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Lipid-lowering medications: Fibrates

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Diagnoses

Anatomy of the coronary circulation
Anatomy clinical correlates: Heart
Coronary artery disease: Pathology review
Anticoagulants: Direct factor inhibitors
Anticoagulants: Heparin
Antiplatelet medications
Thrombolytics
Renal failure: Pathology review
ACE inhibitors, ARBs and direct renin inhibitors
Anatomy of the lungs and tracheobronchial tree
Anatomy clinical correlates: Pleura and lungs
Alveolar surface tension and surfactant
Breathing cycle and regulation
Gas exchange in the lungs, blood and tissues
Pulmonary shunts
Regulation of pulmonary blood flow
Respiratory system anatomy and physiology
Ventilation
Ventilation-perfusion ratios and V/Q mismatch
Zones of pulmonary blood flow
Obstructive lung diseases: Pathology review
Anatomy of the abdominal viscera: Liver, biliary ducts and gallbladder
Anatomy clinical correlates: Other abdominal organs
Bile secretion and enterohepatic circulation
Liver anatomy and physiology
Cirrhosis: Pathology review
Anatomy of the heart
Anatomy of the coronary circulation
Anatomy of the inferior mediastinum
Anatomy of the superior mediastinum
Anatomy clinical correlates: Heart
Anatomy clinical correlates: Mediastinum
Cardiac afterload
Cardiac contractility
Cardiac cycle
Cardiac preload
Cardiac work
Cardiovascular system anatomy and physiology
Changes in pressure-volume loops
Frank-Starling relationship
Measuring cardiac output (Fick principle)
Microcirculation and Starling forces
Pressure-volume loops
Stroke volume, ejection fraction, and cardiac output
Heart failure: Pathology review
Anatomy of the coronary circulation
Anatomy clinical correlates: Heart
Cardiovascular system anatomy and physiology
Atherosclerosis and arteriosclerosis: Pathology review
Coronary artery disease: Pathology review
Anatomy of the cerebral cortex
Anatomy of the limbic system
Anatomy clinical correlates: Cerebral hemispheres
Dementia: Pathology review
Mood disorders: Pathology review
Selective serotonin reuptake inhibitors
Serotonin and norepinephrine reuptake inhibitors
Tricyclic antidepressants
Monoamine oxidase inhibitors
Atypical antidepressants
Pancreas histology
Diabetes mellitus: Pathology review
Dyslipidemias: Pathology review
Lipid-lowering medications: Fibrates
Lipid-lowering medications: Statins
Miscellaneous lipid-lowering medications
Enteric nervous system
Esophageal motility
Gastrointestinal system anatomy and physiology
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Hypertension: Pathology review
ACE inhibitors, ARBs and direct renin inhibitors
Adrenergic antagonists: Beta blockers
Calcium channel blockers
Thiazide and thiazide-like diuretics
Anatomy of the thyroid and parathyroid glands
Thyroid and parathyroid gland histology
Endocrine system anatomy and physiology
Thyroid hormones
Hyperthyroidism: Pathology review
Anatomy of the thyroid and parathyroid glands
Thyroid and parathyroid gland histology
Endocrine system anatomy and physiology
Thyroid hormones
Hypothyroidism: Pathology review
Introduction to the skeletal system
Bone remodeling and repair
Bone disorders: Pathology review
Anatomy of the abdominal viscera: Pancreas and spleen
Anatomy clinical correlates: Other abdominal organs
Pancreas histology
Pancreatic secretion
Pancreatitis: Pathology review
Anatomy of the diaphragm
Anatomy of the larynx and trachea
Anatomy of the lungs and tracheobronchial tree
Anatomy of the nose and paranasal sinuses
Anatomy of the pleura
Bones and joints of the thoracic wall
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Vessels and nerves of the thoracic wall
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
Alveolar surface tension and surfactant
Anatomic and physiologic dead space
Breathing cycle and regulation
Gas exchange in the lungs, blood and tissues
Lung volumes and capacities
Pulmonary shunts
Regulation of pulmonary blood flow
Respiratory system anatomy and physiology
Ventilation
Ventilation-perfusion ratios and V/Q mismatch
Zones of pulmonary blood flow
Pneumonia: Pathology review
Drug misuse, intoxication and withdrawal: Alcohol: Pathology review
Drug misuse, intoxication and withdrawal: Hallucinogens: Pathology review
Drug misuse, intoxication and withdrawal: Other depressants: Pathology review
Drug misuse, intoxication and withdrawal: Stimulants: Pathology review
Atypical antidepressants
Nasal, oral and pharyngeal diseases: Pathology review
Anatomy of the abdominal viscera: Kidneys, ureters and suprarenal glands
Anatomy of the female urogenital triangle
Anatomy of the male urogenital triangle
Anatomy of the perineum
Anatomy of the urinary organs of the pelvis
Anatomy clinical correlates: Female pelvis and perineum
Anatomy clinical correlates: Male pelvis and perineum
Renal system anatomy and physiology
Urinary tract infections: Pathology review
Anatomy of the lungs and tracheobronchial tree
Fascia, vessels and nerves of the upper limb
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Clot retraction and fibrinolysis
Coagulation (secondary hemostasis)
Platelet plug formation (primary hemostasis)
Deep vein thrombosis and pulmonary embolism: Pathology review
Anticoagulants: Direct factor inhibitors
Anticoagulants: Heparin
Anticoagulants: Warfarin

Clinical conditions

Abdominal quadrants, regions and planes
Anatomy of the abdominal viscera: Blood supply of the foregut, midgut and hindgut
Anatomy of the abdominal viscera: Esophagus and stomach
Anatomy of the abdominal viscera: Innervation of the abdominal viscera
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Liver, biliary ducts and gallbladder
Anatomy of the abdominal viscera: Pancreas and spleen
Anatomy of the abdominal viscera: Small intestine
Anatomy of the anterolateral abdominal wall
Anatomy of the diaphragm
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Appendicitis: Pathology review
Diverticular disease: Pathology review
Gallbladder disorders: Pathology review
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Acid-base map and compensatory mechanisms
Buffering and Henderson-Hasselbalch equation
Physiologic pH and buffers
The role of the kidney in acid-base balance
Acid-base disturbances: Pathology review
Anatomy of the abdominal viscera: Kidneys, ureters and suprarenal glands
Kidney histology
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Anatomy of the basal ganglia
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Anatomy clinical correlates: Posterior blood supply to the brain
Nervous system anatomy and physiology
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Drug misuse, intoxication and withdrawal: Alcohol: Pathology review
Drug misuse, intoxication and withdrawal: Hallucinogens: Pathology review
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Drug misuse, intoxication and withdrawal: Stimulants: Pathology review
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Introduction to the central and peripheral nervous systems
Introduction to the muscular system
Introduction to the skeletal system
Introduction to the somatic and autonomic nervous systems
Anatomy of the ascending spinal cord pathways
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Anatomy of the muscles and nerves of the posterior abdominal wall
Anatomy of the vertebral canal
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Anatomy of the breast
Anatomy of the coronary circulation
Anatomy of the heart
Anatomy of the inferior mediastinum
Anatomy of the lungs and tracheobronchial tree
Anatomy of the pleura
Anatomy of the superior mediastinum
Bones and joints of the thoracic wall
Muscles of the thoracic wall
Vessels and nerves of the thoracic wall
Anatomy clinical correlates: Breast
Anatomy clinical correlates: Heart
Anatomy clinical correlates: Mediastinum
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
Cardiovascular system anatomy and physiology
Respiratory system anatomy and physiology
Aortic dissections and aneurysms: Pathology review
Coronary artery disease: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Pleural effusion, pneumothorax, hemothorax and atelectasis: Pathology review
Anatomy of the abdominal viscera: Esophagus and stomach
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Small intestine
Anatomy of the gastrointestinal organs of the pelvis and perineum
Gastrointestinal system anatomy and physiology
Enteric nervous system
Colorectal polyps and cancer: Pathology review
Diverticular disease: Pathology review
Laxatives and cathartics
Anatomy of the diaphragm
Anatomy of the larynx and trachea
Anatomy of the lungs and tracheobronchial tree
Anatomy of the nose and paranasal sinuses
Anatomy of the pleura
Bones and joints of the thoracic wall
Muscles of the thoracic wall
Vessels and nerves of the thoracic wall
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Lung cancer and mesothelioma: Pathology review
Nasal, oral and pharyngeal diseases: Pathology review
Obstructive lung diseases: Pathology review
Pneumonia: Pathology review
Restrictive lung diseases: Pathology review
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Small intestine
Anatomy of the gastrointestinal organs of the pelvis and perineum
Bile secretion and enterohepatic circulation
Enteric nervous system
Gastrointestinal system anatomy and physiology
Inflammatory bowel disease: Pathology review
Malabsorption syndromes: Pathology review
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Staphylococcus aureus
Vibrio cholerae (Cholera)
Yersinia enterocolitica
Anatomy of the heart
Anatomy of the lungs and tracheobronchial tree
Anatomy of the pleura
Anatomy clinical correlates: Heart
Anatomy clinical correlates: Mediastinum
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
Alveolar surface tension and surfactant
Anatomic and physiologic dead space
Breathing cycle and regulation
Diffusion-limited and perfusion-limited gas exchange
Gas exchange in the lungs, blood and tissues
Pulmonary shunts
Regulation of pulmonary blood flow
Respiratory system anatomy and physiology
Ventilation
Ventilation-perfusion ratios and V/Q mismatch
Zones of pulmonary blood flow
Cardiac afterload
Cardiac contractility
Cardiac cycle
Cardiac preload
Cardiac work
Frank-Starling relationship
Measuring cardiac output (Fick principle)
Pressure-volume loops
Stroke volume, ejection fraction, and cardiac output
