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Clinical Pharmacology and Therapeutics > Cholesterol Pharmacology > Flashcards

Cholesterol Pharmacology Flashcards

1
Q

If we reduce total cholesterol by 10%, what happens to CHD risk?

A

15% decrease in CHD mortality

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2
Q

What is the primary target in preventing CHD?

A

LDL cholesterol

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3
Q

What does LDL do to vessels?

A

It infiltrates arterial walls and is trapped in the intima where it undergoes oxidation

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4
Q

Why is oxidised LDL bad?

A

It is pro-atherogenic - inhibits macrophage motility, induces T cell activation, is toxic to endothelial cells, and causes platelet aggregation.

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5
Q

What is the most commonly used class of lipid lowering drug?

A

Statins

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6
Q

What effect can statins have on LDL, TAG and HDL?

A

LDLs fall by 5-35%
TAG falls by 10-35%
HDLs increase by 5%

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7
Q

How do statins work?

A

Inhibit HMG co-a reductase which is integral in cholesterol synthesis

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8
Q

What is the result of the action of statins?

A

Increased LDL and IDL clearance due to increased LDL receptor expression
Decrease VLDL and LDL production

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9
Q

What are the indications for statins?

A

CV risk prevention (Q risk score)

Familial hypercholesterolaemia

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10
Q

What is the most common adverse effect of statins?

A

Myopathy i.e. muscle aches

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11
Q

Which enzyme is affected by statins, and in who? (Not HMG co-a reductase, more of an ADR)

A

Aminotransferase levels are increased in 0.1-2.5% of pts treated. Transient and no long lasting liver damage.

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12
Q

When is it most common for myopathy to be experienced with statins?

A

At higher doses, and if given at the same time as certain other drugs (cyclosporin, gemfibrozil, erythromycin, niacin).

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13
Q

Aside from lowering LDL and TAG, what other beneficial affects do statins have?

A

Anti-inflammatory
Plaque reduction
Improved endothelial function
Reduced thrombotic risk

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14
Q

What is the intestinal absorption of statins like?

A

Variable - 30-85% absorption

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15
Q

Why is bioavailability of statins only 5-30% of administered dose?

A

Variable intestinal absorption as well as extensive 1st pass metabolism

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16
Q

When is the peak of cholesterol production in the day/night?

A

Early in the morning

17
Q

When do pts take short acting statins like simvastatin and why?

A

Just before bed/at night to coincide with cholesterol produciton peak

18
Q

What is the benefit of long acting statins?

A

Superior efficacy

19
Q

Aside from statins, what are the other main drugs can we give to lower lipids?

A

Fibrates/Fibric acid derivatives
Nicotinic acid/niacin
Cholesterol lipase inhibitors

20
Q

How do fibric acid derivatives work?

A

Peroxisome proliferator-activated receptor agonist

Production of lipoprotein lipase so TAG reduced by a lot

21
Q

What effect do fibric acid derivatives have on LDL?

A

Modest reduction that depends on which drug is used

22
Q

What are the indications for fibric acid derivatives?

A

Adjunct with diet modification
Hypertriglyceridaemia
Combined hyperlipidaemia with low HDL

23
Q

What are the ADRs associated with fibric acid derivatives?

A

GI upset
Gallstones
Myositis
Abnormal LFTs

24
Q

When are fibric acid derivatives contraindicated?

A

Hepatic or renal dysfunction

Pre-existing gall bladder disease

25
Q

What are the fibirc acid derivatives that can be prescribed?

A

Clofibrate

Gemfibrozil

26
Q

Which drug is the best at bringing up HDL levels?

A

Nicotinic acid

27
Q

How does nicotinic acid lower lipids?

A

Inhibits lipoprotein (a) synthesis

28
Q

What adverse effects can nicotinic acid have?

A 
Flushing
Itching
Headaches
Hepatotoxicity
Peptic ulcers
Hyperglycaemia
29
Q

When is nicotinic acid contraindicated?

A

Active liver disease
Abnormal LFTs that are unexplained
Peptic ulcer disease

30
Q

How does ezetimide work?

A

Inhibits intestinal cholesterol absorption and cholesterol lipase enzyme

31
Q

What effects does ezetimide have in the body?

A
  • Decreases cholesterol delivery to the liver
  • Increases LDL receptor expression in the liver
  • Decreases cholesterol content in atherogenic particles
32
Q

What are the ADRs associated with ezetimide?

A

Headaches
Nausea
Abdo pain
Diarrhoea

33
Q

What can we combine for the most effective lowering of lipids?

A

Statin plus another therapy

34
Q

What therpies can we combine with statins?

A 
Fibrate, not gemfibrozil
Nicotinic acid
Ezetimibe
Omega-3 Fatty acids
Resins
35
Q

How do we decide which therapy to comine with statins?

A

3 factors - cost, benefit, and ADRs.

36
Q

Why is statin combined with a fibrate potentially contraindicated?

A

Increased risk for myopathy and rhabdomyolysis

37
Q

What dietary factors can lower lipids?

A

Fish oils
Fibre
Vitamin C/E
Alcohol (HDL)

38
Q

What dietary elements should we cut down/out to lower lipids?

A

Fat
Dairy
Cake/biscuits
Alcohol (TAG)

Clinical Pharmacology and Therapeutics (26 decks)

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