Tag: Anti-Dyslipidemic Drugs

Anti-Dyslipidemic Drugs

ANTI-DYSLIPIDEMIC DRUGS

Q. 1

Fibrates — false is

 A

They increase lipoprotein lipase activity through PPAR alpha, and cause increased lipolysis of triglycerides.

 B

They are better absorbed when taken on empty stomach, than when taken with food

 C

Cause utricaria, rashes, alopecia, myopathy and G.I. distress.

 D

Are first line of drugs in severe dysbetalipoproteinemias and hypertriglyceridemias.

Q. 1

Fibrates — false is

 A

They increase lipoprotein lipase activity through PPAR alpha, and cause increased lipolysis of triglycerides.

 B

They are better absorbed when taken on empty stomach, than when taken with food

 C

Cause utricaria, rashes, alopecia, myopathy and G.I. distress.

 D

Are first line of drugs in severe dysbetalipoproteinemias and hypertriglyceridemias.

Ans. B

Explanation:

They are better absorbed when taken on empty stomach, than when taken with food [Ref Katzung 10t1ie p 569]

Fibric acid derivations (Fibrates)

  • The class includes:?

– Bezafibrate

– Ciprofibrate

– Fenofibrate and

– Getnfibrozil

  • The original fibrate clofibrate is obselete.

Mechanism of action:

  • The.4, drugs act by activating lipoprotein lipase which is a key enzyme in the degradation of VLDL.
  • This effect is exerted through nuclear receptor, PPAR a (peroxisome proliferators activated receptor alpha)

– The PPAR a are class of intracellular receptor that modulate carbohydrate and fat metabolism and adipose tissue differentiation.

  • Major effect of the fibrates is to reduce triglycerides TG (contained in VLDL) and to increase HDL.
  • Fibrates also reduce plasma fibrinogen level.
  • They are first line drugs in dysbetalipoproteinenzias and hypertriglyceridimias

Pharmacokinetics of fibrates:?

  • Fibric acid derivatives are well absorbed from the gastrointestinal tract, extensively bound to plasma proteins and are excreted mainly by the kidney as unchanged drug or metabolite.
  • Absorption of fibrates in improved when the drug in taken with food.
  • They are contraindicated when hepatic or renal function is severely impaired.

Adverse effects of fibrates:?

  • Fibrates can induce a myositis like syndrome, the risk is greater in patient with poor renal function and in those who are also receiving a statin.
  • Other adverse effects include rashes, gastrointestinal symptoms, arryhthmias, hypokalenzia and high blood level of aminotransferases or alkaline phosphatase.

Some more features of fibrates

  • Fenofibrate is a prodrug with longest half life.
  • It has miximum LDL cholesterol lowering action.
  • Clofibrate is not used now becuase it results in increased mortality (due to malignancies and post cholecystectomy) complications and did not prevent fatal MI.

Q. 2 Rate limiting step in cholesterol synthesis is:
 A HMG CoA synthetase
 B HMG CoA reductase
 C Thiokinase
 D Mevalonate kinase
Q. 2 Rate limiting step in cholesterol synthesis is:
 A HMG CoA synthetase
 B HMG CoA reductase
 C Thiokinase
 D Mevalonate kinase
Ans. B

Explanation:

HMG CoA reductase


Q. 3

A 54-year-old man has a total cholesterol of 272 and LDL level of 210. His therapy is initiated with dietary modification and an exercise regimen, but he is unresponsive and so is prescribed nicotinic acid (Niacin). Which of the following symptoms will this patient likely experience from this drug?

 A

Bradycardia

 B

Facial flushing

 C

Hypoalbuminemia

 D

Hypoglycemia

Q. 3

A 54-year-old man has a total cholesterol of 272 and LDL level of 210. His therapy is initiated with dietary modification and an exercise regimen, but he is unresponsive and so is prescribed nicotinic acid (Niacin). Which of the following symptoms will this patient likely experience from this drug?

 A

Bradycardia

 B

Facial flushing

 C

Hypoalbuminemia

 D

Hypoglycemia

Ans. B

Explanation:

Niacin, or vitamin B3, is an agent that results in the following physiologic changes: LDL reductions tend to occur in 5-7 days with the maximal effect seen in 3-5 weeks; triglycerides and VLDL are reduced by 20% to 40% in 1-4 days; and HDL levels can increase by 20%.

This agent is indicated as adjunctive therapy in patients with elevated cholesterol and triglycerides when diet and other nondrug therapies are inadequate. 

The most common adverse effect of this agent is generalized flushing with a sensation of warmth, especially in the facial area.

This reaction may be so severe in some patients that they discontinue therapy.

Other common adverse effects include hepatotoxicity, tachycardia, hypoalbuminemia, hyperglycemia, nausea, vomiting, hyperuricemia, glucose intolerance, pruritus, peptic ulcer disease, and dry skin.


Q. 4

A 67-year-old man with an 18-year history of type 2 diabetes mellitus presents for a routine physical examination. His temperature is 36.9 C (98.5 F), his blood pressure is 158/98 mm Hg and his pulse is 82/minute and regular. On examination, the physician notes a non tender, pulsatile, mass in the mid-abdomen. A plain abdominal x-ray film with the patient in the lateral position reveals spotty calcification of a markedly dilated abdominal aortic walI. Following surgery, the patient is placed on a low-fat diet to reduce the risk of continued progression of his atherosclerotic disease. A bile acid sequestrant is added to interrupt enterohepatic circulation of bile acids. Which of the following agents was MOST likely prescribed?

 A

Atorvastatin

 B

Cholestyramine

 C

Clofibrate

 D

Gemfibrozil

Q. 4

A 67-year-old man with an 18-year history of type 2 diabetes mellitus presents for a routine physical examination. His temperature is 36.9 C (98.5 F), his blood pressure is 158/98 mm Hg and his pulse is 82/minute and regular. On examination, the physician notes a non tender, pulsatile, mass in the mid-abdomen. A plain abdominal x-ray film with the patient in the lateral position reveals spotty calcification of a markedly dilated abdominal aortic walI. Following surgery, the patient is placed on a low-fat diet to reduce the risk of continued progression of his atherosclerotic disease. A bile acid sequestrant is added to interrupt enterohepatic circulation of bile acids. Which of the following agents was MOST likely prescribed?

 A

Atorvastatin

 B

Cholestyramine

 C

Clofibrate

 D

Gemfibrozil

Ans. B

Explanation:

Cholestyramine and colestipol are bile acid sequestrants that bind bile acids in the intestine, thereby interrupting enterohepatic circulation of bile acids. This has an indirect effect to enhance LDL clearance and lower lipids in the blood.

Atorvastatin and lovastatin are lipid-lowering drugs that competitively inhibit HMG-CoA reductase, an early step in cholesterol biosynthesis.
 
