Lipid lowering Drugs

Nurs 2019-20
INTRODUCTION
• Lipids carried in particles called lipoproteins that act as
transport vehicles delivering cholesterol to various body
tissues to be used, stored or excreted
Types of lipoproteins
chylomicrons (triglyceride)
VLDL - very low density lipoproteins (triglyceride)
unable to pass through blood vessel wall
LDL - low density lipoproteins (cholesterol)
due to size easily penetrates vascular endothelium
HDL - high density lipoproteins (cholesterol);
Transports cholesterol away from arteries and back to the
liver to be eliminated. Removes excess cholesterol from
plaques, slowing growth.
Hyperlipidaemia (dyslipidemia)
Primary
- may involve
• cholesterol (hypercholesterolaemia)
• triglycerides (hypertriglyceridaemia)
• or both (mixed)

Secondary - to another disease

eg. diabetes mellitus, alcoholism, obstructive
liver disease, drugs (thiazide diuretics, -AR
antagonists)
Hyperlipidemia: Can lead to the development of
atherosclerosis and Coronary Artery Disease.
• VLDLs and LDLs are atherogenic lipoproteins while
HDL is inversely related to the incidence of CAD.
• Hence, treatments for hyperlipidemia aim to
➢  LDL levels &  HDL levels.
➢reduce progression of atherosclerosis and improve
survival in patients with established CV disease
➢reduce premature cardiac morbidity and mortality
in people at high risk of CV disease
Lipid lowering drugs

• HMG-CoA Reductase Inhibitors (Statins)

• Bile Acid binding resins
• Nicotinic acid (niacin)
• Fibric Acid Derivatives (Fibrates)
• Cholesterol absorption inhibitors (ezetimibe)

• https://www.youtube.com/watch?v=9dghtf7Z7fw
HMG-CoA Reductase Inhibitors (Statins)
eg: Atorvastatin ,Simvastatin , Lovastatin
MOA:
• Block an enzyme ( HMG-CoA Reductase ) necessary
for formation of cholesterol
• Reduces cholesterol in hepatocytes which
promotes increased expression of LDL receptors
(increasing clearance)

• Most effective at lowering LDL (18—60%)

• Maximum therapeutic benefit seen after 4 weeks of
therapy

• Lipoproteins: ↓↓LDL, ↓TG, HDL

Adverse effects
• Elevation of liver enzymes:
• liver enzymes should be monitored
regularly (at 3, 6 and 12 months, then
yearly.)
• Myopathy
• Rhabdomyolysis: break down of muscles, rare in
monotherapy.
• Others: headache, abdominal pain, nausea and
vomiting, insomina.
USES of Statins
▪ Atherosclerosis vascular disease : Primary
prevention in high risk patients (DM, Hypertension)
▪ Secondary prevention- Irrespective of Lipid levels Post
MI, Cerebral vascular accidents
▪ Familial hypercholesterolemia,
▪ Familial combined hyperlipoproteinemia
Because of diurnal rhythm of cholesterol synthesis, statins
(except Atorvastatin ) should be given at night if a single
dose is used
Contraindication

• Pregnancy
• Children < 8 years of age (Myelination of CNS -
incomplete),
• Liver diseases
• Myopathies
Bile Acid binding resins:
Cholestyramine , Colestipol
MOA:
• bind with bile acids and promote their excretion
• reabsorption of bile acids (exogenous cholesterol)
•  metabolism of endogenous cholesterol to bile
salt
•  intracellular cholesterol in hepatocytes
•compensatory increase in LDL receptors
• Resins can also bind to other drugs and fat-soluble
vitamins, decreasing their absorption in the body,
so take other medications at least 1 hour before or
4 to 6 hours after
Adverse effects
• Constipation
• Bloating and gas
• Feelings of fullness
• Vitamin K deficiency
• USES:
• Elevated cholesterol
• Pruritus
• CONTRAINDICATIONS:
• Biliary tract obstruction.
• Inflammatory bowel disease
NICOTINIC ACID: Niacin
MOA:
• inhibits VLDL secretion from liver
•Decreases Lp(a)
• Reduces production and release of LDL through the
inhibition of lipolysis in adipose tissue.
• ↓LDL, ↓TG, HDL

SIDE EFFECTS:
• GI upset., Cutaneous Flushing, Pruritus
• Reactivation of peptic ulcer
• Impaired Glucose tolerance
• Hyperuricemia
• Hepatotoxicity
Uses:
• Hypercholesterolaemia,
• Hypertriglyceridemia,
• Low levels of HDL cholesterol

Contraindications
• Gout
• Peptic ulcer
• Hepatic disease
• Diabetes mellitus
Fibric Acid Derivatives/Fibrates
eg: Gemfibrozil, Fenofibrate , Bezafibrate
MOA:
• PPAR (peroxisome proliferator activated nuclear
receptor) alpha agonists
•stimulate lipoprotein lipase (LPL) (muscle &
adipose tissue)
• decrease hepatic VLDL production
•increase hepatic LDL uptake

• Lipoproteins: ~↓LDL, ↓↓ TG, HDL

Adv effects:
• Nausea, Skin rashes, GI upset
• ↑Cholesterol gall stones formation
• Hepatic dysfunction
• ↑ risk of myopathy (used along with Statins)
USES:
• Hypertriglyceridemias, ↑ VLDL,
• Mixed dyslipidemia
• Hyperlipidemia with hyperuricemia (Fenofibrate:
Uricosuric agent),
• Pts with low HDL.
CHOLESTEROL ABSORPTION
INHIBITORS: Ezetimibe
MOA:
• Inhibits selective intestinal absorption of
cholesterol
• Inhibits reabsorption of cholesterol excreted in the
bile.
• Compensatory ↑ in the no. of LDL receptors →
clearance of LDL from the blood → thus ↓ plasma
LDL
Uses
• Hypercholesterolaemia (synergistic with Statins)
Side effects
• ↑ risk of hepatic toxicity with Statin
• Not recommended with fibrates
• Back pain, Joint & Muscle pain
• Diarrhea, abdominal pain
• Fatigue, Dizziness, Headache

FISH OIL -Contains Omega 3 fatty acids (PUFA) -

Eicosapentaenoic acid, Dosahexaenoic acid.
↓ Plasma TGs level & have Antioxidant action.
Uses : Prophylaxis in high risk patients of coronary
artery disease
 Comparison of Effects of Cholesterol
Lowering Drugs:
LDL HDL TG

Resins ↓↓↓ ↑ ↑
Statins ↓↓↓↓ ↑↑ ↓↓
Niacin ↓↓ ↑↑↑↑ ↓↓↓

Fibrates ↓ ↑↑↑ ↓↓↓↓

Ezetimibe ↓ ↑ ↓