Miscellaneous lipid-lowering medications

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Miscellaneous lipid-lowering medications

Innere Medizin

Innere Medizin

Immunodeficiencies: Clinical
Antihistamines for allergies
Glucocorticoids
Non-corticosteroid immunosuppressants and immunotherapies
Advanced cardiac life support (ACLS): 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
Cholinomimetics: Direct agonists
Cholinomimetics: Indirect agonists (anticholinesterases)
Sympathomimetics: Direct agonists
Muscarinic antagonists
Sympatholytics: Alpha-2 agonists
Adrenergic antagonists: Presynaptic
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
Antiplatelet medications
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
Adrenal insufficiency: Clinical
MEN syndromes: Clinical
Hyperthyroidism medications
Hypothyroidism medications
Insulins
Hypoglycemics: Insulin secretagogues
Miscellaneous hypoglycemics
Adrenal hormone synthesis inhibitors
Mineralocorticoids and mineralocorticoid antagonists
Esophageal disorders: Clinical
Esophagitis: Clinical
Gastroesophageal reflux disease (GERD): Clinical
Peptic ulcers and stomach cancer: Clinical
Gastroparesis: Clinical
Diarrhea: Clinical
Malabsorption: Clinical
Inflammatory bowel disease: Clinical
Colorectal cancer: Clinical
Diverticular disease: Clinical
Anal conditions: Clinical
Gastrointestinal bleeding: Clinical
Gallbladder disorders: Clinical
Pancreatitis: Clinical
Jaundice: Clinical
Viral hepatitis: Clinical
Cirrhosis: Clinical
Laxatives and cathartics
Antidiarrheals
Acid reducing medications
Fever of unknown origin: Clinical
Fat-soluble vitamin deficiency and toxicity: Pathology review
Water-soluble vitamin deficiency and toxicity: B1-B7: Pathology review
Zinc deficiency and protein-energy malnutrition: Pathology review
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
Heme synthesis disorders: 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
Thrombolytics
Hematopoietic medications
Ribonucleotide reductase inhibitors
Topoisomerase inhibitors
Platinum containing medications
Anti-tumor antibiotics
Microtubule inhibitors
DNA alkylating medications
Monoclonal antibodies
Antimetabolites for cancer treatment
Pneumonia: Clinical
Tuberculosis: Pathology review
Urinary tract infections: Clinical
Meningitis, encephalitis and brain abscesses: Clinical
Bites and stings: Clinical
Skin and soft tissue infections: Clinical
HIV and AIDS: Pathology review
Protein synthesis inhibitors: Aminoglycosides
Antimetabolites: Sulfonamides and trimethoprim
Antituberculosis medications
Miscellaneous cell wall synthesis inhibitors
Protein synthesis inhibitors: Tetracyclines
Cell wall synthesis inhibitors: Penicillins
Miscellaneous protein synthesis inhibitors
Cell wall synthesis inhibitors: Cephalosporins
DNA synthesis inhibitors: Metronidazole
DNA synthesis inhibitors: Fluoroquinolones
Integrase and entry inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs)
Protease inhibitors
Hepatitis medications
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Neuraminidase inhibitors
Herpesvirus medications
Azoles
Echinocandins
Miscellaneous antifungal medications
Anthelmintic medications
Antimalarials
Anti-mite and louse medications
Hypernatremia: Clinical
Hyponatremia: Clinical
Hyperkalemia: Clinical
Hypokalemia: Clinical
Metabolic and respiratory acidosis: Clinical
Metabolic and respiratory alkalosis: Clinical
Toxidromes: Clinical
Medication overdoses and toxicities: Pathology review
Environmental and chemical toxicities: Pathology review
Acute kidney injury: Clinical
Chronic kidney disease: Clinical
Nephritic and nephrotic syndromes: Clinical
Renal tubular defects: Pathology review
Renal tubular acidosis: Pathology review
Osmotic diuretics
Carbonic anhydrase inhibitors
Potassium sparing diuretics
Asthma: Clinical
Chronic obstructive pulmonary disease (COPD): Clinical
Cystic fibrosis: Clinical
Diffuse parenchymal lung disease: Clinical
Venous thromboembolism: Clinical
Acute respiratory distress syndrome: Clinical
Pleural effusion: Clinical
Pneumothorax: Clinical
Lung cancer: Clinical
Bronchodilators: Beta 2-agonists and muscarinic antagonists
Bronchodilators: Leukotriene antagonists and methylxanthines
Pulmonary corticosteroids and mast cell inhibitors
Joint pain: Clinical
Rheumatoid arthritis: Clinical
Seronegative arthritis: Clinical
Systemic lupus erythematosus (SLE): Clinical
Sjogren syndrome: Clinical
Inflammatory myopathies: Clinical
Vasculitis: Clinical
Acetaminophen (Paracetamol)
Non-steroidal anti-inflammatory drugs
Opioid agonists, mixed agonist-antagonists and partial agonists
Antigout medications
Osteoporosis medications

Transcript

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Lipid-lowering medications work to decrease levels of cholesterol and triglycerides in the body.