Clofibrate and gemfibrozil are fibric acid derivatives that may increase the activity of lipoprotein lipase.
Ref: Bersot T.P. (2011). Chapter 31. Drug Therapy for Hypercholesterolemia and Dyslipidemia. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

Q. 5

Nicotinic acid is useful in all types of hyperlipoproteinemias, EXCEPT:

 A

Type-I

 B

Type-II

 C

Type-Ill

 D

Type-IV

Q. 5

Nicotinic acid is useful in all types of hyperlipoproteinemias, EXCEPT:

 A

Type-I

 B

Type-II

 C

Type-Ill

 D

Type-IV

Ans. A

Explanation:

Niacin is a drug (Vitamin B3) that causes a decrease in LDL cholestrol, VLDL and triglycerides along with an increase in HDL cholesterol.

It acts by inhibiting lipolysis in the adipose tissue. Further, it can also decrease lipoprotein(a) and fibrinogen.

It is useful for type IIb, III and IV hyperlipoprotein disorders.

Also Know:
  • Niacin is the best agent available for increasing HDL-C (30-40%).
  • In patients with diabetes mellitus, niacin should be used cautiously because niacin-induced insulin resistance can cause severe hyperglycemia.
  • Niacin also elevates uric acid levels and may reactivate gout. A history of gout is a relative contraindication for niacin use.
Ref: Bersot T.P. (2011). Chapter 31. Drug Therapy for Hypercholesterolemia and Dyslipidemia. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e

Q. 6

Rate limiting step in cholesterol synthesis is catalysed by which of the following enzyme?

 A

HMG CoA synthetase

 B

HMG CoA reductase

 C

Thiokinase

 D

Mevalonate kinase

Q. 6

Rate limiting step in cholesterol synthesis is catalysed by which of the following enzyme?

 A

HMG CoA synthetase

 B

HMG CoA reductase

 C

Thiokinase

 D

Mevalonate kinase

Ans. B

Explanation:

Conversion of HMG CoA to mevalonate by HMG CoA reductase is the rate limiting step in the synthesis of cholesterol.
  • Cholesterol is an allosteric inhibitor of HMG CoA reductase 
  • Statin drugs acts as competitive inhibitors with mevalonate for binding to HMG CoA reductase.
  • Insulin favors the active form of HMG CoA reductase and increases cholesterol synthesis.
  • Glucagon favours the inactive form and decreases cholesterol synthesis.
Ref: Biochemistry By John W. Pelley, page 89.

Q. 7

Which of the following is the rate limiting step in cholesterol synthesis?

 A

HMG CoA synthase

 B

HMG CoA reductase

 C

Thiokinase

 D

Mevalonate kinase

Q. 7

Which of the following is the rate limiting step in cholesterol synthesis?

 A

HMG CoA synthase

 B

HMG CoA reductase

 C

Thiokinase

 D

Mevalonate kinase

Ans. B

Explanation:

Initially in cholesterol synthesis, two molecules of acetyl-CoA condense to form acetoacetyl-CoA catalyzed by cytosolic thiolase.
Acetoacetyl-CoA condenses with a further molecule of acetyl-CoA catalyzed by HMG-CoA synthase to form HMG-CoA, which is reduced to mevalonate by NADPH in a reaction catalyzed by HMG-CoA reductase.
This last step is the principal regulatory step in the pathway of cholesterol synthesis and is the site of action of the most effective class of cholesterol-lowering drugs, the statins, which are HMG-CoA reductase inhibitors.
 
Ref: Botham K.M., Mayes P.A. (2011). Chapter 26. Cholesterol Synthesis, Transport, & Excretion. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper’s Illustrated Biochemistry, 29e.

Q. 8

Familial hypercholesterolemia is:

 A

Deficient LDL receptors

 B

Deficient HDL receptors

 C

receptorsHMG CoA reductase deficiency

 D

Deficient VLDL receptors

Q. 8

Familial hypercholesterolemia is:

 A

Deficient LDL receptors

 B

Deficient HDL receptors

 C

receptorsHMG CoA reductase deficiency

 D

Deficient VLDL receptors

Ans. A

Explanation:

A i.e. Deficient LDL receptor


Q. 9

In cholesterol synthesis, which is rate limiting amino acid:

 A

HMG CoA reductase

 B

HMG CoA synthetase

 C

7 alpha hydroxylase

 D

Phosphofructokinase

Q. 9

In cholesterol synthesis, which is rate limiting amino acid:

 A

HMG CoA reductase

 B

HMG CoA synthetase

 C

7 alpha hydroxylase

 D

Phosphofructokinase

Ans. A

Explanation:

A i.e. HMG COA reductase


Q. 10

Hypolipidemic agents act on:

 A

HMG CoA synthetase

 B

HMG CoA oxygenase

 C

HMG CoA reductase

 D

HMG CoA hydratase

Q. 10

Hypolipidemic agents act on:

 A

HMG CoA synthetase

 B

HMG CoA oxygenase

 C

HMG CoA reductase

 D

HMG CoA hydratase

Ans. C

Explanation:

C i.e. HMG COA reductase


Q. 11

Statins act on which enzyme –

 A

Acyl CoA synthetase

 B

Acyl CoA reductase

 C

HMG CoA Synthetase

 D

HMG CoA reductase

Q. 11

Statins act on which enzyme –

 A

Acyl CoA synthetase

 B

Acyl CoA reductase

 C

HMG CoA Synthetase

 D

HMG CoA reductase

Ans. D

Explanation:

Ans. is ‘d’ i.e., HMG CoA reductase

Statins (Lovastatin) competitively inhibit the conversion of HMG-CoA to mevalonate (rate limiting step in cholesterol synthesis) by inhibiting the enzyme HMG-CoA reductase.


Q. 12

HMG-CoA reductase is inhibited by ‑

 A

Cholestyramine

 B

Gemfibrozil

 C

Lovastatin

 D

Clofibrate

Q. 12

HMG-CoA reductase is inhibited by ‑

 A

Cholestyramine

 B

Gemfibrozil

 C

Lovastatin

 D

Clofibrate

Ans. C

Explanation:

Ans. is ‘c’ i.e., Lovastatin


Q. 13

Lipid lowering agents statins acts in all the following ways except-

 A

Decreased hepatic cholesterol synthesis

 B

Decreased LDL receptors

 C

Inhibiting HMG CoA reductase

 D

Decreasing VLDL

Q. 13

Lipid lowering agents statins acts in all the following ways except-

 A

Decreased hepatic cholesterol synthesis

 B

Decreased LDL receptors

 C

Inhibiting HMG CoA reductase

 D

Decreasing VLDL

Ans. B

Explanation:

Ans. is ‘b’ i.e., Decreased LDL receptor

o Statins do not decrease LDL receptors, but instead increases their number.


