HYPOLIPEMIC drugs (used in hyperlipidemia)

Question 1

groups of dugs included:

Answer 1

1. HMG-CoA reductase inhibitors = STATINS
2. fibrates
3. bile-acid binding RESINS (“anion exchange resins”)
4. NIACIN + derivatives (nicotinic acid = vit. B3)
5. CHOLESTEROL absorption inhibitor
6. fish oil
7. others

Question 2

statins → drug names:

Answer 2

1. pitavastatin
2. rosuvastatin
3. atorvastatin
4. simvastatin
5. pravastatin
6. lovastatin
7. fluvastatin

Question 3

statins → mechanism of action:

Answer 3

1. competitive inhibitors of HMG-CoA reductase (rate limiting enzyme in cholesterol synthesis)
2. inhibition of HMG-CoA reductase → decrease in hepatic cholesterol, & increased synthesis of LDL receptors with increase of LDL clearance
3. decrease LDL & TG level + may increase HDL-cholesterol

Question 4

statins → pharmacokinetics:

Answer 4

1. statins with shorter t1/2 → are taken in the EVENING or at BEDTIME to ensure inhibition of nocturnal cholesterol biosynthesis
2. atorvastatin & rosuvastatin → longer t1/2 → can be taken at ANY time of day

Question 5

statins → clinical effects:

Answer 5

1. ↓ T-Ch → 20-30%
2. ↓ LDL → 30-40%
3. ↑ HDL → 0-10%
4. ↓ TG → 0-10%

Question 6

statins → indications:

Answer 6

1. heterozygous familial hypercholesterolemia
2. symptomatic atherosclerosis disease in pat. at risk for CHD
3. coronary heart disease

Question 7

statins → CONTRAindications:

Answer 7

1. pregnancy

2. lactation

Question 8

statins → side effects:

Answer 8

1. myositis (in combination with fibrates)
2. diabetes mellitus
3. mild GIT symptoms
4. insomnia: lovastatin & simvastatin → cross the BBB → can cause sleep disturbances in some pat.
5. rash
6. hepatitis
7. angio-edema
8. interaction with CYP3A4 inhibitors (grapefruit juice 200ml/day)
9. myopathy, rhabdomyolysis
10. increase effect of warfarin

Question 9

fibrates → drug names:

Answer 9

1. gemfibrozil
2. fenofibrate
3. bezafibrate
4. ciprofibrate

Question 10

fibrates → mechanism of action:

Answer 10

1. stimulation of lipoprotein lipase → ↑ hydrolysis of TG in chylomicrons & VLDL
2. through PPAR-α: (peroxisome proliferator-activated receptor alpha / NR1C1)
   1. ↓ hepatic VLDL production
   2. ↑ hepatic LDL uptake
   3. inhibition of HMG-CoA reductase

Question 11

fibrates → clinical effects:

Answer 11

1. ↓ TG → 20-60%
2. ↓ T-Ch → 10-30%
3. ↓ LDL → 15-30% or ↑ by 25%
4. ↑ HDL → 0-30%

Question 12

fibrates → indication:

Answer 12

treatment of HYPERTRIGLYCERIDEMIAS → particularly type III hyperlipidemia

Question 13

fibrates → CONTRAindications:

Answer 13

1. gemfibrozil & simvastatin together

2. severe hepatic or renal dysfunction

Question 14

fibrates → side effects:

Answer 14

1. mild GI-tract symptoms
2. increase biliary cholesterol → stones
3. myositis can occur
4. myopathy & rhabdomyolysis (if combined with statin)
5. increase effects of warfarin (monitor INR)

Question 15

NIACIN + derivatives → drug names:

Answer 15

1. nicotinic acid / niacin (= vit. B3)

2. acipimox (a niacin derivative)

Question 16

NIACIN + derivatives → mechanism of action:

Answer 16

1. inhibits lipolysis in AT → ↓ production of FFA → FFA precursor for TG-synthesis, so ↓ liver TG → ↓ hepatic VLDL production → ↓ LDL-C plasma
2. DECREASE plasma cholesterol & TG
3. the most effective agent for INCREASING HDL!!

