7.2- Cholesterol drugs Flashcards
Describe the infiltration and entrapment of LDL in the arterial wall
- LDL enters endothelium–> gets OXIDISED,enabling it to:
- inhibits macrophage motility
- Induces T-cell activation and VSMC division/differentiation
- Toxic to endothelial cells
- Enhances platelet aggregation
State the 4 main classes of lipid lowering drugs
- Statins e.g. Simvastatin
- Cholesterol lipase inhibitors e.g. Ezetimibe
- Nicotinic acid/niacin
- Fibrates e.g. Fenofibrate
What are the indications for the use of statins?
- CV risk prevention (CVD+DM)
- Familial hypercholesterolaemia
Describe the mechanism of action of statins
- Inhibits HMG-CoA reducatase in the pathway to cholesterol synthesis from Acetyl-Co-A
- Thereore inhibits choleserol synthesis in hepatocytes
- Increases clearance of LDL and IDL ( by increased synthesis of LDL receptor)
- Decreases production of VLDL and LDL
Give 3 adverse drug reactions of statins
- Inreased transaminsase levels ( sign of liver damage)
- Myopathy
- Miscellaneous; GI complaints, anthralgias, headaches and memory loss
What is seen in Myopathy resulting as a statin ADR?
- Diffuse muscle pain
- CK> 10 x upper normal limit
With which statin drug combos is a myopathy seen?
- Seen when HIGHER doses of statins are used in combination with
- Cyclosporine
Erythromycin and niacin
What are some secondary benefits of statin treatment? ( APIR)
- Anti-inflammatory
- Plaque reduction
- Improved endothelial cell function
- Reduced thrombotic risk
What statin therapy is recommended as part of primary prevention of CVD in adults w a high QRISK2?
Atorvastatin 20mg
If high 10-year risk of developing CVD
How are statins used as part of secondary prevention?
Atorvastatin 80 mg
How is the level of CVD risk calculated?
using the QRISK2 risk calculator
What is the statin of choice?
Atorvastatin
What are are Fibric Acid Derivatives?
- Ampipathic carboxylic acids
- PPARalpha receptors agonist; increases production of lipoprotein lipase
Describe the mechanism of action of fibric acid derivatives
- PPARalpha receptor agonist; increases production of lipoprotein lipase
- Increases FA uptake and oxidation
- Reduces triglyceride levels
- Increases LDL particle size and HDL-C levels
Direct vascular effects
Name 3 indications for the use of FDA’s
Adjunctive therapy to diet
Hypertriglyceridaemia
Combined hyperliidemia with low HDL who not respond to NA
Describe the efficacy of FDA’s
Decreases trigyleride by up to 50%
LDL decreases but variably
Increases HDL up to 35% in Hypertriglyceridemia
Name 4 side effects of FDA
- GI upset
- Cholelithiasis
- Myositis
- Abnormal LFT’s
Name 2 contraindications for the use of FDA’s
- Hepatic or renal dysfunction
- Pre-existing gallbladder disease
Describe the mechanism of action of nicotinic acid derivatives/ niacin?
- Raises HDL cholesterol
- INHIBITS lipoprotein-A synthesis —> lipid lowering effect
- reduces coronary events
Name 4 adverse effects of nicotinic acid ( niacin)
Hepatotoxicity, GI
Activation of peptic ulcer
Hyperglycemia and reduced insulin sensitivity
Flushing, itching, headache
Name 2 contraindications for the use of Nicotinic acid
Peptic ulcer disease
Activ liver disease or unexplained LFT elevations
Give an example of a cholesterol lipase inhibitor
EZETIMIBE
How does Ezetimibe work?
selectively inhibits intestinal cholesterol absorption, therefore causing
- DECREASED intestinal delivery of cholesterol to the liver
- INCREASED expression of hepatic LDL receptors
- DECREASED cholesterol content of atherogenic particles
Describe the PK of ezetimibe
Ezetimibe and its active glucoronide metabolite circulate enterophepatically
- delivers agent back to the site of action
- therefore limits systemic exposure
Give 3 ADR’s of ezetimibe
Headache
Abdominal Pain
Diarrhoea
What drugs are given as part of combination therapy?
Statin plus any one of the following:
Fibrate ( not gemfibrozil
Nicotinic acid
Ezetimibe
omega-3 FA’s
What 3 factors are considered when choosing drugs for combo therapy?
Benefit ( CV risk reduction)
Cost
ADRs
Why are fibrates NOT used with statins?
Increased risk for myopathy and rhabdomyolysis
GEMFIBROZIL ( fibrate) may impair glucoronidation of statins
Name 4 POSITIVE dietary factors for cholesterol
and 3 negative ones
Positive factors:
- Fish oils
- Fibre
- Vitamin C/E
- Alcohol (HDL)
Negative factors:
- Dietary cholesterol/fat
- Sugar
- Alcohol (TG)
