Hyperlipidemia Flashcards
Lipids are derived from dietary sources or synthesized in the body using ________ and _________.
Cholesterol
Triglycerides
What is cholesterol made?
liver
Lipids are transported to the sites of use or storage via __________ .
Lipoproteins - VLDL, IDL, LDL, HDL, chylomicrons
Where does LDL accumulate? what does this lead to?
subendothelial space of arteries
foam cells > fatty streaks/fibrous caps > thrombus
What is the drug class of the statins?
HMG-CoA Reductase Inhibitors
What is the most effective drug class for decreasing LDL cholesterol?
Statins
What is the mainstay of lipid-modifying therapy?
Statins
T or F. Statins decrease LDL and TG, increasing HDL.
T
What is the difference between the dose-related effects of statins on HDL and LDL.
Reduction in LDL are dose-dependent.
HDL effects are not dose dependent
What is the MOA of statins?
Reduce hepatic cholesterol synthesis by inhibiting HMG Reductase, an enzyme that catalyses the rate-limiting step in cholesterol synthesis
In addition to LDL/triglycerides, Statins also have the ability to decrease __________.
CRP - thereby decreasing inflammation
T or F. Statins are somewhat anti-inflammatory.
T - they inhibit CRP.
What is the middle man between HMG Co A and Cholesterol?
Mevalonate
Older statins are generally dosed ________. Newer statins can be dosed ________.
In the evening or at bedtime because most of the cholesterol is made at bedtime
Newer statins - amytime
Majority of statins (at least the older ones) undergo _________ metabolism via _____.
Hepatic metabolism via CYP450
T or F. In general, statins are extremely well tolerated.
Well
What are the most frequent effects of statins? other rarer effects? Serious ones?
- Gi complaints- dyspepsia, heart burn, abdominal pain
- Dose dependent AST/ALT elevations
- Myalgia
- Myositis and rhabdo are serious possible effects
How do you monitor statins?
When do you D/C a statin?
- CK at baseline - D/C if CK = >10x NUL
- LFTs 6-12 weeks after initiation - D/C if >3x NUL
- Baseline lipid panels at 6 weeks and every 4-6 months after
Maximal statin effects of given dose usually achieved within____ weeks.
6
What are the contraindications for statins?
- Active or chronic liver disease
- pregnancy category X
Newer statins are more “_______ lipid”.
Pan
Atorvastatin (Lipitor) is ___.
New
fluvastatin (Lescol, Lescol XL)
old
Lovastatin (Altoprev®, Mevacor®) ) is _____.
old - first statin
Pitavastatin (Livalo) is ____.
new
Pravastatin (Pravachol) is _____. How is it different from the other statins?
old
It does not undergo CYP450 metabolism and it is hydrophilic (renally eliminated)
What statin is preferred for patients with hepatic dysfunction or are on CP450 inhibitors?
Pravastatin
Pravastatin should be dose adjusted for those with ______ dysfunction.
Renal
Rosuvastatin (Crestor) is _____.
New
Simvastatin (Zocor) is _____.
old
Newer/older agents are typically more potent.
Newer
What 2 things can patients do to increase HDL?
exercise and red wine
What is the second most effective class of drugs for lowering LDL and can be added to statins?
Bile Acid Sequestrations (BAS)
T or F. BAS lower LDL cholesterol and triglycerides, and increase HDL.
F - they INCREASE triglycerides.
What two things do not like triglycerides?
pancreas and CV system
How do the BAS agents work?
Bind bile acids in intestine > interrupt enterohepatic circulation of bile acids > Increase fecal excretion of bile acids > depletes cholesterol content of liver cells > inrease LDL receptor expression (because LDL is used to make bile acid) >increase removal of LDL from the blood stream
What is the AE expected with BAS agents?
GI - constipation, abdominal complaints, taste is yucky
Which hyperlipidemia drug comes in powder form?
BAS agents
A patient with already high (>400 mg/dL) triglycerides should not be prescribed ______ as monotherapy.
BAS
Caution should be used in patients with triglycerides >_____ when considering BAS agents
> 300 mg/dL
What is another con for BAS other than that they increase triglycerides?
they’re sticky!
many drug interactions.
Patients on warfarin and levothyroxine may experience subtherapeutic levels from decreased absorption.
What is the least sticky BAS agent?
Colesevelam (WelChos)
What are the two stickiest BAS agents? What is their contraindication?
Colestipol and Cholestyramine
Bowel obstruction
What is the oldest known lipid agent still in use?
Nicotinic acid (Niacin)
What is the only known agent to reduce levels of lipoprotein A?
Niacin
T or F. Niacin lowers LDL and triglycerides, but cannot raise HDL.
F - can also raise HDL
T or F. Niacin is available as an extended release (Niacor) and single dose each morning.
F - Niaspan, bedtime
What is the less serious AE of niacin? How can you reduce this?
Flushing of the face and trunk
May be reduced by giving it during/after meals, avoiding hot showers and hot liquids at least 30 mins before each dose, take ASA 325 mg 30 min before morning dose (ASA reduces PGs)
What are the 2 serious AEs of niacin?
Hyperglycemia and hepatotoxicity are severe effects that can occur typically at doses >2 gm/day.
Use niacin with caution in patients with what conditions?
Do NOT use with…
Type 2 or prediabetes, peptic ulcer disease, or gout
NOT - chronic liver disease
What drug class can be used as monotherapy or combo therapy to decrease triglycerides?
Fibric Acid Derivatives (Fibrates)
What are the AEs of fibrates?
- GI complaints
- Risk of myositis and rhabdo if used with statins
Which fibrate has a lower incidence of drug interactions with statins?
Fenofibrate
G is dosed _____ and F is dosed ______.
BID
daily
Patients with severe renal impairment should not take ______ to lower triglycerides.
Gemfibrozil.
T or F. Cholesterol Absorption Inhibitors work well as monotherapy.
F- only add ons
Ezetimibe falls under what drug category and primarily has what affect?
CAI Lowers LDL (primarily) and T, increase H
Those on Ezetimibe may not be able to get thru the day with doing what? Why?
pooping themselves
these drugs block the absorption of triglycerides and they end up in your poop
Omega-3 Acid Ethyl Esters is another name for what?
Fish Oil (Lovaza)
When do you use Lovaza? Benefit?
Adjunct to reduce very high TG levels (>500 mg/dl) in adult patients).
Unknown mechanism for cardiovascular benefit
Why is Lovaza difficult to tolerate?
Taste perversion, belching, flatulence, regurgitation, loose stools, body odor.
Can try to freeze the drugs to avoid them.
Use Lovaza with caution in patients with…
- Fish allergy
- on anticoagulants - can prolong BT
Which 3 drug classes are the best for decreasing triglycerides?
- Fibrates
- Niacin
- Fish oil
Which drug class is the best at raising HDL?
Niacin
-Fibrate is second
Which drug class can increase LDL?
Fish oil
Alirocumab (Praluent) is a _______ and works by ________.
PCSK9 inhibitor (Ab) – preserve # of LDL receptors on the liver PCSK 9 – decreases # of receptors
Alirocumab is used as _____.
- Adjunct to diet and maximally tolerated statin therapy and still aren’t seeing drops
- have familial hypercholesterolemia
How is Alirocumab administered? maintained?
self-administered SQ once q 2 weeks
refrigerated, then warmed to room temp
What is the second-in-class agent of the PCSK9 inhibitors? How is it different?
Evolocumab (Repatha) - can be given every month, but is very expensive
