Lipid Lowering Drugs Flashcards
List the four main lipid lowering classes of drug
- Statins
- Fibrates/fibric acid derivatives
- Niacin/nicotinic acid/vitamin B3
- Cholesterol absorption inhibitors (Ezetimibe)
Describe the indications for statin prescription
- Primary prevention of CVD/stroke, I.e. Before the disease has occurred. Preventing the onset
- Secondary prevention, I.e. A previous MI in which all patients are offered a statin.
- Diabetes mellitus, in which fish of CVD is significantly increased.
- Hypertension, obesity, when risk of CVD is significantly increased.
- Familial hypercholesterolaemia (type IIa)
- Hypothyroidism, in which high cholesterol level are seen.
- High cholesterol due to diet.
Describe the mechanism of action of statins.
Statins function by inhibiting the enzyme HMG CoA reductase, which is the rate limiting step in cholesterol synthesis.
- Statins also increase the synthesis of LDLR, hence reducing circulating LDL.
Why are some statins taken before bed?
The majority of cholesterol synthesis occurs at night. Some Statins, such as simvastatin, have a short half life so are most effective when taken directly before bed. For statins with longer half lives, e.g. Atorvastatin, Rosuvastatin, they can be taken any time of the day.
What are the serious adverse effects of statin therapy?
- Myopathy - this can manifest as significant muscle aches (myalgia) and pains.
- Rhabdomyolysis - a cause of acute renal failure, acute tubular necrosis.
- Statins can cause hepatic damage, however this is rare. Here, raised ALT and AST levels can rise.
The risk of adverse drug reactions increases with higher statin dose and when taken in combination with fibrates.
Name some side effects commonly reported with statin therapy.
- Nausea
- Diarrhoea and constipation
- Indigestion
- Muscle and joint pain
What monitoring needs to be done for patients receiving statin therapy?
Liver function tests should be done after starting statin therapy.
Monitoring of CK is not indicating unless muscle pain has been reported.
What baseline tests should be done for patients starting statin therapy?
Baseline LFT, CK and Lipids.
What patient groups should not be considered for statin therapy?
Patients with liver failure or dysfunction.
Individuals with a history of alcohol abuse.
Pregnant women, where statins have been associated with birth defects.
Describe how fibrates/fibric acid derivates work.
Fibrates work by activating PPAR-a, which is a receptor involved in the regulation of lipid and carbohydrate metabolism. They are structurally related to TZDs (glitazones). They increase the production of lipoprotein lipase to reduce blood triacylglyceride levels.
What are the side effects of treatment with fibrates?
Nausea, abdominal pain, diarrhoea, myosotis, rhabdomyolysis (especially when used with statins
What monitoring should be done with fibrate therapy?
When used in combination with a statin, CK and LFTs should be regularly monitored.
What are the contraindications of treatment with fibrates?
Liver disease, end stage renal failure, pregnancy.
A statin should not be prescribed while taking fibrates
How do niacins work as a lipid lowering therapy?
Niacin, or nicotinic acid, or vitamin B3, is a lipid lowering therapy which works by reducing hepatic synthesis of lipoproteins containing apoprotein B, I.e. LDL, vLDL, and increasing those containing apoprotein A, I.e. HDL. It does this by inhibiting DAG acetyltransferase-2, which is involved in TAG synthesis. As a result ApoB is degraded to a greater extend.
What are the side effects of niacin therapy?
Abdominal pain, nausea, diarrhoea, myosotis, dyspepsia, vasodilation.
What monitoring must be done with niacin therapy?
Monitor hepatic and renal function due to the risk of renal and hepatic failure.
What are the main contraindications of niacin therapy?
Pregnancy, breastfeeding, liver failure, peptide ulcer disease.
What dietary changes should patients consider to lower their cholesterol non-pharmacologically?
A diet high in fibre is beneficial in lowering LDL/cholesterol. Fibre can be found in plant-based foods, nuts, oats etc. It works by inhibiting bile reabsorption in the terminal ileum, forcing the liver to synthesise new bile acids from cholesterol.
How does ezetimibe work as a lipid lowering therapy?
Ezetimibe can be used as an adjuvant therapy to reduce blood cholesterol, however with a statin there is an increased risk of rhabdomyolysis. It works by inhibiting/reducing cholesterol absorption from the intestine.
What are the side effects of Ezetimibe use?
Nausea, abdominal pain, diarrhoea, myosotis, rhabdomyolysis.
What are the contraindications for Ezetimibe use?
Hepatic disease and pregnancy/breast feeding.
What are PSK-9 inhibitors?
PSK-9 inhibitors are a new class of lipid-lowering drug which function to inhibit PSK-9. This protein is involved in signalling the degradation of the LDL receptor, however it’s inhibition reduces the breakdown and hence reduces blood LDL.
Describe the main drug-drug interactions associated with statin therapy.
Statins are highly protein bound and so can act as a percipient drug. Object drugs which are effected include warfarin, which can increase INR. Dose adjustment is necessary.
Fibrates can be taken with statins but this can increase the risk of myalgia and rhabdomyolysis. Here, fibrates can block the OATP2 channel which mediates statin uptake into hepatocytes. They also inhibit glucuronidation.
Describe the pharmacokinetics of metformin.
Administration - taken orally 2-3 times a day due to its shorter half life.
Distribution - little protein binding
Metabolism - does not undergo metabolism
Excretion - really excreted in the urine unchanged
