Pharmology Of Agents Used Hyperlipidaemia Flashcards
What is the MOA of Statins?
Inhibit HMG CoA reductase in the liver.
HMG CoA reductase is an enzyme which catalysts the rate limiting step in cholesterol synthesis
What are the pharmacokinetics of statins?
First pass metabolism
Half-life of 1-3 hours (atorvastatin - 14hours)
Given in the evening as a single dose.
What are the adverse effects of statins?
Headaches, insomnia, rash, liver problems.
Myalgia
Myopathy or myositis with rhabdomyolysis with renal failure. Reversible on discontinuation.
What are the contra indications of statins?
Lactating women
Pregnancy
What drug interactions occur with statins?
Increased risk of myopathy with: gemfribrozil, niacin, other cytochrome p450 enzyme metabolized drugs.
Decrease levels of: warfarin, digoxin and propranolol.
Name a bile acid absorption inhibitor.
Colestyramine
What is the MOA of colestyramine?
Forms a soluble complex with bile salts, excreted in faeces. Body compensates by increasing LDL receptors and oxidizing cholesterol to bile acids thus removing LDL and Cholesterol from system.
What are the pharmacokinetics of colestyramine?
Not absorbed from the GIT. The resin absorbs bile acids and is ecpxcreted in the faeces.
What are the adverse effects of colestyramine?
Bloated feeling
Committing
Constipation
May aggravate hypertriglyceridaemia
What are the contra indications of colestyramine?
Complete biliary obstruction
Active peptic ulcer
Sensitivity to tartrazine
What drug interactions are associated with colestyramine?
Fat soluble vitamins interfere with absorption
Reduces absorption of: warfarin, digoxin, thiazides, barbiturates, aspirin, tetracyclines, thyroxine
List the fibrates.
Bezafibrate
Fenofibrate
Gemfribrozil
What is the MOA of fibrates?
Regulate gene expression through the preoxisomal proliferator receptor alpha system.
Act at several points in lipid and lipoprotein metabolism.
Pharmacokinetics of fibrates
Cross placenta and excreted in breast milk
What are the adverse effects of fibrates?
Myalgia/myositis-like syndrome Arrhythmias Insomnia Impotence Increased risk for gallstone formation
What are the contra indications of fibrates?
Hypersensitivity to fibrates
Severe renal/hepatic failure
Primary biliary cirrhosis
What are the drug interactions associated with fibrates?
Displaces warfarin from albumin binding sites -> need to reduce warfarin dosage
What are the hormone sensitive lipase inhibitors?
Nicotine acid/ Niacin (diabetogenic)
Acipimox (not diabetogenic)
What is the MOA of hormone sensitive lipase inhibitors?
Decrease adipose tissue hormone sensitive lipase activity-> decrease peripheral tissue TG catabolism -> decreases FFAs in liver -> decrease rate of hepatic TG synthesis
What are the pharmacokinetics of hormone sensitive lipase inhibitors?
Metabolized in liver
Renal excretion
What are the adverse effects of hormone sensitive lipase inhibitors?
Hyperglycemia Diabetogenesis Hepatotoxicity Cutaneous flushing Vasodilation Rashes Hyperuricaemia Headache
What are the contra indications of hormone sensitive lipase inhibitors?
Pregnancy, lactation
Uncontrolled DM
Recent gout, active peptic ulcer disease, liver disease
What are the drug interactions associated with hormone sensitive lipase inhibitors?
Enhanced risk of rhabdomyolysis if taken with statins
Name the cholesterol absorption inhibitors.
Phytosterols
Ezetemibe
What is the MOA of cholesterol absorption inhibitors?
Inhibits intestinal cholesterol absorption resulting in reduction of LDL-cholesterol levels and works synergistically with statins.
What are the pharmacokinetics of cholesterol absorption inhibitors?
Low plasma conc d/t extensive glucoronidation in liver and excretion into bile.
What are the adverse effects of cholesterol absorption inhibitors?
Headache, ab pain, diarrhoea
+statin: constipation, flatulence, nausea, increased ALT/AST, myalgia and rhabdomyolysis
What are the contra indications of cholesterol absorption inhibitors?
Moderate to severe hepatic impairment
Children under 10yrs
What drug interactions are associated with cholesterol absorption inhibitors?
Ezetemibe conc increased when taken with cyclosporine.
Colestyramine significantly decreases the LDL lowering effects of ezetemibe.
What are the HMG CoA Reductase Inhibitors/Statins?
Simvastatin Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin
