Overview
Definition
Lipid control agents are a group of medications (other than statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins), which manage levels of LDL, HDL, and triglycerides through a variety of mechanisms.
Dyslipidemia
- Abnormal levels of:
- LDL
- Triglycerides
- HDL
- Can be primary or secondary
- Places individuals at risk for:
- Cardiovascular complications such as:
- Stroke
- Coronary artery disease
- Peripheral vascular disease
- Pancreatitis (e.g., hypertriglyceridemia)
- Cardiovascular complications such as:
- Mechanisms for controlling lipid levels:
- Alter cholesterol and lipid:
- Synthesis
- Metabolism
- Hepatic uptake
- Inhibit intestinal cholesterol absorption or bile acid reabsorption
- Alter cholesterol and lipid:
Lipid control agents
- Statins
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
- Fibrates
- Ezetimibe
- Bile acid sequestrants (BAS)
- Bempedoic acid
- Niacin
- Omega-3 fatty acids
PCSK9 Inhibitors
Medications in the class
- Alirocumab
- Evolocumab
Pharmacodynamics
Mechanism of action:
- Monoclonal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to PCSK9
- Block the binding of PCSK9 to LDL receptors on hepatocytes → ↓ LDL receptor degradation
- ↑ Recycling of LDL receptors → ↑ LDL cleared from the blood
Physiologic effect:
- ↓ LDL: 40%–70%
- ↓ Triglycerides: 12%–31%
- ↑ HDL: 5%–9%
PCSK9 is an enzyme secreted by the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver into the bloodstream, which binds to LDL receptors (both inside and outside the hepatocyte) and subsequently promotes LDL receptor endocytosis for degradation.
Image by Lecturio.
The PCSK9 inhibitors (the blue, y-shaped antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins) bind to and block PCSK9, which stops the degradation of the LDL receptor and allows more LDL uptake into hepatocytes.
Image by Lecturio.
Pharmacokinetics
- Absorption:
- Subcutaneous
- Not absorbed orally
- Distribution: limited
- Metabolism: protein degradation
- Cleared by:
- Reticuloendothelial system
- Target-mediated disposition (binding of the antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins to the pharmacologic targets)
Indications
- Hyperlipidemia:
- Monotherapy or in combination with other lipid-lowering drugs
- Associated with ↓ cardiovascular risk
- Homozygous familial hypercholesterolemia (HoFH): adjunct therapy
- Secondary prevention of major adverse cardiovascular events in individuals with cardiovascular disease
Adverse effects
- Nasopharyngitis and upper respiratory tract infections
- Myalgia
- Injection site reactions
Drug interactions
No clinically significant interactions exist.
Fibrates
Medications in the class
- Fenofibrate
- Gemfibrozil
Pharmacodynamics
Mechanism of action:
- Activate peroxisome proliferator-activated receptor alpha (PPARα) in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver:
- Multiple effects:
- ↓ Apolipoprotein (Apo) C-III
transcription
Transcription
Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination.
Stages of Transcription
- Apo C-III normally inhibits lipoprotein lipase (LPL) activity
- ↓ Apo C-III synthesis → ↑ activity of LPL
- ↑ Breakdown and clearance of serum triglycerides
- ↑ Apo A-I and Apo A-II → ↑ synthesis of HDL
- Additionally:
- ↑ VLDL catabolism
- ↑ Fatty acid oxidation → ↓ triglyceride synthesis
- ↓ Apolipoprotein (Apo) C-III
transcription
Transcription
Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination.
Stages of Transcription
Physiologic effect:
- ↑ HDL: 5%–20%
- ↓ LDL: approximately 10%
- ↓ Triglycerides: 20%–50%
Pharmacokinetics
- Absorption: well-absorbed orally
- Distribution: highly protein-bound
- Metabolism:
- Fenofibrate:
- Prodrug: metabolized to fenofibric acid (active metabolite) by plasma esterases
- Fenofibric acid undergoes glucuronidation
- Gemfibrozil:
- UGT2B7 hepatic oxidation
- The active metabolite is a major CYP2C8 inhibitor.
- Fenofibrate:
- Excretion: urine > feces
Indications
- Hypertriglyceridemia:
- In conjunction with diet and lifestyle modifications
- Particularly for individuals at risk for hypertriglyceridemia-induced pancreatitis
- Other hypercholesterolemia/mixed dyslipidemia:
- Not the preferred therapy
- Not recommended in the absence of hypertriglyceridemia
Adverse effects
- ↑ Transaminases
- Hepatotoxicity
- Cholesterol gallstones
- Dyspepsia
- ↓ Blood cell counts
- Myopathy (↑ risk with concomitant statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins)
Contraindications
- Active liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease
- Severe renal impairment
- Gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract disease
- Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Drug interactions
- Statins: ↑ risk of myopathy
- BAS: ↓ absorption of fibrates
- Coumadin: ↑ INR and risk of bleeding
- Ezetimibe: ↑ risk of myopathy and cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis
Ezetimibe
Pharmacodynamics
Mechanism of action:
- ↓ Cholesterol absorption in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine via inhibition of the Niemann-Pick C1-Like 1 (NPC1L1) receptor
- Limits both:
- Absorption of dietary cholesterol
- Reabsorption of biliary-excreted cholesterol
- ↓ Delivery of cholesterol to the
liver
Liver
The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.
