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cvs pharmaco > Lipid Lowering Drugs > Flashcards

Lipid Lowering Drugs Flashcards

1
Q

Name the 6 drug classes to treat dyslipidemias

A
  1. Omega-3-acid ethyl esters
  2. PCSK9 inhibitors
  3. Fibrates
  4. Resins
  5. HMG-CoA reductase inhibitors (Statins)
  6. Ezetimibe
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2
Q

Name 3 examples of statins

A

Atorvastatin, pravastatin, simvastatin

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3
Q

MOA of statins

A
  1. Competitive inhibitor of HMG-CoA reductase (rate limiting enzyme for endogenous cholesterol synthesis), reduce conversion of HMG-CoA to mevalonic acid, thus overall decreasing cholesterol synthesis
  2. Upregulates LDL receptor on cell surface: Decreased intracellular cholesterol causes the cell to increase specific cell-surface LDL receptors that can bind and internalise circulating LDLs
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4
Q

2 clinical uses of statins

A
  1. Lower LDL levels in all types of dyslipidemias
  2. Reduce the risk of coronary events or mortality in patients with IHD
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5
Q

Which time of the day are statins commonly given?

A

Evening (because dietary cholesterol is low, so body needs to produce more endogenously, thus statins most effective)

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6
Q

Give 2 ADRs of statin use

A
  1. Biomedical abnormalities in liver function
  2. Muscles: myopathy and rhabdomyolysis (causes tea coloured urine)
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7
Q

Statins are contraindicated in (4 types of patients)… because…

A
  1. Pregnancy
  2. Nursing mothers
  3. Children
  4. Teenagers
    Known to affect neurodevelopment in foetus and child
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8
Q

State 2 examples of PCSK9 inhibitors

A
  1. Evolocumab
  2. Alirocumab
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9
Q

MOA of PCSK9 inhibitor

A

Inhibits PCSK9 which targets LDL receptors for degradation by lysosomes.
Thus reduces degradation of LDL receptors, so increases the number of cell-surface LDL receptors that can bind and internalise circulatory LDL

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10
Q

State 2 clinical uses of PCSK9 inhibitors

A
  1. Lower LDL levels in the blood in familial hypercholesterolemia patients especially if they’re intolerant to statins
  2. Clinically significant atherosclerotic CVD patients requiring additional LDL lowering therapy after being on diet control and maximally tolerated statin therapy
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11
Q

Administration of PCSK9 inhibitors

A

IV (monoclonal antibody)

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12
Q

Advantage of taking PCSK9 in combination with statins

A

Can lower LDL levels by about 50-60% more than if statins are used alone

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13
Q

Give 2 ADRs of PCSK9 inhibitor use

A
  1. Inflammatory reactions at the site of injection
  2. Increased incidence of nasopharyngitis and sinusitis
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14
Q

PCSK9 inhibitors are contraindicated in patients that develop…

A

Hypersensitivity reactions

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15
Q

Name 2 examples of fibrates / fibric acid derivatives

A
  1. Gemfibrozil
  2. Fenofibrate
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16
Q

MOA of fibrates

A

Direct ligand for PPAR-alpha. Interaction with PPAR-alpha increases activity of lipoprotein lipase (LPL).
Effects:
- Increased breakdown of plasma TAG
- Plasma VLDL decreases in part due to decreased secretion by liver
- Plasma HDL rises moderately

17
Q

Clinical use of fibrates

A

Treatment of hypertriglyceridemia with VLDL elevation, especially in patients with dysbetalipoproteinemia

18
Q

Name 4 ADRs of fibrate use

A
  1. GI effects: nausea
  2. Skin rashes
  3. Gallstones
  4. Myositis
19
Q

Name a omega-3-acid ethyl ester drug

A

Omacor

20
Q

State the 2 omega-3-acid ethyl ester components in omacor

A

EPA and DHA

21
Q

MOA of omega-3-acid ethyl esters

A
  1. Reduces TG production and increases TG clearance from VLDLs
  2. DHA and EPA are weak substrates for diglyceride acyltransferase enzyme, thus omacor is a functional inhibitor of the enzyme, which reduces TG biosynthesis
  3. Increased fatty acid breakdown by beta oxidation
22
Q

2 clinical uses for omega-3-acid ethyl esters

A
  1. Used with dietary measures in hypertriglyceridemia (type IV)
  2. Used with statins for familial combined hyperlipidemia (type IIb)
23
Q

2 types of dyslipidemias where omega-3-acid ethyl esters are NOT useful

A
  1. Hyperchylomicronemia (type I)
  2. Familial hypercholesterolemia (Type IIa): LDL related issue, thus not effective
24
Q

Omega-3-acid ethyl esters are contraindicated in patients…

A

Allergic to fish

25
Q

Name 3 possible ADRs of omega-3-acid ethyl esters use

A
  1. GI symptoms: diarrhoea, flatulence, pain, dyspepsia, constipation, abdominal distension
  2. Decrease production of thromboxane A2 (thus could increase bleeding time, use in caution with patients on anticoagulants)
  3. Potential increase in LDL in some patients due to DHA
26
Q

Use of omega-3-acid ethyl esters should be cautioned in patients on…

A

Anticoagulants (due to decreased thromboxane A2 production, causing increased bleeding time)

27
Q

Name a bile acid binding resin

A

Cholestyramine

28
Q

MOA of cholestyramine

A

Bind to negatively charged bile acids and bile salts in the small intestine.
This lowers the bile acid concentration recycled back to the liver, thus liver increases conversion of cholesterol to bile acids, thus intracellular cholesterol concentration decreases.
Results in increased hepatic uptake of cholesterol-containing LDL particles, causing a fall in LDL in plasma

29
Q

2 clinical uses of cholestyramine

A
  1. Treat primary hypercholesterolemia (type IIa)
  2. With niacin: LDL elevations in familial combined hyperlipidemia (type IIb)
30
Q

Mode of administration of cholestyramine

A

Oral

31
Q

2 ADRs of cholestyramine use

A
  1. GI symptoms: constipation, nausea, flatulence
  2. Decreased absorption of fat soluble vitamins: ADEK
32
Q

MOA of ezetimibe

A

Inhibitor of NPC1L1 sterol transporter which reduces the intestinal absorption of sterols like cholesterol

33
Q

Clinical use of ezetimibe

A

To reduce plasma LDL levels
*Greater decrease in LDL when used with statins (eg ezetimibe with simvastatin = Vytorin)

34
Q

2 ADRs of ezetimibe use

A
  1. GI effects: diarrhoea, flatulence
  2. Rhabdomyolysis (common when used with statins)
35
Q

Ezetimibe use is associated with low incidence of

A

Hepatotoxicity

cvs pharmaco (6 decks)

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