38 terms

Antihyperlipidemics

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HMG CoA Reductase Inhibitors (Statins)
lovastatin
atorvastatin
fluvastatin
pravastatin
simvastatin
rosuvastatin
pitavastatin
Statin Indications
reduce LDL
reduce trigylcerides (modest)
increase LDL (modest)
Statin MoA
competitively inhibit HMG-CoA Reductase;
inhibit de novo synthesis of cholesterol in hepatocytes; induce increase in high-affinity LDL receptors
Statin Toxicity
elevated serum aminotransferase (hepatic tox.)
elevated serum Scr (muscle pain/weakness)
elevated HbA1c and fasting BS
myopathy (rhabdomyolysis)
cognitive impairment
Niacin Indication
decrease triglyerides (hypertriglyceridemia)
decrease LDL
decrease plasma lipoprotein level
increase HDL
Niacin MoA
inhibit VLDL secretion from hepatocytes
inhibit intracellular lipase
induce clearance of VLDL
decrease catabolic rate for HDL
Niacin Toxicity
skin flushing (prostaglandins/vasodilation)
pruritis
glucose intolerance
hyperuriciemia (gout)
hepatotoxicity
Fibric Acid Derivatives
gemfibrozil (only one that decreases CV risks)
fenofibrate
fenofibric acid
Fibric Acid Derivative Indications
decreases VLDL
decrease trigylcerides (30-50%) (hypertriglyceridemia)
increase HDL (maybe?)
decrease LDL (? but may increase if it decreases triglycerides)
Fibric Acid Derivative MoA
bind to PPAR-alpha and induce lipolysis of VLDL triglycerides via LDL; decrease intracellular lipolysis in adipose tissue -> decrease flux of free fatty acids to liver
Fibric Acid Derivative Toxicity
myopathy (when combo with statins)
cholesterol gallstones (due to cholesterol in bile)
Fibric Acid Derivative Contraindication
liver disease
gallbladder disease
Bile Acid Sequestrants
colestipol
cholestyramine
colesevelam
Bile Acid Sequestrants Indications
primary hypercholesterolemia
reduce LDL (20%)
increase HDL
Bile Acid Sequestrants MoA
bind to anionic bile acid in intestine and prevent reabsorption; increase excretion of bile acids; increase metabolic conversion of cholesterol to bile acids in liver; decreased cholesterol causes up-regulation of LDL-receptors -> increased uptake of LDL and IDL from plasma
Bile Acid Sequestrants Toxicity
constipation
heartburn
nausea
bloating
decrease folic acid
impaired absorption of some other drugs
Inhibitors of Intestinal Sterol Absorption
Ezetimibe
Inhibitors of Intestinal Sterol Absorption Indications
reduce LDL
increase HDL (minimal)
Inhibitors of Intestinal Sterol Absorption MoA
inhibits intestinal absorption of dietary/biliary cholesterol/phytosterols; targets NPC1L1
Inhibitors of Intestinal Sterol Absorption Toxicity
diarrhea
fatigue
URTI
arthralgia

RARE:
elevation in liver transaminase
hepatitis
cholecystitis
myalgia
myopathy/rhabdomyolysis
thrombocytopenia
Omega-3 Polyunsaturated Fatty Acids (Fish Oil)
Lovaza
Vascepa
Omega-3 Polyunsaturated Fatty Acid Indications
severe hypertriglyceridemia
decrease triglycerides (20-50%)
decrease LDL (maybe? Lovaza due to DHA)
Omega-3 Polyunsaturated Fatty Acid MoA
reduce triglyceride production and increase triglyceride clearance; proposed MoAs:
1)inhibit acyl CoA:1,2 diaclyglcerol acetyltransferase
2)increase hepatic mitochondrial/peroxisomal beta-oxidation
3)reduction in hepatic synthesis of triglycerides
4)increase plasma lipoprotein lipase activity
Omega-3 Polyunsaturated Fatty Acid Toxicity
well-tolerated
dyspepsia
unpleasant aftertaste
worsening glycemic control
inhibition of platelet aggregation
increased bleeding time
Antisense Oligonucleotides
mipomersen
Antisense Oligonucleotide Indications
homozygous familial hypercholesterolema (HoFH)
used in combo with other agents and low-fat diet to reduce cholesterol levels in pts with HoFH
Antisense Oligonucleotide MoA
binds to mRNA that encodes ApoB ->
results in degradation/disruption of mRNA ->
decreases synthesis of VLDL and LDL
Antisense Oligonucleotide Toxicity
severe injection site rxns
flu-like symptoms
nausea
headache
hepatotoxicity
What is ApoB?
principle apoprotein in LDL and VDL lipoproteins
Microsomal Triglyceride Transfer Protein (MTP) Inhibitors
lomitapide
Microsomal Triglyceride Transfer Protein (MTP) Inhibitors Indications
homozygous familial hypercholesterolemia (HoFH)
used in combo with other agents and low-fat diet to reduce cholesterol in pts with HoFH
Microsomal Triglyceride Transfer Protein (MTP) Inhibitors MoA
binds to and inhibits MPT->
prevents assembly/formation of ApoB-contatining lipoproteins->
inhibits synthesis of chylomicrons and VLDL->
inhibits synthesis of LDL
Microsomal Triglyceride Transfer Protein (MTP) Inhibitors Toxicity
GI adverse effects (NVD, dyspepsia, ab. pain)
hepatotoxicity
Which antihyperlipidemic drug is a substrate and inhibitor of CYP3A4?
lomitapide (Microsomal Triglyceride Transfer Protein (MTP) Inhibitor)
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors
alirocumab
evolocumab (SQ)
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors Indication
decrease LDL-C
HETEROZYGOUS familial hypercholesterolemia
clinical atherosclerotic CAD
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors MoA
binds PCSK9 and prevents it from binding LDL receptors-> rapid recycling of LDL receptor and enhanced uptake/clearance of LDL-C
Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors Toxicity
injection-site rxns
myalgia

RARE:
nuerocognitive effects (dementia, memory impairment, confusion)
hypersensitivity rxns
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