Q. 14

All are true about HMG CoA reductase inhibitors except-

 A

The CNS accumulation of simvastatin and lovastatin is high and less for pravastatin and fluvastatin

 B

Simvastatin is rapidly metabolised and pravastatin is least

 C

Bioavailability is minimally modified when pravastatin is taken with food

 D

Fibrinogen levels are increased by pravastatin

Q. 14

All are true about HMG CoA reductase inhibitors except-

 A

The CNS accumulation of simvastatin and lovastatin is high and less for pravastatin and fluvastatin

 B

Simvastatin is rapidly metabolised and pravastatin is least

 C

Bioavailability is minimally modified when pravastatin is taken with food

 D

Fibrinogen levels are increased by pravastatin

Ans. D

Explanation:

Ans. is ‘d’ i.e., Fibrinogen levels are increased by provastatin

o Fibrinogen levels are not increase but decreased by Provastatin.

o Simvastatin and Lovastatin are lipophilic drugs therefore their CNS penetration is more than pravastatin and fluvastatin which are hydrophilic drugs.

o All statins, except rosuvastatin and pravastatin are metabolized.

o Absorption of the statins is enhanced by taking the dose with food, except for pravastatin whose absorption is only minimally affected.


Q. 15

Maximum oral bioavailability among statins is of which drug –

 A

Fluvastatin

 B

Atorvastatin

 C

Pravastatin

 D

Simvastatin

Q. 15

Maximum oral bioavailability among statins is of which drug –

 A

Fluvastatin

 B

Atorvastatin

 C

Pravastatin

 D

Simvastatin

Ans. A

Explanation:

Ans. is ‘a’ i.e., Fluvastatin

o All statins can be absorbed orally (maximum fluvastatin). Food increases absorption of all drugs except pravastatin.


Q. 16

Most potent statin –

 A

Simvastatin

 B

Pravastatin

 C

Rosuvastatin

 D

Simvastatin

Q. 16

Most potent statin –

 A

Simvastatin

 B

Pravastatin

 C

Rosuvastatin

 D

Simvastatin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Rosuvastatin

o Two most potent statins are     

Pitavastatin (most potent) and rosuvastatin most potent).


Q. 17

Which of the following `statins’ has the longest half life ?

 A

Cerivastatin

 B

Rosuvastatin

 C

Atorvastatin

 D

Simvastatin

Q. 17

Which of the following `statins’ has the longest half life ?

 A

Cerivastatin

 B

Rosuvastatin

 C

Atorvastatin

 D

Simvastatin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Rosuvastatin


Q. 18

Statin induced myopathy is NOT exacerbated by which of the following drugs –

 A

Nicotinic acid

 B

Enalapril

 C

Erythromycin

 D

Clofibrate

Q. 18

Statin induced myopathy is NOT exacerbated by which of the following drugs –

 A

Nicotinic acid

 B

Enalapril

 C

Erythromycin

 D

Clofibrate

Ans. B

Explanation:

Ans. is ‘b’ i.e., Enalapril

Statin induced myopathy is increased by nicotinic acid, gemfibrozil, erythromycin, clofibrate (Harrison), ketoconazole, cyclosporine and HIV protease inhibitors

Quiz In Between


Q. 19

Drug that binds bile acids in the intestine and prevents their return to liver via the enterohepatic circulation is-

 A

Niacin

 B

Fenofibrate

 C

Cholestyramine

 D

Gugulipid

Q. 19

Drug that binds bile acids in the intestine and prevents their return to liver via the enterohepatic circulation is-

 A

Niacin

 B

Fenofibrate

 C

Cholestyramine

 D

Gugulipid

Ans. C

Explanation:

Ans. is ‘c’ i.e., Cholestyramine

“Chlestyramine is a bile acid sequesterant”


Q. 20

Mechanism of action of cholestyramine is ?

 A

Bind to bile acid

 B

Decrease HMG-COA

 C

Increase excretion of cholesterol

 D

Decrease utilization of cholesterol

Q. 20

Mechanism of action of cholestyramine is ?

 A

Bind to bile acid

 B

Decrease HMG-COA

 C

Increase excretion of cholesterol

 D

Decrease utilization of cholesterol

Ans. A

Explanation:

Ans. is ‘a’ i.e., Bind to bile acid

“Chlestyramine is a bile acid sequesterant”


Q. 21

All are fibric acid derivatives except –

 A

Clofibrate

 B

Gemfibrozil

 C

Fenofibrate

 D

Lovastatin

Q. 21

All are fibric acid derivatives except –

 A

Clofibrate

 B

Gemfibrozil

 C

Fenofibrate

 D

Lovastatin

Ans. D

Explanation:

Ans. is ‘d’ i.e., Lovastatin

  • Fibric acid derivatives are clofibrate, gemfibrozil, bezafibrate, fenofibrate.

Quiz In Between


Q. 22

Fibrates – False is –

 A

They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

 B

They are better absorbed when taken on empty stomach, than when taken with food

 C

Cause urticaria, rashes, alopecia, myopathy and GI distress

 D

Are first line of drugs in severe dysbetalipopro­teinemias and hypertriglyceridemias

Q. 22

Fibrates – False is –

 A

They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

 B

They are better absorbed when taken on empty stomach, than when taken with food

 C

Cause urticaria, rashes, alopecia, myopathy and GI distress

 D

Are first line of drugs in severe dysbetalipopro­teinemias and hypertriglyceridemias

Ans. B

Explanation:

Ans. is ‘b’ i.e., They are better absorbed when taken on empty stomach, than when taken with food

  • Fibrates function primarily as ligands for the nuclear transcription receptor, peroxisome proliferator-activated receptor alpha (PPAR-a).

o They increase lipolysis of triglycerides via lipoprotein lipase.

o Absorption of gemfibrazil is improved when the drug is taken with food.

  • Rare adverse effects include rashes, GI symptoms, myopathy, arrhythmias, hypokalemia and high blood levels of aminotransferases or alkaline phosphatase.

o These drugs are used in hypertriglyceridemia and dysbetalipoproteinemia.


Q. 23

Lipoprotein lipase is activated by which drug?

 A

Atorvastatin

 B

Clofibrate

 C

Cholestramine

 D

Nicotinic acid

Q. 23

Lipoprotein lipase is activated by which drug?

 A

Atorvastatin

 B

Clofibrate

 C

Cholestramine

 D

Nicotinic acid

Ans. B

Explanation:

Ans. is ‘b’ i.e., Clofibrate

o Fibrates (e.g. clofibrate) activate lipoprotein lipase, therefore, enhance lipolysis of triglycerides in VLDL.


Q. 24

Mechanism of action of clofibrate is ?

 A

Inhibits HMG CoA reductase

 B

Inhibit HMG CoA synthase

 C

Inhibit absorption of cholesterol

 D

Increased lipolysis of TGs

Q. 24

Mechanism of action of clofibrate is ?

 A

Inhibits HMG CoA reductase

 B

Inhibit HMG CoA synthase

 C

Inhibit absorption of cholesterol

 D

Increased lipolysis of TGs

Ans. D

Explanation:

Ans. is ‘d’ i.e., Increased lipolysis of TGs

Quiz In Between


Q. 25

Mechanism of Action of fibrates ?

