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LIPIDS > LIPIDS PHARMACOLOGY > Flashcards

LIPIDS PHARMACOLOGY Flashcards

1
Q

Complexes for transporting lipids

A

Lipoproteins

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2
Q

Sources of lipids

A

Exogenous
Endogenous

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3
Q

Storage site for triglycerides

A

Adipocytes

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4
Q

Dietary TGs are packaged as….

A

Chylomicrons

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5
Q

Endogenous TGs are packaged into……….

A

VLDL

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6
Q

Transporter for GI uptake of TGs

A

Nieman-Pick C1 Like 1 (NPLC1L1)

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7
Q

Function of HMG-CoA reductase

A

Reduces HMG CoA to mevalonate

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8
Q

Lipoproteins in terms of increasing density

A

HDL
LDL
IDL
VLDL
Chylomicrons

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9
Q

Source of LDL

A

When VLDL becomes dense after action of Lipoprotein lipase

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10
Q

Function of HDL

A

Reverse cholesterol transport
From peripheral tissues to liver

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11
Q

Transporter and apoprotein of reverse cholesterol transport

A

ABCA1 transporter
apo A1

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12
Q

Classes of hyperlpidemia

A

Primary (inherited/genetic)
Secondary (acquired)

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13
Q

Examples of primary dyslipidaemias

A

Familial hypertriglyceridemia
Familial hypercholesterolemia
Familial combined hyperlipidemia
Familial hyperapobetalipoprotein

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14
Q

Familial hypercholesterolemia

A

LDL receptor defect
Apo B receptor defect
Reduced LDL clearance or uptake
High levels of LDLc
Normal TGs

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14
Q

Familial hypertriglyceridemia

A

Mutated LPL gene
Endogenous overproduction of VLDL
High TGs and low HDL

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15
Q

Familial hyperapobetalipoprotein (Broad beta disease)

A

Defects in ApoE gene
Reduced clearance of chylomicrons, IDL and beta VLDL
High total cholesterol and TGs

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16
Q

Familial combined hyperlipidemia

A

Most common type
No single gene defect responsible
High LDL and TGs

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17
Q

Disease conditions that can cause dyslipidemia

A

Type 2 DM
CKD
Hypothyroidism
Polycystic ovary disease

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18
Q

Role of thyroid hormones in lipids

A

TH stimulates both lipogenesis and lipolysis, although when TH levels are elevated, the net effect is fat loss

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19
Q

Therapeutic options for dyslipidemia

A

Bile acid resins
Ezetemibe
Statins
Fibrates
Nicotinic acid derivatives
Fish oil derivatives (EPA, DHA)
Orlistat
PCSK9 inhibitors

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20
Q

Bile acid binding resins

A

Cholestyramine
Colesevelam
Colestipol

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21
Q

Which enzyme is upregulated by bile acid binding resins

A

7 alpha hydroxylase

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22
Q

Function of 7 alpha hydroxylase

A

Biosynthesis of bile acids from cholesterol

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23
Q

Effects of bile acid binding resins on lipid profile

A

Reduce LDL
No effect on HDL
Increase TGs

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24
Q

Side effects of bile acid sequestrants

A

Constipation
Diarrhea
Bloating
Dyspepsia
Reduced absorption of fat soluble vitamins
Reduced absorption of some drugs (digoxin, warfarin)

25
Q

Contraindication to bile acid binding resins

A

Biliary and bowel obstruction disorders

26
Q

Ezetimibe mechanism

A

Inhibits cholesterol absorption by blocking NPC1L1 transporter

27
Q

Effect of statins on lipid profile

A

Reduce LDL
Reduce TGs
Increase HDL

28
Q

Use of statins with these lipid lowering agents increases risk of adverse effects

