L47-anti Dyslipidymic Agents Flashcards
What are anti dyslipidemic agents
Diverse group of drugs that reduce the level of lipids and lipoproteins
Types of anti-dyslipidemic agents
Anti-hypercholesterolemia agents: Statins,ezetimibe Anti-hypertriglyceridemia agents: Fibrates,omega 3 fatty acids Mixed:niacin
What do statins inhibit
HMG COA reductase
they inhibit cholesterol synthesis as well as intermediate compounds involved in differentiation proliferation and mobilization
How to statins inhibit cholesterol synthesis
In the liver by reversible competitive inhibition of the rate limiting step when this occurs deliver senses that cholesterol is inhibited so it up regulates LDL receptors that will uptake the circulating cholesterol thus reducing its blood level
What is the purpose of statins inhibiting intermediate compounds
They are involved in inflammatory reactions especially those link to cholesterol accumulation
Involved in expression of proteins linked to synthesis and clearance of verified lipo proteins
How are statins classified
According to lipid solubility into hydrophilic lipophilic mixed According to duration of action According to potency
How are the hydrophilic agents eliminated
By the kidney and they have minimal drug interactions
Describe lipophilic agents
Metabolized by the liver and have many drug interactions
Cause dose dependent elevation in hepatic enzymes that requires regular check up
more liable to induce different degrees of myopathy which can be diagnosed by CK levels by an increase to 3.5 fold upwards
How can the duration of action affect dose of statins
Some have a long half-life thus they are taken once daily any time while others are short acting so they are given twice daily one at night at the peak time of endogenous cholesterol synthesis
Why are statins major anti cholesterolemic agents used in treatment of dyslipidemia
Statins can variably modulate lipid profile by a significant dec mainly in total cholesterol and LDL-C
Can induce some reduction in TG and an elevation in HDL-C
Drug of choice in hypercholestrolemia in diabetics
Statins
Drugs never used in pregnancy
Statins
Fibrates
What does ezetimibe do
Inhibit selective cholesterol transporter:
NPC1L1
Inhibits exogenous cholesterol intake which stimulates liver to upregulate its LDL-R
When is ezetimibe given
Given as monotherapy in mild cases of hypercholestrolemia but its given more as adjuvant to statins in resistant cases of hypercholestrolemia since it has a safe profile
PPAR-a agonists
Fibrates
What is PPAR
Transcription factor which when binds to agonist Fibrates modulates gene:
Expression: of lipoprotein lipase-FFA transporters-enzymes of beta oxidation and ketogenesis-apo AI and AII
repression: of enzymes of FFA and TG synthesis-cytokines-adhesion mol-some mediators of inflammation
When are fibrates used
As monotherapy in hypertriglycerdemia
Combined with statins in mixed
Better with hydrophilic agents since myopathy could occur with lipophyllic
Can improve glucose tolerance and suppress serum uric acid if elevated
Used cautiously in renal and hepatic impairment
Fibrates
What do omega 3 fatty acids do
Possess a weak PPAR-a agonist effect and are protective to cell membrane especially against oxidative stress
Inhibits TXA2, vit K dependent clotting factors and alter PAI-1 synthesis
Adjuvant therapy in hypercholestrolemia
Can inhibit platelet aggregation so they are cardio protective
What does niacin do
Vit b3 that:
▪️Acts on a specific receptor in adipose tissue to inhibit hormone sensitive lipase decreasing lipolysis and availability of FFA and TG synthesis in liver
▪️activates lipoprotein lipase to inc VLDL circulatory clearance
▪️dec clearance of apoA from plasma thus inc its blood levels
Dec efficiently hypertriglycerdemia and hypercholestrolemia and its the best drug to elevate HDL
When is niacin used
As monotherapy especially when there is contraindications for fibrates or statins as combined therapy with them
Problems with niacin
Produces pruritus
Sensation of warmth
Flushing
Can induce myalgia especially when combined to statin or fibrates
Can elevate blood glucose and uric acid so diabetics should avoid
How can problem of niacin effects be solved
Taking an aspirin an hour before its intake or using slow release formulations
