Lipid-lowering Flashcards
Name HMG-CoA Reductase inhibitors
Atorvastatin
Pravastatin
Simvastatin
MOA of HMG-CoA reductase inhibitors
Competitively inhibit enzyme, the rate-limiting step in CRL synthesis
Upregulate LDL receptors on cell surface - depletion of intracellular CRL cause cell to raise specific cell-surface LDL receptors that can bind and internalize circulation LDL-Cs
Uses of HMG-CoA reductase inhibitors
Lower LDL-C levels in all hyperlipidemias.
Lower coronary events and mortality in ISD.
ADR of HMG-CoA reductase inhibitors
Liver - liver function abnormalities
Muscle - Myopathy, rhabdomyolysis (urine colour change to tea colour)
Can affect neurodevelopment of fetus and child
PCSK9 inhibitor names
Evolocumab
Alirocumab
MOA of PCSK9 inhibitors
Inhibit hepatic PCSK9 which targets LDL receptors for degradation in lysosomes. More LDL receptors bind and internalize circulation LDLs.
USes of PCSK9 inhibitors
For Familial hypercholesterolaemias, especially those intolerant to statins
For clinically significant atherosclerotic CVD needing more LDL-C lowering after being on diet control and maximally tolerated statin therapy
ADR of PCSK9 inhibitors
Hypersensitivity reactions e.g. vasculitis or allergies
Injection site inflammation
Nasopharyngitis and sinusitis
ADR of PCSK9 inhibitors
Hypersensitivity reactions e.g. vasculitis or allergies
Injection site inflammation
Nasopharyngitis and sinusitis
MOA of Fibrates/Fibric acid
Ligands for PPAR-a protein. Interaction with PPAR-a raises activity of LPL.
Stimulated LPL lowers plasma TG levels.
Lower VLDL partly due to lower secretion by liver.
HDL levels rise abit.
NAme of Fibrates/Fibric ACid
Gemfibrozil
Fenofibrate
Uses of Fibrates/Fibric acid
Treat HyperTGmias with VLDL elevation, especially Dysbetalipoproteinemia
ADR of Fibrates/Fibric Acid
GI effects - nausea
Skin rashes
Gallstones
Myositis
ADR of Fibrates/Fibric Acid
GI effects - nausea
Skin rashes
Gallstones
Myositis
MOA of Omacor - Omega 3 acid ethyl esters
Lower hepatic TG production and raises TG clearance from VLDL.
Inhibit Diglyceride Acyltransferase (responsible for TG biosynthesis) as EPA and DHA (Omega Acids) are poor substrates for enzyme.
3Increase FFA breakdown
MOA of Omacor - Omega 3 acid ethyl esters
Lower hepatic TG production and raises TG clearance from VLDL.
Inhibit Diglyceride Acyltransferase (responsible for TG biosynthesis) as EPA and DHA (Omega Acids) are poor substrates for enzyme.
3Increase FFA breakdown
Uses of Omacor
Used for Type 4 monotherapy
For Type 2B together with statins
Not for Type 1
ADR of Omacor
Contraindicated for those allergic to fish
GI effects e.g. Constipation, Diarrhoea, dyspepsia, flatulence, Abdominal distension
DHA can raise LDL-C
Lower TXA2 prod, causing longer bleeding time
Name of Vitamin B3 drug?
Niacin
MOA of Niacin?
Inhibit lipolysis in adipose tissue. TG in VLDL and CRL in VLDL and LDL are lowered.
Increase HDL-CRL levels
Lower fibrinogen and raise TPA, niacin can reverse thrombosis linked to Hypercholesterolemia and Atherosclerosis
Use of Niacin?
For Type 2B AND 4 Hypolipoproteinemia
ADR of Niacin?
Intense cutaneous flush and pruritus
Hyperuricemia, gout
Name of Bile Acid Binding Resins?
Cholestyramine
MOA of Bile Acid Binding resins?
- Anion exchange resins bind negatively charged bile acids and bile salts in SI.
- Lower BA conc cause hepatocytes to convert more CRL to BA. Intracellular CRL conc falls.
- Raise hepatic uptake of CRL-containing LDL particles, lowering plasma LDL.
- Can raise VLDL but little effect on HDL
Use of Cholestyramine?
Type 2a hyperlipidemia
Treat LDL elevations with Type 2B hyperlipidemia, together with Niacin
ADR of Cholestyramine?
GI effects - nausea, flatulence
Impaired absorption of Vitamins ADEK
Name of Intestinal sterol absorption inhibitor?
Ezetimibe
Vytorin (Ezetimibe + Simvastatin)
MOA of Intestinal sterol absorption inhibitor?
Selectively inhibit CRL transport protein, NPC1L1
Use of Intestinal sterol absorption inhibitor?
Lower LDL. More potent as Vytorin
ADR of Intestinal sterol absorption inhibitor?
Low incidence of reversible impaired liver function
Which drug is banned in pregnancy?
HMG-CoA Reductase Inhibitors - Statins.
Can affect neurodevelopment of child
