HLD drugs Flashcards
Rate limiting step of cholesterol synthesis inhibited by statins
HMG-CoA reductase
Result in liver from blocking intrinsic cholesterol synthesis
Upregulation of hepatic LDL receptors resulting in decreased plasma LDL
Therapeutic effect of statins
Decrease in LDL, VLDL, and triglycerides
Mild increase in HDL
Secondary prevention of heart disease by statins
Improve endothelial function
Modulate inflammatory response
Maintain plaque stability
Increase NO and decrease mRNA for endothelin-1 –> vasodilation
Drug interactions of statins
Inhibitors of CyP450 –> grapefruit juice and red yeast rice
Adverse effects of statins
Myopathy
Hepatoxicity
Risk of myopathy in statins increases with what?
Concurrent therapy of gemfibrozil and/or nicotinic acid (niacin/vit B3)
Types of bile acid sequestrants used for HLD
Cholestyramine
Colestipol
Colesevelam
Secondary use of cholestyramine (not HLD)
Used in pruritis due to biliary obstruction
Mechanism of bile acid sequestrans
Bind bile acids in GIT to form insoluble complex that is excreted in the feces
Cholesterol used to make more bile –> results in lowered LDL
Contraindication of bile acid sequestrants
Hypertriglyceridemia –> increases VLDL and triglycerides
Adverse effects of bile acid sequestrants
Fat malabsorption –> steatorrhea
Malabsorption of fat soluble vitamins
Vitamin with lipid lowering effect at high doses
Niacin/nicotinic acid/vit B3
Mechanism of high dose niacin in HLD
Inhibit hepatic production of VLDL and LDL
Decreases HDL clearance
Increases lipoprotein lipase activity
Catalyzes hydrolysis of triacylglycerol component of circulating chylomicrons and VLDL
Lipoprotein lipase
Therapeutic effects of high dose niacin
Lower VLDL, LDL, and triglycerides
Increases HDL
Fibrates used for HLD
Fenofibrate
Gemfibrozil
Peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonists that regulates gene transcription controlling carbohydrate and fat metabolism to increase activation of lipoprotein lipase.
Fibrates
Therapeutic effect of fibrates for HLD
Decrease VLDL, triglycerides, and LDL
Mild increase in HLD
Clinical indication for use of fibrates
Hypertriglyceridemia (>500 mg/dL)
Adverse effects of fibrates
Myositis (with statin)
Hepatitis
Cholelithiasis
Cholesterol uptake inhibitor that inhibits Niemann Pick C1 like protein, a cholesterol transporter, in the intestine
Ezetimibe
Used effectively with statin to reach LDL goals in pts post MI
Ezetimibe
Therapeutic effect of ezetimibe
Moderate decrease in LDL
Adverse effects of ezetimibe
HA
Myalgia
Sinusitis and pharyngitis
Antisense oligonucleotide against Apo B-100 mRNA used for homozygous familial hypercholesterolemia
Mipomerson (subQ injection)
Adverse effects of Mipomerson
Hepatic fat accumulation
Pain at injection site
PCSK9 inhibitors that decrease recycling of LDL
Evolocumab (Repatha)
Alirocumab (Praluent)
Indications for use of PCSK9 inhibitors
Heterozygous familial hypercholesterolemia
Adjunct to statin
In pts who cannot tolerate statin
Adverse effects of PCSK9 inhibitors
Injection site reaction
Hypersensitivity reaction
Increase in ALT and AST
Musculoskeletal pain
Amphetamine derivatives that increase norepinephrine release. They have an anorexiant effect used for weight loss
Phentermine
Diethylpropion
Mechanism of Orlistat
Blacks gastric and pancreatic lipases to decrease fat absorption
Mechanism of Lorcaserin
5-HT2c agonist with anorexiant effect
