Antihyperlipidemia and anti-hypertriglycerides Drugs Flashcards
3 types of dietary lipids
Triglycerides (TGs)
- neutral fat
- energy source
- accounts for 90% of lipids
Phospholipids
- essential building blocks for plasma membranes
Cholesterol
- needed to produce vitamin D
- body make enough so we really dont need any extra input
Lipoprotein functions
Carriers of lipid molecules through the blood stream
- since lipids are naturally hydrophobic
Consist of cholesterol TGs and phospholipids
Also consist of an apoprotein which is the protein carrier for lipoproteins
3 types of lipoproteins
LDL
- transports cholesterol from liver to tissues and organs
- VERY BAD: contributes to plaque deposits and CAD
- carries highest level of cholesterol
VLDL
- formed by liver
- major carrier of TGs
- becomes LDL as it passes through the body
HDL
- created by the liver and small intestines
- reverse cholesterol transport (take cholesterol from tissues -> liver)
- GOOD cholesterol (prevents binding to tissue and vessels and removes plaque deposits
Familial hypercholesterolemia
A genetic disorder where lipoproteins are dysfunction, but being made. Or not being made at all.
Normal/ good levels of lipids in a lipid panel
Total cholesterol = <200mg
- want to be lower
LDL = <100mg
- want to be lower
HDL = >60mg
- want to be higher (but not too high)
TGs = <149mg
- want to be lower
1st line of treatment for dyslipidemia
Always lifestyle changes
- monitor blood-lipid levels
- maintain weight
- get 30-45 min of cardio per day
- reduce sat fats and cholesterol
- increase soluble fiber in diets
Drug therapy for dyslipidemia
Always 2nd line (but usually required especially in elderly)
HMG-CoA (Statins)
- fluvastatin, lovastatin, rosuvastatin, Simvastatin
MOA:
1) interfere w/ synthesis of cholesterol
- does this by inhibiting HMG-CoA reductase in the liver
- also enhances the uptake of LDL in the liver by up-regulating hepatic LDL receptors via increase of Sterol Regulatory Element Binding Protein (SREBPs)
- always 1st drug of choice when treating for dyslipidemia and is very efficacy at reducing serum LDL levels*
- The most efficacy statin is rosuvastatin, followed by Atorvastatin*
- the least efficacious statins are fluvastatin/ pravastatin*
PK: often given as pro drugs since most statins go through extensive 1st-pass metabolism.
ADRs:
- liver damage due to elevated liver enzymes (contraindicated and must stop if present)
- myopathy (can lead to rhabdomyolysis in which case is contraindicated and must stop if present)
- TERATOGENIC (contraindicated in pregnancy)
- “ all my joints and muscles ache” is common
- short half life statins (lovastatin/simvastatin/fluvastatin) should be given at night
- due to endogenous cholesterol biosynthesis being the greatest at night time (6pm-5am)*
Statin lipid effects
Decrease LDL by 22-25%
Decrease TGs/VLDLs by 10-30%
Increase HDL by 5-15%
PCSK9 inhibitors
Alirocumab/Evolocumab
MOA: MABs that prevent PCSK9 protein actions which work to promote the degradation of LDL receptors
- high levels of PCSK9 prevent liver from metabolizing cholesterol, you want to stop this
- 1st line therapy in patients w/ familial hypercholesterolemia*
- can still be used in other patients however
PK: only intramuscular injections (1 every 2 weeks)
ADRs:
- nasopharyngitis
- hypersensitivity
Bile-Acid sequestrants (BAS)
Cholestyramine, colestipol, Colesevalam
MOA: bind bile salts in the intestines inhibiting them to prevent cholesterol recycling in the liver
- seems counterintuitive at first, however it actually lowers blood cholesterol since the liver (assuming it has no bile salts) will take cholesterol in the blood to produce more bile salts
1st line in patients who have no gallbladder
PK: PO however it is a huge pill so it can be grinned up as sprinkled on food.
- can be synergetic w/ statins
- also is non-systemic so usually less severe ADRs
ADRs:
- severe constipation (really poor patient adherence)
- can raise serum triglycerides
- cant take with other drugs (binds them and disables bioavailability)
- if taking other drugs, must take 4 hours apart
Niacin
MOA: vitamin B3 derivative That increases the activity of lipase enzymes in liver
- decreases TGs, LDLs and increase HDL levels
PK: PO but requires very high does and is not a monotherapy. (Usually used w/ statins)
ADRs: (because of high does, has a lot of ADRs)
- flushing (most common, can use aspirin to counter act this)
- Pruritus
- GI distress
- Rhabdomyolysis
- Hepatotoxicity (must monitor liver enzymes and stop if too high)
Contraindicated
- diabetes
- gout patients
- liver failure patients
- peptic ulcer disease
Fibrates
- Gemfibrozil, Fenofibrate
MOAs: Fibrin acid derivatives that increase the activation of lipase in liver
- also suppresses the release of free fatty acids from fat tissue and inhibit TGs synthesis in the liver
PK: PO and primarily only used to lower hypertriglyceridemias
- not the greatest at lowering LDL levels
ADRs:
- thins blood (counteracts warfarin)
- if taken with statins, will increase risk/severity of myalgia and rhabdomyolysis
- increases risk for gallstones
- abdominal discomfort,diarrhea, nausea
Ezetimibe
MOA: inhibits absorption of cholesterol in the gut
- reduces total cholesterol, LDLs and triglycerides as a monotherapy
- much better when combines with statins
PK: PO and is really only recommended for patients that have not responded/cant handle other regiments
ADRs: serious but very rare
Omega-3 fatty acids
Eicospenatenoic acid, Docosahexaenoic acid
MOA: reduces triglyceride biosynthesis through PPARa activation (similar to fibrates)
PK: requires high doses of PO and is not a monotherapy
- often added to drug therapy’s that are bad at lowering plasma TGs
ADRs
- increases LDL levels (can only be used in hyper triglyceride cases
