Lipid control medications are a group of drugs, which decrease plasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products lipid levels. The groups differ with respect to mechanism of action, type of lipid altered, and degree of alteration. The medications may be used in addition to statin therapy or for individuals unable to tolerate or respond sufficiently to statinsStatinsStatins 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. Ezetimibe, niacin, bile acid sequestrantsBile Acid SequestrantsAntidiarrheal Drugs (BAS), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors primarily reduce LDL. Fibrates and fishFISHA type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Chromosome Testing oil (omega-3 fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance) are the primary triglyceride-lowering therapies. Adverse effects vary based on the drug class but often include myalgiasMyalgiasPainful sensation in the muscles.Tick-borne Encephalitis Virus, GI symptoms, and transaminaseTransaminaseA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Catabolism of Amino Acids elevation. Response to prior treatment modalities, route of administration, drug interactions, contraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation, and pharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics factor into the choice of therapy.
Lipid control agents are a group of medications (other than statinsStatinsStatins 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 triglyceridesTriglyceridesFatty Acids and Lipids through a variety of mechanisms.
PancreatitisPancreatitisInflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis.Acute Pancreatitis (e.g., hypertriglyceridemiaHypertriglyceridemiaA condition of elevated levels of triglycerides in the blood.Lipid Disorders)
Mechanisms for controlling lipid levels:
Alter cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism and lipid:
Inhibit intestinal cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol MetabolismabsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption or bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy acid reabsorption
Lipid control agents
StatinsStatinsStatins 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
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
Omega-3 fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Block the binding of PCSK9 to LDL receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors on hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy → ↓ LDL receptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors degradation
↑ Recycling of LDL receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors → ↑ LDL cleared from the blood
PCSK9 is an enzyme secreted by the 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) bind to and block PCSK9, which stops the degradation of the LDL receptor and allows more LDL uptake into hepatocytes.
Image by Lecturio.
PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption:
Subcutaneous
Not absorbed orally
Distribution: limited
Metabolism: protein degradation
Cleared by:
Reticuloendothelial system
Target-mediated disposition (binding of the antibodiesAntibodiesImmunoglobulins (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: Types and Functions to the pharmacologic targets)
Indications
Hyperlipidemia:
Monotherapy or in combination with other lipid-lowering drugs
Secondary prevention of major adverse cardiovascular events in individuals with cardiovascular disease
Adverse effects
Nasopharyngitis and upper respiratory tract infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Mechanism of action:
Activate peroxisome proliferator-activated receptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors alpha (PPARα) in the liverLiverThe 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: Anatomy:
Multiple effects:
↓ Apolipoprotein (Apo) C-III transcriptionTranscriptionTranscription 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 lipaseLipaseAn enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats.Malabsorption and Maldigestion (LPL) activity
PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption: well-absorbed orally
The active metabolite is a major CYP2C8CYP2C8A liver microsomal cytochrome p450 hydroxylase that oxidizes a broad spectrum of substrates including steroids, fatty acids, and xenobiotics. Examples of pharmaceutical substrates for cyp2c8 include; paclitaxol; torsemide; and; amodiaquine.Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) inhibitor.
In conjunction with diet and lifestyle modifications
Particularly for individuals at risk for hypertriglyceridemia-induced pancreatitisPancreatitisInflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis.Acute Pancreatitis
Other hypercholesterolemiaHypercholesterolemiaA condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Lipid Disorders/mixed dyslipidemia:
Not the preferred therapy
Not recommended in the absence of hypertriglyceridemiaHypertriglyceridemiaA condition of elevated levels of triglycerides in the blood.Lipid Disorders
Adverse effects
↑ TransaminasesTransaminasesA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Autoimmune Hepatitis
CholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol MetabolismgallstonesGallstonesCholelithiasis (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
MyopathyMyopathyDermatomyositis (↑ risk with concomitant statinsStatinsStatins 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)
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
Active liverLiverThe 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: Anatomy disease
Severe renal impairment
GallbladderGallbladderThe 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: Anatomy disease
BreastfeedingBreastfeedingBreastfeeding 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
StatinsStatinsStatins 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: ↑ risk of myopathyMyopathyDermatomyositis
BAS: ↓ absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of fibrates
CoumadinCoumadinAn anticoagulant that acts by inhibiting the synthesis of vitamin k-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.Anticoagulants: ↑ INR and risk of bleeding
Ezetimibe: ↑ risk of myopathyMyopathyDermatomyositis and cholelithiasisCholelithiasisCholelithiasis (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
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Mechanism of action:
↓ CholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol MetabolismabsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption in the small intestineSmall intestineThe 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: Anatomy via inhibition of the Niemann-Pick C1-Like 1 (NPC1L1) receptorReceptorReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors
Limits both:
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of dietary cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism
Reabsorption of biliary-excreted cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism
↓ Delivery of cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism to the liverLiverThe 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: Anatomy → ↓ hepatic cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism stores:
Causes the upregulation of LDL receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors on the surface of hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy
Ezetimibe inhibits cholesterol absorption in the small intestine, ultimately causing a compensatory mechanism to increase the clearance of LDL from the blood.
