Pharmacovigilance, Pharmacogenetics & Hyperlipidaemia Flashcards

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1
Q

Compare Type A and Type B Adverse Drug Reactions (ADR)

A

Type A;

  • Dose dependent
  • Frequent
  • Predictable
  • Overdose
  • Explained by pharmacological effect

Type B;

  • Dose independent
  • Rare
  • Unpredictable
  • Not explained by pharmacological effect
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2
Q

2 examples of Type A ADRs

A
  • Bleeding after anticoagulants

- Hypoglycaemia after insulin

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3
Q

What are 4 methods of action for an ADR

A
  • Exaggerated response
  • Desired pharmacological effect at alternative site
  • Additional pharmacological effect
  • Triggering immunological effect (anaphylaxis)
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4
Q

What scheme is in place to report ADRs

A

Yellow Card scheme

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5
Q

Most cholesterol is made in the body, how much comes from diet?

Suggest some uses of it

A

25%

  • Membrane integrity
  • Production of steroid hormones, Bile acids and Vit D
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6
Q

Below what level should total cholesterol be?

A

5.2 mmol/l

>6.2 is high

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7
Q

How do Statins work?

A
  • Competing inhibition of HMG-CoA Reductase

- Upregulation of LDL receptors-> Increased clearance of circulating LDL

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8
Q

How do Statins improve endothelial function?

A

Increased NO and Vascular Endothelial Growth Factor

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9
Q

How do Statins improve atherosclerotic plaque stabilisation?

A

Reduced SMC proliferation and increased Collagen

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10
Q

How do Statins improve haemostasis?

A
  • Reduced fibrinogen
  • Increased platelet aggregation
  • Increased fibrinolysis
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11
Q

How do Statins improve anti-inflammatory function?

A

Reduced proliferation of inflammatory cells into plaque

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12
Q

How are Statins anti-oxidants?

A

Reduced Superoxide formation

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13
Q

How do Simvastatin and Atorvastatin?

A

Simvastatin;

  • Is a prodrug
  • Half life of 2 hours

Atorvastatin;

  • Is an active drug
  • Half life of 24 hours
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14
Q

List some ADRs of Statin therapy

A
  • GI disruption + nausea
  • Headaches
  • Myalgia (due to Myopathy, check CK levels)
  • RARELY Rhabdomyolysis
  • Raised Liver enzymes
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15
Q

List 4 contraindications of statin therapy

A
  • Pregnancy
  • Breastfeeding
  • Renal impairment
  • Hepatic impairment
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16
Q

Why is CYP 3A4 important in Statin metabolism?

A

Drugs such as Amlodipine, Diltiazem and Macrolides inhibit the enzyme, thus increasing [plasma statin]

17
Q

Describe the statin therapy prescription for Primary Prevention

(Elevated cholesterol but no CVS disease/ event)

A

20mg Atorvastatin once daily

This still counts as high intensity

18
Q

Describe the statin therapy prescription for Secondary Prevention

(Elevated cholesterol WITH CVS disease/ event)

A

80mg Atorvastatin once daily

19
Q

What’s the target for statin therapy?

A

> 40% reduction in non-HDL Cholesterol at 3 months

20
Q

How does grapefruit juice affect CYP 3A4?

A

Inhibits it

21
Q

What is the Nocebo effect?

A

Patient thinks they’ll have side effects, so they experience them

22
Q

How can Fibrates (Fibric acid derivatives) help in treating hyperlipidaemia?

A

Activation of a nuclear transcription factor that regulates expression of a gene controlling Lipoprotein metabolism

(PPAR-Alpha)

Thus, increased LPL production

23
Q

What are some ADRs of Fibrates?

A
  • GI Upset
  • Myositis (rare)
  • Cholelithiasis (Gall stones)
24
Q

What are some contraindications of using Fibrates?

A
  • Photosensitivity

- Gall bladder disease

25
Q

How may Fibrates such as Fenofibrate interact with Warfarin?

A

May increase anticoagulation

26
Q

How do Cholesterol Aborption Inhibitors work?

Name one example

A

Inhibit NPC1L1 transporter-> reduced gut cholesterol absorption

Ezetimibe (A prodrug, mostly stays in enterohepatic circulation)

27
Q

List 2 ADRs and 1 contraindication for using Ezetimibe

A
  • GI Upset
  • Ab pain
  • Hepatic failure
28
Q

What can happen if Ezetimibe is taken alongside Statins and Ciclosporin?

A

Statins;
- Increased risk of Rhabdomyolysis

Ciclosporin;
- Increased systemic concentration of Ezetimibe

29
Q

How can Ezetimibe be incorporated into a prescription?

A
  • Can be taken on its own or alongside a statin

- No dose escalation (always 10mg)

30
Q

In Secondary Prevention of Hyperlipidaemia suggest targets for;

  • LDL Cholesterol
  • Total Cholesterol
A

LDL: 2mmol/L

Total: 4mmol/L

31
Q

How do PCSK9 Inhibitors work?

Give 2 examples

A

Inhibit the PCKS9 protein, which binds endocytosed LDL-Receptor and directs degradation

  • Alirocumab
  • Evolocumab (these drugs are Monoclonal AntiBodies)
32
Q

PCSK9 Inhibitors are x100 expensive than statins and need to be taken as injections.

When are they currently recommended for use by NICE?

A

Primary and Secondary prevention in Resistant Familial Hypercholesterolaemia

33
Q

Describe the effects and use of Plant Sterols

A
  • Some LDL-C lowering effects
  • Naturally in grains, legumes etc
  • Work with statins but not Ezetimibe (PSs and E compete)