L47-anti Dyslipidymic Agents

Question 1

What are anti dyslipidemic agents

Answer 1

Diverse group of drugs that reduce the level of lipids and lipoproteins

Question 2

Types of anti-dyslipidemic agents

Answer 2

Anti-hypercholesterolemia agents:
Statins,ezetimibe 
Anti-hypertriglyceridemia agents:
Fibrates,omega 3 fatty acids
Mixed:niacin

Question 3

What do statins inhibit

Answer 3

HMG COA reductase
they inhibit cholesterol synthesis as well as intermediate compounds involved in differentiation proliferation and mobilization

Question 4

How to statins inhibit cholesterol synthesis

Answer 4

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

Question 5

What is the purpose of statins inhibiting intermediate compounds

Answer 5

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

Question 6

How are statins classified

Answer 6

According to lipid solubility into hydrophilic 
lipophilic 
mixed
According to duration of action
According to potency

Question 7

How are the hydrophilic agents eliminated

Answer 7

By the kidney and they have minimal drug interactions

Question 8

Describe lipophilic agents

Answer 8

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

Question 9

How can the duration of action affect dose of statins

Answer 9

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

Question 10

Why are statins major anti cholesterolemic agents used in treatment of dyslipidemia

Answer 10

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

Question 11

Drug of choice in hypercholestrolemia in diabetics

Answer 11

Statins

Question 12

Drugs never used in pregnancy

Answer 12

Statins

Fibrates

Question 13

What does ezetimibe do

Answer 13

Inhibit selective cholesterol transporter:
NPC1L1
Inhibits exogenous cholesterol intake which stimulates liver to upregulate its LDL-R

Question 14

When is ezetimibe given

Answer 14

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

Question 15

PPAR-a agonists

Answer 15

Fibrates

Question 16

What is PPAR

Answer 16

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

Question 17

When are fibrates used

Answer 17

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

Question 18

Used cautiously in renal and hepatic impairment

Answer 18

Fibrates

Question 19

What do omega 3 fatty acids do

Answer 19

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

Question 20

What does niacin do

Answer 20

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

Question 21

When is niacin used

Answer 21

As monotherapy especially when there is contraindications for fibrates or statins as combined therapy with them

Question 22

Problems with niacin

Answer 22

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

Question 23

How can problem of niacin effects be solved

Answer 23

Taking an aspirin an hour before its intake or using slow release formulations