Pharmacovigilance, Pharmacogenetics & Hyperlipidaemia Flashcards
(33 cards)
Compare Type A and Type B Adverse Drug Reactions (ADR)
Type A;
- Dose dependent
- Frequent
- Predictable
- Overdose
- Explained by pharmacological effect
Type B;
- Dose independent
- Rare
- Unpredictable
- Not explained by pharmacological effect
2 examples of Type A ADRs
- Bleeding after anticoagulants
- Hypoglycaemia after insulin
What are 4 methods of action for an ADR
- Exaggerated response
- Desired pharmacological effect at alternative site
- Additional pharmacological effect
- Triggering immunological effect (anaphylaxis)
What scheme is in place to report ADRs
Yellow Card scheme
Most cholesterol is made in the body, how much comes from diet?
Suggest some uses of it
25%
- Membrane integrity
- Production of steroid hormones, Bile acids and Vit D
Below what level should total cholesterol be?
5.2 mmol/l
>6.2 is high
How do Statins work?
- Competing inhibition of HMG-CoA Reductase
- Upregulation of LDL receptors-> Increased clearance of circulating LDL
How do Statins improve endothelial function?
Increased NO and Vascular Endothelial Growth Factor
How do Statins improve atherosclerotic plaque stabilisation?
Reduced SMC proliferation and increased Collagen
How do Statins improve haemostasis?
- Reduced fibrinogen
- Increased platelet aggregation
- Increased fibrinolysis
How do Statins improve anti-inflammatory function?
Reduced proliferation of inflammatory cells into plaque
How are Statins anti-oxidants?
Reduced Superoxide formation
How do Simvastatin and Atorvastatin?
Simvastatin;
- Is a prodrug
- Half life of 2 hours
Atorvastatin;
- Is an active drug
- Half life of 24 hours
List some ADRs of Statin therapy
- GI disruption + nausea
- Headaches
- Myalgia (due to Myopathy, check CK levels)
- RARELY Rhabdomyolysis
- Raised Liver enzymes
List 4 contraindications of statin therapy
- Pregnancy
- Breastfeeding
- Renal impairment
- Hepatic impairment
Why is CYP 3A4 important in Statin metabolism?
Drugs such as Amlodipine, Diltiazem and Macrolides inhibit the enzyme, thus increasing [plasma statin]
Describe the statin therapy prescription for Primary Prevention
(Elevated cholesterol but no CVS disease/ event)
20mg Atorvastatin once daily
This still counts as high intensity
Describe the statin therapy prescription for Secondary Prevention
(Elevated cholesterol WITH CVS disease/ event)
80mg Atorvastatin once daily
What’s the target for statin therapy?
> 40% reduction in non-HDL Cholesterol at 3 months
How does grapefruit juice affect CYP 3A4?
Inhibits it
What is the Nocebo effect?
Patient thinks they’ll have side effects, so they experience them
How can Fibrates (Fibric acid derivatives) help in treating hyperlipidaemia?
Activation of a nuclear transcription factor that regulates expression of a gene controlling Lipoprotein metabolism
(PPAR-Alpha)
Thus, increased LPL production
What are some ADRs of Fibrates?
- GI Upset
- Myositis (rare)
- Cholelithiasis (Gall stones)
What are some contraindications of using Fibrates?
- Photosensitivity
- Gall bladder disease