 A

They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

 B

Inhibits lipolysis in adipose tissue

 C

Inhibits HMG CoA reductase

 D

Bind bile acids and bile salts in small intestine

Q. 25

Mechanism of Action of fibrates ?

 A

They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

 B

Inhibits lipolysis in adipose tissue

 C

Inhibits HMG CoA reductase

 D

Bind bile acids and bile salts in small intestine

Ans. A

Explanation:

Ans. is ‘a’ i.e., They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides


Q. 26

Nicotinic acid acts by –

 A

 Inhibiting lipolysis

 B

Inhibiting HMG-CoA synthatase

 C

Inhibiting HMG CoA reductase

 D

Decreasing absorption of cholesterol

Q. 26

Nicotinic acid acts by –

 A

 Inhibiting lipolysis

 B

Inhibiting HMG-CoA synthatase

 C

Inhibiting HMG CoA reductase

 D

Decreasing absorption of cholesterol

Ans. A

Explanation:

Ans. is ‘a’ i.e., Inhibiting lipolysis

o Niacin (Nicotinic acid) inhibits intracellular lipolysis by inhibiting hormone sensitive lipase –> intracellular FFA to liver —> triglyceride synthesis.


Q. 27

The best agent for increasing HDL cholesterol is –

 A

Statin

 B

Nicotinic acid

 C

Gugulipids

 D

Fibrates

Q. 27

The best agent for increasing HDL cholesterol is –

 A

Statin

 B

Nicotinic acid

 C

Gugulipids

 D

Fibrates

Ans. B

Explanation:

Ans. is ‘b’ i.e., Nicotinic acid

o Nicotinic acid is the most effective drug to raise HDL cholesterol.

Quiz In Between


Q. 28

All of the following are adverse effects of nicotinic acid except-

 A

Vasodilation

 B

Pancreatitis

 C

Liver dysfunction

 D

Hyperpigmentation

Q. 28

All of the following are adverse effects of nicotinic acid except-

 A

Vasodilation

 B

Pancreatitis

 C

Liver dysfunction

 D

Hyperpigmentation

Ans. B

Explanation:

Ans. is ‘b’ i.e., Pancreatitis

o Adverse effects of nicotinic acid —> 1) Marked flushing, itching (pruritis) and heat due to cutaneous vasodilatation, 2) Dyspepsia, vomiting and diarrhoea, 3) Liver dysfunction, 4) Hyperpigmentation and dryness of skin, 5) Hyperglycemia and hyperuricemia.


Q. 29

For treatment of hypertriglyceridemia drug used in the primary stage –

 A

Cholestyramine

 B

Nicotinic acid

 C

Gemfibrozil

 D

Resins

Q. 29

For treatment of hypertriglyceridemia drug used in the primary stage –

 A

Cholestyramine

 B

Nicotinic acid

 C

Gemfibrozil

 D

Resins

Ans. C

Explanation:

Ans. is ‘c’ i.e., Gemfibrozil

Fibrates are drugs of choice for hypertriglyceridemia (type IV) and chylomicronemia (type I).

Goodman & Gilman 11″‘/e 958 o Fibrates are also the DOC for familial dysbetalipoproteinemia.

o Statins are DOC for hypercholesterolemia (type II) and familial combined hyperlipademia (type V).— Laurence 9th/e 525


Q. 30

Ezetimibe acts on ?

 A

LPL

 B

PPAR

 C

NPC ILI

 D

HMG-CoA reductase inhibitor

Q. 30

Ezetimibe acts on ?

 A

LPL

 B

PPAR

 C

NPC ILI

 D

HMG-CoA reductase inhibitor

Ans. C

Explanation:

Ans. is ‘c’ i.e., NPC1LI

Quiz In Between


Q. 31

All of the following statements about Non Alcoholic Fatty Liver disease are true, except:

 A

Common in Diabetics

 B

Clofibrate provides effective treatment

 C

Commonest cause of cryptogenic cirihosis

 D

Associated with elevated transminases

Q. 31

All of the following statements about Non Alcoholic Fatty Liver disease are true, except:

 A

Common in Diabetics

 B

Clofibrate provides effective treatment

 C

Commonest cause of cryptogenic cirihosis

 D

Associated with elevated transminases

Ans. B

Explanation:

Answer is B (Clofibrate provides effective treatment):

Non Alcoholic fatty Liver Disease (NAFLD) is common in Diabetics Commonest Associations of NAFLD / NASH (Robbins)

  • Obesity
  • Dyslipidemia
  • Hyperinsulinemia (Insulin resistance is a charachteristic.feature2)
  • Diabetes

NAFLD is believed to be the commonest cause of cryptogenic cirrhosis

NAFL is now considered the most common cause of ‘ctyptogenic cirrhosis’ – Robbins 7th/908 Spectrum of NAFLD

  • Simple steatosis (Early)
  • Steatohepatitis (NASH) : Non Alcoholic Steatohepatitis) (Intermediate)
  • Fibrosis and cirrhosis (Advanced)

NAFLD is associated with elevated transminases (transaminitis)

‘Most patients with NAFLD come to medical attention as a result of incidentally elevated liver enzymes’ – Harrison

  • ALT > AST
  • Aminotransferases are usually only mildly elevated 2 times normal

Q. 32

Mechanism of action of statins is:

 A

Inhibition of HMG CoA synthetase

 B

Inhibition of HMG CoA reductase

 C

Indirect increase of LDL receptors synthesis

 D

Inhibition of intestinal cholesterol absorption

Q. 32

Mechanism of action of statins is:

 A

Inhibition of HMG CoA synthetase

 B

Inhibition of HMG CoA reductase

 C

Indirect increase of LDL receptors synthesis

 D

Inhibition of intestinal cholesterol absorption

Ans. B

Explanation:

Q. 33

Statin having longest half life:  

September 2012

 A

Rosuvastatin

 B

Pravastatin

 C

Simvastatin

 D

Lovastatin

Q. 33

Statin having longest half life:  

September 2012

 A

Rosuvastatin

 B

Pravastatin

 C

Simvastatin

 D

Lovastatin

Ans. A

Explanation:

Ans. A i.e. Rosuvastatin

Rosuvastatin

  • It is a competitive inhibitor of the enzyme HMG-CoA reductase, having a mechanism of action similar to that of other statins.
  • Its approximate elimination half life is 19 h and its time to peak plasma concentration is reached in 3-5 h following oral administration.