A

Fibrates
Niacin

29
Q

Most potent statins

A

Atorvastatin
Rosuvastatin

30
Q

Least potent statin

A

Fluvastatin`

31
Q

Long acting statins

A

Pravastatin
Rosuvastatin
Atorvastatin

32
Q

Short acting statins

A

Lovastatin
Simvastatin

33
Q

Which statins are not metabolised throug Cyp 450 pathway

A

Rosuvastatin
Pravastatin

34
Q

Adverse effects of statins

A

GI disturbances
Increased liver enzymes
Insomnia
Rash
Rhabdomyolysis
Myositis

35
Q

Examples of fibrates

A

Bezafibrate
Fenofibrate
Gemfibrozil
Clofibrate

36
Q

Effects of fibrates on lipid profile

A

Reduce VLDL
Reduce TGs
Reduce LDL
Increase HDL

37
Q

Mechanism of fibrates

A

Agonists at PPAR-alpha
Increase transcription of genes for LPL, apoA1 and apoA5
Stimulate beta oxidation of fatty acids
Inhibit NF-Kb

38
Q

Clinical use of fibrates

A

Hypertriglyceridemia
Mixed dyslipidemia
Dysbetalipoproteinemia

39
Q

Which agent is preferred in dysbetalipoproteinemia

A

Fibrates

40
Q

Adverse effects of fibrates

A

GI symptoms
Pruritis
Rash
Myositis
Rhabdomyolysis
AKI

41
Q

How do statins and fibrates cause AKI

A

Myoglobin infiltration

42
Q

How do fibrates cause cholelithiasis

A

Increasing secretion of cholesterol into bile acids

43
Q

Contraindications of fibrates

A

Gallbladder disease
Impaired renal function

44
Q

Which fibrate has a better safety profile

A

Fenofibrate

45
Q

Mechanism of nicotinic acid derivatives

A

Activates HM74A receptor
Inhibit TG production and VLDL secretion
Increase half life of apoA1

46
Q

Effect of nicotinic acid derivaties on lipid profile

A

Reduce TGs
Reduce LDL
Increase HDL

47
Q

Effect of activation of HM74A receptor

A

Inhibits lipolysis
Reduces flux of FFAs to the liver

48
Q

Examples of nicotinic acid derivatives

A

Niacin
Acipimox

49
Q

Adverse effect of nicotinic acid derivatives (NAD)

A

Cutaneous flushing
Pruritis
Palpitations
GI distrubances
Hyperuricemia
Impaired insulin sensitivity
Hepatotoxicity

50
Q

Contraindication to nicotinic acid derivatives

A

Active peptic ulcer disease
Caution in gout

51
Q

How do nicotinic acid derivatives cause cutaneous flushing

A

Release of PGD2 AND PGE2 in the skin

52
Q

How is cutaneous flushing due to nicotinic acid derivatives treated

A

Aspirin 30minutes before taking the nicotinic acid derivatives

53
Q

Examples of omega-3 fatty acids

A

Eicosapentanoic acid EPA
Docosahexanoic acid DHA

54
Q

Effect of fish oils on lipid profile

A

Reduce TGs
Some studies show increase in LDL but not conclusive

55
Q

Mechanism of orlistat

A

Inhibits pancreatic and intestinal lipase activity

56
Q

Mechanism of lomitapide

A

Inhibits microsomal triglyceride transfer protein (MTP)
hinders producing lipoproteins that contain apo-B in the hepatocytes and the enterocytes and leads to a decrease in generating very-low-density lipoprotein (VLDL) and chylomicrons

57
Q

Role of microsomal triglyceride transfer protein (MTP)

A

Transfers lipids (TGs, cholesteryl esters, and phosphatidylcholine) into apoB-containing lipoproteins such as very-low-density lipoprotein (VLDL) particles originating from the liver.
Transfers lipids to chylomicrons originating from the intestine

58
Q

Effect of lomitapide on lipid profile

A

Reduce LDL

59
Q

Examples of PCSK9 inhibitors

A

Alirocumab
Evolocumab

60
Q

Role of PCSK9

A

Proprotein convertase subtilisin kexin 9 (PCSK9) is involved in LDL receptor regulation
PCSK9 is a protease that degrades the LDL receptor, thereby regulating its expression

LIPIDS (3 decks)

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