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.