W4, 5 Control dyslipidemia (pharma) Flashcards
Importance of cholesterol
Cholesterol is a necessary component of cell membranes and is a precursor of steroid hormones.
From where we get cholesterol
Cholesterol is derived from both exogenous (dietary)
and endogenous (synthesized in the liver) sources.
Four major types of lipoproteins:
Lipids including cholesterol and triglycerides are transported in the plasma as β¦β¦β¦β¦.
lipoproteins
Dyslipidemias can be classified into:
- Hypercholesterolemia
- Hypertriglyceridemia
- Mixed (i.e. hypercholesterolemia and hypertriglyceridemia).
What are THERAPEUTIC STRATEGIES of dyslipidemia
What is Dyslipidemia/ Hyperlipidemia
How does treatment of dyslipidemia work?
Main types of Lipid Lowering Drugs:
- Statins
- Fibrates
- Inhibitors of Cholesterol absorption (Resins and Ezetimibe)
- Nicotinic acid
- Omega-3-fatty acids
- PCSK9 Inhibitors
Statins drug examples
Statins eg lovastatin, Atorvastatin
MOA of statins
Other actions of statins unrelated to its actions on lipids:
Mean half-life in the plasma of statins is
14 hours
Half-life of inhibitory activity for HMG-CoA reductase is β¦. hours & why?
20 to 30 hours due to the contribution of active metabolites
Uses of statins
Adverse effects of statins
β’ Long treatment may cause a rise in serum levels of the liver
enzyme, transaminase.
β’ Other adverse effects include myopathy and ocular damage
(cataract)
Fibrates drug exampls
Fibrates e.g. Clofibrate, gemfibrozil
Mechanism of Action of fibrates
Pharmacokinetics of fibrates
a. Route of administration
b. Half life
c. Metabolism & excretion
Uses of fibrates
β’ Clofibrate is used to treat hyperlipidemias of various etiologies in
which there is an increase in VLDL levels.
β’ It has mild antidiuretic action in individuals with mild or moderate
diabetes insipidus (ADH not produced in diabetes insipidus = increased urine production)
Adverse effects of fibrates
What DRUGS AFFECT PLASMA CHOLESTEROL? Whatβs their MOA?
What are the uses of these drugs?
β’ Treatment of hyperlipidemias.
β’ Cholestyramine is the drug of choice for hypercholesterolemia.
Whatβs their Adverse effects:
- Quite safe, because not absorbed in the intestine.
- Abdominal pain, constipation, nausea.
- Interfere with absorption of some drugs like warfarin and digitalis
What drugs inhibit Cholesterol Absorption
Ezetimibe, resins
Which is more potent? Ezetimibe or resins?
Ezetimibe
MOA of Ezetimibe?
Inhibits intestinal absorption of cholesterol, specifically in the brush border of enterocytes in the duodenum.
Adverse effects of ezetimibe
- Well tolerated, may cause fatigue, abdominal pain, diarrhea.
MOA of Nicotinic Acid (Niacin)
Therapeutic Uses of Nicotinic Acid:
- Treatment of combined hyperlipidemia.
- Most effective agent for increasing HDL.
Adverse effects of Nicotinic Acid:
- Weight gain due to inhibition of lipolysis
- Hyperuricemia precipitates gout, intense cutaneous flush, nausea, abdominal pain, hyperglycemia, jaundice
MOA of Probucol?
Uses of probucol:
Adverse effects of probucol:
β’ Adverse effects are usually mild and of short duration.
β’ They include nausea, diarrhea, flatulence, abdominal pain, Nausea, Vomiting.
Omega-3-fatty acids MOA in dyslipidemia
β’ Used for triglyceride (TG) lowering.
β’ Inhibit VLDL and TG synthesis in the liver.
Omega 3 fatty acids sources
Found in marine sources & available as over-theβcounter fish oil capsules.
Uses of omega 3 FA
Can be used as adjunct to other lipid-lowering therapies for individuals with elevated TG.
Common side effects of omega 3 FA
GI effects (nausea & vomiting)
& a fishy aftertaste.
First-line drug for patients at high risk of myocardial infarction due to hypercholesterolemia.
Statins
Most effective agent for increasing HDL.
Nicotinic Acid
drug of choice for hypercholesterolemia.
Cholestyramine
What drugs are agonists at the Ξ± peroxisomal-proliferator activator receptors (PPARΞ±), which are nuclear transcription factors?
Fibrates
used to treat hyperlipidemias of various etiologies in which there is an increase in VLDL levels & has mild antidiuretic action
Clofibrate
This drug canβt be given to a patient with diabetes
Nicotinic Acid
Miscellaneous Drugs (slide)
Treatment of primary hypercholesterolemia associated with elevated LDL
probucol
Mcq:
1. What is given to a patient with high risk of MI due to hypercholesteremia?/ What is the suggestive prevention for a patient at risk of myocardial infarction because of his hypercholesterolemia?
A. Statins
B. Resin
C. Fibrates
A. Statins
Mcq: Which drug inhibits HMG coA reductase?
Statins
Mcq: What is the MOA of clofibrate?
A. PPAR Alpha / increase LPL activity
B.PCSK9
C. Inhibits cholesterol absorption in GI
A. PPAR Alpha / increase LPL activity
Mcq: Which drug causes myopathy as an adverse effect?
A. Lovastatin
B. Clofibrate
A. Lovastatin
Mcq: A drug that causes elevated liver enzymes as a side effect?
A. Lovastatin
Note (they also mention that it is a statin in Q)
Mcq: What is the suggestive prevention for a patient at risk of myocardial infarction because of his hypercholesterolemia?
A. Aspirin
B. Lovastatin
Lovastatin
Mcq: Which drug affects PPAR-a?
A. Clofibrate
Mcq: Which of the following drugs inhibit lipolysis?
A. Clofibrate
Mcq: Weight gain when using Clofibrate is due to?
A. Inhibiting Lipolysis
B. Activating lipolysis
A. Inhibiting Lipolysis
Mcq: Which of the following decrease bile acid salt absorption in the intestine?
A. Simvastatin
B. Clofibrate
C. Cholestyramine
D. Nicotinic Acid
C. Cholestyramine
Mcq: Consequences of using a drug that prevent absorption of cholesterol into gastrointestinal tract like Cholestyramine?
A. Increase the density of LDL receptors
Mcq: What is the best drug for increasing HDL levels?
A. Nicotinic Acid
Mcq: What is the mechanism of weight gain in a patient receiving nicotinic acid?
A. Inhibition of lipolysis in lipid tissue
Mcq: Which of the following may be an adverse effect of Nicotinic acid?
A. Gout due to hyperuricemia
B. Weight loss
C. Myalgia
D. Arthralgia
A. Gout due to hyperuricemia
Mcq: Which of the following drugs complex with bile salts to prevent their reabsorption?/ which of the following drugs prevents the absorption of bile acids by intestine by forming insoluble complex with bile acid salt?
A. Colestipol
B. Ezetimibe
C. Niacin
A. Colestipol
Mcq: What is the mechanism of action of lovastatin?
A. Decrease the LDL in the blood
B. Increase the LDL in the blood
A. Decrease the LDL in the blood
Mcq: What is the mechanism of action of clofibrate?
A. PPAR alpha agonist
B. PPAR gamma agonist
C. PPAR gamma antagonist
D. HMG CoA reductase inhibitors
A. PPAR alpha agonist