Antihyperlipidemic Drugs Flashcards
Causes of hyperlipidemia:
Primary:
Secondary:
1-
2-
3-
4-
Familiar history
1-diabetes
2-liver disease
3-alcoholism
4-hypothyrodism
Statins or ———:
Natural:1——-(from—–)
Semi-synthetic:1—–2—-
Sunthetic:1——2—–3——
HMG coA reductase inhibitors
Natural: lovastatin (from fungus)
Semi:1-simva 2-prava
Synthe: 1-fluva 2-atorva 3-rosuva
Mechanism of action of statins:
1-
2-
Inhibut hmgcoa leading to dec of choles
2- low cholesterol stimulate LDL receptors —–uptake of LDL from blood
3- low cholesterol decrease secretion of VLDL
Effects of statins:
1-
2-
3-
4-
5-
Decrease LDL TG
Increase HDL
Improve indothelial function
Decrease CRP levels (anti-inflammatory)
Inhibit platelet thrombus formation
Pharmacokinetics of statins
Oral absorption
Plasma protein binding
——,——– and —— are primarily metabolized by CYP3A4
——– and —– are insignificantly metabolized
Half life of : atorva and rosuvastatin
Others?
Oral absorption is variable
High plasma proteins binding
Ator,lova,simvastatins
Prava and rosuva
Atorva(14 hr) rosuva ( 20hr )
Others 1-4 hr
Side effects of statins:
1-
2-
3-
4-
1- GI discomfort
2-hepatotoxicity and elevation of trans
3-myopathy and rhabdomyolysis
4-grapefruit juice incr the side effects
Cyp3A4 inhibitors
1-
2-
3-
4-
5-
6-
Anti retrovirals
Ketoconazole
Cimetidine
Grapefruit
Fibrates
Erythromycin
Macrolides
Bile acid binding resins:
1-
2-
Cholestyramine
Colestipol
(Oldest and safest)
T or F
Bile acid binding resins are first line of therapy
False second
T or F
Cholestyramine reduces LDL by 40%
False
20%
BAS are—– charged they bind to —– charges bile acids
Because of their large size the resin is not absorbed and the bile acide are ——-
Then hepatic bile-acid synthetis will—- then there is —— of cholesterol
Positive
Negative
Via stool
Increase
Depletion
Bseru mtl l statins mn hun
Pharmacokinetics of BAS:
Oral?
Metabolized by intestine?
Yes orall because its not soluble in water and very large
Not metabolized by any directly excreted by feces
Adverse effects of BAS
GI: constipation,nausea,flatulence
Drug-drug: (BAS)
They bind and decrease absorption of many drugs:
1-some thiazides
2-digoxin
3-warfarin
4-some statins (prava and fluva)
These drugs should be taken 1-2 hr before or 4-6 after
Niacin:
Form:
Role:
Mode of adm:
Converted to:
Water soluble vitamin B3
Precursor of NADH and NADPH
DNA repair/production of steroid hormones in the adrenal gland
Orally
Nicotinamide
Mode of action:
Inhibit lipolysis in adipose
Decr TG decr VLDL dec LDL
Decr in cholesterol(LDL,VLDL) TG(VLDL)
Increase HDL
Boost tissue plasminogen(reverse thrombose and atherosclerose)
Therapeutic uses of niacin:
1-
2-
1-tx of familial hypercholesterolimia
2-pootent antihypelipidemic agent for raisinggggg HDL
Side effects of niacin:
1-
2-
3-
4-
5-
1-Flushing affects compliance
2- dyspepsia
3- diarrhea
4- severe hepatotoxicity
5- inc uric acid (they inhibit tubular secretion of uric acid)
Fibrates:
Mode of action:
Names:
1-
2-
Activates PPAR (peroxisome proliferation receptors)
Activation of PPAR causes transpcription of number of genes that ficulitate lipid metabolism
After activation of PPAR: incr LPL lipoprotein lipase (incr hydrolysis of chylomicrons and VLDL),express apoA-I and apoAII so they increase HDL
Stimulate synthesis of acyl coA dehydrogenase then decrease TG liver synthesis yaane decrease VLDL
1-fenofibrate
2-gemfibrozil
Adverse effects of fibrates:
1-
2-
3-
GI
Myalgia
Gallstones
Drug drug interaction:
1
2-
Potentiate oral anticoagulant and some hypoglycemic drugs displacing them from plasma proteins
Cause myopathy when co-administered with statins
T or F
Fibrates can be used in pregnant or lactating women
False
Not used
Ezetimibe inhibits——
This will lead to refuction of —–
Intestinal absorption of dietary and billiary cholesterol in small intestine
Reduction of hepatic cholesterol stores and an increase clearance of cholesterol
Ezetimibe lowers LDL by 17% TG by 20% and increase HdL by 1.3%
False
TG by 6%
