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Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference
Introduction:
Introduction:
Bile acid sequestrants are a unique class of medications primarily used to manage hypercholesterolemia by lowering low-density lipoprotein (LDL) cholesterol levels in the blood. These agents work through a distinctive mechanism: they bind to bile acids in the intestine, preventing their reabsorption and promoting their excretion. As a result, the liver converts more cholesterol into bile acids to compensate for the loss, thereby reducing overall cholesterol levels.
Originally developed to treat high cholesterol, bile acid sequestrants have found additional roles in medical therapy. They are sometimes used off-label for conditions such as chronic diarrhea, pruritus associated with liver disease, and even in certain cases of type 2 diabetes to improve glycemic control. Despite being older drugs, their safety profile—particularly the fact that they are not absorbed systemically—makes them a suitable option for specific patient populations, including pregnant women and children.
However, they are not without drawbacks. Their gastrointestinal side effects, such as bloating, constipation, and abdominal discomfort, can limit patient adherence. Moreover, they may interfere with the absorption of fat-soluble vitamins and other medications, requiring careful timing of doses.
Overall, bile acid sequestrants represent a fascinating example of how a medication can be both highly effective and versatile, with evolving applications in modern pharmacotherapy.
MOA
Bile acid sequestrants are a class of drugs used primarily to lower cholesterol levels. Their mechanism of action involves the following steps:
Bile acid sequestrants are a class of drugs used primarily to lower cholesterol levels. Their mechanism of action involves the following steps:
1. Binding of Bile Acids: Bile acid sequestrants are polymers that are not absorbed by the body. When taken orally, they pass through the gastrointestinal tract and bind to bile acids in the small intestine. Bile acids are derivatives of cholesterol and are normally required for the digestion and absorption of dietary fats.
1. Binding of Bile Acids: Bile acid sequestrants are polymers that are not absorbed by the body. When taken orally, they pass through the gastrointestinal tract and bind to bile acids in the small intestine. Bile acids are derivatives of cholesterol and are normally required for the digestion and absorption of dietary fats.
2. Prevention of Bile Acid Reabsorption: The binding of bile acids to the sequestrant prevents their reabsorption in the ileum (the last part of the small intestine). Normally, bile acids are reabsorbed from the intestine back into the liver, where they are recycled and used again to aid in fat digestion.
2. Prevention of Bile Acid Reabsorption: The binding of bile acids to the sequestrant prevents their reabsorption in the ileum (the last part of the small intestine). Normally, bile acids are reabsorbed from the intestine back into the liver, where they are recycled and used again to aid in fat digestion.
3. Increased Bile Acid Excretion: With the bile acids bound to the sequestrant, they are excreted in the feces instead of being recycled. This results in a decrease in the total bile acid pool in the body.
3. Increased Bile Acid Excretion: With the bile acids bound to the sequestrant, they are excreted in the feces instead of being recycled. This results in a decrease in the total bile acid pool in the body.
4. Compensatory Cholesterol Synthesis: To replace the lost bile acids, the liver increases the synthesis of new bile acids, using cholesterol as a precursor. This leads to a decrease in the liver's cholesterol levels.
4. Compensatory Cholesterol Synthesis: To replace the lost bile acids, the liver increases the synthesis of new bile acids, using cholesterol as a precursor. This leads to a decrease in the liver's cholesterol levels.
5. Increased Hepatic LDL Receptor Activity: To maintain cholesterol homeostasis, the liver increases the number of LDL (low-density lipoprotein) receptors on its surface. These receptors help clear more LDL cholesterol from the bloodstream.
5. Increased Hepatic LDL Receptor Activity: To maintain cholesterol homeostasis, the liver increases the number of LDL (low-density lipoprotein) receptors on its surface. These receptors help clear more LDL cholesterol from the bloodstream.
6. Reduced Plasma LDL Cholesterol: The increased clearance of LDL from the bloodstream lowers the overall concentration of LDL cholesterol, which is often referred to as "bad" cholesterol.
6. Reduced Plasma LDL Cholesterol: The increased clearance of LDL from the bloodstream lowers the overall concentration of LDL cholesterol, which is often referred to as "bad" cholesterol.
In summary, bile acid sequestrants reduce plasma LDL cholesterol by preventing the reabsorption of bile acids, leading to increased cholesterol usage for bile acid synthesis, and enhanced clearance of LDL cholesterol from the blood.
In summary, bile acid sequestrants reduce plasma LDL cholesterol by preventing the reabsorption of bile acids, leading to increased cholesterol usage for bile acid synthesis, and enhanced clearance of LDL cholesterol from the blood.
Examples of Medication Brand Names
Cholestyramine (generic and various proprietary names)
Colestipol (Colestid, Colestipid)
Colesevelam (Cholestagel in Europe, Welchol in the US, Lodalis in Canada)
Indication
1. Primary Hypercholesterolemia
Used to reduce elevated LDL-C levels.
Especially helpful for:
Patients intolerant to statins.
Combination therapy with niacin or ezetimibe.
2. Heterozygous Familial Hypercholesterolemia
FDA-approved for adolescents aged 10–17 years.
One of the few long-term lipid-lowering therapies safe for children.
3. Type 2 Diabetes Mellitus (Colesevelam only)
Approved as an adjunct to diet and exercise.
Helps lower HbA1c in patients who haven't met glycemic or lipid goals.
4. Bile Acid Malabsorption / Chronic Diarrhea (Off-label use)
Used to treat chronic diarrhea caused by bile acid malabsorption.
5. Pruritus due to Cholestasis
Effective in reducing itching caused by accumulation of bile acids in liver diseases.
6. Graves’ Disease (Adjunct Therapy – Off-label)
Helps reduce enterohepatic recycling of thyroid hormones in hyperthyroidism.
Side Effects
Bile acid sequestrants are designed to stay in the gut; in general, they do not have systemic side effects. However, they may cause problems in the gastrointestinal tract, such as constipation, diarrhea, bloating, and flatulence. Some patients complain of the bad taste.
Because bile acid sequestrants are not well-absorbed from the gut, they are generally regarded as safe in pregnant women. However, by interfering with vitamin absorption (see below), they could cause vitamin deficiencies that may affect the fetus. So, vitamin supplementation may be considered, with appropriate intervals between dosing of the vitamins and bile acid sequestrants
Precautions & Contraindications
Precautions:
1. Gastrointestinal Issues:
May cause constipation, bloating, nausea, and abdominal discomfort.
Use with caution in patients with a history of bowel obstruction or severe constipation.
2. Fat-Soluble Vitamin Deficiency:
Can reduce the absorption of vitamins A, D, E, and K.
Long-term use may require vitamin supplementation.
3. Drug Interactions:
Can bind to other medications (e.g., warfarin, digoxin, fat-soluble vitamins), reducing their effectiveness.
Other medications should be taken at least 1 hour before or 4–6 hours after the bile acid sequestrant.
4. Diabetes:
Colesevelam may improve blood glucose control in type 2 diabetes, but others may worsen glycemic levels.
5. Pregnancy and Breastfeeding:
Generally safe due to minimal absorption, but should still be used under medical supervision.
Contraindications
1. Bowel Obstruction:
Absolute contraindication, as these drugs can worsen the condition.
2. Severe Hypertriglyceridemia:
Should not be used in patients with triglyceride levels above 300 mg/dL, as they may increase triglyceride levels further.
3. Dysbetalipoproteinemia (Type III Hyperlipoproteinemia):
Not recommended due to worsening lipid abnormalities.
4. Severe Liver Disease:
Use with caution, as bile acid metabolism may be impaired.
5. Phenylketonuria (PKU):
Some formulations contain phenylalanine, which is harmful to individuals with PKU.
Monographs
pharma (3).pdfColestipol
ps.pdfCholestyramine
Ghada Elsakka pharma (1).pdfColesevelam
ghada2.pdfColestilan
Reference
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