Liver → ↓ hepatic cholesterol stores:
- Causes the upregulation of LDL receptors on the surface of hepatocytes
- ↑ Removal of LDL from the blood
Physiologic effect:
- ↓ LDL: 15%–20%
- May ↑ HDL: approximately 3%
- ↓ Triglycerides: approximately 8%
Ezetimibe inhibits cholesterol absorption in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine, ultimately causing a compensatory mechanism to increase the clearance of LDL from the blood.
Image by Lecturio.Pharmacokinetics
- Absorption: oral
- Distribution: highly protein-bound
- Metabolism:
- Prodrug
- Glucuronidation to active metabolite occurs in:
- Liver
- Small intestine
- Excretion:
- Mainly in the feces
- May undergo enterohepatic recirculation
Indications
- Hyperlipidemia:
- Often used in combination with statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins
- Can be given as monotherapy (if unable to tolerate statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins)
- Associated with improvement in cardiovascular outcomes
- HoFH
Adverse effects
- Headache
- Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
- Arthralgia and myalgia
- Sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis
- ↑ Transaminases (with statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins)
Contraindications
Ezetimibe in combination with statin therapy should be avoided with:
- Active liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease
- Pregnancy
- Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
Drug interactions
- Fibrates: ↑ risk of myopathy and cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis
- BAS: ↓ ezetimibe absorption
- Statins: possible ↑ risk of hepatotoxicity
Bile Acid Sequestrants (BAS)
Medications in the class
- Cholestyramine
- Colestipol
- Colesevelam
Pharmacodynamics
Mechanism of action:
- Nonabsorbable, positively charged resins
- BAS bind to bile acids in the intestine → prevents reabsorption
- The
liver
Liver
The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.
Liver makes more bile acids from cholesterol → ↓ hepatic cholesterol stores, causing:
- Upregulation of LDL receptors on the surface of hepatocytes
- Removal of LDL from the blood
Physiologic effect:
- ↓ LDL: 15%–20%
- ↑ in HDL: minimal
Bile acid sequestrants (also known as resins) bind bile acids in the GI tract to reduce reabsorption. To compensate, the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver converts cholesterol to bile acids, which reduces hepatic cholesterol stores, inducing upregulation of LDL receptors and increasing hepatic uptake of serum LDL.
Image by Lecturio.Pharmacokinetics
- Absorption: not absorbed orally
- Metabolism: none
- Excretion: feces
Indications
- Hyperlipidemia:
- Monotherapy or in combination with statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins
- For individuals without hypertriglyceridemia
- Pruritus associated with cholestasis (cholestyramine)
Adverse effects
- Nausea
- Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
- Bloating
- Abdominal cramping
- ↑ Transaminases
- ↓ Absorption of fat-soluble vitamins
Contraindications
- Complete intestinal or biliary obstruction
- Avoid in individuals with triglycerides ≥ 300 mg/dL (can ↑ triglyceride levels)
Drug interactions
BAS limits the absorption of many drugs including, but not limited to:
- Levothyroxine
- Tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines
- NSAIDs
- Methotrexate
- Raloxifene
- Coumadin
- Furosemide
- Thiazides
- Beta-blockers
- Digoxin
- Fibrates
- Ezetimibe
- Valproic acid
Bempedoic Acid
Pharmacodynamics
Mechanism of action:
- ATP citrate lyase (ACLY) inhibitor → blocks the conversion of citrate to acetyl-CoA in hepatocytes (not muscle)
- Halts cholesterol synthesis → ↓ cholesterol levels in hepatocytes
- Results in upregulation of LDL receptors on the hepatocytes → ↑ uptake of LDL from the blood
Physiologic effect:
- Alone: ↓ LDL approximately 24%
- Added to high-intensity statin: ↓ LDL approximately 14%
- Bempedoic acid/ezetimibe combined and added to a high-intensity statin: ↓ LDL approximately 34%
Mechanism of action of bempedoic acid:
In hepatocytes, bempedoic acid is converted to bempedoic acid-CoA (the active form), which blocks the action of ATP citrate lyase, inhibiting the conversion of citrate to acetyl-CoA in the cholesterol synthesis pathway. The resultant decrease in hepatic cholesterol levels causes the upregulation of LDL receptors (the green receptors on the blue
cell membrane
Cell Membrane
A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules.
The Cell: Cell Membrane), which increases the uptake of LDL from the bloodstream. Note B-100 is an apolipoprotein carrier protein, which transports LDL in the bloodstream.