Several medications fall outside the more commonly used classes like statins and fibrates, so in this video, we're going to discuss the bile acid resins, niacin or vitamin B3, ezetimibe, and the PCSK9 inhibitors.

Although it’s got a bad reputation, cholesterol is actually a critical component of our cells and is used to build the cell membrane.

It also has other uses like the synthesis of: steroid hormones, vitamin D, and bile.

Normally, we get our cholesterol from the food we eat, but it can also be synthesized by the liver.

So when we eat a box of chili fries, the fats and cholesterol are absorbed in the small intestine.

However, they’re 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 fats 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 adipose tissue and the liver.

Now, the liver can also synthesize intrinsic cholesterol through the mevalonate pathway, which happens in the smooth endoplasmic reticulum of liver cells.

It begins with 2 acetyl-CoA molecules getting joined together by the enzyme acetyl-CoA acyl-transferase. The result is a 4-carbon molecule called acetoacetyl-CoA.

Next, the enzyme HMG-CoA synthase combines acetoacetyl-CoA and acetyl-CoA to form a 6-carbon molecule called 3-hydroxy-3-methylglutaryl CoA, or HMG-CoA.

Then, an enzyme called HMG-CoA reductase reduces HMG-CoA into mevalonate. This step with HMG-CoA reductase is the rate-limiting step of cholesterol synthesis.

In other words, the rate of this reaction determines the overall rate of cholesterol synthesis, it’s like the slowest step of an assembly line in a factory.

Mevalonate is the precursor molecule that will eventually become cholesterol.

Okay, in the liver, cholesterol and a lot of triglycerides 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 and carry the energy-rich triglycerides to the rest of the body.

Now, after unloading their triglycerides, the VLDL and the remaining cholesterol become 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 but 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 released 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, the tissues in the body will take in the LDLs, as well as the cholesterol that’s contained in them.

So, if we have too much LDL, we get cholesterol build up in these tissues.

One of the most clinically relevant tissues is the endothelium that lines the blood vessels.

Increased cholesterol here will lead to the formation of fatty deposits called plaques, and these will increase the risk of cardiovascular complications like strokes, myocardial infarctions, and peripheral vascular disease.

Now, our miscellaneous lipid lowering agents act at several points during lipid metabolism.

The first group of medications are the bile acid resins like cholestyramine, colestipol, and colesevelam.

These are large, positivity charged molecules that bind to the negatively charged bile acid in the intestine.

Being stuck to the resin keeps bile acid from being reabsorbed, and they get excreted with the stool.

So, since we are depleting bile acid, the liver will compensate by increasing the production of bile salts, and this uses up a lot of cholesterol.

To get more cholesterol from the rest of the body, the hepatic cells increase the number of LDL receptors on their surface, which facilitates the uptake of cholesterol-rich LDLs, thus further lowering cholesterol levels in the blood.

However, the liver also increases the synthesis of HMG-CoA reductase, which synthesizes more cholesterol.

This means these medications are not as effective as the statins in decreasing LDL cholesterol, since statins increase the LDL receptors and inhibit HMG-CoA. So bile acid resins are usually used together with statins.

Next, the LDL receptors also very slightly increase the uptake of VLDL.

Although these drugs can also cause a very small increase in HDL, their main use is to treat high levels of LDL cholesterol.

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. "Cholestyramine" Can Med Assoc J (1971)
  5. "Cholestyramine treatment of healthy humans rapidly induces transient hypertriglyceridemia when treatment is initiated" American Journal of Physiology-Endocrinology and Metabolism (2017)
  6. "Bile Acid Malabsorption in Chronic Diarrhea: Pathophysiology and Treatment" Canadian Journal of Gastroenterology (2013)
  7. "Statins for children with familial hypercholesterolemia" Cochrane Database of Systematic Reviews (2017)
  8. "Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events" Cochrane Database of Systematic Reviews (2018)
  9. "Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease" New England Journal of Medicine (2017)