Lipid-lowering

Question 1

Name HMG-CoA Reductase inhibitors

Answer 1

Atorvastatin
Pravastatin
Simvastatin

Question 2

MOA of HMG-CoA reductase inhibitors

Answer 2

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

Question 3

Uses of HMG-CoA reductase inhibitors

Answer 3

Lower LDL-C levels in all hyperlipidemias.

Lower coronary events and mortality in ISD.

Question 4

ADR of HMG-CoA reductase inhibitors

Answer 4

Liver - liver function abnormalities

Muscle - Myopathy, rhabdomyolysis (urine colour change to tea colour)

Can affect neurodevelopment of fetus and child

Question 5

PCSK9 inhibitor names

Answer 5

Evolocumab
Alirocumab

Question 6

MOA of PCSK9 inhibitors

Answer 6

Inhibit hepatic PCSK9 which targets LDL receptors for degradation in lysosomes. More LDL receptors bind and internalize circulation LDLs.

Question 7

USes of PCSK9 inhibitors

Answer 7

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

Question 8

ADR of PCSK9 inhibitors

Answer 8

Hypersensitivity reactions e.g. vasculitis or allergies

Injection site inflammation

Nasopharyngitis and sinusitis

Question 9

ADR of PCSK9 inhibitors

Answer 9

Hypersensitivity reactions e.g. vasculitis or allergies

Injection site inflammation

Nasopharyngitis and sinusitis

Question 10

MOA of Fibrates/Fibric acid

Answer 10

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.

Question 11

NAme of Fibrates/Fibric ACid

Answer 11

Gemfibrozil
Fenofibrate

Question 12

Uses of Fibrates/Fibric acid

Answer 12

Treat HyperTGmias with VLDL elevation, especially Dysbetalipoproteinemia

Question 13

ADR of Fibrates/Fibric Acid

Answer 13

GI effects - nausea
Skin rashes
Gallstones
Myositis

Question 14

ADR of Fibrates/Fibric Acid

Answer 14

GI effects - nausea
Skin rashes
Gallstones
Myositis

Question 15

MOA of Omacor - Omega 3 acid ethyl esters

Answer 15

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

Question 16

MOA of Omacor - Omega 3 acid ethyl esters

Answer 16

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

Question 17

Uses of Omacor

Answer 17

Used for Type 4 monotherapy
For Type 2B together with statins
Not for Type 1

Question 18

ADR of Omacor

Answer 18

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

Question 19

Name of Vitamin B3 drug?

Answer 19

Niacin

Question 20

MOA of Niacin?

Answer 20

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

Question 21

Use of Niacin?

Answer 21

For Type 2B AND 4 Hypolipoproteinemia

Question 22

ADR of Niacin?

Answer 22

Intense cutaneous flush and pruritus

Hyperuricemia, gout

Question 23

Name of Bile Acid Binding Resins?

Answer 23

Cholestyramine

Question 24

MOA of Bile Acid Binding resins?

Answer 24

1. Anion exchange resins bind negatively charged bile acids and bile salts in SI.
2. Lower BA conc cause hepatocytes to convert more CRL to BA. Intracellular CRL conc falls.
3. Raise hepatic uptake of CRL-containing LDL particles, lowering plasma LDL.
4. Can raise VLDL but little effect on HDL

Question 25

Use of Cholestyramine?

Answer 25

Type 2a hyperlipidemia

Treat LDL elevations with Type 2B hyperlipidemia, together with Niacin

Question 26

ADR of Cholestyramine?

Answer 26

GI effects - nausea, flatulence
Impaired absorption of Vitamins ADEK

Question 27

Name of Intestinal sterol absorption inhibitor?

Answer 27

Ezetimibe
Vytorin (Ezetimibe + Simvastatin)

Question 28

MOA of Intestinal sterol absorption inhibitor?

Answer 28

Selectively inhibit CRL transport protein, NPC1L1

Question 29

Use of Intestinal sterol absorption inhibitor?

Answer 29

Lower LDL. More potent as Vytorin

Question 30

ADR of Intestinal sterol absorption inhibitor?

Answer 30

Low incidence of reversible impaired liver function

Question 31

Which drug is banned in pregnancy?

Answer 31

HMG-CoA Reductase Inhibitors - Statins.
Can affect neurodevelopment of child