Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CVS drugs > Lipid lowering drugs > Flashcards

Lipid lowering drugs Flashcards

1
Q

Name all the classes of Lipid lowering drugs

A
  1. Statins (HMG-coA reductase inhibitors)
  2. Fibrates
  3. PCSK9 inhibitors
  4. Omega-3-acid ethyl esters
  5. Bile acid binding resins/sequestrants
  6. Ezetimibe
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name the common statins

A

Atorvastatin
Simvastatin
Lovastatin
(suffix ends with -statin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the mechanism of statins?

A
  • Competitively inhibits HMG-CoA reductase
  • HMG-CoA reductase unable to convert HMG-CoA to mevalonate (the rate limiting step of cholesterol synthesis)
  • Cholesterol is reduced and hence VLDL concentration and hence triglycerides
  • Reduced intrahepatic cholesterol biosynthesis
  • Decreases cholesterol intracellularly will induce synthesis of more LDL-Receptors to take in more LDL from the bloodstream
  • Depletion of intracellular cholesterol causes
    the cell to increase the number of specific
    cell-surface LDL receptors that can bind and
    internalize circulation LDL-Cs.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Statins are indicated for?

A

All types of hyperlipidemia

First line treatment for hypercholesterolemia

Significantly reduces the risk of mortality in patients suffering from CAD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does statins influence the lipid levels

A

Decreases LDL (MOST)

Decreases TGA

Increases HDL (Slightly)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Pleotropic effects of statins

A
  • NO synthesis ↑
  • LDL cholesterol oxidation ↓
  • Inflammatory processes ↓
  • Coagulation processes ↓
  • Endothelial and plaque stabilisation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Route of administration of statins

A

Oral, given in evening

Reasons:
- Typically stop eating in the evening
- Body has lower cholesterol levels
- Evening will synthesise cholesterol thus HMG-CoA reductase more active
- Hence statins are used to increase efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Adverse effects of statins

A

General:
1. Headache
2. GI (Constipation, diarrhoea)

Hepatic
1. Increase in LFTs (involvement of cyp450 in breakdown of statins

Myopathy (decrease coenzyme Q synthesis and impair energy production)

Myalgia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Statins contraindicated in?

A
  • Hypersensitivity
  • Active liver disease
  • Muscle disorder
  • Pregnancy, breastfeeding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Name some common PCSK9 inhibitors

A
  1. Alirocumab
  2. Evolocumab
    -mab: Monoclonal antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Route of administration for PCSK9 inhibitors?

A

IV route

Cannot be oral as monoclonal antibodies will be digested

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mechanism of actions of PCSK9 inhibitors?

A
  • Inhibition of hepatic proprotein convertase subtilisin-kexin 9 (PCSK9) which targets LDL receptors for degradation in lysosomes
  • Reduced LDL receptor degradation: more cell-surface LDL receptors that can bind and internalise circulation LDLs.
  • Increasedremoval ofLDLfrom the blood stream
  • ↓↓↓LDL,↑HDL,↓triglyceride
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the clinical indications for PCSK9 inhibitors?

A
  1. Familial hypercholesterolemia (Typically an alternative for those intolerant to statins)
  2. Patients with significant artherosclerotic CVD requiring more LDL-C lowering after being on diet control and statins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

PCSK9 inhibitors frequently combined with?

A

Statins to lower LDL-C levels 50%-60% above that achieved by statin therapy alone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Adverse effects of PCSK9 inhibitors

A
  1. Hypersensitivity
    • EG: hypersensitivity vasculitis or serious allergies requiring hospitalization
  2. Injection site inflammatory reactions (erythema, itchiness, swelling, pain or tenderness)
  3. Increased incidence of nasopharyngitis and sinusitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Name the common fibrates

A
  1. Fenofoibrate
  2. Gemfibrozil
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Route of administration of fibrates

A

Oral

18
Q

Mechanism of fibrates?

A
  • Ligands for the peroxisome proliferators-activated receptor-alpha (PPAR-α) protein
  • Results in increased activity of lipoprotein lipase (Interacts with Apo-C2)
  • Stimulating lipoprotein lipase activity, which cleaves triglycerides to form glycerol and fatty acids
19
Q

How does fibrates influence the lipid levels

A

↓ LDL,↑HDL,↓↓↓triglyceride

lowers LDL through increasing Beta-oxidation of FAs, lower VLDL is produced and secreted by liver, LDL being derived from VLDL will decrease also

20
Q

Clinical uses of fibrates

A

Treatment of hypertriglyceridemias with VLDL elevations especially for dysbetalipoproteinemia

Typically only used for hypertriglyceridemias when TGA levels are too high

21
Q

Adverse effects of Fibrates?