Question 17

NIACIN + derivatives → pharmacokinetics:

Answer 17

1. ORALLY
2. excreted in urine
3. CAN be used in combination with STATINS → available as fixed dose with lovastatin & long-acting niacin

Question 18

NIACIN + derivatives → clinical effects:

Answer 18

1. ↓ TG → up to 90%
2. ↓ T-Ch → 10-70%
3. ↓ LDL → 10-40%
4. ↑ HDL increase → 0-10%

Question 19

NIACIN + derivatives → indications:

Answer 19

1. familial hyperlipidemias

2. severe hypercholesterolemia (often in combination with other drugs)

Question 20

NIACIN + derivatives → CONTRAindication:

Answer 20

hepatic disease

Question 21

NIACIN + derivatives → side effects:

Answer 21

1. intense cutaneous flush & pruritus
2. nausea & abdominal pain
3. headache
4. postural hypotension
5. diarrhea
6. IGT
7. peptic ulcer exacerbation
8. myalgia, myopathy
9. predispose to hyperuricemia & gout

Question 22

CHOLESTEROL absorption inhibitor → drug name:

Answer 22

1. ezetimibe

Question 23

CHOLESTEROL absorption inhibitor → mechanism of action:

Answer 23

1. inhibits dietary & biliary Ch absorption → ↓ delivery of Ch to liver → ↓ of hepatic Ch stores & ↑ clearance from the blood
2. effective even when Ch not ingested → due to inhibition absorption of Ch excreted in bile

Question 24

CHOLESTEROL absorption inhibitor → indications:

Answer 24

1. treatment of high blood-Ch

2. also indicated in pat. not tolerating statins

Question 25

CHOLESTEROL absorption inhibitor → clinical effects:

Answer 25

1. ↓ LDL → 15-18% (synergistic with statins 25%)

2. ↑ HDL → 2-3%

Question 26

CHOLESTEROL absorption inhibitor → side effects:

Answer 26

1. reversible impairment of liver function

2. myositis → very rare when combined with statins

Question 27

fish oil → mechanism of action:

Answer 27

1. decrease of TG
2. ↓ of VLDL synthesis
3. anti-inflammatory effect

Question 28

fish oil → indications:

Answer 28

1. hypertriglyceridemia

2. protect against CHD

Question 29

fish oil → CONTRAindication:

Answer 29

type IIa → increase LDL cholesterol

Question 30

fish oil → drug name:

Answer 30

1. omega-3

Question 31

other hypolipemic drugs → names:

Answer 31

1. evolocumab
2. mipomersen
3. lomitapide

Question 32

other hypolipemic drugs → mechanism of action:

Answer 32

evolocumab:
1. monoclonal antibody against PCSK (proprotein convertase subtilisin/kexin)

2. PCSK → bind to LDL receptor acc. their degradation → reducing rate of removal of LDL cholesterol
3. blocking PCSK9 & LDL interaction with AB that binds to PCSK9 → lowering LDL cholesterol in pat. with hypercholesterolemia

mipomersen:
inhibition of protein translation to decrease apo B (apolipoprotein B) conc.

lomitapide:
microsomal triglyceride transfer protein inhibitor

Question 33

other hypolipemic drugs → indication:

Answer 33

evolocumab → familial hypercholesterolemia

Question 34

other hypolipemic drugs → side effects:

Answer 34

evolocumab:

1. arthropathy
2. headache
3. fatigue

mipomersen:

1. injection-site reactions
2. fatigue, pyrexia ,chills, malaise
3. myalgia, arthralgia
4. increased liver fat content & liver dysfunction

lomitapide:

1. increased fat content
2. liver dysfunction