Cardio-pharm-Antihyperlipidemics-Lynch Flashcards
(77 cards)
1
Q
What are triglycerides as a dietary lipid?
A
Neutral fat • Energy source • Account for 90% of total lipids in body
2
Q
What is the role of phospholipids as a dietary lipid?
A
Essential to building plasma membranes
3
Q
What is the role of cholesterol as a dietary lipid?
A
Necessary for production of Vitamin D, Bile Acids, Cortisol, Estrogen, Testosterone
• Body makes enough cholesterol, not necessary in the diet
4
Q
What are lipoproteins?
A
Carriers of lipid molecules
5
Q
What do lipoproteins consist of?
A
Consist of cholesterol, triglycerides, and phospholipids with protein carrier
6
Q
What is another name for protein carrier in lipoproteins? And what is its role?
A
Protein carrier is known as apoprotein
- Apoproteins allow the lipoprotein to bind tissue receptors
- Missing or defective in Familial Hypercholesterolemia
7
Q
What are the 3 type of lipoproteins?
A
Low-density lipoprotein (LDL)
- Very low-density lipoprotein (VLDL)
- High-density lipoprotein (HDL)
8
Q
What are VLDLs, where are they formed, and what do they do?
A
- Formed by the liver
- Major carrier of triglycerides in the blood
mainly made up of triaglycerol
• Becomes an LDL as it passes through the body
9
Q
What are LDL’s and what do they do?
A
made up mainly of cholesterol
- LDL transports cholesterol from liver to tissues and organs
- Used to build plasma membranes and synthesize other steroids
- Carries highest amount of cholesterol
- “Bad” cholesterol
- Contributes to plaque deposits and coronary artery disease
10
Q
What are HDLs?
A
- Manufactured in liver and small intestine
- Reverse cholesterol transport • Assists in transport of cholesterol away from body tissues and back to liver
- “Good” cholesterol • Transports cholesterol for destruction and removal from body
Vacuum cleaner
11
Q
What is reverse cholesterol transport of HDLs?
A
Assists in transport of cholesterol away from body tissues and back to liver
12
Q
HDLs mainly consist of which macromolecule?
A
protein
13
Q
Which enzyme reduces HMG CoA to cholesterol?
A
HMG-CoA reductase
14
Q
From what are bile acids made?
A
cholesterol
15
Q
Total cholesterol lab values for high risk, moderate risk, and high risk?
A
<200 Desireable
200-240 Moderate
>240 High risk
16
Q
LDL optimal level?
A
<100
17
Q
HDL desireable level?
A
>60
18
Q
triglycerides desireable level?
A
<149
19
Q
What lifestyle changes can help control hyperlipedemia?
A
- Monitor blood-lipid levels
- Maintain weight; exercise
- Reduce dietary saturated fats and cholesterol
- Increase soluble fiber in diet
20
Q
What are the 7 drug therapies for dyslipidemia?
A
- Inhibitors of HMG-CoA Reductase 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
- PCSK9 Inhibitors
- Bile Acid Sequestrants
- Niacin
- Fibric Acid Agents
- Ezetimibe
- Omega-3 Fatty Acids
21
Q
What are statins?
A
Inhibitors of HMG-CoA Reductase
22
Q
What do statins do in regards to cholesterol?
A
• Interfere with the synthesis of cholesterol
23
Q
What are the first drugs of choice to reduce blood-lipid levels?
A
Statins (Inhibitors of HMG-CoA Reductase)
24
Q
How do statins (Inhibitors of HMG-CoA Reductase) work?
A
Interfere with the synthesis of cholesterol
and
enhances the uptake of LDL by the liver which reduce serum LDL levels
25
How do statins uptake LDL into the liver?
Upregulate expression of LDL receptors which in turn takes up more LDL into the liver
26
Which two are the high-intensity statins?
