Page 654 - Basic _ Clinical Pharmacology ( PDFDrive )

640 SECTION VI Drugs Used to Treat Diseases of the Blood, Inflammation, & Gout

Subclass, Pharmacokinetics, Toxicities,
Drug Mechanism of Action Effects Clinical Applications Interactions
BILE ACID SEQUESTRANTS
• Colestipol Binds bile acids in gut Decreases LDL Elevated LDL, digitalis Oral • taken with meals • not absorbed
• prevents reabsorption toxicity, pruritus • Toxicity: Constipation, bloating • interferes
• increases cholesterol with absorption of some drugs and vitamins
catabolism • upregulates LDL
receptors

• Cholestyramine, colesevelam: Similar to colestipol
STEROL ABSORPTION INHIBITOR
• Ezetimibe Blocks sterol transporter Inhibits reabsorption of Elevated LDL, Oral • duration 24 h • Toxicity: Low incidence
NPC1L1 in intestine brush cholesterol excreted in bile phytosterolemia of hepatic dysfunction, myositis
border • decreases LDL and phytosterols
NIACIN
Decreases catabolism of Increases HDL • decreases Low HDL • elevated VLDL, Oral • large doses • Toxicity: Gastric irritation,
apo AI • reduces VLDL lipoprotein(a) [Lp(a)], LDL Lp(a); elevated LDL in flushing, low incidence of hepatic toxicity
secretion from liver statin-unresponsive or • may reduce glucose tolerance
intolerant patients
• Extended-release niacin: Similar to regular niacin
• Sustained-release niacin (not the same as extended-release product): Should be avoided
PCSK9 HUMANIZED MONOCLONAL ANTIBODIES
Evolocumab Complexes PCSK9 Inhibits catabolism of LDL Familial Parenteral • Cost ~ $14,000/year • Toxicity:
receptor hypercholesterolemia not injection site reactions, nasopharyngitis,
responsive to oral therapy flu-like symptoms, rarely myalgia,
neurocognitive and ophthalmologic events
• Alirocumab Similar to evolucumab

PREP AR A TIONS REFERENCES
A V AIL ABLE Afshar M, Thanassoulis G: Lipoprotein(a): new insights from modern genomics.
Curr Opin Lipidol 2017;28:170.
Ballantyne CM et al: Efficacy and safety of a novel dual modulator of adenosine
GENERIC NAME TRADE NAMES triphosphate-citrate lyase and adenosine monophosphate-activated protein
Alirocumab Praluent kinase in patients with hypercholesterolemia: Results of a multicenter, ran-
domized, double-blind, placebo-controlled, parallel-group trial. J Am Coll
Atorvastatin Generic, Lipitor
Cardiol 2013;62:1154.
Cholestyramine Generic, Questran, Prevalite
Boekholdt SM et al: Levels and changes of HDL cholesterol and apolipoprotein
Colesevelam Welchol A-I in relation to risk of cardiovascular events among statin-treated patients:
Colestipol Generic, Colestid A meta-analysis. Circulation 2013;128:1504.
Evolocumab Repatha Bonow RO, Yancy CW: High-intensity statins for secondary prevention. JAMA
Cardiol 2017;2:55.
Ezetimibe Generic, Zetia
Cannon CP et al: Ezetimibe added to statin therapy after acute coronary
Fenofibrate Generic, Tricor, Antara, Lofibra syndrome. N Engl J Med 2015;372:2387.
Fluvastatin Generic, Lescol, Lescol XL Chou R et al: Statins for prevention of cardiovascular disease in adults: Evidence
Gemfibrozil Generic, Lopid report and systematic review for the US Preventive Services Task Force.
JAMA 2016;316:2008.
Lomitapide Juxtapid
Dron JS, Hegele RA: Complexity of mechanisms among human proprotein
Mipomersen Kynamro convertase subtilisin-kexin type 9 variants. Curr Opin Lipidol 2017;28:161.
Lovastatin Generic, Mevacor, Altoprev Elam M, Lovato E, Ginsberg H: The role of fibrates in cardiovascular disease
Generic only prevention, The ACCORD–lipid perspective. Curr Opin Lipidol 2011;22:55.
Niacin, nicotinic acid, vitamin B 3
Omega-3 fatty acids–marine Lovaza Gaudet D et al: Antisense inhibition of apolipoprotein C-III in patients with
hypertriglyceridemia. N Engl J Med 2015;373:438.
Pitavastatin Livalo
Gouni-Berthold I et al: Systematic review of published phase 3 data on anti-
Pravastatin Generic, Pravachol PCSK9 monoclonal antibodies in patients with hypercholesterolaemia. Br J
Rosuvastatin Generic, Crestor Clin Pharmacol 2016;82:1412.
Simvastatin Generic, Zocor International Atherosclerosis Society: IAS Position Paper: Global Recommenda-
tions for the Management of Dyslipidemia. Available at: www.athero.org/
COMBINATION TABLETS
IASPositionPaper.asp.
Ezetimibe/simvastatin Vytorin
Jacobson TA et al: On behalf of the NLA Expert Panel. National Lipid Association
Niacin/lovastatin extended-release Advicor recommendations for patient-centered management of dyslipidemia: Part 2.
Niacin/simvastatin extended-release Simcor J Clin Lipidol 2015;9:S1.