Image by Lecturio.
PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption: oral
LiverLiverThe 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: Anatomy
Small intestineSmall intestineThe 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: Anatomy
Excretion:
Mainly in the feces
May undergo enterohepatic recirculation
Indications
Hyperlipidemia:
Often used in combination with statinsStatinsStatins 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 statinsStatinsStatins 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
HeadacheHeadacheThe symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders.Brain Abscess
DiarrheaDiarrheaDiarrhea 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
SinusitisSinusitisSinusitis 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
↑ TransaminasesTransaminasesA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Autoimmune Hepatitis (with statinsStatinsStatins 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)
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
Ezetimibe in combination with statin therapy should be avoided with:
Active liverLiverThe 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: Anatomy disease
PregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care
BreastfeedingBreastfeedingBreastfeeding 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 myopathyMyopathyDermatomyositis and cholelithiasisCholelithiasisCholelithiasis (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 absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption
StatinsStatinsStatins 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: possible ↑ risk of hepatotoxicityHepatotoxicityAcetaminophen
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Mechanism of action:
Nonabsorbable, positively charged resins
BAS bindBINDHyperbilirubinemia of the Newborn to bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: AnatomyacidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance in the intestine → prevents reabsorption
The liverLiverThe 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: Anatomy makes more bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: AnatomyacidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance from cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism → ↓ hepatic cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism stores, causing:
Upregulation of LDL receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors on the surface of hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy
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 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.
PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption: not absorbed orally
Metabolism: none
Excretion: feces
Indications
Hyperlipidemia:
Monotherapy or in combination with statinsStatinsStatins 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 hypertriglyceridemiaHypertriglyceridemiaA condition of elevated levels of triglycerides in the blood.Lipid Disorders
PruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema) associated with cholestasis (cholestyramine)
Adverse effects
NauseaNauseaAn unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Antiemetics
ConstipationConstipationConstipation 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
↑ TransaminasesTransaminasesA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Autoimmune Hepatitis
↓ AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of fat-soluble vitamins
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
BAS limits the absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of many drugs including, but not limited to:
TetracyclinesTetracyclinesTetracyclines 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
MethotrexateMethotrexateAn antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.Antimetabolite Chemotherapy
RaloxifeneRaloxifeneA second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.Other Antiresorptive Drugs
CoumadinCoumadinAn anticoagulant that acts by inhibiting the synthesis of vitamin k-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.Anticoagulants
FurosemideFurosemideA benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency.Loop Diuretics
Thiazides
Beta-blockersBeta-blockersDrugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Class 2 Antiarrhythmic Drugs (Beta Blockers)
DigoxinDigoxinA cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small.Cardiac Glycosides
Fibrates
Ezetimibe
Valproic acidValproic acidA fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels.First-Generation Anticonvulsant Drugs
Bempedoic Acid
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Mechanism of action:
ATP citrate lyase (ACLY) inhibitor → blocks the conversion of citrate to acetyl-CoAAcetyl-CoAAcetyl CoA participates in the biosynthesis of fatty acids and sterols, in the oxidation of fatty acids and in the metabolism of many amino acids. It also acts as a biological acetylating agent.Citric Acid Cycle in hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy (not muscle)
Halts cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol MetabolismsynthesisSynthesisPolymerase Chain Reaction (PCR) → ↓ cholesterolCholesterolThe principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Cholesterol Metabolism levels in hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy
Results in upregulation of LDL receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors on the hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy → ↑ 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), 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
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PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption: oral
Distribution: highly protein-bound
Metabolism:
ProdrugProdrugNitroimidazoles: converted to the active metabolite in hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy by acyl-CoA synthetase 1
Converged by UGT2B7 to inactive glucuronide conjugates in the liverLiverThe 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: Anatomy
Excretion: urine and feces
Indications
Bempedoic acid is an adjunct to diet and statinsStatinsStatins 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
↑ TransaminasesTransaminasesA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Autoimmune Hepatitis
Muscle spasmsSpasmsAn involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle.Ion Channel Myopathy
Back and extremity painPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
AnemiaAnemiaAnemia 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 and Types
HyperuricemiaHyperuricemiaExcessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women.Gout (due to inhibition of renal organic anion transporter (OAT) 2 → risk of goutGoutGout 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)
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
Bempedoic acid is not recommended during pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care or breastfeedingBreastfeedingBreastfeeding 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
Inhibits OAT1B1 and OAT1B3, leading to ↑ levels of:
EstradiolEstradiolThe 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.Noncontraceptive Estrogen and Progestins
PravastatinPravastatinAn antilipemic fungal metabolite isolated from cultures of nocardia autotrophica. It acts as a competitive inhibitor of hmg CoA reductase.Statins and simvastatinSimvastatinA derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase, which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic ldl receptors, it increases breakdown of ldl cholesterol.Statins
FluoroquinolonesFluoroquinolonesFluoroquinolones 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 B3Vitamin B3A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties.Water-soluble Vitamins and their Deficiencies or nicotinic acid.
