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Pharmacology > Cholesterol and Lipoprotein Metabolism Drugs > Flashcards

Cholesterol and Lipoprotein Metabolism Drugs Flashcards

1
Q

Structure of lipoprotein particles

A
  • Transport cholesterol, TGs and vitamins
  • Contain lipoproteins, ligands for cell-surface receptors
  • Example is a VLDL
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2
Q

Characteristic of plasma proteins

A

Density (g/mL)

  • CM: <0.95
  • VLDL: 0.95-1.006
  • IDL: 1.006-1.019
  • LDL: 1.019-1.063
  • HDL: 1.063-1.210

Total lipid (% weight)

  • CM: 98
  • VLDL: 90
  • IDL: 82
  • LDL: 75
  • HDL: 67
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3
Q

Functions of lipoproteins

A

Deliver triglycerides to muscle and adipose tissue

  • Chylomicrons
  • VLDL

Cholesterol transport

  • HDL
  • Remnants
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4
Q

Metabolism of lipoproteins

A
  • Assembly
  • Intravascular metabolism
  • Receptor-mediated clearance
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5
Q

Absorption of cholesterol and triglycerides

A
  • Cholesterol and TG absorbed by different mechanisms

- Cholesterol is converted to cholesterol esters

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6
Q

Intravascular metabolism of lipoproteins

A

Activation
-Interaction with HDL

Bind to Lipoprotein lipase
-Hydrolysis of triglyceride from core of lipoprotein

Depletion of triglycerides
-Chylomicron or VLDL remnants

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7
Q

Formation and hepatic uptake of remnant particles

A
  • Hepatic lipase metabolizes left over triglycerides

- Taken up by the liver through the LDL receptor

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8
Q

Formation and clearance of LDL particles

A
  • Formed from VLDL through IDL by hepatic lipase
  • Distinct cholesterol ester enriched lipoprotein
  • Can be cleared from the blood by the LDL receptor alone**
  • LDL fuses with LDL receptors in liver and unloads cholesterol
  • Down-regulation of LDL receptors
  • LDLs in circulation
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9
Q

LDL and atherosclerosis

A
  • LDLs migrate to intima of blood vessels
  • Oxidation of LDL leads to lipid peroxidation
  • Scavenger receptors on macrophages internalize LDL
  • Oxidized LDL in macrophages leads to foam cell production
  • Necrotic death of foam cells
  • Free radicals, proteolytic enzymes, cytokine production, impairment of endothelial function, adhesion molecules
  • Local inflammatory response
  • Damage to intima
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10
Q

Goals of hyperlipidemic drugs

A

Decrease LDL circulation in blood
-Relationship between LDL levels and cardiovascular disease
Increase HDL
-Delivers cholesterol to the liver
-Inverse relationship between HDL levels and cardiovascular disease
Decrease TGs because the liver takes TGs and makes VLDL, which gets converted to LDL

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11
Q

Lipid-lowering drugs

A
  • HMG-CoA Reductase Inhibitors (Statins)
  • Cholesterol Absorption Inhibitors
  • Fibric Acid derivatives
  • Niacin
  • Bile Acid Sequestrants
  • Omega 3 Fatty Acids
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12
Q 
Atorvastatin (Lipitor)*
Simvastatin (Zocor)
Rosuvastatin (Crestor)
Pravastatin (Pravachol)
Fluvastatin (Lescol)
Lovastatin (Mevacor)
A

Class:

Mechanism of action:

  • Competitively inhibits HMG-CoA Reductase
  • Synthesis of hepatic LDL receptors**
  • Hepatic uptake of LDL and ID**

Indication:

Pharmacological effects:

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-Rhabdomyolysis leading to kidney failure
-Constipation, diarrhea, stomach pain, nausea

oContraindicated drugs:

  • EtOH increase levels and rhabdomyolysis
  • Erythromycin, itraconazole, ketoconazole: contraindicated with Mevacor; used with caution in others because of increase chance of rhabdomyolysis.

oContraindications:

oWhich analgesic can the patient take:

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13
Q

Ezetimibe (Zetia)

A

Class: Cholesterol Absorption Inhibitor

Mechanism of action:
-Selectively inhibits cholesterol uptake through a brush border protein

Indication:

Pharmacological effects:

  • ↓cholesterol absorption by 50%
  • ↓LDL concentration in the plasma
  • ↓cholesterol content of chylomicrons

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-Abdominal pain
-Diarrhea

oContraindicated drugs:

oContraindications:
-Contraindicated in hepatic impairment

oWhich analgesic can the patient take:

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14
Q

Fenofibrate (TriCor)

Gemfibrozil (Lopid)

A

Class: Fibric Acid Derivatives

Mechanism of action:

  • Binds to a DNA transcription regulator
  • Control the synthesis of lipoprotein metabolizing enzymes

Indication:

Pharmacological effects:

  • ↑muscle expression of lipoprotein lipase
  • ↑uptake of TG containing lipoproteins
  • Increased HDL
  • Lowered TGs
  • Fibrates displace warfarin from albumin binding sites

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

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15
Q

Niacin (Niaspan)

A

Class: Nicotinic acid (Vitamin B3)–large doses 1,500-3,000 mg/day

Mechanism of action:
-Niacin receptor on adipocytes

Indication:

Pharmacological effects:

  • ↑lipase activity
  • ↓fatty acids to liver
  • ↓VLDL production

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:
-Flushing, Itching (these effects can be pre-treated with NSAIDs to prevent)
Gout

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

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16
Q

Lovaza

A

Class: Omega 3 Acid Ethyl Esters

Mechanism of action:
-Potential mechanisms: inhibition of acyl-CoA:l,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal β-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity.

Indication:
-Reduce triglyceride levels

Pharmacological effects:

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

17
Q

Summary of lipid lowering drugs

A

HMG-CoA Reductase Inhibitors

  • Lipitor
  • Rhabdomyolysis
  • Erythromycin, itraconazole, ketoconazole

Fibric Acid Derivative:
-Warfarin levels

Cholesterol Absorption Inhibitor

Niacin

Lovaza

Welchol

18
Q

Welchol

A

Class:

Mechanism of action:
-Non absorbed polymer that sequesters bile acids in the intestines so that they are not reabsorbed.

Indication:
-Adults with primary hyperlipidemia
Boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia
Adjunct with statins

Pharmacological effects:

How this drug might effect dental treatment of patient
oAdverse effects you have to consider:

oContraindicated drugs:

oContraindications:

oWhich analgesic can the patient take:

Pharmacology (15 decks)

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