Lipid-lowering medications: Fibrates

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Lipid-lowering medications: Fibrates

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Anemia: Clinical
Microcytic anemia: Pathology review
Non-hemolytic normocytic anemia: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Extrinsic hemolytic normocytic anemia: Pathology review
Macrocytic anemia: Pathology review
Leukemia: Clinical
Lymphoma: Clinical
Thrombocytopenia: Clinical
Bleeding disorders: Clinical
Thrombophilia: Clinical
Myeloproliferative neoplasms: Clinical
Plasma cell disorders: Clinical
Blood products and transfusion: Clinical
Anticoagulants: Heparin
Anticoagulants: Warfarin
Anticoagulants: Direct factor inhibitors
Antiplatelet medications
Thrombolytics
Hematopoietic medications
Ribonucleotide reductase inhibitors
Topoisomerase inhibitors
Platinum containing medications
Anti-tumor antibiotics
Microtubule inhibitors
DNA alkylating medications
Endocrine system anatomy and physiology
Risk factors for periodontitis
Anatomy of the thyroid and parathyroid glands
Diabetes mellitus: Clinical
Hyperthyroidism: Clinical
Hypothyroidism and thyroiditis: Clinical
Parathyroid conditions and calcium imbalance: Clinical
Thyroid nodules and thyroid cancer: Clinical
Pituitary adenomas and pituitary hyperfunction: Clinical
Hypopituitarism: Clinical
Cushing syndrome: Clinical
Adrenal masses and tumors: Clinical
MEN syndromes: Clinical
Hyperthyroidism medications
Hypothyroidism medications
Insulins
Hypoglycemics: Insulin secretagogues
Miscellaneous hypoglycemics
Adrenal hormone synthesis inhibitors
Mineralocorticoids and mineralocorticoid antagonists
Glucocorticoids
HIV (AIDS)
Human herpesvirus 8 (Kaposi sarcoma)
Chronic kidney disease: Clinical
Chronic obstructive pulmonary disease (COPD): Clinical
Obstructive lung diseases: Pathology review
Inflammatory bowel disease: Clinical
Supraventricular arrhythmias: Pathology review
Ventricular arrhythmias: Pathology review
Heart blocks: Pathology review
Coronary artery disease: Clinical
Heart failure: Clinical
Syncope: Clinical
Pericardial disease: Clinical
Infective endocarditis: Clinical
Valvular heart disease: Clinical
Cardiomyopathies: Clinical
Hypertension: Clinical
Hypercholesterolemia: Clinical
Sympatholytics: Alpha-2 agonists
Adrenergic antagonists: Presynaptic
Adrenergic antagonists: Alpha blockers
Adrenergic antagonists: Beta blockers
ACE inhibitors, ARBs and direct renin inhibitors
Thiazide and thiazide-like diuretics
Calcium channel blockers
cGMP mediated smooth muscle vasodilators
Class I antiarrhythmics: Sodium channel blockers
Class II antiarrhythmics: Beta blockers
Class III antiarrhythmics: Potassium channel blockers
Class IV antiarrhythmics: Calcium channel blockers and others
Lipid-lowering medications: Statins
Lipid-lowering medications: Fibrates
Miscellaneous lipid-lowering medications
Positive inotropic medications
Loop diuretics
Osteogenesis imperfecta
Acyanotic congenital heart defects: Pathology review
Cyanotic congenital heart defects: Pathology review
Cardiomyopathies: Pathology review
Heart failure: Pathology review
Systemic lupus erythematosus (SLE): Clinical
Diabetic retinopathy
Diabetic nephropathy
Congenital adrenal hyperplasia
Primary adrenal insufficiency
Waterhouse-Friderichsen syndrome
Hyperaldosteronism
Adrenal cortical carcinoma
Cushing syndrome
Conn syndrome
Thyroglossal duct cyst
Hyperthyroidism
Graves disease
Thyroid eye disease (NORD)
Toxic multinodular goiter
Thyroid storm
Hypothyroidism
Euthyroid sick syndrome
Hashimoto thyroiditis
Subacute granulomatous thyroiditis
Riedel thyroiditis
Thyroid cancer
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5-alpha-reductase deficiency
Autoimmune polyglandular syndrome type 1 (NORD)
Multiple endocrine neoplasia
Pancreatic neuroendocrine neoplasms
Zollinger-Ellison syndrome
Pheochromocytoma
Neuroblastoma
Opsoclonus myoclonus syndrome (NORD)
Adrenal insufficiency: Pathology review
Adrenal masses: Pathology review
Hyperthyroidism: Pathology review
Hypothyroidism: Pathology review
Thyroid nodules and thyroid cancer: Pathology review
Parathyroid disorders and calcium imbalance: Pathology review
Diabetes mellitus: Pathology review
Cushing syndrome and Cushing disease: Pathology review
Pituitary tumors: Pathology review
Hypopituitarism: Pathology review
Diabetes insipidus and SIADH: Pathology review
Multiple endocrine neoplasia: Pathology review
Immune thrombocytopenia
Mixed platelet and coagulation disorders: Pathology review
Hypertension
Heparin-induced thrombocytopenia
Raynaud phenomenon
Nephritic syndromes: Pathology review
Down syndrome (Trisomy 21)
Rett syndrome
Restrictive lung diseases: Pathology review
Sarcoidosis
Parkinson disease
Cranial nerves
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Chiari malformation
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Syringomyelia
Tethered spinal cord syndrome
Aqueductal stenosis
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Transient ischemic attack
Ischemic stroke
Intracerebral hemorrhage
Epidural hematoma
Subdural hematoma
Subarachnoid hemorrhage
Saccular aneurysm
Arteriovenous malformation
Broca aphasia
Wernicke aphasia
Wernicke-Korsakoff syndrome
Kluver-Bucy syndrome
Concussion and traumatic brain injury
Shaken baby syndrome
Seizures and epilepsy
Febrile seizure
Early infantile epileptic encephalopathy (NORD)
Tension headache
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Migraine
Idiopathic intracranial hypertension
Trigeminal neuralgia
Cavernous sinus thrombosis
Alzheimer disease
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Poliovirus
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Klumpke paralysis
Sciatica
Myasthenia gravis
Lambert-Eaton myasthenic syndrome
Orthostatic hypotension
Horner syndrome
Congenital neurological disorders: Pathology review
Headaches: Pathology review
Seizures: Pathology review
Cerebral vascular disease: Pathology review
Traumatic brain injury: Pathology review
Spinal cord disorders: Pathology review
Dementia: Pathology review
Central nervous system infections: Pathology review
Movement disorders: Pathology review
Neuromuscular junction disorders: Pathology review
Demyelinating disorders: Pathology review
Adult brain tumors: Pathology review
Pediatric brain tumors: Pathology review
Neurocutaneous disorders: Pathology review

Flashcards

Lipid-lowering medications: Fibrates

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USMLE® Step 1 style questions USMLE

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USMLE® Step 2 style questions USMLE

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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?
 
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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)