Quiz In Between


Q. 34

Mechanism of action of statins:

March 2013

 A

HMG-CoA synthase stimulator

 B

HMG-CoA reductase stimulator

 C

HMG-CoA synthase inhibitor

 D

HMG-CoA reductase inhibitor

Q. 34

Mechanism of action of statins:

March 2013

 A

HMG-CoA synthase stimulator

 B

HMG-CoA reductase stimulator

 C

HMG-CoA synthase inhibitor

 D

HMG-CoA reductase inhibitor

Ans. D

Explanation:

Ans. D i.e. HMG-CoA reductase inhibitor

Statins used to lower cholesterol levels, acts by inhibiting the enzyme HMG-CoA reductase


Q. 35

Which of the following lipid lowering drug acts by inhibiting HMG-CoA reductase:          

March 2008, 2010

 A

Resins

 B

Statins

 C

Fibric acid deravatives

 D

Bile acid sequestrants

Q. 35

Which of the following lipid lowering drug acts by inhibiting HMG-CoA reductase:          

March 2008, 2010

 A

Resins

 B

Statins

 C

Fibric acid deravatives

 D

Bile acid sequestrants

Ans. B

Explanation:

Ans. B: Statins

Statins act by competitively inhibiting HMG-CoA reductase, the first committed enzyme of the HMG-CoA reductase pathway.

Because statins are similar to HMG-CoA on a molecular level they take the place of HMG-CoA in the enzyme and reduce the rate by which it is able to produce mevalonate, the next molecule in the cascade that eventually produces cholesterol, as well as a number of other compounds.


Q. 36

Which of the following is used for treatment of hypercholestremia:     

September 2010

 A

Thiamine

 B

Biotin

 C

Pyridoxine

 D

Nicotinic acid

Q. 36

Which of the following is used for treatment of hypercholestremia:     

September 2010

 A

Thiamine

 B

Biotin

 C

Pyridoxine

 D

Nicotinic acid

Ans. D

Explanation:

Ans. D: Nicotinic Acid

Niacin (Nicotinic acid) is a vitamin that lowers cholesterol levels. It is also called Vitamin B3 or nicotinic acid. Severe niacin deficiency in the diet can cause a disease called Pellagra.

Quiz In Between


Q. 37

Vitamin used in the treatment of hyperlipoproteine­mia: 

September 2012

 A

Vitamin B1

 B

Vitamin B6

 C

Niacin/ Nicotinic acid

 D

Vitamin B12

Q. 37

Vitamin used in the treatment of hyperlipoproteine­mia: 

September 2012

 A

Vitamin B1

 B

Vitamin B6

 C

Niacin/ Nicotinic acid

 D

Vitamin B12

Ans. C

Explanation:

Ans: C i.e. Niacin/ Nicotinic acid

Immediate release niacin is effective at lowering cholesterol levels, and has minimal hepatotoxic side effects due to its rapid elimination from the body.


Q. 38

Nicotinic acid ‑

 A

Increases HDL

 B

Increased triglyceride synthesis

 C

Type II hyperlipoproteinemia

 D

Decreased hydrolysis of VLDL

Q. 38

Nicotinic acid ‑

 A

Increases HDL

 B

Increased triglyceride synthesis

 C

Type II hyperlipoproteinemia

 D

Decreased hydrolysis of VLDL

Ans. A

Explanation:

Ans. is ‘a’ i.e., Increases HDL

Nicotinic acid (Niacin)

  • There arc three main type of lipases related to metabolism of lipoproteins
  1. Lipoprotein lipase → Present in blood vessels and causes hydrolysis of tryglyceride content of VLDL and chylomicrones.
  2. Hepatic lipase → Converts IDL to LDL by hydrolysing the triglyceride content of IDL.
  3. Hormone sensitive lipase → Present intracellularly in peripheral tissue and causes intracellular lipolysis by hydrolysing triglycerides.
  • Niacin (Nicotinic acid) inhibits intracellular lipolysis by inhibiting hormone sensitive lipase → intracellular FFA to liver – 4 .1, triglyceride synthesis.
  • Niacin also increases the activity of lipoprotein lipase → T hydrolysis of VLDL triglyceride.
  • Nicotinic acid also reduces the production of VLDL in liver by inhibiting TG-synthesis → indirectly the VLDL degradation products IDL and LDL are also reduced.
  • Nicotinic acid is the most effective drug to raise HDL-CH.
  • Increased HDL is due to interference of direct pathway of HDL cholesterol to liver which involves apo-Ai → Niacin decreases apo- A, mediated hepatic clearance.
  • Nicotinic acid is used in type I, III, IV & V hyperlipoproteinemias.

Q. 39

Drug that decreases LpA in blood ‑

 A

Statin

 B

Nicotinic acid

 C

Ezetimibe

 D

CETP inhibitors

Q. 39

Drug that decreases LpA in blood ‑

 A

Statin

 B

Nicotinic acid

 C

Ezetimibe

 D

CETP inhibitors

Ans. B

Explanation:

Ans. is ‘b’ i.e., Nicotinic acid

  • Nicotinic acid reduces Lp(a) while statins do not have any effect on Lp(a).

Quiz In Between


Q. 40

Mechanism of action of fibrates in treatment of hyperlipidemia is ‑

 A

Activator of lipoprotein lipase

 B

PPAR alpha agonist

 C

Decreased synthesis of VLDL

 D

Inhibitor of CETP

Q. 40

Mechanism of action of fibrates in treatment of hyperlipidemia is ‑

 A

Activator of lipoprotein lipase

 B

PPAR alpha agonist

 C

Decreased synthesis of VLDL

 D

Inhibitor of CETP

Ans. A

Explanation:

Ans. is ‘a’ i.e., Activator of lipoprotein lipase


Q. 41

Gemfibrozil mechanism of action is ‑

 A

HMG CoA reductase inhibitor

 B

Activates lipoprotein lipase

 C

Inhibitor of lipolysis

 D

Bile acid sequestrant

Q. 41

Gemfibrozil mechanism of action is ‑

 A

HMG CoA reductase inhibitor

 B

Activates lipoprotein lipase

 C

Inhibitor of lipolysis

 D

Bile acid sequestrant

Ans. B

Explanation:

Ans. is ‘b’ i.e., Activates lipoprotein lipase

Quiz In Between


Q. 42

Torcetrapib induces its hypolipidemic action by‑

 A

Inhibiting cholesterol ester triglyceride transport protein

 B

Activating lipoprotein lipase

 C

Inhibiting lipolysis

 D

Inhibiting cholesterol absorption

Q. 42

Torcetrapib induces its hypolipidemic action by‑

 A

Inhibiting cholesterol ester triglyceride transport protein

 B

Activating lipoprotein lipase

 C

Inhibiting lipolysis

 D

Inhibiting cholesterol absorption

Ans. A

Explanation:

Ans. is ‘a’ i.e., Inhibiting cholesterol ester triglyceride transport protein


Q. 43

Gemfibrozil/produces hypolipidemic action by‑

 A

Increasing activity of lipoprotein lipase

 B

Decreased production of VLDL

 C

Increase LDL receptors on hepatocytes

 D

Increased conversion of cholesterol to bile acids

Q. 43

Gemfibrozil/produces hypolipidemic action by‑

 A

Increasing activity of lipoprotein lipase

 B

Decreased production of VLDL

 C

Increase LDL receptors on hepatocytes

 D

Increased conversion of cholesterol to bile acids

Ans. A

Explanation:

