Which of the following anti-lipidemic drugs reduces cholesterol levels by reducing the cholesterol absorption in intestine by acting on NPC1L1 receptors?
Ans. a (Ezetimibe) (Ref. KDT 6th/618; H-17th/Table 350-6; p. 2428).KDT 6th/618:Ezetimibe acts by inhibiting inetstinal absorption of cholestroi and phytosterols. It interferes with a specific CH transport protein NPC1C1 in the intsetinal mucosa and reduces absorption of both dietary and biliary CH. It is a weak hypocholestrolemic drug if used alone. Its primary clinical effect is reduction of LDL levels. Reversible hepatic dysfunction and rarley myositis are side effects.CHOLESTEROL ABSORPTION INHIBITORS (EZETIMIBE)# Cholesterol within the lumen of the small intestine is derived from the diet (about one-third) and the bile (about two- thirds) and is actively absorbed by the enterocyte through a process that involves the protein NPC1L1.# Ezetimibe is a cholesterol absorption inhibitor that binds directly to and inhibits NPC1L1 and blocks the intestinal absorption of cholesterol.# The result of inhibition of intestinal cholesterol absorption is likely to be reduction in hepatic cholesterol and an increase hepatic LDL receptor expression.# Effects on TG and HDL-C levels are negligible.# No cardiovascular outcome data have been reported.# When used in combination with a statin, monitoring of liver transaminases is recommended.# USES: Ezetimibe has become the preferred drug to add to a statin in patients who require further LDL-C reduction.# Widely used in patients who are statin-intolerant.DrugMajor indicationsMechanismCommon side effectsHMG-CoA reductase\ inhibitors (statins)Elevated (LDL)|Cholesterol synthesis;| LDL receptors, | hepatic VLDL productionMyalgias, arthralgias, DyspepsiaBile acid sequestrantsElevated TGs| Bile acid excretion and | LDL receptorsBloating, constipation.Nicotinic acidElevated LDL, JHDL, Elevated TG|VLDL hepatic synthesis and | HDL.Cutaneous flushing; GI upset; Elevated glucose, uric acid, LFTsFibric acid derivates(drug class of choice in severe & first line in moderate hypertrigly- ceridemia).Elevated remnants| LPL, |VLDL (their effect is exerted through PPAR-a,a gene transcription regulating receptor in liver,fat,muscle.Dyspepsia myalgia; gallstones.Cholesterol Absorption Inhibitors (Ezetimibe)Preferred to add to a statin in pts who need further LDL-C reduction and in pts who are statin-intolerantInhibits NPC1L1 and blocks the intestinal absorption of cholesterol; Primarily i LDL.Reversible hepatic dysfunction and rarley myositisAdditional Educational Points# HMG-CoA like Lovastatin, atorvastatin, fluvastatin, pravastatin, simvastatin, and rosuvastatin are most effective in reducing LDL. Other effects include decreased oxidative stress and vascular inflammation with increased stability of atherosclerotic lesions.2# FIBRIC ACID DERIVATIVES (FIBRATES) like Gemfibrozil and fenofibrate decrease levels of VLDL and, in some patients, LDL as well. Their effect is exerted through PPAR-a. Fibrates are drug class of choice in severe hypertriglyceridemia & firs dine in moderate hypertriglyceridemia).Q In a patient with poor glycemic control, hypertriglyceridemia, low HDL, fibrates would be best drug for Rx without the risk of myositis. In diabetics, fibrates have some efficacy and should be considered when the HDL is low in the setting of a mild elevation of the LDL. Myopathy is uncommon with fibrates.# Niacin (but not niacinamide) decreases VLDL and LDL levels, and Lp(a) in most patients. It often increases HDL levels significantly (highest efficacy to increase HDL) 0/f significantly increases lipoprotein-a levels.0 Niacin is the most effective available HDL-C-raising therapeutic agent and can be associated with increases in plasma HDL-C by up to -30%. 0# High doses (>2 g/d) may worsen glycemic control and increase insulin resistance. The most frequent side effect of niacin is cutaneous flushing.0 Niacin can raise fasting plasma glucose levels (niacin should not be used in diabetics) -- KPTl6^/p. 618. Thus, in a patient with Type II diabetes mellitus on anti-lipidemic drug therapy for increased LDL and decreased HDL levels if the hyperglycemia worsened, the likely culprit is nicotinic acid.# ACID-BINDING RESINS like Colestipol, cholestyramine, and colesevelam are useful only for isolated increases in LDL. In patients who also have hypertriglyceridemia, VLDL levels may be further increased during Rx with resins.
Ezetimibe
Nicotinic acid
Lovastatin
Fibrates
Hypolipidemic