Lipid Lowering Drugs

Question 1

types of Lipids

Answer 1

Cholesterol - from diet, hepatic synthesis 
Builds cell membrane
Make bile, assist with food digestion
Hormones 
Broken down in liver 

Triglycerides - diet hepatic synthesis
Energy source for cells and tissues
Broken down via lipoprotein lipase into glycerol fatty acids

LDL - “bad”
HDL - “Good”

Question 2

Low density LDL

Answer 2

Bad cholesterol

Responsible for development of atherosclerosis
Bring cholesterol to cells or utilization -> deposit extra cholesterol in vascular tissues
Removed by liver

Question 3

High density HDL

Answer 3

Good cholesterol

Remove extra cholesterol from cells and bring them to liver to be excreted
Can remove cholesterol from artery walls
Stop atherogenic lipoproteins from oxidizing

Question 4

Lab values:

Total cholesterol
LDL
HDL
TGs

Answer 4

GOAL VALUES
Total cholesterol <200
LDL.           <130
HDL.           > 40
TGs.           <150

Question 5

Dyslipidemia

Answer 5

One or ore abnoralities in any blood lipids

Overproduction of TGs or LDL
Deficiency of HDL

Hyperlipidemia is most common disorder (Increased LDL)
Hypertriglceridemia -> increase TGs
Familial hypercholesterolemia -> defective LDL clearance caused by genetics

Question 6

Treatment for Dyslipidemia

Answer 6

Lifestyle:

Diet -> lower fats, high fruits and veggies
Exercise
Alcohol avoidance
Smoking cessation

Medication:

LDL lowering:

Statins
Ezetimibe
Bile acid sequesterants 
PCSK9 inhibitors 
Niacin

TG lowering:

Omega 3s
Niacin
Fibric acid derivatives

Question 7

Statins drugs, clinical uses, MOA

Answer 7

-statin (atrovastatin, rosuvasatan - least muscle issues, simvasatan)

MOA: HMG-CoA reductase inhibitors - increase plaque stability, dec platelet activation, decrease vascular inflammation, decrease endothelial dysfunction
competitive inhibition of HMG-CoA reductive -> decrease synthesis of cholesterol
Block HMG CoA reductive receptors -> increased expression of LDL receptors -> increased cholesterol clearance

Target: primary: LDL >190
Decrease LDL
Increase HDL
Decrease TG

Uses: dyslipoidemia LDL >190
diabetes age >40 or diabetes <40 with ASCVD risk
Old age

Secondary: clinically evident ASCVD, angina STEMI NSTEMI, Stroke, TIA, PAD

Question 8

Statins ADR, potential interactions

Answer 8

ADR: 
pregnancy category X
Hepatic dysfunction - increase LFTs
HA
Constipation
Muscular complications - pain, weakness (rosuvastatin least muscle issues)

Simvastatin and amlodipine = max dose simvastatin 20 mg -> inhibition of simvastatin breakdown. -> muscle issues

Interactions: CYP3A4 inhibitors increase concentration of statins
Grapefruit juice
Protease inhibitors
Antifungals
Warfarin
Amlodipine and simvastatin

Question 9

Bile acid sequesterants

Answer 9

MOA: bind to bile acid in GI tract -> increase excretion -> decrease bile in circulation -> increased cholesterol is utilized to create more bile acid -> decrease cholesterol

Target: LDL
Decrease LDL
Increase HDL
Increase TGs

ADR: poorly tolerated, GI intolerance (constipation/bowel obstruction), increased TGs

Bind to a lot of medications - LAST line of defense for LDL lowering

Question 10

Niacin

Answer 10

Vitamin B3

MOA: decrease VLDL synthesis -> HDL byproduct of VLDL synthesis -> decrease breakdown of HDL

Target: TGs
Decrease LDL
Increase HDL
Decrease TGs

Uses: hypertriglyceridemia, statin intolerant patients
DO NOT combine with statin

ADR: flushing, prutis, increase Uric acid and/or glucose, nausea, GI intolerance

Interactions:
Pregnancy category X
Gout
Peptic ulcer

Question 11

Fibric acid derivatives

Answer 11

MOA: PPAR-alpha receptor agonist
Decrease VLDL synthesis in liver -> increase lipolysis and clearance of TGs

Drug examples: gemfibrozil (CANNOT use with statin), fenofibrate

Target: TGs >500
Decrease LDL
Increase HDL
Decrease TGs

Use: in patients with TGs over 500

ADR: myopathy, increase LFTs, nausea, GI intolerance, skin rash

DO NOT combine with simvastatin - severe renal or liver disease

Question 12

Omega 3 fatty acids

Answer 12

MOA: inhibition of TG secretion from liver - promotes TG metabolism

Drug examples: Vascepa, Lovaza, Fish oil

Target: TGs
Increase LDL
Decrease TGs

ADR: fishy taste, burping, antiplatelet effects at high doses

Question 13

PCSK 9 inhibitors

Answer 13

MOA: monoclonal antibodies bind to LDL receptors -> decrease free LDL receptors -> increase free LDL -> increased LDL clearance

Encourage use with statins

Drug names: alirocumab, evolocumab (EXPENSIVE)

Target: decrease LDL
Can lower LDL up tp 70%

Uses: familial hypercholesterolemia, failing other agents

ADR: injection side reactions, HA, arthralgia, myalgia, limb pain, fatigue

Potential hypersensitivity reactions

Question 14

Direct cholesterol inhibitor

Answer 14

MOA: inhibits absorption of cholesterol into intestines
Decrease: cholesterol, chylomircrons, serum LDL

Drug: ezetimibe

Target: LDL
Lower LDL
Increase HDL
Neutral TGs

Uses: dyslipidemia - after statins or in combo with statins
DO NOT USE with bile acid sequesterants

ADR: diarrhea, athralgia, sinusitis, fatigue, HA, increased LFTs

Interactions: liver disease when combined with statin