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Module 3 > Treatment of lipid disorders > Flashcards

Treatment of lipid disorders Flashcards

1
Q

What is dislipidemia

A

A disorder of lipoprotein metabolism, including
lipoprotein overproduction or deficiency
Increased: total cholesterol/LDL/TG
Decreased: HDL

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2
Q

What are the sources of cholesterol

A

Diet (exogenous)
Liver (endogenous)
Hepatobilliary circulation

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3
Q

Examples of bile acid binding resins

A

colestyramine
colestipol

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4
Q

What is the action of bile acid binding resins

A

Cholesterol is converted into bile acids in the liver and enters the bile ducts
resins bind to the BA and allow excretion as faeces instead of returning to the liver

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5
Q

How do bile acid binding resins reduce lipids

A

decrease cholesterol absorption and enterohepatic circulation of BA/cholesterol in hepatocytes
increases LDLr expression and removal of LDL

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6
Q

What are the adverse drug reactions of bile acid binding resins

A
  • Constipation
  • Reduced absorption of other medicines
  • Fat-soluble vitamin deficiency
  • Increased triglyceride levels
  • Avoid in bowel or biliary obstruction
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7
Q

What is the action of ezetimibe

A

Blocks transport protein NPC1L1 in brush border of n enterocytes
inhibits chylomicron (dietary and billiary cholesterol)

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8
Q

Why are ezetimibes better than bile acid binding resins

A

-does not affect transport of fat-soluble vitamins /TGs/bile acids
-more potent

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9
Q

How does ezetimibe reduce lipids

A

-decrease cholesterol absorption
-increase LDL r expression
-decreases LDL in circulation/small HDL increase
Ezetimibe and its active metabolite circulate enterohepatically - Delivers agent back to the site of action - Limits
systemic exposure

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10
Q

What are the adverse drug reactions of ezetimibe

A
  • GI disturbance
  • Headache
  • Hepato-biliary disorders (rare)
  • Increased risk of rhabdomyolysis if used with a statin
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11
Q

What is an example of fibrates

A

fenofibrate

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12
Q

What is the action of fibrates

A

agonists at PPARa receptor
increases LPL expression in muscle
increases fatty acid uptake and oxidation in muscle cells
decreases TG
Increases apoAI/apoAII synthesis in hepatocytes
increases plasma HDL

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13
Q

What are the adverse drug reactions of fibrates

A
  • GI side-effects most common
  • Myositis-like syndrome
  • Rhabdomyolysis (with statin)
    Avoid: hepato-biliary disorders
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14
Q

Give examples of statins

A

simvastatin
atorvastatin
pravastatin

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15
Q

What is the action of statins

A

Inhibit HMG-CoA reductase

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16
Q

How do statins reduce lipids

A

-decreased cholesterol synthesis
-decreased synthesis and secretion of lipoproteins
-increased LDL r expression
-decreased LDL in circulation
-small increase in HDL

17
Q

What are the adverse drug reactions of statins

A
  • GI disturbances, insomnia, rashes
  • Hepato-biliary effects
  • Monitor LFT’s (baseline, within 3 months and at 12 months)
  • Transaminases
  • Myopathy / rhabdomyolysis
  • Advise patients to seek medical advice if develop muscle pain,
    tenderness or weakness

Contra-indications
* Active liver disease
* Pregnancy, breast-feeding

18
Q

What is rhabdomyolysis

A

breakdown of myoglobin in muscle and kidney
causes kidney toxicity

19
Q

What to avoid when taking simvastatin (CYP450 metabolised)

A

Avoid:
– Antibacterials (Clarithromycin, erythromycin)
– Antifungals (Azoles – ketoconazole, itraconazole)
– Grapefruit juice
Do not exceed simvastatin 20mg/day:
– Amiodarone
– Anticoagulants
– Calcium-channel blockers
* Amlodipine
* Diltiazem
* Verapamil
Do not exceed simvastatin 10mg/day:
– Fibrates (bezafibrate or ciprofibrate)

20
Q

What drug is taken by those who cannot tolerate statins/ezetimibe

A

PCSK9 inhibitors
alirocumab (monoclonal antibody for PCSK9)

21
Q

What is the action of PCSK9 inhibitors

A

PCSK9 normally decreases LDL receptor
alirocumab increases LDL receptors

22
Q

How is alirocumab administered

A

subcutaneously every 2 weeks

Module 3 (6 decks)

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