Ans. is ‘a’ i.e., Increasing activity of lipoprotein lipase


Q. 44

Rate limiting step in cholesterol synthesis –

 A

HMG CoA reductase 

 B

HMG CoA synthase 

 C

Mevalonate kinase

 D

Squalene synthetase

Q. 44

Rate limiting step in cholesterol synthesis –

 A

HMG CoA reductase 

 B

HMG CoA synthase 

 C

Mevalonate kinase

 D

Squalene synthetase

Ans. A

Explanation:

Ans. is ‘a’ i.e., HMG Co A reductase

Reactions Rate limiting enzymes 
Glycolysis Phosphofructokinase 
Glycogen synthesis  Glycogen synthetase 

Glycogenolysis

Glycogen phosphorylase 

TCA cycle

Isocitrate dehydrogenase 
Fatty acid synthesis  Acetyl CoA carboxylase 
Cholesterol synthesis  HMG CoA reductase HMG 
Ketone body synthesis CoA synthase 
Bile acid synthesis  7-a-hydroxylase
Catecholamine synthesis  Tyrosine hydroxylase 
Urea synthesis

Carbamoyl transferase

Quiz In Between


Q. 45

All are true about ketone bodies except ‑

 A

Acetoacetate is primary ketone body

 B

Synthesized in mitochondria

 C

Synthesized in liver

 D

HMG CoA reductase is the rate-limiting enzyme

Q. 45

All are true about ketone bodies except ‑

 A

Acetoacetate is primary ketone body

 B

Synthesized in mitochondria

 C

Synthesized in liver

 D

HMG CoA reductase is the rate-limiting enzyme

Ans. D

Explanation:

Ans. is ‘d’ i.e., HMG CoA reductase is the rate-limiting enzyme 


Q. 46

Not true about hypolipidemic drugs

 A

Cholesterol reducing drugs are contraindicated in child less than 8 years

 B

Gemfibrozil causes myopathy

 C

Gemfibrozil can increase myopathy caused by statins

 D

Lovastatin can cause hepatic dysfunction

Q. 46

Not true about hypolipidemic drugs

 A

Cholesterol reducing drugs are contraindicated in child less than 8 years

 B

Gemfibrozil causes myopathy

 C

Gemfibrozil can increase myopathy caused by statins

 D

Lovastatin can cause hepatic dysfunction

Ans. A

Explanation:

Ans. is ‘a’ i.e., Cholesterol-reducing drugs are contraindicated in child less than 8 years 

  • Contraindication for uses of statins (cholesterol-reducing drugs) are –
    • Pregnancy
    • Breastfeeding
    • Active liver disease
  • Gemfibrozil can cause myopathy and it can aggravate myopathy caused by statins.
  • Lovastatin can cause hepatic dysfunction.

Q. 47

The best agent for increasing HDL cholesterol is ‑

 A

Statin

 B

Nicotinic acid

 C

Gugulipids

 D

Fibrates

Q. 47

The best agent for increasing HDL cholesterol is ‑

 A

Statin

 B

Nicotinic acid

 C

Gugulipids

 D

Fibrates

Ans. B

Explanation:

Ans. is’b’  i.e., Nicotinic acid

Nicotinic acid (Niacin)

  • There are three main type of lipases related to metabolism of lipoproteins
  1. Lipoprotein lipase→ Present in blood vessels and causes hydrolysis of tryglyceride content of VLDL and chylomicrones.
  2. Hepatic lipase → Converts IDL to LDL by hydrolysing the triglyceride content of IDL.
  3. Hormone sensitive lipase → Present intracellularly in peripheral tissue and causes intracellular lipolysis by hydrolysing triglycerides.
  • Niacin (Nicotinic acid) inhibits intracellular lipolysis by inhibiting hormone sensitive lipase→ intracellular FFA to liver→ triglyceride synthesis.
  • Niacin also increases the activity of lipoprotein lipase→ T hydrolysis of VLDL triglyceride.
  • Nicotinic acid also reduces the production of VLDL in liver by inhibiting TG-synthesis → indirectly the VLDL degradation products IDL and LDL are also reduced.
  • Nicotinic acid is the most effective drug to raise HDL-CH.
  • Increased HDL is due to interference of direct pathway of HDL cholesterol to liver which involves apo-A,→ Niacin decreases apo-A, mediated hepatic clearance.
  • Nicotinic acid is used in type I, III, IV & V hyperlipoproteinemias.

Quiz In Between


Q. 48

Mechanism of Action of clofibrate ?

 A

They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

 B

Inhibits lipolysis in adipose tissue

 C

Inhibits HMG CoA reductase

 D

Bind bile acids and bile salts in small intestine

Q. 48

Mechanism of Action of clofibrate ?

 A

They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

 B

Inhibits lipolysis in adipose tissue

 C

Inhibits HMG CoA reductase

 D

Bind bile acids and bile salts in small intestine

Ans. A

Explanation:

Ans. is ‘a’ i.e., They increase lipoprotein lipase activity through PPAR alpha and cause increased lipolysis of triglycerides

  • Fibrates act by transcriptionally upregulating LPL, apo A-I and apo A-1 I, and down regulate apo CIII, an inhibitor of lipolysis by activating a nuclear receptor, PPAR alpha (peroxisome proliferator activated receptor alpha). o Major effect of the fibrates is to ‑
  1. Increased oxidation of fatty acids in liver and striated muscle
  2. Increased lipolysis of lipoprotein triglyceride via LPL.
  3. Reduce TG (contained in VLDL) reduced VLDL secretion by liver.
  4. Increase HDL

Q. 49

Drug that binds bile acids in the intestine and prevents their return to liver via the enterohepatic circulation is‑

 A

Niacin

 B

Fenofibrate

 C

Cholestyramine

 D

Gugulipid

Q. 49

Drug that binds bile acids in the intestine and prevents their return to liver via the enterohepatic circulation is‑

 A

Niacin

 B

Fenofibrate

 C

Cholestyramine

 D

Gugulipid

Ans. C

Explanation:

Ans. is ‘c’ i.e., Cholestyramine


Q. 50

Lipoprotein lipase is activated by which drug?

 A

Atorvastatin

 B

) Clofibrate

 C

Cholestramine

 D

Nicotinic acid

Q. 50

Lipoprotein lipase is activated by which drug?

 A

Atorvastatin

 B

) Clofibrate

 C

Cholestramine

 D

Nicotinic acid

Ans. B

Explanation:

Ans. is ‘b’ i.e., Clofibrate 

  • Fibrates (e.g. clofibrate) activate lipoprotein lipase, therefore, enhance lipolysis of triglycerides in VLDL.

