NSAIDs Quiz

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Which statement best describes the physiological roles of COX-1 and COX-2?

COX-1 is expressed in platelets and produces thromboxane A2, whereas COX-2 is expressed in the gastric mucosa and produces protective prostaglandins. COX-2 is constitutively expressed in most tissues and is responsible for thromboxane A2 production in platelets. COX-1 and COX-2 are both constitutively expressed in most tissues, and both are further upregulated by inflammation. COX-1 is mainly inducible at sites of inflammation, whereas COX-2 is constitutively expressed in most tissues for housekeeping functions. COX-1 is constitutively expressed and produces protective prostaglandins in the gastric mucosa, whereas COX-2 is mainly inducible at sites of inflammation.

A COX-1 is expressed in platelets and produces thromboxane A2, whereas COX-2 is expressed in the gastric mucosa and produces protective prostaglandins.
B COX-2 is constitutively expressed in most tissues and is responsible for thromboxane A2 production in platelets.
C COX-1 and COX-2 are both constitutively expressed in most tissues, and both are further upregulated by inflammation.
D COX-1 is mainly inducible at sites of inflammation, whereas COX-2 is constitutively expressed in most tissues for housekeeping functions.
E COX-1 is constitutively expressed and produces protective prostaglandins in the gastric mucosa, whereas COX-2 is mainly inducible at sites of inflammation. ✓

The answer is E: COX-1 is constitutively expressed and produces protective prostaglandins in the gastric mucosa, whereas COX-2 is mainly inducible at sites of inflammation.

Explanation

Why E is correct

See COX-1 and COX-2. Option E is correct because COX-1 is constitutively expressed, meaning it is made all the time in most tissues, and it carries out housekeeping roles. In the gastric mucosa (the lining of the stomach) it produces protective prostaglandins that maintain mucus and bicarbonate secretion and blood flow; in the kidneys it supports renal blood flow; and in platelets it produces thromboxane A2, which promotes clotting. COX-2 is mainly inducible: its production is switched on by inflammatory signals such as cytokines, so it is concentrated at sites of inflammation. A small amount of COX-2 is expressed constitutively in the kidney, the blood vessel lining and parts of the central nervous system. This pattern explains the effects of NSAIDs: most of their analgesic and anti-inflammatory benefit comes from inhibiting COX-2, while most of the gastrointestinal side effects come from inhibiting COX-1, and that idea led to the development of selective COX-2 inhibitors. A simple memory aid: COX-1 is Constant housekeeping, COX-2 arrives with inflammation.

COX-1: Constitutive housekeeping enzyme that protects the gastric mucosa, supports renal blood flow and makes platelet thromboxane A2.
COX-2: Mainly inducible, switched on at sites of inflammation.
NSAID effects: Benefit comes mostly from COX-2 inhibition and gastrointestinal side effects mostly from COX-1 inhibition.

Why the other options are incorrect

A. COX-1 is expressed in platelets and produces thromboxane A2, whereas COX-2 is expressed in the gastric mucosa and produces protective prostaglandins.: This wrongly assigns gastric protective prostaglandins to COX-2. In normal physiology COX-1 in the gastric mucosa produces the protective prostaglandins, while COX-2 is mainly induced at sites of inflammation.
B. COX-2 is constitutively expressed in most tissues and is responsible for thromboxane A2 production in platelets.: Platelet thromboxane A2 is made by COX-1, not COX-2, and COX-2 is mainly inducible. This is why COX-2 selective drugs have no antiplatelet effect.
C. COX-1 and COX-2 are both constitutively expressed in most tissues, and both are further upregulated by inflammation.: COX-1 is constitutive, but COX-2 is mainly inducible rather than constitutively expressed in most tissues; only small amounts of COX-2 are constitutive in the kidney, endothelium and central nervous system.
D. COX-1 is mainly inducible at sites of inflammation, whereas COX-2 is constitutively expressed in most tissues for housekeeping functions.: This reverses the two isoforms. COX-1 is the constitutive, housekeeping enzyme, and COX-2 is the one induced at sites of inflammation.

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1
Which drug is a COX-2-selective NSAID that generally has less gastrointestinal ulcer risk than non-selective NSAIDs, but still carries cardiovascular risk and has no clinically useful antiplatelet effect?
2
Which of the following renal adverse effects is most directly caused by NSAID inhibition of prostaglandin-mediated afferent arteriolar dilation?

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