TCA: tricarboxylic acid
Pharmacokinetics
- Absorption: oral
- Distribution: highly protein-bound
- Metabolism:
- Prodrug: converted to the active metabolite in hepatocytes by acyl-CoA synthetase 1
- Converged by UGT2B7 to inactive glucuronide conjugates in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
- Excretion: urine and feces
Indications
Bempedoic acid is an adjunct to diet and statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins for individuals requiring additional LDL reduction:
- HoFH
- Atherosclerotic cardiovascular disease
Adverse effects
- ↑ Transaminases
- Muscle spasms
- Back and extremity pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
- Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview
- Hyperuricemia (due to inhibition of renal organic anion transporter (OAT) 2 → risk of gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or "gout flare," followed later by chronic deforming arthritis. Gout development
- Tendon rupture (rare)
Contraindications
Bempedoic acid is not recommended during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care or breastfeeding.
Drug interactions
- Inhibits OAT1B1 and OAT1B3, leading to ↑ levels of:
- Estradiol
- Pravastatin and simvastatin
- ↑ Risk of tendon rupture in individuals taking:
- Corticosteroids
- Fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones
Niacin
Niacin is also known as vitamin B3 or nicotinic acid.
Pharmacodynamics
Mechanism of action:
- Converted to nicotinamide → converted to NAD+ and NADH
- Inhibits hormone-sensitive lipase in adipose:
- ↓ Triglyceride breakdown → ↓ free fatty acids
- ↓ Release of free fatty acids from adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue
- ↓ Delivery to hepatocytes → ↓ triglyceride synthesis
- Inhibits hepatic microsomal diacylglycerol acetyltransferase (DGAT) 2:
- Normally converts diacylglycerol → triglycerides
- Niacin → ↓ triglyceride synthesis
- ↓ Triglyceride synthesis → ↓ VLDL release → ↓ LDL
- ↓ Breakdown of HDL
Physiologic effect:
- ↓ LDL: 5%–20%
- ↓ Triglycerides: 20%–50%
- ↑ HDL: 20%–30%
Niacin affects lipid levels through several mechanisms. One mechanism involves decreasing VLDL release from hepatocytes (caused by a decrease in triglyceride synthesis), leading to decreased LDL levels.
Image by Lecturio.Pharmacokinetics
- Formulation: oral
- Distribution: < 20% is protein-bound
- Metabolism: extensive 1st-pass metabolism
- Excretion: urine
Indications
- Dyslipidemia:
- Not a 1st-line or 2nd-line choice
- Not associated with improved outcomes
- Use has declined
- Pellagra (off-label)
Adverse effects
- Cutaneous vasodilation and flushing (minimize by taking aspirin 30 minutes before niacin)
- Pruritus
- Rash
- Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance and hyperglycemia
- Hyperuricemia
- ↑ Transaminases
- Hepatotoxicity (↑ risk with sustained-release formulation)
- Nausea
- Abdominal discomfort
- Arrhythmias (rare)
Contraindications
- Active liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver disease
- Active peptic ulcer Peptic ulcer Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease
- Hemorrhage (niacin can ↓ fibrinogen)
Drug interactions
- Ethanol: may ↑ risk of flushing and hepatotoxicity
- Oral antihyperglycemic agents: ↓ efficacy with niacin
- BAS: ↓ absorption of niacin
- Statins: ↑ risk of myopathy and hepatotoxicity
Omega-3 Fatty Acids
Omega-3 fatty acids are also known as fish oils.
Pharmacodynamics
Mechanism of action:
- Omega-3 fatty acids are triglycerides → broken down to fatty acids:
- Docosahexaenoic acid (DHA)
- Eicosapentaenoic acid (EPA)
- Potentially ↓:
- Hepatic formation of VLDL
- Hepatic secretion of triglycerides
- Also has antiinflammatory effects
Physiologic effect:
- ↓ Triglycerides: 25%–45%
- Slightly ↑ LDL
- Slightly ↑ HDL
Pharmacokinetics
- Formulation: oral
- Metabolism: oxidized to fatty acids in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
Indications
Omega-3 fatty acids may be used in the management of hypertriglyceridemia:
- Monotherapy or in conjunction with a statin
- Large trials have not found a cardiac benefit.
Adverse effects
- Dyspepsia
- Dysgeusia
- ↑ Bleeding tendency
- Pruritus, rash
- Anaphylaxis
- ↑ LDL
Drug interactions
Increased risk of bleeding may occur with:
- Anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants
- Antiplatelets
References
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1046–e1081. https://doi.org/10.1161/CIR.0000000000000624.
- Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Decision Pathways. J Am Coll Cardiol 2017;70:1785–822. https://doi.org/10.1016/j.jacc.2017.07.745.
- Michos ED, McEvoy JW, Blumenthal RS. Lipid management for the prevention of atherosclerotic cardiovascular disease. N Engl J Med 2019;381:1557–67. https://doi.org/10.1056/NEJMra1806939.
- Creider JC, Hegele RA, Joy TR. Niacin: another look at an underutilized lipid-lowering medication. Nat Rev Endocrinol. 2012 Sep;8(9):517–28. https://doi.org/10.1038/nrendo.2012.22.
- Bhatt DL, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2018 Nov 10; [e-pub]. https://doi.org/10.1056/NEJMoa1812792.
- Malloy MJ, Kane JP. Agents Used in Dyslipidemia. In: Katzung BG. eds. Basic & Clinical Pharmacology [Internet], 14e. New York, NY: McGraw-Hill.
