GI Pharm II

  1. Statins
    • Prototypes: Simvastatin, pravastatin, simvastain, atorvastatin
    • MoA: Competitively inhibit HMG-CoA reductase, decreasing cholesterol synthesis (esp in liver); the SREBP pathway senses the decreased cholesterol and causes hepatocytes to increase HMG-CoA reductase expression and expression of LDL receptors; increased LDL receptors leads to increased internalization of LDL
    • Additional mechanism: stimulate NO production, leading to vasodilation and improving endothelial function
    • Action: Decrease LDL (each doubling dose lowers LDL by 6%)
    • Side effects: Myalgia, rhabdomyolysis, hepatotoxicity
    • Side effects are determined by protein binding and CYP3A4 metabolism
    • Not recommended for: pregnant women, or children (unless they are >7 and have familial hypercholesterolemia) because cholesterol is needed for myelin development
  2. Ezetimibe
    • NPC1L1 inhibitor
    • MoA: competitvely inhibits NPC1L1, the protein responsible for absorption of free (unsterified) cholesterol
    • Action: Decrease LDL and total cholesterol
    • Note: Not very good as monotherapy
    • Big utility: adding ezetimibe to a statin is equivalent to having 3 doublings of the statin alone
  3. Cholestyramine, colestipol
    • Bile acid sequestrants
    • MoA: Positively charged amine resins that bind negatively charged intestinal bile acids and prevent absorption (because amines are too large to be absorbed); bound bile acids are then excreted
    • Unwanted side problem: cholesterol inhibits HMG-CoA reductase, and because you are not reabsorbing cholesterol, there is no inhibition of this enzyme and you get increased cholesterol synthesis (why we want to use a stain with a bile acid sequestrant)
    • Action: Decreases LDL
    • Common SE: Constipation (esp in eldery or in high doses) and intestinal obstruction (in peds)
    • Other SE: abdominal discomfort/pain, bloating, nausea, vomiting, diarrhea, steatorrhea, bleeding from hypoprothrombinemia (caused by vitamin K deficiency from decreased absorption of fat soluble vitamins)
    • Note: These can be used to treat diarrhea in Crohn's patients caused by inability to reabsorb bile acids due to damage to terminal ileum
  4. Niacin
    • aka Vitamin B3
    • MoA: Nicotinic acid binds Gi on adipose tissue to inhibit AC, decreasing values of cAMP, decreasing PKA, and decreasing hormone sensitive lipase (HSL); decreased HSL leads to decreased hydrolysis of TG and decreased FFA efflux, which limits VLDL/TG synthesis in the liver
    • Use: Increasing HDL levels
    • SE: BIG ONE IS FLUSHING; also get dyspepsia, acanthosis nigricans (from hyperglycemia because it induces insulin resistance), hepatotoxicity; not good for pregnancy
  5. Fibrates
    • Prototypes: Gemfibrozil, clofibrate, bezafibrate, fenofibrate
    • MoA: Increase lipoprotein lipase activity (enhances clearance of TG from plasma to muscle, adipose, and liver)
    • Use: To decrease TG!!
    • SE: rash, hives, hair loss, muscle pain, fatigue, headache, impotence, anemia, increased liver transaminase and alk phos, increased myopathy risk with a statin, and increased lithogenicity (cholesterol gallbladder formatoin) of bile
  6. Statins + Bile Acid Sequestrants
    • Must take the statin 1-4 hours before the sequestrant to allow for absorption
    • It is important to prevent HMG-CoA reductase activity because bile acid sequestrants prevent inhibition of this enzyme
    • Statins: Pravastatin, simvastatin, atorvastatin, lovastatin
    • BAS: cholestyramine, colestipol
  7. Statins + NPC1L1 inhibitors
    • Two drugs work synergistically to lead to a large reduction of LDL (adding ezetimibe is equivalent to 3 doublings of statin)
    • Statins: Atorvastatin, simvastatin, lovastatin, pravastatin
    • NPC1L1 inhibitor: Ezetimibe
  8. Statins + Fibrates
    • DO NOT DO
    • Increases the risk of muscle breakdown and kidney damage from rhabdomyolysis because of P450 interaction->fibrates inhibit the enzyme, so statin concentrations increase
  9. Ursodeoxycholic acid (UDCA)
    • MoA: Minor secondary bile acid used to dissolve cholesterol stones
    • Use: treatment of cholesterol stones in gallbladder (doesn't work for pigment stones); improves biliary cirrhosis
  10. Pancreatic enzymes
    • Can be given as enteric-coated for uncoated enzymes; which used depends on the state of the patient
    • Patients who are not in pain should receive enteric coated enzymes because the coating protects the enzyme from gastric contents
    • Patients who are in painshould receive uncoated enzymes: the pain is caused by continual CCK secretion stimulation by monitoring peptide that is not being broken down; uncoated enzymes interrupts the loop of excess CCK secretion and alleviates the pain; must also give an acid suppressor drug with this to prevent degradation
    • In other words: pancreas insufficiency -> decreased trypsin -> increased [monitoring peptide] -> excess CCK -> continuous exocrine secretion -> increased intraductal pressure -> pain
Card Set
GI Pharm II
pharm for second exam