HYPOLIPEMIC drugs (used in hyperlipidemia) Flashcards
groups of dugs included:
- 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
statins → drug names:
- pitavastatin
- rosuvastatin
- atorvastatin
- simvastatin
- pravastatin
- lovastatin
- fluvastatin
statins → mechanism of action:
- 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
statins → pharmacokinetics:
- 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
statins → clinical effects:
- ↓ T-Ch → 20-30%
- ↓ LDL → 30-40%
- ↑ HDL → 0-10%
- ↓ TG → 0-10%
statins → indications:
- heterozygous familial hypercholesterolemia
- symptomatic atherosclerosis disease in pat. at risk for CHD
- coronary heart disease
statins → CONTRAindications:
- pregnancy
2. lactation
statins → side effects:
- 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
fibrates → drug names:
- gemfibrozil
- fenofibrate
- bezafibrate
- ciprofibrate
fibrates → mechanism of action:
- 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
fibrates → clinical effects:
- ↓ TG → 20-60%
- ↓ T-Ch → 10-30%
- ↓ LDL → 15-30% or ↑ by 25%
- ↑ HDL → 0-30%
fibrates → indication:
treatment of HYPERTRIGLYCERIDEMIAS → particularly type III hyperlipidemia
fibrates → CONTRAindications:
- gemfibrozil & simvastatin together
2. severe hepatic or renal dysfunction
fibrates → side effects:
- mild GI-tract symptoms
- increase biliary cholesterol → stones
- myositis can occur
- myopathy & rhabdomyolysis (if combined with statin)
- increase effects of warfarin (monitor INR)
NIACIN + derivatives → drug names:
- nicotinic acid / niacin (= vit. B3)
2. acipimox (a niacin derivative)
NIACIN + derivatives → mechanism of action:
- 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!!
NIACIN + derivatives → pharmacokinetics:
- ORALLY
- excreted in urine
- CAN be used in combination with STATINS → available as fixed dose with lovastatin & long-acting niacin
NIACIN + derivatives → clinical effects:
- ↓ TG → up to 90%
- ↓ T-Ch → 10-70%
- ↓ LDL → 10-40%
- ↑ HDL increase → 0-10%
NIACIN + derivatives → indications:
- familial hyperlipidemias
2. severe hypercholesterolemia (often in combination with other drugs)
NIACIN + derivatives → CONTRAindication:
hepatic disease
NIACIN + derivatives → side effects:
- intense cutaneous flush & pruritus
- nausea & abdominal pain
- headache
- postural hypotension
- diarrhea
- IGT
- peptic ulcer exacerbation
- myalgia, myopathy
- predispose to hyperuricemia & gout
CHOLESTEROL absorption inhibitor → drug name:
- ezetimibe
CHOLESTEROL absorption inhibitor → mechanism of action:
- 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
CHOLESTEROL absorption inhibitor → indications:
- treatment of high blood-Ch
2. also indicated in pat. not tolerating statins
CHOLESTEROL absorption inhibitor → clinical effects:
- ↓ LDL → 15-18% (synergistic with statins 25%)
2. ↑ HDL → 2-3%
CHOLESTEROL absorption inhibitor → side effects:
- reversible impairment of liver function
2. myositis → very rare when combined with statins
fish oil → mechanism of action:
- decrease of TG
- ↓ of VLDL synthesis
- anti-inflammatory effect
fish oil → indications:
- hypertriglyceridemia
2. protect against CHD
fish oil → CONTRAindication:
type IIa → increase LDL cholesterol
fish oil → drug name:
- omega-3
other hypolipemic drugs → names:
- evolocumab
- mipomersen
- lomitapide
other hypolipemic drugs → mechanism of action:
evolocumab:
1. monoclonal antibody against PCSK (proprotein convertase subtilisin/kexin)
- PCSK → bind to LDL receptor acc. their degradation → reducing rate of removal of LDL cholesterol
- 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
other hypolipemic drugs → indication:
evolocumab → familial hypercholesterolemia
other hypolipemic drugs → side effects:
evolocumab:
- arthropathy
- headache
- fatigue
mipomersen:
- injection-site reactions
- fatigue, pyrexia ,chills, malaise
- myalgia, arthralgia
- increased liver fat content & liver dysfunction
lomitapide:
- increased fat content
- liver dysfunction
