Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
60 Cards in this Set
- Front
- Back
|
What are the three sources of cholesterol for the liver?
|
Cholesterol absorbed in small intestine
De novo synthesis Lipoproteins in blood |
|
|
What is the rate limiting enzyme involved in the synthesis of cholesterol?
|
HMG-CoA reductase
|
|
|
"-statin"
|
HMG-CoA Reductase INHIBITORS
|
|
|
MOA: HMG-CoA Reductase INHIBITORS to lower lipids
|
INHIBIT HMG-CoA Reductase
This is the rate limiting enzyme in cholesterol synthesis, causes an INCREASED NEED for cholesterol from other sources such as LDL in the blood. **Upregulates LDL receptors on the liver** |
|
|
What happens to LDL in the blood when a pt. is using a statin?
|
LDL is cleared from the blood
|
|
|
What effect will statins have on TGs?
|
↓VLDL synthesis
↑ Clearance of IDLs by LDL receptors |
|
|
End result of HMG-CoA Reductase INHIBITORS
LDL? TG? HDL? |
-↓LDL --> LARGE
-↓TG--> MODEST -↑HDL--> MODEST |
|
|
When is the greatest LDL lowering effect seen when dosing statins?
|
Usually seen @ starting dose
|
|
|
When doubling a statin dose, how much more will you reduce a pt's LDL?
|
Doubling a stain dose only decreases LDL by about 6% more
|
|
|
Statins :
Increasing dosage may help lower LDL but increases the chance of what? |
Side effects
|
|
|
What is the major cardioprotective effect of statins?
|
↓ in LDL-C and VLDL-C
|
|
|
What are the only class of drugs to demonstrate clear improvements in overall mortality in primary and secondary prevention?
|
Statins
(HMG-CoA reductase INHIBITORS) |
|
|
Why is simvastatin taken @ night?
|
You aren't usually eating at night so the liver is plugging away and making lipids at this time. Simvastatin blocks this process by inhibiting HMG-CoA reductase
|
|
|
What adverse effects can statins have on skeletal muscle?
|
Myalgia
(muscle pain) ↓ Myopathy (myalgia with CK 10x ↑ than normal) ↓ Rhabdomyolysis (extensive skeletal m. damage with myoglobinuria) ↓ DEATH |
|
|
Why should you avoid use of CYP450 INHIBITORS with statins?
|
CYP450 Inhibitors increase the concentrations of statins
(statins are metabolized by CYP450) |
|
|
Your pt. really likes grapefruit juice with his breakfast. He normally takes his statin right after breakfast. What advice would you give him?
|
DO NOT DRINK GRAPEFRUIT JUICE
It inhibits gut wall CYP450 enzymes which increases statin concentration |
|
|
What 3 drug interactions do you want to avoid with statins and why?
|
INCREASED INCIDENCE OF MYOPATHY
Fibrates --> esp. gemofibtozil Niacin CYP450 Inhibitors -Cyclosporine -Azole antifungals (ketocanazole) -Erythromycin -Grapefruit Juice |
|
|
What are 2 contraindications for statin use?
|
- Active Liver Disease
-Pregnancy and lactation |
|
|
"Cole"
|
Bile Acid Binding Resins
|
|
|
What are the 3 Bile Acid Binding Resins?
|
Cholestyramine
Colestipol Colesevelam |
|
|
What happens to 95% of the bile acids secreted in the intestine?
|
Recycled back to the liver
|
|
|
MOA: Bile Acid Binding Resins
|
Binds bile acids in small intestine and prevents their recycling
|
|
|
Bile Acid Binding Resins exchange what for anionic bile acids?
|
Cl-
|
|
|
What is the end result of using Bile Acid Binding Resins?
|
Upregulation of LDL rec. on liver cell
Increased clearance of LDL from blood |
|
|
What do Bile Acid Binding Resins do to HMG-CoA reductase activity?
|
Increase
|
|
|
Would you combine a Bile Acid Binding Resin with a statin?
|
YES
BARBs and Statins work through different mechanisms to cause MORE UPREGULATION OF LDL RECEPTOR Also, BARBs ↑ HMG-CoA reducatase activity, so a statin will help ↓ that extra activity. |
|
|
What do BABRs do to LDL, TGs, and HDL respectively?
|
Decrease LDL
Increase TG Increase HDL |
|
|
Would cholestyramine be indicated for the tx of HYPERTRIGLYCERIDEMIA?
|
No, it is a BABR that ↑TG
|
|
|
Why should Colestipol be taken BEFORE meals?
|
Colestipol is a BABR
You want it to be in the intestine before eating causes the release of bile acids |
|
|
What can cause impaired absorption of anionic drugs?
|
BABRs
|
|
|
When should you take other durgs in relation to taking cholestyramine?
|
**BABR**
1 hour before or 4 hours after BABR |
|
|
Ezetimibe is what class of drug?
|
Cholesterol Absorption Inhibitor
|
|
|
MOA: Cholesterol Absorption INHIBITORS in Gut
|
Cholesterol absorption is blocked by INHIBITING NPC1L1 PROTEIN (serves as a gate into enterocyte)
|
|
|
What happens to chylomicrons in the gut after tx with Ezetimibe?
|
↓cholesterol content --> ↓chylomicrons
|
|
|
What happens to cholesterol delivery to the liver after a tx with Ezetimibe
|
↓ delivery of cholesterol to liver
|
|
|
After a tx with Ezetemibe, hepatic cholesterol stores are depleted. What does this do to the clearance of cholesterol from blood?
|
**Upregulates LDL Receptor**
More LDL pulled from blood |
|
|
What is the main side effect of Ezetemibe?
|
Upset GI
|
|
|
MOA: Niacin in adipodcytes
|
Niacin binds to GPR109A receptors on adipocytes
↓ ↓CAMP and PKA activity ↓ ↓Hormone Sensitive Lipase (HSL) ↓ ↓TG |
|
|
MOA: Niacin in hepatocytes
|
Niacin inhibits DGAT2 in hepatocytes during VLDL synthesis --> ↓TG synthesis
(↑ApoB degredation d/t low TG) |
|
|
What is the end result of niacin use in the liver?
|
↓TG synthesis leads to less assembly of ApoB containing lipoproteins --> ↓VLDL, LDL
↓TG Synthesis also leads to ↓ Small, dense LDLs and ↑ Large, buoyant LDLs. |
|
|
What's the deal with large, buoyant LDLs?
|
They are less atherogenic than small, dense LDLs
|
|
|
What does Niacin do to ApoB?
|
Niacin increases ApoB degredation by inhibiting TG synthesis
|
|
|
How big of an increase does HDL have after a pt. is tx'ed with Niacin?
|
Large increase in HDL (15-35%)
|
|
|
What does combining Niacin with statins do?
|
You would have a larger reduction in TGs
↓↓LDL, ↑↑HDL |
|
|
What would happen if you combined niacin with cholestyramine?
|
↓↓LDL
↓↓TG ↑↑HDL |
|
|
How does niacin cause flushing?
|
Niacin ACTIVATES GPR109A in Langerhans cells --> ERK --> ↑PGD2 -->Vasodilation--> Flushing
|
|
|
What's up with flush-free niacin?
|
It contains inositol hexanicotinate instead of nicotinic acid
IT DOES NOT DECREASE Flushing |
|
|
Which type of niacin causes the least amount of flushing?
|
Sustained Release
|
|
|
Why might niacin give abnormal liver fxn tests?
|
It causes ↑ transaminase activity
|
|
|
Which type of niacin is more likely to cause hepatotoxicity?
|
Sustained release
|
|
|
Why is niacin more likely to cause hyperglycemia in type II diabetics?
|
• ↑ fasting glucose
• ↑ insulin resistance |
|
|
What does niacin do to uric acid?
|
Niacin inhibits tubular secretion of uric acid --> hyperuricemia --> GOUT
|
|
|
What are the contraindications for niacin?
|
-Chronic Liver Disease
- Active Peptic ulcer - Gout - High doses with Type II Diabetes |
|
|
Fibric Acid Derivatives? Gimme it
|
Gemfibrozil
Fenofibrate Fenofibric Acid |
|
|
"-fibr-
|
Fibric Acid Derivatives
|
|
|
MOA: Fibric Acid Derivatives
|
Activates PPAR-α receptor
↓ Increase extrahepatic lipoprotein lipase activity ↓ Increase VLDL catabolism/clearance ↓ Less small, dense LDLs, and MORE large, buoyant LDLs |
|
|
End result after using fibric acid derivatives?
|
Decrease TG (20-50%)
Increase HDL (10-35%) Variable change in LDL |
|
|
Explain the variable change in LDL levels with the use of Fibric Acid Derivatives
|
-↓ 5-20% in nonhyperTG patients
-may INCREASE in hyperTG patients |
|
|
How could Fibric Acid Derivatives cause cholelithiasis?
|
Increases the saturation of cholesterol in bile.
|
|
|
What drug when used with Fibric acid derivatives could cause myopathy and rhabdomyolysis?
|
Statins
|