Fibric acid derivatives

  • Fibric acid derivatives are clofibrate, gemfibrozil, bezafibrate, fenofibrate.
  • They activate lipoprotein lipase -4 T degradation of VLDL→ TG.
  • This effect is excerted through paroxisome proliferator – activated receptor a (PPARa).
  • They also increase HDL, LDL and decrease release of free fatty acids from adipose tisse.
  • Decrease in LDL level is due to ‑
  • Changes in cholesterol and triglyceride contents of LDL that are mediated by CETP, such changes alter the affinity of LDL for LDL receptors.
  • There is increase in SREBP -1 production which is mediated by PPAR a → T LDL receptors.
  • Increase in HDL cholesterol is due to increased expression of apo-A l which is the major apolipoprotein of HDL.
  • In some patients with hypertriglyceridaemia LDL-CH may rise, partly because of inability of LDL receptor to clear excess number of LDL particles generated by enhanced VLDL catabolism.

Q. 51

Drug of choice for familial hypercholesterolemia ‑

 A

Gemfibrogil

 B

Nicotinic acid

 C

Lovastatin

 D

Ceholestgramin

Q. 51

Drug of choice for familial hypercholesterolemia ‑

 A

Gemfibrogil

 B

Nicotinic acid

 C

Lovastatin

 D

Ceholestgramin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Lovastatin

Quiz In Between



Anti-Dyslipidemic Drugs

ANTI-DYSLIPIDEMIC DRUGS


ANTI-DYSLIPIDEMIC DRUGS

  • First line drugs:
    • Statins, bile acid binding resins & intestinal cholesterol absorption inhibitors.
  • Second line drugs:
    • Fibrates & niacin.

A). STATINS

MOA:

  • HMG CoA reductase catalyzes in cholesterol biosynthesis, mainly conversion of HMG CoA to mevalonate.
  • This is rate limiting step.
  • Statins act by inhibiting HMG CoA reductase enzyme competitively.

Effect of statins:

  • Decreases cholesterol synthesis in liver:
    • By inhibiting HMG CoA reductase enzyme.
  • Decreases bile acids & steroid hormones synthesis:
    • Indirectly affected due to decreased cholesterol.
  • Lowers plasma LDL levels:
    • Most powerful LDL lowering agents.
    • As an aftereffect of all above steps (decreasing cholesterol, bile acids & steroid synthesis).
    • All steps are compensated by, increasing LDL receptors on its surface & thus, LDL uptake from plasma.
  • Also lowers TG, IDL & VLDL & increases HDL slightly.
  • No effect on lipoprotein.
  • Decreases plasma fibrinogen levels – Mainly Pravastatin.
  • Pleotropic effects:
    • Antioxidant properties.
    • Anti-inflammatory properties.
    • Anti-proliferative properties.
    • Clinical benefits – Helps lower risk of stroke & MI.

Drugs:

  • Pitavastatin, rosuvastatin, atorvastatin, fluvastatin & lovastatin
  • Pravastatin approved for children ≥ 8 years.
  • Other statins approved for children ≥ 10 years.

Adverse effects:

  • Myopathy & hepatotoxicity (Major).
    • Myopathy chances increase on co-administration with fibrates (maximum with gemfibrozil) or niacin.
    • Myopathy proceeds to rhabdomyolysis & then, renal shutdown.
    • Pravastatin is safer in this regard.
  • Be avoided in pregnancy & lactation.

Uses:

  • First line drugs for type IIa, type IIb & secondary hyperlipoproteinemia.
    • Because these conditions, cholesterol level is raised more than TG.
  • In children with heterozygous familial hypercholesterolemia.

Properties of individual drugs:

1. Half-life:

  • Long-acting drugs:
    • Rosuvastatin (t1/2 – 19 hours) – Longest acting statin.
    • Atorvastatin (t1/2 – 14 hours)
    • Hence can be administered at any time of day.

2. Drug administration & timing:

  • Drugs administered at night:
    • Activity of HMG CoA reductase maximum at night – Hence, most drugs administered at night.
  • Drugs administrated any time of day:
    • Long-acting drugs like Rosuvastatin & Atorvastatin – Due to longer half-life.

3. Metabolism:

  • All statins absorbed orally (maximum fluvastatin).
    • Food increases absorption of all drugs, except pravastatin.
  • Undergo first pass metabolism
    • Lovastatin & simvastatin – Extensive first-pass metabolism & administered as prodrugs
    • Pravastatin, fluvastatin, atorvastatin & rosuvastatin – Administered as active drugs.
  • All drugs are metabolized extensively by hepatic microsomal enzymes, except pravastatin.
    • Pravastatin metabolized by sulfation (non-microsomal) –> Least chances of drug interactions.
    • Hence, Pravastatin confined to liver & is safer.

4. Drug potency:

  • Pitavastatin (Most potent statin) > Rosuvastatin > fluvastatin > lovastatin (least potent statins).

B). INTESTINAL CHOLESTEROL ABSORPTION INHIBITOR

  • Drug: Ezetimibe
  • MOA: 
    • Inhibits transporter NPC1L1, involved in intestinal absorption of cholesterol.
    • Due to decreased absorption, liver cholesterol content decreases & in turn increases LDL receptor synthesis.
  • Uses:
    • Type IIa & IIb hyperlipoproteinemia – Used alone or combined with statins.

C). BILE ACID BINDING RESINS

MOA:

  • Binds to bile acids in intestinal lumen –> Decreases its reabsorption –> results in more excretion via feces.
  • Depletes liver cholesterol pool, because it is utilized for bile acid formation.
  • Liver acquires cholesterol from plasma, by increasing LDL receptors.
  • Bile acids inhibit TG production in liver & their deficiency results in TGs elevation.

Uses:

  • Only for type IIa disorder (TGs are normal in this condition).

Drugs:

  • Cholestyramine, colestipol & colesevelam.
  • Cholestyramine & colestipol –  
    • Available as sachets.
    • Mixed with water, kept for some time (to increase palatability) & then taken with meals.
  • Colesevelam – 
    • Available as tablet.
    • Has better patient compliance.

Adverse effect:

  • Constipation (Major).

D). FIBRIC ACID DERIVATIVES

MOA:

  • Acts by activating LPL by activating nuclear receptor, PPARα (peroxisome proliferator-activated receptor alpha).

Major effects:

  • Reduces TG (contained in VLDL).
  • Increases HDL.
  • Reduces plasma fibrinogen level.

Drugs:

  • Clofibrate, gemfibrozil, fenofibrate, bezafibrate.
  • Clofibrate – Not used now.
    • Due to increased mortality from malignancies, post-cholecystectomy complications & fatal MI. 
  • Gemfibrozil, fenofibrate & bezafibrate – Currently available.

Fenofibrate:

  • Prodrug with longest half-life.
  • Has maximum LDL cholesterol-lowering action.
  • Uricosuric

Uses:

  • DOC in hypertriglyceridemia (type III & IV).
  • In combination with other drugs in type IIb.
  • For hyperuricemia (Fenofibrate – uricosuric)

Adverse effects:

  • GI distress.
  • Elevation of aminotransferases.
  • Increased myopathy risk – On combining with statins, except bezafibrate.

