L3 - Hypolipidemic Agent

Front 1

Predisposing factors for Hyperlipidemias

Back 1

athersclerosis
coronary artery disease.

Front 2

Predisposing factors for Hypertriglyceridemia

Back 2

Pancreatitis

Front 3

Role of Drug Therapy for Hypolipidemic Agents.

Back 3

1. ↓cholesterol in lipoprotein fractions which deliver cholesterol to peripheral tissues (vLDL, LDL, IDL, ...)
2. ↑lipoprotein fractions which extract cholesterol from peripheral tissues (HDL)
3. ↓circulating triglycerides when indicated.

Front 4

Cholestryamin
(QUESTRAN)

Back 4

Bile Acid-Binding Resin

Front 5

Colestipol
(COLESTID)

Back 5

Bile Acid-Binding Resin

Front 6

Colesevelam
(WELCHOL)

Back 6

Bile Acid-Binding Resin

Front 7

Bile Acid-Binding Resins

-MOA
-Adminstration

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MOA
-Non-absorbable cationic exchange resins which bind to bile acid
-Interfer with enterohepatic circulationg of bile acids →→→ cholesterol-lowering effect

Administration
-Take it with meals (time when bile acid secretion is optimal)
[Meal → colocystokinins → bile acid release stimulated → bile acids emulsify fats for absorption]

Front 8

Niacin
[Nicotinic acid]

-MOA

Back 8

MOA
-↓cholesterol & ↓triglycerides at high doses compared to vitamin requirement.
-↓hepatic esterification of triglycerides and ↓vLDL (↓Tg liver → ↓vLDL → ↓Tg in ciruclation)

Front 9

gemfibrozil
(LOPID)

Back 9

Fibric acid derivative

Primarily excreated unchanged in the urine

Front 10

fenofibrate
(TRICOR)

Back 10

Fibric acid derivative

hydrolyzed by esterases in the gut and absrobed. Major fractions excreted include urinary glucuronide and in teh feces.

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Fibric Acid Derivatives

-MOA

Back 11

-Ligand of PPAR-α (Peroxisome proliferator-activated receptor)
- Reduces vLDL particle secreation

-↑Lipoprotein lipase activity
-↓vLDL triglycerides

-↓lipolysis in adipose tissue → reflex ↑HDL →→ ↓development of atherscloerotic plaque

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Fibric Acid Derivative

-Problems

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-↑biliary cholesterol may induce cholelithiasis.

↑hepatotoxity and myopathy
-hepatotoxicty due to interferance with PPAR-alpha

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Atorvastatin
(LIPITOR)

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HMG-CoA Reductase Inhibitor

Front 14

Fluvastatin
(LESCOL)

Back 14

HMG-CoA Reductase Inhibitor

Front 15

Lovastatin
(MEVACOR)

Back 15

HMG-CoA Reductase Inhibitor

Front 16

Pravastatin
(PRAVACHOL)

Back 16

HMG-CoA Reductase Inhibitor

Front 17

Rosuvastatin
(CRESTOR)

Back 17

HMG-CoA Reductase Inhibitor

Front 18

Simvastatin
(ZOCOR)

Back 18

HMG-CoA Reductase Inhibitor

Front 19

HMG-CoA Reductase Inhibitors

Back 19

Atorvastatin (LIPITOR)
Fluvastatin (LESCOL)
Lovastatin (MEVACOR)
Pravastatin (PRAVACHOL)
Rosuvastatin (CRESTOR)
Simvastatin (ZOCOR)

Front 20

Statins: Disposition

-Admin, metabolism, excreation.

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-CYP 3A4 & 2C9 metabolism (↑DDI risk)
-High First pass extraction
-Administration in evenings for optimum effect upon cholesterol synthesis.
-Drugs and metabolites excreted primarily in bile

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Statins:

-Side-effects, additional MOA, counteridication

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-↑myopathy risk (as compared to other agents)
-Hepatotoxicity may be dose independent

-anti-inflammatory effect (add to statin effect)

Counterindication: pregnant women and nursing mothers

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Counterindication for all hypolipidemic agents

Back 22

Pregnant women OR
Nursing mothers

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Ezetimibe
(ZETIA)

-MOA

Back 23

Cholesterol Absorption Inhibitors

-Inhibits cholesterol absorption from the small intestine.
-↓circulating cholesterol, LDL, & Tg
-↑HDL

Front 24

Combo Therapies

Fibric Acid & Resin

Back 24

FA ↓vLDL associated TG and Re can ↑vLDL as a reflexive response (one will offset the vLDL associated TG reflex). Net benefit of both ↓LDL and ↓vLDL cholesterol

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Combo Therapies

Statin & Resin

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Resin are gonna take away bile acids, liver may respond by stimulating the uptake of LDL but also the synthesis of cholester (by ↑HMG-CoA) ← statin offsets this response

Front 26

Combo Therapies

Niacin & Resin

Back 26

sever hypertiglyceridemia along with elevelated LDL/vLDL. Niacin: good job with ↓triglycerides; if resin causes reflex ↑in TG, niacin will get rid of this reflex.

i. Resin ↑TG, and pt already has ↑TG, couple this with niacin, to prevent TG reflex ↑. (may want to use FA with Resin) ← remember niacin and FA are cousins (they go after vLDL associated TG).

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Combo Therapies

Niacin & Statin

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CAUTION: it tends to ↑(ability to lower LDL cholesterol), but also ↑hepatotoxicty (2 hepatotoxins in the hepatocyte)

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Combo Therapies

Resin & Niacin & Statin

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Sever hyperlipoproteimia: Resin (block reuptake of bile acids) → ↑HMG-CoA r (block with Statin). And than reduce over all amt of LDL (hit it with niacin).

i. Problem with hepatotixicty
ii. Resins: ↓in solubalization ability. Statins: abiliy to ↓introhepatic cholesterol

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Combo Therapies

Statin & Ezetimibe

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hyperportenemia: inhibit uptake of cholesterol and synthesis of cholesterol. (in this case ur staying away from a resin)

Front 30

Combo Therapies

Fibric Acid & Statin

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DON’T USE: FA and Statins: presents the most problems with hepatoxicities

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Bile Acid-Binding Resins

-SideEffects
-Counterindication

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SideEffects
-DDI due to entric binding of other drugs
-GI disconformation
-May cause hypertriglyceridemia

Counterindication
-Pre-existing hepato-biliary tract disease [BABR ↓entrohepatic circulation of bile acids and effecti fluidity of the bile acids]

Front 32

Niacin
[Nicotinic acid]

-Kinetics
-SideEffects
-Montoring
-Counterindication

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Kinetics: inactive metabolite and unchanged drug in urine.
SideEffects
-cutaneous vasodilation (→ itching mediated by prostaglandins). Prevent with aspirin or ibuprofen.
-Hepatotoxicity is dose-dependent
-GI upset and Ulcerations
-Hyperglycemia
Monitor: Liver function tests
Counterindication: Pregnancy