HYPOLIPEMIC drugs (used in hyperlipidemia) Flashcards
1
Q
groups of dugs included:
A
- HMG-CoA reductase inhibitors = STATINS
- fibrates
- bile-acid binding RESINS (“anion exchange resins”)
- NIACIN + derivatives (nicotinic acid = vit. B3)
- CHOLESTEROL absorption inhibitor
- fish oil
- others
2
Q
statins → drug names:
A
- pitavastatin
- rosuvastatin
- atorvastatin
- simvastatin
- pravastatin
- lovastatin
- fluvastatin
3
Q
statins → mechanism of action:
A
- competitive inhibitors of HMG-CoA reductase (rate limiting enzyme in cholesterol synthesis)
- inhibition of HMG-CoA reductase → decrease in hepatic cholesterol, & increased synthesis of LDL receptors with increase of LDL clearance
- decrease LDL & TG level + may increase HDL-cholesterol
4
Q
statins → pharmacokinetics:
A
- statins with shorter t1/2 → are taken in the EVENING or at BEDTIME to ensure inhibition of nocturnal cholesterol biosynthesis
- atorvastatin & rosuvastatin → longer t1/2 → can be taken at ANY time of day
5
Q
statins → clinical effects:
A
- ↓ T-Ch → 20-30%
- ↓ LDL → 30-40%
- ↑ HDL → 0-10%
- ↓ TG → 0-10%
6
Q
statins → indications:
A
- heterozygous familial hypercholesterolemia
- symptomatic atherosclerosis disease in pat. at risk for CHD
- coronary heart disease
7
Q
statins → CONTRAindications:
A
- pregnancy
2. lactation
8
Q
statins → side effects:
A
- myositis (in combination with fibrates)
- diabetes mellitus
- mild GIT symptoms
- insomnia: lovastatin & simvastatin → cross the BBB → can cause sleep disturbances in some pat.
- rash
- hepatitis
- angio-edema
- interaction with CYP3A4 inhibitors (grapefruit juice 200ml/day)
- myopathy, rhabdomyolysis
- increase effect of warfarin
9
Q
fibrates → drug names:
A
- gemfibrozil
- fenofibrate
- bezafibrate
- ciprofibrate
10
Q
fibrates → mechanism of action:
A
- stimulation of lipoprotein lipase → ↑ hydrolysis of TG in chylomicrons & VLDL
- through PPAR-α: (peroxisome proliferator-activated receptor alpha / NR1C1)
- ↓ hepatic VLDL production
- ↑ hepatic LDL uptake
- inhibition of HMG-CoA reductase
11
Q
fibrates → clinical effects:
A
- ↓ TG → 20-60%
- ↓ T-Ch → 10-30%
- ↓ LDL → 15-30% or ↑ by 25%
- ↑ HDL → 0-30%
12
Q
fibrates → indication:
A
treatment of HYPERTRIGLYCERIDEMIAS → particularly type III hyperlipidemia
13
Q
fibrates → CONTRAindications:
A
- gemfibrozil & simvastatin together
2. severe hepatic or renal dysfunction
14
Q
fibrates → side effects:
A
- mild GI-tract symptoms
- increase biliary cholesterol → stones
- myositis can occur
- myopathy & rhabdomyolysis (if combined with statin)
- increase effects of warfarin (monitor INR)
15
Q
NIACIN + derivatives → drug names:
A
- nicotinic acid / niacin (= vit. B3)
2. acipimox (a niacin derivative)
16
Q
NIACIN + derivatives → mechanism of action:
A
- inhibits lipolysis in AT → ↓ production of FFA → FFA precursor for TG-synthesis, so ↓ liver TG → ↓ hepatic VLDL production → ↓ LDL-C plasma
- DECREASE plasma cholesterol & TG
- the most effective agent for INCREASING HDL!!
17
Q
NIACIN + derivatives → pharmacokinetics:
A
- ORALLY
- excreted in urine
- CAN be used in combination with STATINS → available as fixed dose with lovastatin & long-acting niacin
18
Q
NIACIN + derivatives → clinical effects:
A
- ↓ TG → up to 90%
- ↓ T-Ch → 10-70%
- ↓ LDL → 10-40%
- ↑ HDL increase → 0-10%
19
Q
NIACIN + derivatives → indications:
A
- familial hyperlipidemias
2. severe hypercholesterolemia (often in combination with other drugs)
20
Q
NIACIN + derivatives → CONTRAindication:
A
hepatic disease
21
Q
NIACIN + derivatives → side effects:
A
- intense cutaneous flush & pruritus
- nausea & abdominal pain
- headache
- postural hypotension
- diarrhea
- IGT
- peptic ulcer exacerbation
- myalgia, myopathy
- predispose to hyperuricemia & gout
22
Q
CHOLESTEROL absorption inhibitor → drug name:
A
- ezetimibe
23
Q
CHOLESTEROL absorption inhibitor → mechanism of action:
A
- inhibits dietary & biliary Ch absorption → ↓ delivery of Ch to liver → ↓ of hepatic Ch stores & ↑ clearance from the blood
- effective even when Ch not ingested → due to inhibition absorption of Ch excreted in bile
24
Q
CHOLESTEROL absorption inhibitor → indications:
A
- treatment of high blood-Ch
2. also indicated in pat. not tolerating statins
25
CHOLESTEROL absorption inhibitor → clinical effects:
1. ↓ LDL → 15-18% (synergistic with statins 25%)
| 2. ↑ HDL → 2-3%
26
CHOLESTEROL absorption inhibitor → side effects:
1. reversible impairment of liver function
| 2. myositis → very rare when combined with statins
27
fish oil → mechanism of action:
1. decrease of TG
2. ↓ of VLDL synthesis
3. anti-inflammatory effect
28
fish oil → indications:
1. hypertriglyceridemia
| 2. protect against CHD
29
fish oil → CONTRAindication:
type IIa → increase LDL cholesterol
30
fish oil → drug name:
1. omega-3
31
other hypolipemic drugs → names:
1. evolocumab
2. mipomersen
3. lomitapide
32
other hypolipemic drugs → mechanism of action:
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
33
other hypolipemic drugs → indication:
evolocumab → familial hypercholesterolemia
34
other hypolipemic drugs → side effects:
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