A
  1. Dyspepsia

2 Myopathy
- When combined with statins particularly
- CYP-450 inibitor prevents breakdown of statins into metabolites, increasing co-enzyme Q

  1. Cholelithiasis
    - Fibratesinhibitcholesterol 7α hydroxylase→ decreasedbile acidsynthesis→ supersaturation ofbilewithcholesterol(↑cholesterol:bile acidratio)
22
Q

Fibrates are contraindicated in

A
  1. Renal insufficiencies (dose adjustments needed)
  2. Liver failure
  3. Gall bladder diseases (eg. cholelithiasis)
23
Q

Name the common Omega-3-acid ethyl ester

A

Omacor
Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) ethyl esters

24
Q

Mechanism of Omega-3-acid ethyl ester

A
  • Reduces hepatic triglycerides (TG) production and increases TG clearance from VLDL
  • Functional inhibition of diglyceride acyltransferase (responsible for TG biosynthesis) as EPA and DHA are poor substrates for the enzyme.
    Diglyceride acyltransferase adds the 3d fatty acid to the chain, drug produces a 3rd fatty acid chain that has kinks in it thus enzyme take longer to synthesise new chain
  • Increase fatty acids breakdown (via beta-oxidation)
25
Q

Clinical indications for Omega-3-acid ethyl ester

A
  • Used (in conjunction with dietary measures) for Hypertriglycerideaemia (Type IV) monotherapy
  • Used for Familial Combined Hyperlipidaemia (Type IIb) in combination with statins (when control of TG is insufficient)
  • Not indicated for hyperchylamicronaemia because chylomicrons come from dietary origins not synthesised in liver hence no effect as this drug targets the synthesis of TAG
26
Q

Route of administration for Omega-3-acid ethyl ester

A

Oral (2-4g or more per day)
Taken with food

27
Q

How is Omega-3-acid ethyl ester metabolised

A

In the liver

28
Q

How does Omega-3-acid ethyl ester influence the lipid levels

A

↓↓↓ triglyceride synthesis in the liver

29
Q

Adverse effects of Omega-3-acid ethyl ester

A
  1. GI effects
    - Medication used as food source for bacteria may lead to abdominal distention, pain, flatulence, diarrhoea, constipation
  2. DHA may lead to increase in LDL-C needs close monitoring eg. patients with familial hypercholesterolemias
  3. Competes with Arachidonic Acid for COX enzymes By occupying the active sites on COX, omega-3 fatty acids decrease the production of thromboxane A2 from arachidonic acid. Reducing the production of TbA2 can lead to increased bleeding time (special monitoring for patients on anticoagulants like warfarin and aspirin)
30
Q

Name some common bile acid binding resins

A

Cholystyramine, Colestipol, Colesevelam

31
Q

Mechanism of bile acid binding resins

A
  1. Positively charged bile resins bind negatively charged bile acids and bile salts in small intestines, increasing excretion in faeces
  2. Lowering bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids
  3. Increase synthesis of LDL receptors
  4. Activates an increased hepatic uptake of cholesterol containing LDL particles, reducing plasma LDL
32
Q

How does Bile acid binding resins influence the lipid levels

A

↓↓↓ LDL

may lead to increase in VLDL
- When bile acids are bound and excreted by cholestyramine, the liver compensates by increasing the synthesis of new bile acids from cholesterol. This increased cholesterol synthesis can result in increased production of VLDL particles by the liver to transport the excess cholesterol to peripheral tissues.

33
Q

Route of administration of Bile acid binding resins

A

Oral only

34
Q

Clinical indications of Bile acid binding resins

A
  1. Primary hypercholesterolemia
  2. +Niacin: Treat elevations in persons with combined hyperlipidemia
35
Q

Adverse effects of Biel acid binding resins

A
  1. GI
    - constipation, nausea and flatulence
  2. Impaired absorption of fat soluble vitamins A,D,E,K
    - Bile acids facilitate process of fats and vitamins
  3. May slightly increase triglycerides levels, leading to hyper-triglyceridemia
36
Q

Name common intestinal cholesterol absorption inhibitors

A

Ezetimibe

37
Q

Mechanism of Ezetimibe

A
  1. Reduces cholesterol absorption at the small intestine, brush border of enterocytes by inhibition of the sterol transporter Niemann-Pick C1-Like-1 (NPC1L1)
  2. Decreases the chylomicrons formed from cholesterols
  3. Lipoprotein lipase breaks down less chilomicrons into less chilomicrons remnants, which is transported to liver
  4. Less chilomicron remnants thus lower chlesterol and hence less VLDL and triglyceride formations
  5. Increases LDL receptors, increasing uptake of LDLs from bloodstream
38
Q

Combination therapy for ezetimibe?

A

Combination with simvastatin
Ezetimibe + Simvastatin -> Vytorin

39
Q

Route of administration of ezetimibe?

A

Oral

40
Q

Adverse effects of ezetimibe?

A
  1. Rhabdomyolysis breakdown of skeletal muscle tissues (More common when combined with statins)
  2. Low incidence of reversible hepatotoxicity
  3. Contraindicated to use with a statin during active liver disease
  4. Angioedema
  5. Myalgia

CVS drugs (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions