + platelets cannot synthesise new enzymes

This explains the prolonged antiplatelet effect of aspirin.

Question 23

Explain why a patient on warfarin who takes ibuprofen develops GI bleeding.

Answer 23

• NSAIDs ↓ platelet function
• NSAIDs cause gastric mucosal damage
• Warfarin inhibits clotting
• → Combined → high bleeding risk

This combination significantly increases the risk of bleeding complications.

Question 24

Explain the mechanism for acute kidney injury in an elderly patient taking NSAIDs.

Answer 24

• ↓ prostaglandins
• Afferent arteriole constriction
• ↓ renal blood flow
• ↓ GFR
• → Kidney injury

This outlines how NSAIDs can adversely affect renal function.

Question 25

Why does a patient’s blood pressure increase after starting **NSAIDs**?

Answer 25

* ↓ renal prostaglandins * Vasoconstriction + Na⁺/water retention * → ↑ blood volume → ↑ BP ## Footnote This mechanism explains the hypertensive effects of NSAIDs.

Question 26

Why are **NSAIDs** avoided in late pregnancy?

Answer 26

* ↓ prostaglandins * → Premature closure of ductus arteriosus * → Fetal circulation problems ## Footnote This highlights the risks associated with NSAID use during pregnancy.

Question 27

Why is **bicarbonate** given to a patient with salicylate poisoning?

Answer 27

* Alkalinises urine * ↑ Sal⁻ (ionised form) * Cannot be reabsorbed * → Increased excretion ## Footnote This treatment helps enhance the elimination of salicylate from the body.

Question 28

Why does ionised salicylate get **“trapped”** in urine?

Answer 28

* Charged molecules cannot cross lipid membranes → cannot be reabsorbed ## Footnote This principle is important in understanding drug excretion.

Question 29

What happens if urine becomes **acidic** in salicylate poisoning?

Answer 29

* More HSal (uncharged) * Reabsorbed into blood * → Worse toxicity ## Footnote This emphasizes the importance of urine pH in drug elimination.

Question 30

Should a patient with asthma, CKD, and on anticoagulants take **NSAIDs**?

Answer 30

No — risks include: * Bronchoconstriction (leukotrienes) * Kidney injury (↓ GFR) * Bleeding (platelets + GI damage) ## Footnote This highlights the compounded risks of NSAID use in vulnerable populations.

Question 31

Why can **COX-2 inhibitors** increase cardiovascular risk?

Answer 31

* ↓ prostacyclin (vasodilator, anti-platelet) * TXA₂ unchanged * → Pro-thrombotic state ## Footnote This mechanism explains the cardiovascular concerns associated with selective COX-2 inhibition.