Dyslipidaemia Flashcards
What drugs can cause lipidaemia?
Beta blockers –> dec HDL-C, inc TG
Diuretic = inc TC
Oral contraceptives = atherogenic effect at high dose
Lipid neutral cardiac drugs = ACEi, ARBs, CCB, nitrates, hydralazine, methyldopa, clonidine
List drugs that manage hypercholesterolaemia
Bild acid binding resins
Ezetimibe
Fibric acid derivatives
Nicotinic acid
Statins
List the relevant bile acid binding resins
cholestyramine, colestipol
Discuss the efficacy of bile acid binding resins
Moderately effective, very safe, commonly used in younger populations
What is the MOA for bile acid binding resins?
Large MW polymers containing chloride ions (exchanged for bile acids in gut) bind to bile acid –> binds to bile-acid resin complex –> complex is excreted –> prevent enterohepatic cycling of bile
Forces liver to synthesise more bile from cholesterol –> LDL taken from blood + inc LDL-R on liver
What drug interactions are associated with bile acid binding resins?
digoxin, thiazides, frusemide, thyroxin
take other meds 1 hr before or 4-6 hrs after
What is ezetemibe?
cholesterol absorption inhibitor –> block absorption from gut
It is an adjunct therapy to diet and statins, can be used alone
Combined = more effective that simvastatin or ezetimibe alone
What is the MOA of ezetemibe?
absorbed from intestines and localised in brush border of small intestines –> inhibit absorption of biliary and dietary cholesterol —> dec delivery of chol –> inc LDL-R
List the ADRs of ezetemibe
Well tolerated
headache, myalgia
What is the MOA of fibric acid derivates?
Inc PPARalpha-mediated lipoprotein lipase expression
Also dec expression of apolipoprotein C-III (inhibits LPL)
Inc LDL-R expression
What are some ADRs of fibric acid derivates?
GI disturbances, pancreatitis, photosensitivity, blood cell deficiencies, rhabdomyolysis, other myopathies
Which drugs interact with fibric acid derivates?
HMG-CoA reductase inhibitors
Cholestryamine
Discuss niacin (Vit B3) role in hyperlipidaemia treatment and MOA
MOA = inhibits TG production (secondary) and VLDL secretion (primary = due to inhibition of lipolysis in adipose tissue –> reduces supple of free fatty acids)
It dec the LDL occupying HDL —> inc blood HDL
What are the ADRs of Niacin?
Vasodilation + flushing + pruritis of skin
Elevated liver enzymes, hepatitis
Nacine induced insulin resistance –> sever hyperglycaemia
What drug interact with Naicin?
statins –> myopathy
List the relevant HMG-COA reductase inibitors
atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin
Briefly discuss some facts about statins
highly effective, good safety record with once daily dosing = good patient compliance
Most taken at bedtime –> inhibit nocturnal cholesterol biosynthesis
Low oral bioavailability due to first pass metabolism
Which statins can be taken at any time of the day?
Atorvastatin, rosuvastatin = longer half lives
Which statins are pro drugs?
lovastatin, simvastatin
activated in the liver
What is the MOA of statins?
Competitive inhibitors of HMG-CoA reductase –> inhibits the conversion of HMG-CoA to mevalonic acid –> inhibiting cholesterol biosynthesis
What affect do statins have on cholesterol?
Inc LDL-R –> dec serum LDL –> less LDL available to form vLDL
10% inc HDL, 20-40% dec in LDL
Serum TG = decreased
List some ADRs of statins
myalgia, GIT disturbances, elevated hepatic enzymes, mild GI distress
hepatotoxicity, pancreatitis, diabetes, alopecia, CNS
Most serious = rhabdomyolysis
Discuss statin-induced rhabdomyolysis
Inihbit chol synthesis –> statins alter muscle cell mem comp
Early stage statin myopathy = myalgia w/ elevated CK (reversible 2-3 wks w/ no statins)
Later stage = myositis (muscle inflam) –> muscle pain, leakage of muscle CK into plasma, elevated CK
Late stage = myositis becomes rhabdomyolysis –> muscle cells destroyed –> myoglobin accumulate in kidney –> acute renal failure (dark urine)
Which drugs interact with HMG-CoA reductase inhibitors?
Fibric acid derivates = cause myopathies
Other drugs metabolised by CYP3A4 and CYP2C9
Erythromycin and itraconazole
Warfarin
What statins are metabolised by CYP3A4?
Atorvastatin, simvastatin
What statins are metabolised by CYP2C9?
Rosuvastatin, fluvastatin