Atorvastatin and Rosuvastatin
27
Its important to move from intensity statins to intensity statins to ensure that statins will not work with a patient with side effects.
high, low
28
When is the absolute time to stop statins?
elevation in liver enzymes ( as it can cause liver damage)
29
What is another serious ADE of statins other than liver damage?
Myopathy (muscle pain), possibly leading to the serious condition **rhabdomyolysis**
## Footnote
**this can also lead to kidney damage as myoglobin is being released in the blood and damaging kidneys**
30
What are the more mild ADEs associated with statins?
Mild, transient GI disturbances
• Rash, Headache
31
Oral administration of statins has first-pass metabolism. This means that they metabolized most likely by which two CYPs?
extensive, CYP450, 3A4
32
Lovastatin, simvastatin, and atorvastatin are all metabolized in the liver by which liver enzymes?
CYP450, CYP3A4
33
Fluvastatin is metabolized in the liver by which 2 liver enzymes?
CYP450, 2C9
34
Which 3 statins are pro-drugs?
**Lovastatin, Atorvastatin, and Simvastatin** are pro-drugs and are activated after being metabolized by CYP 3A4
35
What should one monitor while using statins?
liver enzymes
36
What is the pregnancy category of statins?
Pregnancy Category **X**
37
Why are the shorter half-life statins given at night (**Lovastatin**)?
**Endogenous cholesterol biosynthesis** occurs mostly at **night,** and is where the **HMG-CoA Reductase is most active.** The short half-life statins can do their best work at this time.
38
Lovastatin, simvastatin, and fluvastatin have a shorter half-life and can be administered at _._
**Night** for the most efficacious effect
39
HMG-CoA Reductase Inhibitors
**• Lipid effects**
* Decrease by 22 – 55 % • Decreased endogenous cholesterol biosynthesis increases the uptake of plasma LDL by the transcription of the LDL receptor gene
* Decrease by 10 – 30% which also decreases production
* Increase HDL by 5 – 15% • Increase the synthesis of apoA-I
LDL; stimulating; triglycerides; VLDL
40
What is the next step if a patient cannot tolerate the least potent statin?
If patient can not tolerate it then move to **bile acid sequestrant ± ezetimibe**
41
what are the 3 gene mutations involving Familial hypercholesterolemia?
1. LDL receptor gene
2. apoB-100 gene
3. PCSK9 gene
42
Which gene mutation on chromosome 1 promotes degradation of LDL receptors on the surface of hepatocytes?
PCSK9 gene
43
What is the result of blocking the chromosome 1 gene mutation PCSK9?
If you block this protein you can **prevent LDL receptors from being broken down** and thus **more LDL cholesterol would be taken up by the liver**
44
What are PCSK9 inhibitors?
monoclonal Abs that bind to PCSK9 that inhibit them from binding to LDL receptor and degradation of that receptor.
45
What are 2 important PCSK9 inhibitors?
Alirocu**mab**, Evolocu**mab**
39-62% reductions in LDL cholesterol!
46
What is the route of administration of PCSK9 inhibitors?
By **injection only.**...but only 1x every 2 weeks
47
What are the 3 main ADEs of PCSK9 inhibitors?
* Nasopharyngitis (11%)
* Injection site reactions (7%)
* Influenza symptoms (5.7%)
48
Bile-acid sequestrants (BAS) are ion-exchange resins and bind in the intestine to prevent recycling by the _._
bile salts; liver
49
How do bile-acid sequestrants, that bind bile salts in the intestine and prevent recycling in the liver, lower cholesterol?
By binding the bile salts, they **cannot be recycled**, and the liver has to sequester more cholesterol to synthesize more bile salts- hence, reducing cholesterol
50
What are the names of the 3 bile acid sequestrants?
3 C's
* Cholestyramine
* Colestipol
* Colesevalam
51
Bile acid sequestrants can **reduce/increase** LDL levels and **reduce/incresse** HDLs?
reduce; increase
52
With what drug can you have a synergistic effect with Bile Acid Sequestrants (BAS) for reducing LDLs?
statins
53
What is the major advantage of BAS concerning absorption?
they are not systemically absorbed, it acts only in the gastrointestinal system
54
What are some ADEs of BAS?
