Drugs to lower Cholesterol and Triglycerides Flashcards
First line therapy to lower cholesterol and triglycerides
Diet therapy
Resin
Cholestyramine, Colesevelam, Colestipol
Cholestyramine
Resin
Cholesevelam
Resin
Colestipol
Resin
Resin: MoA
Increase fecal excretion of bile acids
Decrease negative feedback by 7 alpha hydroxylase
Increase conversion of hepatic cholesterol to bile acids
Increase # of hepatic LDL receptors (lower LDL-C)
Bile acid negative feedback
7 alpha hydroxylase
Resins remove negative feedback
Resins: contra
Statins
Resin can be used in pregnancy
Resin: ADR
GI issues (bloating, constipation, stomach pain)
Resin: metabolism
Must be staggered with other drugs, especially fat soluble vitamins (ADEK) and acidic anionic drugs
Not absorbed in GI tract or biotransformed by liver
{No alteration with P450 or binding displacement}
Statins (HMG CoA reductase inhibitors)
Atorvastatin, Simvastatin, Lovastatin, Rosuvastatin, Pravastatin, Fluvastatin, Pitavastatin
“-statin”
Statins
Statin: MoA
Reversible competitive inhibitors of cholesterol biosynthesis at liver
(HMG CoA >|| Mevalonate > Cholesterol}
Increase # of hepatic plasma LDL
Lower cholesterol levels
Statins that lower cholesterol and triglycerides
Atorvastin, Rosuvastin
Statin: ADR
Elevate plasma ALT/AST
Increase CPK (creatine phosphokinase)
Myalgia {must withdraw if happens}
(Myalgia less with Fluva and Prava}Statin: contra
Pregnancy
Nursing mother
Acute liver disease {ALT/ AST}
Statins: pediatric use
8 yo: Pravastatin
10 yo: Other statins
Statin: administration and bioavailability
Midnight-2AM (peak cholesterol synthesis)
Higher bioavailability with food: Fluva, Lova, Simva
Lower bioavailability with food: Prava, Pitava {Don’t eat Peas at dinner}
Atovastatin and Rosuvastatin: MoA
Longer half life
Higher increase in LDL receptor
Increase clearance of IDL (ApoE)
Statin: prodrug
Lovastatin, Simvastatin
{Converted by intestinal carboxyesterase and CYP3A4}
Statin: CYP3A4
Atorva, Lova, Simva
Avoid CYP3A4 inhibitors and Grapefruit juice
Statin: CYP2CP
Rosuva, Fluva
Statin: CYP2D6
Simvastatin
Statin: polymorphism
Simvastatin induced muscle pain
Higher with CYP2D6*4 allele (higher half life)
SCLO1B1 SNP lowers hepatic uptake higher plasma levels
Ezetimibe: MoA
Inhibit cholesterol absorption at brush border of small intestine
Inhibit cholesterol absorption at enterocytes
Inhibit NPC1L1 transporter protein
Target dietary cholesterol
Lower LDL-C by 20%
Better with statin than statin*2
Ezetimibe: ADR
Minimal GI side effects, diarrhea after fatty meal
Ezetimibe: contra
Hepatic dysfunction (enterohepatic recirculation)
Resins
Stain increase transaminase levels
PCSK9 inhibitors
Alirocumab, Evolocumab
Proprotein convertase subtilisin kexin 9 inhibitors
Alirocumab
PCSK9 inhibitors
Evolocumab
PCSK9 inhibitors
PCSK9 inhibitors: MoA
More LDL receptor # than statin
Subcutaneous injection per 2-4wk
PCSK9: ADR
Hypersensitivity
Fibrates
Gemfibrozil, Clofibrate, Fenofibrate {-fib-}
Gemfibrozil
Fibrate
Clofibrate
Fibrate
Fenofibrate
Fibrate
Fibrates: MoA
Lower triglycerides
Increase HDL by increasing APO AI and AII
Binds to PPAR alpha & stimulates fatty acid oxidation)
PPAR alpha reduces apoCII expression
Result in increased lipoprotein lipase activity (decrease APO CIII)
PPAR decrease hepatic production of VLDL
ApoCIII function
Inhibit lipoprotein lipase and VLDL ligand clearance
Reduced by Fibrates
Fibrates: ADR
Gallstone risk (Clofibrate only)
Myopathy when combined with Statin
(worse with Gem and Clo) (least with Feno)
{Gembifrozil inhibit OATP2 (Atova, Prava, Rosuvastatins)}
Fibrate: contra
Liver dysfunction
Renal disease
Preexisting gallbladder disease (Clofibrate)
Nicotinic acid: MoA
Decrease production of hepatic VLDL
Inhibit lipolysis, decrease FFA delivery to liver
Inhibit hormone sensitive lipase in adipose tissue
Increase lipoprotein lipase activity (increase VLDL clearance)
Nicotinic acid: use
Lower triglycerides and cholesterol (both)
Nicotinic acid: ADR
Itching and Flushing (alleviated by Aspirin)
{inhibit prostaglandin synthesis causing flushing}
Elevate ALT/ AST (stop if x3 elevated)
Peptic ulcer
Hyperuricemia and glucose intolerance
Nicotinic acid: cautions
Monitor Creatine kinase (CK) when combined with Statin
Can’t interchange dose between immediate/ extended release
Titration over 4wk
Nicotinic acid: contra
Bleeding disorders (peptic ulcer with statin)
Active liver disease
Active peptic ulcer
Familial hyperchylomicronemia
Type I
Elevated Chylomicrons and triglycerides
Defect in Lipoprotein lipase activity or in Apo C-II
Control with diet therapy, Fibrates (Gem), Nicotinic acid
Familial hypercholesterolemia
Type IIa Elevated Cholesterol and LDL Increased CVD risk Decreased LDL clearance Control with Statins, Ezetimibe, Resins
Familial combined hyperlipoproteinemia
Type IIb
Elevated Triglycerides (VLDL) and Cholesterol (LDL)
Control with Statin (Atorva, Lova, Rosuva), Nicotinic acid
Familial dysbetalipoproteinemia
Type III
Elavated Triglycerides, Cholesterol, IDL, Chylomicron remnants
Decreased VLDL catabolism= IDL accumulation
ApoE2
Increased VLDL production
Most sensitive to Fibrates
Familial hypertriglyceridemia
Type IV
Elevated Triglycerides and VLDL
Associated with Hyperuricemia and Glucose intolerance
Control with Fibrates
Uric acid and blood glucose control worse with Nicotinic acid
Secondary cause of cholesterol elevation
Biliary disease, Renal disease, Hypothyroidism, Diabetes mellitus
Secondary cause of Triglycerides elevation
Alcoholism, Renal disease, Diabetes mellitus
Elevation of lipids by Thiazide diuretics
Elevate Cholesterol and Triglycerides
Elevation of lipids by non-specific beta blockers
Elevate triglycerides
Decrease HDL
Lipids elevated by Oral contraceptive
Elevate Triglycerides
Estrogen/ Progesterone comb
Drugs that lower cholesterol
Statin, Resins, Nicotinic acid
For patients with diabetics taking oral hypoglycemic agents
Use Lovastatin
{Nicotinic acid makes diabetes worse}
Avoided in first trimester of pregnancy
Statins (in all trimester)
