Antidyslipidaemics Flashcards
(47 cards)
What is the main drug class studied in the lecture?
HMG-CoA Reductase Inhibitors (Statins)
Specific example: atorvastatin, a pleiotropic drug.
What is the role of LDL-cholesterol in cardiovascular disease?
High plasma concentrations of LDL-cholesterol form a major risk factor in atherosclerosis.
What are some examples of therapeutics mentioned alongside Statins?
- Cholesterol Uptake inhibitors: ezetimibe
- PCSK9 Inhibitors: evolocumab
What are Statins structurally analogous to?
3-hydroxy-3-methylglutaric acid (HMG).
What is the mechanism of action of Statins?
Potent reversible inhibitors of hepatic de novo cholesterol biosynthesis through HMG CoA.
What are the primary effects of Statins on LDL levels?
↑LDL clearance → ↓plasma LDL-cholesterol & TGs.
What additional therapeutic actions do Statins have?
Potentially therapeutic mechanisms independent of their hypocholesterolemic properties.
What is one of the pleiotropic effects of Statins?
Anti-inflammatory effects by reducing binding of inflammatory transcription factor NFκB to DNA target.
How do Statins affect nitric oxide release?
Endogenous nitric oxide (NO) release is maintained to promote systemic vasodilation.
What is the pharmacokinetic profile of Atorvastatin?
- Oral dosing - peak plasma concentration within 1-2h
- Poor bioavailability 14%
- Highly protein bound (98%)
- Extensively metabolised in liver
What are some major adverse drug reactions (ADRs) of Statins?
- Elevated liver enzymes
- Myopathy & Rhabdomyolysis
- Cognitive impairment (mild reversible)
What factors can increase the risk of cognitive impairment with Statins?
- Advanced age
- Hepatic/renal disease
- Hyperthyroidism
True or False: Statins should be avoided in pregnancy.
True
What is the role of PCSK9 in cholesterol metabolism?
PCSK9 binds to and degrades LDL receptors, leading to less LDL cholesterol uptake by liver cells.
What are the five main classes of lipoproteins?
- Chylomicrons
- Very low density lipoproteins (VLDL)
- Low density lipoproteins (LDL)
- High density lipoproteins (HDL)
- Intermediate density lipoproteins (IDL)
What is the primary function of HDL?
Reverses cholesterol transport and protects against atherosclerosis.
How is cholesterol transported in the body?
Transported in lipoproteins (HDL, LDL, IDL, VLDL, Chylomicrons).
What is the relationship between plasma cholesterol levels and coronary heart disease (CHD) risk?
CHD risk increases as plasma cholesterol levels increase.
What effect does raised intracellular cholesterol have on HMG CoA reductase?
Decreases activity of HMG CoA reductase.
What is the impact of LDL receptor degradation on cholesterol levels?
Leads to less LDL cholesterol uptake by liver cells and higher blood levels.
What are the clinical presentations associated with ischemia from arterial occlusion?
- Angina Pectoris
- Myocardial Infarction
- Transient Ischemic Attack
- Stroke
- Renal impairment
Fill in the blank: Statins are indicated as adjunctive therapy to diet in adults with all forms of _______.
[hyperlipidemias]
What is the relationship between dyslipidemias and cardiovascular disease?
High association between dyslipidemias and cardiovascular disease, particularly in diabetes.
How does increased LDL contribute to atherosclerosis?
Uptake of oxidised LDL by macrophages leads to cholesterol loading and foam cell formation.