Acid-base map and compensatory mechanisms
Buffering and Henderson-Hasselbalch equation
Physiologic pH and buffers
The role of the kidney in acid-base balance
Apnea, hypoventilation and pulmonary hypertension: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
Heart failure: Pathology review
Lung cancer and mesothelioma: Pathology review
Obstructive lung diseases: Pathology review
Pleural effusion, pneumothorax, hemothorax and atelectasis: Pathology review
Pneumonia: Pathology review
Restrictive lung diseases: Pathology review
Tuberculosis: Pathology review
Introduction to the cardiovascular system
Introduction to the lymphatic system
Microcirculation and Starling forces
Cirrhosis: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
Heart failure: Pathology review
Hypothyroidism: Pathology review
Nephrotic syndromes: Pathology review
Renal failure: Pathology review
Antidiuretic hormone
Phosphate, calcium and magnesium homeostasis
Potassium homeostasis
Renin-angiotensin-aldosterone system
Sodium homeostasis
Diabetes insipidus and SIADH: Pathology review
Electrolyte disturbances: Pathology review
Parathyroid disorders and calcium imbalance: Pathology review
Anxiety disorders, phobias and stress-related disorders: Pathology Review
Apnea, hypoventilation and pulmonary hypertension: Pathology review
Mood disorders: Pathology review
Psychological sleep disorders: Pathology review
Adrenergic antagonists: Beta blockers
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Opioid agonists, mixed agonist-antagonists and partial agonists
Tricyclic antidepressants
Cytokines
Inflammation
Anatomy of the abdominal viscera: Blood supply of the foregut, midgut and hindgut
Anatomy of the abdominal viscera: Esophagus and stomach
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Small intestine
Anatomy of the gastrointestinal organs of the pelvis and perineum
Anatomy of the vessels of the posterior abdominal wall
Anatomy clinical correlates: Viscera of the gastrointestinal tract
Gastrointestinal bleeding: Pathology review
Anatomy of the blood supply to the brain
Anatomy of the cranial base
Anatomy of the cranial meninges and dural venous sinuses
Anatomy of the nose and paranasal sinuses
Anatomy of the suboccipital region
Anatomy of the temporomandibular joint and muscles of mastication
Anatomy of the trigeminal nerve (CN V)
Bones of the cranium
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Anatomy clinical correlates: Temporal regions, oral cavity and nose
Anatomy clinical correlates: Trigeminal nerve (CN V)
Anatomy clinical correlates: Vessels, nerves and lymphatics of the neck
Headaches: Pathology review
Anatomy of the abdominal viscera: Liver, biliary ducts and gallbladder
Anatomy of the abdominal viscera: Pancreas and spleen
Anatomy clinical correlates: Other abdominal organs
Gallbladder histology
Liver histology
Bile secretion and enterohepatic circulation
Liver anatomy and physiology
Pancreatic secretion
Jaundice: Pathology review
Anatomy of the elbow joint
Anatomy of the glenohumeral joint
Anatomy of the hip joint
Anatomy of the knee joint
Anatomy of the radioulnar joints
Anatomy of the sternoclavicular and acromioclavicular joints
Anatomy of the tibiofibular joints
Joints of the ankle and foot
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Anatomy clinical correlates: Leg and ankle
Anatomy clinical correlates: Wrist and hand
Gout and pseudogout: Pathology review
Rheumatoid arthritis and osteoarthritis: Pathology review
Seronegative and septic arthritis: Pathology review
Anatomy of the knee joint
Anatomy clinical correlates: Knee
Rheumatoid arthritis and osteoarthritis: Pathology review
Seronegative and septic arthritis: Pathology review
Candida
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Enterobacter
Enterococcus
Escherichia coli
Proteus mirabilis
Pseudomonas aeruginosa
Staphylococcus aureus
Bacterial and viral skin infections: Pathology review
Skin histology
Skin anatomy and physiology
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Pigmentation skin disorders: Pathology review
Skin cancer: Pathology review
Vesiculobullous and desquamating skin disorders: Pathology review
Anatomy of the heart
Anatomy of the vagus nerve (CN X)
Aortic dissections and aneurysms: Pathology review
Cardiomyopathies: Pathology review
Coronary artery disease: Pathology review
Heart blocks: Pathology review
Supraventricular arrhythmias: Pathology review
Valvular heart disease: Pathology review
Ventricular arrhythmias: Pathology review
Hunger and satiety
Anxiety disorders, phobias and stress-related disorders: Pathology Review
Breast cancer: Pathology review
Colorectal polyps and cancer: Pathology review
Dementia: Pathology review
Diabetes mellitus: Pathology review
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Heart failure: Pathology review
HIV and AIDS: Pathology review
Hyperthyroidism: Pathology review
Inflammatory bowel disease: Pathology review
Jaundice: Pathology review
Lung cancer and mesothelioma: Pathology review
Malabsorption syndromes: Pathology review
Mood disorders: Pathology review
Tuberculosis: Pathology review