NICOTINIC ACID

  • Note: Niacin (not nicotinamide).
  • An inexpensive drug (vitamin B)

MOA:

  • Acts by inhibiting lipolysis in adipose tissue.

Effects:

  • Decreases LDL cholesterol & VLDL triglycerides.
  • Increases HDL cholesterolMaximum HDL increasing property (Among all hypolipidemic drugs).
  • Decreases lipoprotein (a) & fibrinogen.

Uses:

  • Useful in patients having increased risk of CAD (due to maximum HDL increasing property).
  • For type IIb, III & IV disorders.

Adverse effects:

  • Cutaneous flushing & pruritis – Main compliance limiting feature.
    • Due to vasodilatory effect via PGs release.
    • Prevented by aspirin pretreatment.
  • To minimize side effects, niacin should be started at low doses.

Other adverse effects:

  • GI toxicity.
  • Hyperuricemia.
  • Hepatotoxicity (manifested by fall in both LDL & HDL).

MISCELLANEOUS DRUGS

1. Probucol:

  • Useful for its antioxidant action.
  • MOA: Inhibits LDL oxidation –> Reduces both HDL & LDL cholesterol levels.

2. Gugulipid: 

  • Drug developed by Central Drug Research Institute, Lucknow.
  • Causes modest LDL reduction & slight HDL increase.
  • Diarrhea – Only adverse effect.

NEW DRUGS

1. Avasimibe:

  • Inhibits ACAT-1 (acyl-coenzyme A: cholesterol acyltransferase-1) enzyme.
  • ACAT-1 forms cholesterol ester from cholesterol.

2. Torcetrapib & anacetrapib:

  • Increases HDL cholesterol by inhibiting enzyme CETP (cholesterol ester triglyceride transport protein).

3. Lomitapide:

  • Acts by inhibiting MTP (microsomal triglyceride transfer protein).
  • MTP necessary for VLDL assembly & secretion in liver.

Exam Important

ANTI-DYSLIPIDEMIC DRUGS

  • First line anti-dyslipidemic drugs are statins, bile acid binding resins & intestinal cholesterol absorption inhibitors.
  • Second line anti-dyslipidemic drugs are fibrates & niacin.
  • Statins act by inhibiting HMG CoA reductase enzyme competitively.
  • HMG CoA reductase catalyzes in cholesterol biosynthesis, mainly conversion of HMG CoA to mevalonate.
  • Rate-limiting step in cholesterol biosynthesis is conversion of HMG CoA to mevalonate, catalyzed by HMG CoA reductase.
  • Statins decrease cholesterol synthesis in liver, by inhibiting HMG CoA reductase enzyme.
  • Statins decrease bile acids & steroid hormones synthesis.
  • Statins are most powerful LDL lowering agents.
  • Statins decrease TG, IDL & VLDL & increases HDL slightly.
  • Statins have no effect on lipoprotein.
  • Statins mainly pravastatin decreases plasma fibrinogen levels.
  • Statins exhibit pleiotropic effects like antioxidant, anti-inflammatory & anti-proliferative properties.
  • Pitavastatin, rosuvastatin, atorvastatin, fluvastatin & lovastatin are drugs included under statins.
  • Pravastatin approved for children ≥ 8 years.
  • Major adverse effect of statins includes Myopathy & hepatotoxicity.
  • Pravastatin is safer with regard to causing myopathy.
  • Statins are first-line drugs for type IIa, type IIb & secondary hyperlipoproteinemia.
  • Long-acting statins are Rosuvastatin (t1/2 – 19 hours) & Atorvastatin (t1/2 – 14 hours).
  • Rosuvastatin with t1/2 19 hours is the longest acting statin.
  • Activity of HMG CoA reductase maximum at night, hence most statins are administered at night.
  • Long-acting drugs like Rosuvastatin & Atorvastatin are administrated any time of day, due to their longer half-life.
  • All statins absorbed orally, maximum with fluvastatin.
  • Lovastatin & simvastatin are administered as prodrugs & have extensive first-pass metabolism.
  • Pravastatin, fluvastatin, atorvastatin & rosuvastatin are administered as active drugs.
  • All statins are metabolized extensively by hepatic microsomal enzymes, except pravastatin.
  • Pravastatin metabolized by sulfation (non-microsomal).
  • Most potent statin is Pravastatin; Least potent statin is lovastatin.
  • Ezetimibe is an intestinal cholesterol absorption inhibitor.
  • Ezetimibe acts by inhibiting NPC1L1 transporter, involved in intestinal absorption of cholesterol. 
  • Intestinal cholesterol absorption inhibitor like Ezetimibe indicated in type IIa & IIb hyperlipoproteinemia.
  • Bile acid binding resins bind to bile acids in intestinal lumen –> Decreases its reabsorption –> results in more excretion via feces.
  • Bile acid binding resins are indicated only for type IIa disorder.
  • Drugs included under bile acid binding resins cholestyramine, colestipol & colesevelam.
  • Fibric acid derivatives act by activating LPL by activating nuclear receptor, PPARα (peroxisome proliferator-activated receptor alpha).
  • Fibric acid derivatives reduces TG (contained in VLDL), increases HDL & reduces plasma fibrinogen level.
  • Drugs included under fibric acid derivatives are Clofibrate, gemfibrozil, fenofibrate, bezafibrate.
  • Fenofibrate is prodrug with longest half-life.
  • Fenofibrate has maximum LDL cholesterol-lowering action & are uricosuric.
  • DOC in hypertriglyceridemia (type III & IV) is Fenofibrate.
  • Nicotinic acid acts by inhibiting lipolysis in adipose tissue.
  • Main effects of nicotinic acid increase HDL cholesterol, decrease LDL cholesterol, VLDL triglycerides, lipoprotein (a) & fibrinogen.
  • Among all hypolipidemic drugs, nicotinic acid is maximum HDL increasing property.
  • Due to maximum HDL increasing property, Nicotinic acid is useful in patients having increased risk of CAD.
  • Except for type-I disorders, nicotinic acid is useful in type IIb, III & IV disorders.
  • Main limiting feature of nicotinic acid is cutaneous flushing & pruritis.
  • Probucol is an anti-dyslipidemic drug useful for its antioxidant action.
  • Probucol inhibits LDL oxidation resulting in reducing both HDL & LDL cholesterol levels.
  • Gugulipid causes modest reduction of LDL & slight increase of HDL.
  • Avasimibe is a new anti-dyslipidemic drug that acts by inhibiting ACAT-1 (acyl-coenzyme A: cholesterol acyltransferase-1) enzyme.
  • Torcetrapib & anacetrapib is an anti-dyslipidemic drug, which increases HDL cholesterol, by inhibiting enzyme CETP (cholesterol ester triglyceride transport protein).
  • Anti-dyslipidemic drug, Lomitapide acts by inhibiting MTP (microsomal triglyceride transfer protein).
Don’t Forget to Solve all the previous Year Question asked on ANTI-DYSLIPIDEMIC DRUGS

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