14 hypercholesterol& Dyslipidemia Flashcards
Many clinical trials demonstrate that increase of LDL levels induce formation of what?
Atherosclerosis plaques
What are the lipid lowering drugs?
Statins
Nicotinic Acid (Niacin)
Resins
Fibric Acid derivatives
Inhibitors of cholesterol absorption
PCSK9 Inhibitors
What are the 6 statins that are FDA approved?
Lovastatin
Simvastatin
Pravastatin
Atorvastatin
Rosuvastatin
Fuvastatin
Effects on LDL-C, HDL-C, triglycerides are dose related, meaning?
Dose should be set to achieve target LDL-C levels
What is Statin MOA?
Competitive inhibitors of HMG-CoA reductase
- > prevents mevalonte synthesis
- > dec in endogenous cholesterol synthesis by liver
- > up regulation of LDL receptors in liver
- > reduction in blood LDL levels
What is HMG-CoA?
Precursor for cholesterol synthesis
Integral ptn. of ER membranes
What is the major adverse effect of statin?
Myopathies
What is myopathy?
Intense myalgia
Serum creatinine levels elevated 10x
When taking a Statin, what drugs greatly increase myopathic symptoms?
Use with other lipid lowering drugs (fibrates)
= Gemfibrozil
drugs that inhibit P450 isoenzymes
Avoid administering statins with what drugs?
Fibrates
Antibiotics
Antifungals
HIV protease inhibitors
What are statin contraindications?
Active liver disease
Grapefruit juice
Pregnancy
What happens when a statin is taken with oral contraceptives, such as estrogens? What about progestins?
Estrogens:
Inc HDL
Dec LDL
Progestins:
opposite
What statin can be given to children 8 and older? 11 and older?
8: prova
11: atora, lova
What does Niacin refer to?
Nicotinic acid
&
Nicotinamide (B3)
What does a deficiency in vit B3 cause?
(along with def in tryptophan)
pellagra
What is considered the best agent to increase HDL levels?
Nicotinic acid
= Niacin
What does Nicotinic acid do?
Inc HDL
Dec triglyceride
Dec LDL
What are adverse effects of Niacin (nicotinic acid)?
Dyspesia accentuated by coffee, tea, alcohol
Flushing
Pruritus
What drug should you limit for pt with diabetes? Why?
Niacin
Inc uric acid = gout
What are bile-acid sequestrates?
Resins
What is the safest lipid lowering agents?
Resins
What is Bile-acid sequestrates (resins) MOA?
High (+) charged resins bind (-) charged bile acids
Resins are not absorbed & arrest bile acids
deplete cholesterol content
up regulate LDL
Inc triglyceride
What are the 3 bile acid resins drugs?
Cholestyramine
Colestipol
Colesevelam
What are resins drug interactions?
Interfere with absorption of Statins
Give statins 1 hr prior or 3-4 hr after
What is fibric acid derivatives MOA?
Bind to PPAR activated receptors & stimulate beta oxidation of fatty acids
What is the best way to decrease triglyceride levels?
Fibric Acid Derivatives
What drug is given to pt with severe hypertriglyceridemia?
Genfibrozil
What drug is given to pt with high triglycerides & high cholesterol?
Fenofibrate
What are beneficial effects do fibric acids have independent of lipid lowering activity?
Antithrombotic
Immunomodluation
Antiinflammatory
What drug does inhibition of dietary cholesterol uptake?
Ezetimibe
What is Ezetimibe MOA?
Blocks NPC1L1, which facilitates cholesterol absorption
What drug is used to prevent the compensatory increase in endogenous cholesterol synthesis when taking Ezetimbe?
Statins
What should not be combined with Ezetimibe? Why?
Bile Acid Sequestrants
They inhibit absorption
What are side effects of Ezetimibe?
Myopathy
Rhabdomyolysis
Myalgia
Hepatitis
Eczema
Fatigue
Headache
What is PCSK9 inhibitors MOA?
dec LDL receptor degradation
inc recirculation of the receptor to the hepatocytes
-> lowers LDL in blood
What drug do PCSK9 inhibitors work with?
Statins that inc LDL receptor expression