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Lipid-lowering medications: Fibrates

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A 41-year-old man presents to the office for a routine follow-up. He is asymptomatic and feels well. Past medical history is significant for type II diabetes mellitus and hypertension. Current medications include metformin, simvastatin, and lisinopril. Family history is significant for myocardial infarction in the patient’s father. He smokes two packs of cigarettes daily and does not use alcohol or illicit drugs. Vitals are within normal limits. Physical examination reveals the findings shown below. Recent laboratory workup revealed an elevated triglyceride level and a normal liver function test. The patient is prescribed gemfibrozil for the management of hypertriglyceridemia. Which of the following is most helpful in monitoring for potential complications of statin and fibrate combination therapy?
 
Image reproduced from Wikimedia Commons

External References

First Aid

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Bezafibrate p. 325

Transcript

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Content Reviewers

Fibrates are a group of lipid-lowering medications, along with statins and niacin.

These medications are very effective at lowering triglyceride levels in the blood, but are less effective at controlling cholesterol.

Now, triglycerides make up most of your body fat, and they consist of a glycerol and 3 fatty acids.

So when we eat a box of chili fries, the fatty acids and cholesterol are absorbed into the cells in the small intestine.

The fatty acids are then converted into triglycerides.

However, triglycerides and cholesterol are not water soluble, so they can’t travel freely in the blood. To fix this, our body makes “shipping boxes” called lipoproteins.

These containers consist of a shell made of phospholipids and protein tags that act as instructions for their destination.

So after absorption, the small intestinal cells package the triglycerides and cholesterol into the largest, but least dense lipoproteins, called chylomicrons.

These are released into the lymphatic system and then enter the bloodstream via the subclavian vein. Then, they travel through the blood to reach the liver and other tissues in the body.

Now in the blood vessels near these tissues, we have an enzyme called lipoprotein lipase, which can break down triglycerides into fatty acids.

Cells in the nearby tissue can then use these fatty acids to generate ATP.

Adipose tissue can synthesize a lot of lipoprotein lipases, which means they have access to a lot of fatty acids.

Now, instead of using the fatty acids for energy, they pick them up, convert them back into triglycerides, and store them for later use.

Okay, so we can also synthesize fatty acids from glucose in the liver which are then converted into triglycerides.

These triglycerides and some cholesterol are packed into the next kind of lipoproteins called very-low-density lipoproteins or VLDL, which are smaller and more dense than chylomicrons.

This package is sent into the bloodstream to carry the energy-rich triglycerides to the rest of the body.

Now, lipoprotein lipases in the blood vessels will once again convert the triglycerides in the VLDLs into fatty acids, which can enter the cells; and the leftover VLDLs are called VLDL remnants.

This and the remaining cholesterol are converted into a new kind of lipoprotein, called a low-density lipoprotein, or LDL, which are even smaller and more dense than VLDL.

These will travel around the bloodstream and deliver cholesterol to cells in the rest of the body.

The final lipoprotein is the HDL, or high-density lipoprotein, which are smaller and denser than LDLs.

These are like the boxes you get when you try to return an item you bought online.

In this case, the liver produces HDL and releases them into the blood, where they pick up excess cholesterol from the peripheral tissues and brings them back to the liver.

So in essence, it’s the opposite of LDL, which carries cholesterol from the liver to the peripheral tissues.

Now, triglycerides are atherogenic which means they can cause atherosclerosis, increasing the risk of cardiovascular complications like strokes and myocardial infarctions.

Extremely high triglyceride levels can also lead to acute pancreatitis.

Okay, so if we want to lower triglyceride levels we can use a class of medications called fibrates.

Sources

  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "PPAR Agonists and Metabolic Syndrome: An Established Role?" International Journal of Molecular Sciences (2018)
  5. "Fibrates for primary prevention of cardiovascular disease events" Cochrane Database of Systematic Reviews (2016)
  6. "PPAR-Induced Fatty Acid Oxidation in T Cells Increases the Number of Tumor-Reactive CD8+ T Cells and Facilitates Anti–PD-1 Therapy" Cancer Immunology Research (2018)
  7. "Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: propensity matched cohort study" BMJ (2019)