MOA of Antihyperlipidemic Drugs Quiz

Fibric Acid Derivatives

• The substituent R1 in fibric acid derivatives affects the drug's activity, with its presence or absence influencing the compound's potency.
• Esters play a crucial role in fibric acid derivatives, as they can be converted into active drugs through esterase-mediated hydrolysis.
• The anionic nature of fibric acid derivatives is essential for their activity, with the presence of anionic groups facilitating their binding to the target enzyme.

Niacin

• Phase 2 conjugation of niacin results in its primary effect, which is the formation of a water-soluble glucuronide conjugate.
• Extended release formulations of niacin reduce its side effects, such as flushing and pruritus.

Prodrugs

• A prodrug is a compound that is converted into an active drug through enzymatic or chemical reactions.
• The presence of esters (R2) in a compound makes it a prodrug, as it requires esterase-mediated hydrolysis to become active.

Statins

• The primary mechanism of statins involves the inhibition of HMG-CoA reductase, a rate-limiting enzyme in the cholesterol biosynthesis pathway.
• The high affinity of statins for the enzyme is attributed to their lipophilic nature and ability to bind to the active site.
• Esterases play a crucial role in the metabolism of statin prodrugs, converting them into active drugs.
• Lovastatin, simvastatin, and atorvastatin are metabolized by the cytochrome P450 enzyme CYP3A4.
• Pravastatin is resistant to CYP3A4 metabolism, but is oxidized in the gut and liver.
• Lipophilic groups are essential for the transport of statin molecules into the liver, where they can exert their pharmacological activity.

Drug Interactions

• Naringin in grapefruit juice inhibits CYP3A4, leading to increased levels of statins and other drugs metabolized by this enzyme.
• Bile sequestrants, such as cholestyramine and colestipol, interact with anionic drugs like NSAIDs and anticoagulants, reducing their absorption.
• The recommended timing for taking most drugs in relation to bile sequestrants is to take them one hour before or four hours after administration.
• Bile sequestrants affect the absorption of digoxin and tricyclic antidepressants, leading to reduced efficacy.
• The general drug interaction pattern of bile sequestrants with regard to HMG-CoA reductase inhibitors is a reduction in the absorption of statins.

HMG-CoA Reductase

• The enzyme is membrane-bound, with a hydrophobic domain responsible for its association with the membrane.
• The specific feature of HMG-CoA reductase that binds to the co-enzyme NADPH is the cis loop.
• The cis loop is essential for the enzyme's catalytic activity, facilitating the reduction of HMG-CoA to mevalonate.

Fibric Acid Derivatives (continued)

• The presence of lipophilic substituents in fibric acid derivatives affects their oral absorption, with more lipophilic compounds exhibiting improved absorption.
• The anionic nature of fibric acid derivatives is crucial for their activity, as it facilitates their binding to the target enzyme.
• The presence of a bulky alkyl group in fibric acid derivatives reduces their lipophilicity, affecting their absorption and activity.
• The formation of a prodrug in fibric acid derivatives affects their lipophilicity, making them more or less lipophilic depending on the substituent.

Test your knowledge about the mechanism of action of antihyperlipidemic drugs with this quiz. Explore how these drugs inhibit lipolysis, decrease plasma lipids, reduce VLDL particle size, and increase HDL formation.