Antihyperlipidemic Drugs Flashcards
How are lipids mostly transported?
As lipoproteins
How do we pharmacologically reduce hyperlipidaemia?
- reduce the synthesis of the cholesterol — statins/PCSK9-inhibitors/MTP & ApoB inhibitors/Fibrates/Niacin
- reduce the absorption of cholesterol from the diet — Ezetimibe/bile acid sequestrants
—statins— MOA: Used for: ADR: Precaution: Examples:
MAO1: Statins inhibit HMG-CoA reductase and this reduces cholesterol synthesis
MAO2: The reduction of colostral sentences increases expression of LDL on liver cells and so your increasing the chance of LDL being degraded by liver cells and thus a reduction of LDL occurs
— used for the prevention of cardiovascular diseases and hypercholesterolemia/hypertriglyceridemia and high LDL
— ADR: muscle weakness/myalgia/liver dysfunction
— precautions: liver function tests recommended before and after starting treatment.
— examples: Atrovastatin, Rosuvastatin, Simvastatin
Brown colored urine is observed after administering statins, what is the reason? And how can it cause acute renal failure?
Rabdomyolysis is occurring where breakdown of muscle tissue and release of myoglobin and intracellular electrolytes into the circulation causing brown urine.
(Can lead to intratubular precipitation of myoglobin causing acute renal failure)
Drug interactions of statins include:
— Red yeast rice - the major ingredient in red yeast rice is monacolin K which has statin like activity, in addition it reduced the levels of coenzyme Q10 which may increase the risk of statin induced myopathy (AVOID IN PREGNANCY AND LACTATION)
— Other lipid lowering drugs
— Drugs that could increase plasma levels of statins (CYP inhibitors)
Name drug interactions of atorvastatin:
Red yeast rice
P450 modulators
Gemfibrozol
PCSK9 inhibitors mechanism of action:
PCSK9 attach to the LDL receptors and they get degraded at the lysosome
So
We use a PCSK9 inhibitor to keep the LDL receptors for picking up LDL from the blood.
SAFE IN PREGNANCY
—PCSK9 inhibitors—
Route of admin:
Used for:
ADR:
EVOLOCUMAB / ALIROCUMAB
Administered subcutaneously
— used in adjunct with diet and other LDL lowering therapies in treating primary hyperlipidemia as well as treating heterozygous familial hypercholesterolemia
— ADR: nasopharyngitis
—MTP and ApoB inhibitors— MOA: Used for: ADR: Boxed warning: DI:
MTP inhibitor - Lomitapide ORAL
ApoB inhibitor - Mipomersen SC
— MOA: both inhibit the assembly of VLDL in liver and decrease LDL in blood
— used for treating homozygous familial hypercholesterolemia (used in adjunct with low fat diet and other lipid lowering treatments)
— ADR: lomitapide - diarrhea/contraindicated in pregnancy
Mipomersen - injection site reaction/antibody development
— boxed warning: risk of hepatotoxicity for both
— DI: Lomitapide - CYP3A4 modulators/Mipomersen
Mipomersen - Lomitapide
—Fibrates—
Used for:
ADR:
Precaution:
GEMFIBROZIL/FENOFIBRATE
— used for hypertriglyceridemia
— ADR: dyspepsia (indigestion)
— precautions: may increase the risk of malignancy in humans
—Niacin—
MAO:
Used for:
ADR:
Water soluble vitamin B3
— MOA: decreases VLDL in liver and decreases LDL in blood
— used as an adjunct for reducing LDL and TG levels
— ADR: flushing/hepatotoxicity
— precaution: liver diseases/ alcoholics
—Ezetimibe—
MOA:
used for:
ADR:
MAO: inhibits the absorption of cholesterol in the small intestine by acting on NPC1L1
Used for: primary hypercholesterolemia in combination with diet
ADR: diarrhea/fatigue/liver toxicity
—Bile acid sequestrants— MOA: Used for: ADR: DI:
CHOLESTYRAMINE RESIN/COLESTIPOL
MOA: prevents the reabsorption of bile acids in intestine which causes an decrease in LDL in the blood
Used for: elevated LDL
ADR: constipation/muscle weakness/reduce of absorption of lipid soluble vitamins
DI: reduces absorption of several drugs (niacin,thiazides,loop diuretics)
What are omega-3-acid ethyl esters, and what do they do?
They are a combination of the ethyl esters of EPA and DHA which are possibly poor substrates for the enzyme that produces triglycerides and thus you can take it to reduce TG levels
