Pharm treatment of hyperlipidemias - Lee Flashcards
hyperlipidemia causes
-build up of LDL, not enough HDL
pharm treatment for hyperlipidemaia
-slide 8
HMG-CoA reductase inhibitors***
-STATINS*
MOA**
- inhibit HMG-CoA reductase –> inhibit cholesterol synthesis*
- intracellular cholesterol levels decline –> synthesize and upregulate LDL receptors –> uptake LDL from blood reducing plasma levels***
indications
-immediately following MI** despite lipid levels
contraindications
-pregnancy** –> lactation
effect on triglyceride levels
-substantial decrease
effect on LDL levels
-dose dependent effect* –> REDUCE 6% with each doubling of dose
effect on HDL levels
-independent of dose* –> INCREASE in 5-10%
pharmacokinetics
- short half life (1-4 hr.) –> give in evening since cholesterol synthesis occurs at night**
- enhance absorption if taken with food
- metabolized by CYP3A4/CYP2C9** (worry about toxicity or decreased effect with other drugs)
adverse effects
- hepatotoxicity*** - 3x elevated liver transaminase with underlying liver disease/EtOH abuse
- myopathy and rhabdomyolysis***
- increase risk of diabetes*
drug interactions
- CYP3A4/CYP2C9 inhibitors or inducers*
- amiodarone* or verapamil* are inducers –> increase risk of myopathy**
- GRAPEFRUIT***–> increase statin bioavailability/plasma levels by degrading CYP3A4
lovastatin
pharmacokinetics
- same as above
- taken in evening and with food*
- 70% that is circulating is attributed to active metabolites**
drug interactions
- same as above
- drugs that inhibit or induce CYP3A4
pravastatin
pharmacokinetics
- half life 77hr. –> taken orally as single dose at any time of day**
- taken with or without food (same effects)**
- 20% excreted in urine, 70% excreted in feces –> very lipophilic**
- NOT metabolized by CYP450***
Cholestyramine
-bile acid binding resins
MOA
-binds to bile acids in intestinal lumen preventing reabsorption (stays in GI; lost in feces)*** –> reduces hepatic cholesterol –> upregulate LDL receptors
indications
- isolated increase in LDL
- statin intolerance (2nd go to drug)
contraindications
-homozygous familial hypercholesterolemia (lack LDL-R and PCSK9/apoB)*
adverse effects
- reduce absorption of concomitant oral meds
- interfere with fat metabolism –> prevent absorption of fat soluble vit.**
Nicotinic acid (niacin, vit. B3)
MOA
-inhibit hormone-sensitive lipase** in adipose tissue –> prevent TAG breakdown into FAs and transport of FAs to liver –> decrease liver TAG synthesis –> inhibit VLDL secretion –> decrease production of LDL**
pharmacokinetics
-fast absorption from GI
indications
- combine with resin or statin
- heterozygous familial hypercholesterolemia*
- severe lipedema
- most effective for increasing HDL level*
- hyperlipoproteinemia, familial dysbetalipoproteinemia
contraindications
- acanthosis nigricans** (due to insulin resistance)
- liver disease (toxicity), gout (hyperuricemia)*, arrhythmias
adverse effects
- harmless cutaneous vasodilation and warmth after each dose
- tachyphylaxis to flushing response*
- impaired carbohydrate intolerance
- GI issues
drug interactions
- potentiates antihypertensives
- interfere with tetracycline metabolism
Gemfibrozil
-fibric acid derivative
MOA
- activation of nuclear transcription receptor peroxisome proliferator-activated receptor alpha (PPAR-a)* –> upregulates lipoprotein lipase removing TAGs from plasma
- PPAR-a also upregulates apoA-I (increases plasma HDL level)* and apoA-II and downregulates apoC-III
- decrease in VLDL, increase in HDL
indications
- hypertriglyceridemia in which VLDL predominates
- type III hyperlipoproteinemia
contraindications
- hepatic or renal dysfunction
- biliary tract disease
adverse effects
- arrhythmias
- hypokalemia
- high aminotransferase or alkaline phsophatase levels*
- gallstones
drug interactions
-increase coumadin anticoagulation effects**
ezetimibe
-inhibits intestinal sterol absorption
MOA
- blocks cholesterol absorption in enterocytes** by inhibiting transport protein NPC1L1 –> reduce LDL levels
- synergistic effects on LDL when combined with statins
indications
-hypercholesterolemia
pharmacokinetics
- prodrug
- conjugated to active glucuronide in liver and small intestines
adverse effects
-low incidence of reversible hepatic impairment
drug interactions
- fibrates –> increase plasma levels
- cholestyramine –> decrease plasma levels
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
- evolocumab
- alirocumab
- inhibitor of PCSK9 enzyme preventing destruction of LDL receptor and facilitates recycling of LDL receptors –> enhance removal from blood
- antibody drugs**
alirocumab
MOA
-inhibits PCSK9
-injected (IV)**
pharmacokinetics
- given subcu once every 2 weeks
- max suppression of PCSK9 in 4-8hr.
- half life 17-20 days (long acting)
indications
- adjunct therapy if statins are not enough –> lower LDL in patients with HeFH*
- atherosclerotic CV disease
- not FDA approved for hyperlipidemia with those intolerant to statins*
contraindications
- pregnancy (cross placenta)
- breastfeeding (milk)
adverse effects
- pain, swelling at injection site**
- nasopharyngitis, flu
- allergic rxns*
Lomitapide
-MTP inhibitor
MOA
-binds and inhibits microsomal TAG transfer protein (MTP) –> inhibit synthesis of chylomicrons and VLDL
risk of hepatotoxicity*
Mipomersen
- antisense inhibition of apoB-100 synthesis
- targets mRNA for apoB-100
risk of hepatotoxicity
combination treatments
- simcor –> for primary hypercholesterolemia and Fredricksom type IIa and IIb
- vytorin –> for primary hyperlipidemia and homozygous familial hypercholesterolemia
- advicor –> for patients where both niacin XR and lovastatin are indicated
- caduet –> for patients where amlodipine and atorvastatin is indicated
