Cholestrol Metabolism Flashcards
(29 cards)
What is the normal levels of total cholesterol in a patient?
5 mmol/L or less
What are normal fasting cholesterol levels in a patient?
3 mmol/L or less
What are the normal HDL levels in a patient?
About 1.2 mmol/L or above
How is an atherosceloritc plaque formed?
Endothelial dysfunction, leading to infiltration or entrapment of LDL in the arterial wall, and LDL oxidation as well as inflammatory changes, and deposition of connective tissue components and a fibrous capsules with can rupture and form a substrate for thrombosis
What are some of the proatherogenic effects of oxidised LDL?
Inhbits macrophage motility, induces T cell activation, platelet aggregation, and toxic to endothiael cells
What are some of the different classes of lipid lowering drugs?
Statins, cholestrol lipase inhbitors, nitonic acid, resins, fibrates and omega 3 fatty acids
Name some statins
Simvastatin, arvosratin and risuvastatin
What is the mechanism of action of statins?
HMG coa reductase inhibitors that inhibit the formation of cholesterol in hepatocytes, and depleting intracellular cholesterol leads to a increase in surface LDL receptor which decreases the amount of cholesterol in the blood stream, and may also help stabilise arthematous plaques
Describe the pharmacokientics of statins?
They vary a lot, and intestinal absorption waries between 30-85%, and there is an extensive hepatic first pass metabolism and therefore the systemic availability is 5-30% of the adminstered dose
Which of the statins has the shortest half life?
Simvastatin which has a half life of 4 hours and is given at night to conincide with peak cholestrol production in the morning
Describe the half lives of arvostatin and rasuvastatin?
They have a half life of around 20 hours, and can be given any time of day and therefore have a souperior efficacy
Describe the pharamcodynamics of statins
Display non linear pharmaocydumasics, and therefore a doubling of dose results in a 6 % reduction in LDL
What are some of the ADRs of statins?
Usually well tolerated, can increase transanimase levels in paitents, can cause a myopathy, and headache, as well as GI complaints and portential for memory loss
How do statins interact with OATP2 inhbitors- gemofibrizil?
They also inhibit statin glucordination, and administration results in a syngeristically increased risk of myopathy
How do statins inteact with cyp inducers?
Will increase the plasma levels of the statin
How do statins interact with cyp inhbitors?
Increases the risk of myopathy
Name some of the fibric acid derivatives?
Fenofibrate and gemofibrizil
What is the mechansim of action of fibrates?
Is a PPARa ( a perixosome proliferator activated receptor agonist) that increases the production of lipoprotein lipsase, and increases the uptake and oxidation of fatty acis, reduces trigylceride levels, and increases LDL particle size and HDLc levels
When would a fibric acid derivative be indicated?
Combinded hyperlipidemia with LDL and no response to nictonic acid or as an adjunct to diet, amd hypertrigluceriama
What are some of the ADRs of fibrates?
Abnormal LFTs and cholestasis, as well as GI upset
When would a fibrate be contraindicated?
In hepatic or renal dailure, or in prexisting gall bladder disease
What are some of the features of the pharmacokientics of fenofibrate?
Is a pro drug that is converted to fenofibric acid
What is the mechanism of action of nitconic acid?
Inhbits lipoportein a systhensis in adipose tissue reducing the production of free fayy acids that are used in the liver for triglyceride systehis, and this decreases heaptic LDL production and decreases LDL c plasma peoctuib
What are some of the adrs of nictonic acid?
Itching, headache, heaptotoxcitgm activation of peptic ulcers and hyperglycemia
