18-Drugs for Lipid Disorders Flashcards
3 main types of lipids
- Triglycerides (90% of lipids, source of energy)
- Phospholipids (plasma membrane)
- Steroids (cholesterol)
Why is cholesterol important?
- essential part of the plasma membrane
- building block for bile acids, vitamin D, cortisol, estrogen & testosterone
Which organ synthesizes cholesterol?
the liver (makes all the cholesterol we need)
Lipoproteins (what is it, 3 major types)
Complex of TGs, cholesterol and phospholipids packaged w/ an apoprotein (protein carrier) in order to be soluble in the plasma and be distributed to body tissues. 3 major types = HDL, LDL, VLDL
LDL functions (3)
- transports cholesterol from liver to tissues
- creates plasma membranes & other steroids
- can be stored for later use
Which lipoprotein is the primary carrier of triglycerides?
VLDL
Role of VLDL
reduced/converted to LDL
HDL
- “reverse cholesterol transport” –> brings cholesterol from tissues to liver (liver recycles it)
- the cholesterol is eliminated from the body via bile in the feces
Hyperlipidemia
- high cholesterol/LDL –> increases risk for atherosclerosis/CAD
- associated with genetic alterations in fat metabolism and with excessive dietary intake of fats (genetics can predispose us to having high LDL levels)
Dyslipidemia
- abnormal blood lipid levels, such as high LDL and triglycerides and low HDL. Hyperlipidemia is a type of dyslipidemia
When should you screen for dyslipidemia?
Men + women over the age of 40
What is the max dietary cholesterol that should be consumed?
300 mg/day
How do plant sterols/stanols help decrease cholesterol?
- Sterols and stanols complete with cholesterol for absorption (prevents it from being absorbed)
- Eat foods high in in soluble fiber such as: nuts, olive oil, corn, rye, oats, rice and wheat
What is the target goal for reducing LDL levels?
Reducing LDL by 50% (or less than 2.0 mmol/L)
HMG-CoA reductase
Synthesizes cholesterol from HMG-CoA
Statins
- blocks HMG-CoA reductase –> no cholesterol produced
- less cholesterol produced –> liver increases # of LDL receptors –> more LDL removed from blood
- effects are reversible, may take up to a month to have an effect
What is the first-line therapy for treating lipid disorders?
statins
T or F: Statins should not be combined with other cholesterol lowering or antihypertensive meds.
False, they can be combined.
Contraindications of statins & side effects
- Contraindicated in pregnancy
- Adverse effects: headache, heart burn, GI upset (take with evening meal)
Rhabdomyolysis:
- What is it
- What increases the risk of developing this
- breakdown of muscles
- waste products cause acute renal failure –> severe muscle pain
- risk is increased when taken with drugs that inhibit CYP 450 enzymes (i.e. antibiotics like clarithromycin)
Drug-drug interactions of statins
- avoid alcohol & grapefruit juice
- increases the effects of warfarin (increased risk of bleeding)
- increases estrogen levels in women using COCs
- proton-pump inhibitors and H2RA antagonists increase bioavailability of some statin drugs
Do statins increase risk of T2DM and why?
- statins can increase glucose levels in some patients –> monitor blood glucose
- longer use of statins is associated with new onset T2DM
Ezetimibe (what does it do & side effects)
- Inhibits intestinal cholesterol absorption
- Common SE = GI distress
What drugs can ezetimibe be combined with and what can it not be co-administered with?
- co-administer with statins when patients fail to reach their LDL target with statins alone
- do not co-administer with bile acid resins bc they reduce the efficacy of ezetimibe
Bile acid resins / sequestrants Function
- Binds to bile acids –> prevents recirculation to the liver –> instead, bile acids & cholesterol are excreted in the feces
- prevents less absorption of bile acids
Result: less cholesterol going to the liver
Which drug class can statins be combined with for a higher efficacy?
bile acid resins
Bile acid resins (drug-drug interactions and side effects)
SEs: GI upset (abdominal pain, bloating, diarrhea, steatorrhea, constipation)
Interferes with the absorption of other drugs (Thiazide diuretics, warfarin, thyroid hormones, corticosteroids)
Take other medications 1 hour before, or 4 hours after!
Vitamin deficiency may occur with what drug class?
Bile acid resins, decreases fat-soluble vitamins (A, D, E, K)
PCSK9 inhibitors (action, efficacy, route of administration)
- Inhibit PCSK9 proteins that target liver LDL receptors for degradation
- Monoclonal antibodies (the inhibitors) bind to PCSK9, preventing it from binding to LDL receptors
- lowers LDL levels by 50-70% (greater than statins)
Why is niacin not typically used?
Not routinely used due to toxicity profile; only used if client is at a very high risk for CV events with significant contraindications for statins or bile-acid sequestrants.
Framingham Risk Score
Estimates a client’s 10 year cardiovascular disease risk.
Takes the following into consideration: Age of the client HDL level Total cholesterol level BP Smoking Diabetes
Is LDL good or bad?
bad
Is HDL good or bad?
good
What allows for proteins to move through the body?
apoprotein
After menopause does the risk become high or lower? and Why
becomes higher due to less estrogen resulting in more difficulty to maintain healthy cholesterol levels
Is hypercholesterolemia more prominent in men or women?
men over non menopausal women
What is the issue when one consumes to many fats?
- body cannot control or deal with such high levels
- stored in vasculature
- atheroscelerosis occurs as a result
T/F: moderate alcohol consumption increases HDL levels?
true
Non pharmacological management of lipid disorders include
- eliminate smoking
- moderate alcohol consumption
- weight maintenance
- regular exercise and stress reduction
- reduce dietary fats (trans and saturated)
- increase consumption of sterols and stanols and soluble fibre
Which Cholesterol has the most to least apoprotein?
VLDL- lowest
HDL- most
LDL- middle
Which ethnic groups are at a greater risk?
- south asian or first nations
Function of bile salts
allows for us to digest and get nutrients from fat-soluble foods
How is cholesterol formed
- acetyl CoA
- HGM-COA
- Cholesterol
- Gall Bladder
- bile salts
- get nutrients
- abosorption of lipids into liver
- HGM-COA forms cholesterol
Do statins have a high or low efficacy?
High
Do statins need short or long term therapy in order to have control?
Long term
When administering statins do you want a high or lose does and with combination or no combination
- high does leads to more adverse effects
- therefore we want a LOW dose with combination with other hypertensive medications
What drug is a ezetimibe?
selective cholesterol absorption inhibitor
What are the functions of selective cholesterol absorption inhibitors ?
- inhibit enterophepatic circulation of bile acids
- increase the excretion of cholesterol
- reduce blood cholesterol levels
- reduction in cholesterol levels induces the formation of additional LDL receptors
- reduce risk of major cardiovascular events
Are statins and selective cholesterol absorption inhibitors equally effective
no
- statins > SCAI
How are PCSK9 inhibitors given?
Subc every two weeks or once a month
