Pharm - Lipid Lowering

Question 1

Statins

Mechanism, Effect, Side Effects, High potency strains, Interactions

Answer 1

M: block HMG CoA Reductase (decrease liver chol synthesis = more chol influx from LDL in blood = more LDL-Rs expressed on liver
E: reduce LDL-C by 20-60%
HPS: Atorvastatin, Rosuvastatin
Other types: Simvastatin, Lovastatin, Fluvastatin, Pravastatin
SE: Hepatotoxicity, Myopathy
I: CYP3A4, CYP2C9 (fluvastatin), grapefruit juice

Question 2

PCSK9 Inhibitors
(Mechanism, Effect, Route, Side Effects, Clinical Use)

Answer 2

M: inhibit PCSK9 = disinhibit LDLR expression = more chol sequestration = lower LDL in blood
E: lower LDL-C 50% on top of high intensity statin
R: IV injection every 2-4 wks
SE: myalgias, delirium, dementia
CU: Adjunctive to statins in F. Hypercholesterolemia patients

Question 3

Ezetimibe

Mechanism, Effect

Answer 3

M: block NPC1L1 Enterocyte Chol. Transporter = inhibits gut uptake of chol
E: 2nd line LDL-C lowering

Question 4

Bile Acid Sequestrants

Mechanism, Effect

Answer 4

M: binds bile acids in gut to prevent resorption = more de novo bile acid synthesis = lower chol in liver = more LDLR production = lower LDL-C in blood
E: 2nd line LDL-C lowering

Question 5

Fibrates

Mechanism, Effect, Side Effect, Contraindications, Clinical Use

Answer 5

PPAR-alpha agonists
M: 1. inhibits VLDL secretion = lowers TG, 2. lowers ApoC3 expression (normally blocks LL) = more LL activity = lower TG, 3. increases ApoA1/A2 synthesis = raise HDL-C
E: Lowers TG 20-50%, may lower or raise LDL-C
SE: dyspepsia, gallstones, myopathy
CI: severe renal/hepatic disease
CU: lowering TG

Question 6

Niacin

Mechanism, Effects, Side Effects, Contraindications, Clinical Use

Answer 6

M: 1. lower liver TG synthesis = lower VLDL = lower LDL-C and lower TG, 2. lower adipose TG mobilization = lower TG, 3. lower apoA1 degradation = raise HDL-C
E: lowers LDL-C 5-25%, Lower TG 20-50%, raises HDL-C 15-35%
SE: Flushing, GI distress, hyperuricemia, hepatotoxicity, hyperglycemia
CI: liver disease, severe gout, peptic ulcer disease
CU: lowering TG, no clinical benefit to combine with statin

Question 7

Omega-3 Fatty Acids

Mechanism, Clinical Use

Answer 7

M: EPA/DHA = lower liver VLDL and ApoB Synthesis = lower TG
CU: lowering TG

Question 8

Tx Approach for High LDL-C

Answer 8

1. STATINS

2. Controversial 2nd line (bile acid resin - colesevelam, or ezetimibe)

Question 9

Tx Approach for Low HDL-C

Answer 9

no evidence based therapy to improve outcomes, but best drug to use is niacin

Question 10

Tx Approach for High TG

Answer 10

1. Make sure high TG is not 2/2 other condition (DM/hypothyroid)
2. If TG > 500, fibrates and Omega-3’s to lower risk of pancreatitis