**Question:** All are true about HMG CoA reductase inhibitors EXCEPT:

A. They inhibit the enzyme HMG CoA reductase, which is involved in cholesterol synthesis.
B. They can cause myopathy and rhabdomyolysis due to increased intramuscular cholesterol concentration.
C. They can cause hyperuricemia, as HMG CoA reductase inhibitors are not directly involved in uric acid synthesis.
D. They are contraindicated in patients with liver disease due to increased risk of hepatotoxicity.

**Correct Answer:** D. They are contraindicated in patients with liver disease due to increased risk of hepatotoxicity.

**Core Concept:**
HMG CoA reductase inhibitors, also known as statins, are a class of medications used to lower low-density lipoprotein (LDL) cholesterol and triglyceride levels, thereby reducing cardiovascular risk. They achieve this by inhibiting the enzyme HMG CoA reductase, which is involved in the mevalonate pathway, leading to reduced cholesterol synthesis.

**Why the Correct Answer is Right:**
Statins are generally safe and well-tolerated; however, they can cause myopathy and rhabdomyolysis due to increased intramuscular cholesterol concentration. This is a direct consequence of inhibiting cholesterol synthesis, which results in intracellular cholesterol depletion. The excess cholesterol is then transported to the mitochondria where it serves as a substrate for the synthesis of ubiquinone, an essential cofactor for the functioning of the electron transport chain. Depletion of ubiquinone leads to impaired electron transport chain function, which in turn causes muscle cell dysfunction and muscle pain/weakness.

**Why Each Wrong Option is Incorrect:**
A. This statement is correct as HMG CoA reductase inhibitors primarily target cholesterol synthesis.
B. While statins can cause myopathy, the statement about causing rhabdomyolysis is incorrect. Rhabdomyolysis is a severe condition characterized by muscle cell breakdown leading to myoglobinuria (a dangerous condition). Myopathy can occur due to statin use, but rhabdomyolysis is an extraordinarily rare event.
C. This statement is incorrect because HMG CoA reductase inhibitors primarily target cholesterol synthesis and do not directly influence uric acid production.
D. This statement is incorrect because liver function tests are typically normal in patients on statins, and hepatotoxicity is not a common side effect. Liver enzymes are not significantly affected, and hepatotoxicity is a rare event.

**Clinical Pearl:**
When using HMG CoA reductase inhibitors, clinicians should carefully monitor patients for myopathy symptoms and liver enzyme elevations, as these events are more common side effects of statin use. However, the risk of hepatotoxicity is low and not a significant concern.