G.I. bloating, constipation, irritation.
• May **raise serum triglycerides!**
may **bind** to other drugs in intestine
55
What acid based drugs do bile acid sequestrants bind to in the intestine?
• Thiazides, Furosemide, Digoxin, Coumarin, levothyroxine, ….etc
(avoid this by taking them **4 hours apart**)
56
Which drug is used mainly to increase HDLs?
Niacin, B3
57
What can niacin, B3, do as a hyperantilipidemic?
• **Primary use is to reduce VLDL’s triglycerides**; i**ncrease HDL levels** • TG Decrease up to 45% • LDL Decrease up to 20% • HDL increase up to 30%
58
Which antihyperlipidemic alters the activity of **lipase enzymes** that metabolize triglycerides and lipids?
Niacin, B3
59
Niacin can decrease apoA-I which in turn increases HDLs and can inhibit lipase which decreases synthesis.
clearance; triglycrides
60
Niacin has several side effects but the most serious is what?
**hepatotoxicity**
also
* Flushing (blocked by aspirin, implication?)
* Pruritus
* GI distress
* Rhabdomyolysis
* Worsens gout –avoid with gout
* Impaired glucose control – avoid with diabetes
61
It is important to monitor liver function, uric acid levels, and blood gluclose levels with someone taking which antihyperlipidemic?
Niacin, B3
62
What effect does niacin have on those with peptic ulcer disease?
It can **worsen** the condition
63
What can relieve the Niacin ADE flushing?
take **aspirin** one hour prior
64
Which antihyperlipidemic works to **activate lipase** (breaking down cholesterol), **suppresses the release of free fatty acids** from adipose tissue, and i**nhibits synthesis of triglycerides** in the liver?
Fibric acid derivatives (fibrates)
65
What are the 2 fibric acid derivatives (fibrates)?
Gemfibrozil, Fenofibrate
66
Fibrartes or fibric acid derivatives activate which receptor?
**PPAR**- peroxisome proliferatior-activated receptor
67
What does PPAR (peroxisome proliferator-activated receptor) accomplish when activated by fibrates?
**increases HDL** and **decreases plasma triglycerides**
68
Fibrates are used mainly to treat high levels of .
triglycerides or **hypertriglyceridemia**
69
Fibrates have some worrisome interactions with which two types of drugs?
1. **Oral anticoagulants**
2. **Statins**- Risk for myositis, myalgias, and rhabdomyolysis is increased
70
What type of effect can fibrates have on Hbg, Hct, and WBC?
It can decrease all of those.
71
What type of effect do fibrates have on clotting time, lactate dehydrogenase level, and bilirubin level?
Increases all of them
72
What are the main 2 ADEs of fibrates?
§ Adverse Effects:
§ **Abdominal discomfort, diarrhea, nausea**
§ Blurred vision, headache
§ **Increased risk of gallstones** (Clofibrate, older drug)
§ Prolonged prothrombin time
§ Liver studies may show increased enzyme levels
73
2 things to consider monitoring while taking fibrates are?
1. Assess for complaints of **GI distress** before starting drug
2. Monitor prothrombin time/international normalized ratio **(PT/INR)** **if taking warfarin** as it may potentiate anticoagulant effects.
74
Which antihyperlipidemia is only recommneded when patients do not respond to statins?
Ezetimibe (Zetia)
75
What is the main use for Ezetimibe?
• Inhibits the absorption of cholesterol from the gut, and cholesterol eventually excreted.
76
EZETIMIBE can be combined with a **statin** called _?_
Vytorin
77
Which other antihyperlipidemic activates the PPARa receptor to decrease plasma triglycerides levels other than fibrates?
Omega-3 fatty acids (fish oils)
## Footnote
**OMACOR**