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Mechanism of action:
Converted to nicotinamide → converted to NADNAD+A coenzyme composed of ribosylnicotinamide 5′-diphosphate coupled to adenosine 5′-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). Pentose Phosphate Pathway+ and NADH
↓ Triglyceride breakdown → ↓ free fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance
↓ Release of free fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance from adipose tissueAdipose tissueAdipose 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: Histology
↓ Delivery to hepatocytesHepatocytesThe main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules.Liver: Anatomy → ↓ triglyceride synthesisSynthesisPolymerase Chain Reaction (PCR)
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.
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PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
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
PellagraPellagraA disease due to deficiency of niacin, a b-complex vitamin, or its precursor tryptophan. It is characterized by scaly dermatitis which is often associated with diarrhea and dementia (the three d’s).Water-soluble Vitamins and their Deficiencies (off-label)
Adverse effects
Cutaneous vasodilationVasodilationThe physiological widening of blood vessels by relaxing the underlying vascular smooth muscle.Pulmonary Hypertension Drugs and flushing (minimize by taking aspirinAspirinThe prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis.Nonsteroidal Antiinflammatory Drugs (NSAIDs) 30 minutes before niacin)
PruritusPruritusAn intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.Atopic Dermatitis (Eczema)
Insulin resistanceInsulin resistanceDiminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis.Diabetes Mellitus and hyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus
HyperuricemiaHyperuricemiaExcessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women.Gout
↑ TransaminasesTransaminasesA subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins.Autoimmune Hepatitis
NauseaNauseaAn unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Antiemetics
Abdominal discomfort
Arrhythmias (rare)
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
Active liverLiverThe 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: Anatomy disease
Active peptic ulcerPeptic ulcerPeptic 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 ↓ fibrinogenFibrinogenPlasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products.Hemostasis)
Drug interactions
EthanolEthanolA clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages.Ethanol Metabolism: may ↑ risk of flushing and hepatotoxicityHepatotoxicityAcetaminophen
Oral antihyperglycemic agents: ↓ efficacy with niacin
BAS: ↓ absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of niacin
StatinsStatinsStatins 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: ↑ risk of myopathyMyopathyDermatomyositis and hepatotoxicityHepatotoxicityAcetaminophen
Omega-3 Fatty Acids
Omega-3 fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance are also known as fishFISHA type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.Chromosome Testing oils.
PharmacodynamicsPharmacodynamicsPharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.”Pharmacokinetics and Pharmacodynamics
Mechanism of action:
Omega-3 fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance are triglyceridesTriglyceridesFatty Acids and Lipids → broken down to fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance:
Docosahexaenoic acid (DHA)
Eicosapentaenoic acidEicosapentaenoic acidImportant polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.Fatty Acids and Lipids (EPA)
PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
Formulation: oral
Metabolism: oxidized to fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance in the liverLiverThe 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: Anatomy
Indications
Omega-3 fatty acidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance may be used in the management of hypertriglyceridemiaHypertriglyceridemiaA condition of elevated levels of triglycerides in the blood.Lipid Disorders:
DysgeusiaDysgeusiaA condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality.Nitroimidazoles
AnaphylaxisAnaphylaxisAn acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death.Type I Hypersensitivity Reaction
↑ LDL
Drug interactions
Increased risk of bleeding may occur with:
AnticoagulantsAnticoagulantsAnticoagulants 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
AntiplateletsAntiplateletsDrugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.Heart Failure and Angina Medication
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.
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