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15 Cards in this Set
- Front
- Back
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Resins |
- metabolites of cholesterol - (cholestyramine, colestipol, colevelam) - large nonabsorbable polymers - bind to bile acids and similar steroids in intestine and prevent absorption -cause reduction in LDL cholesterol - no effect on HDL -in some patients with genetic mutations increases VLDL and triglycerides - mainly for hypercholesterolemia -absorption of vitamins and drugs is impaired - toxicities include bloating, constipation, and an unpleasant gritty taste. |
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Ezetimibe |
-first in class of cholesterol absorption inhibitors -site of action NPC1L1 cholesterol transporter (enterocytes) -selectively inhibits cholesterol absorption, and plant sterols -active glucuronide metabolite circulate enterohepatically - used for hypercholesterolemia and phytosterolemia -Toxic when combined with HMGCoA - increases hepatic toxic |
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Niacin (Nicotinic Acid) |
- delivers agent back to site of action/ water soluble vitamin B3 - nicotinamide - incorporated (NAD) - -reduces VLDL which reduces LDL -DECREASES LDL AND TGA but INCREASES HDL -Toxicities include - cutaneous flushing, mediated by prostaglandin release , carbohydrate tolerance and hyperurecemia |
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Fibric Acid Derivatives |
-activates peroxisome proliferator activated receptor alpha (PPAR-alpha) a transcription factor that regulates genes that control lipid metabolism -expressed in liver and brown adipose tissue - lesser in kidney, heart, and skeletal muscle -reduces apoC-III (increases LDL synthesis), and increases apoCI, and apoCII (increases HDL) Toxicities - myopathy risk increase in patients , cholesterol increase of bile/gallstones, |
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Combination Therapy |
-Hyperlipidemia - first treated with dietary modification - drugs then added - to reduce toxicity and achieve lower LDL, VLDL, and HDL - some challenges - resins interefere with HMGcoA -must be given at least 1 hour before or 4 hours after resins - - combination of reductase inhibitors with either fibrates or niacin increases risk of myopathy |
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Classification of lipoproteins |
chylomicrons - VLDL - LDL - HDL |
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SREBP |
... |
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HMG CoA |
.... |
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HMG coa Reductase inhibitors |
Statins mainly - atorvastatin, simvastatin, rosuvastatin - mainly treat dyslipidemia - inhibitors of 3 hydroxy 3 methylglutaril coenzyme A reductase, ( same thing converts HMG-CoA to melavonate) -rate limiting step in cholesterol biosynthesis |
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Statin Mechanism |
- in high cholesterol diet - inhibits HMG-CoA reductase - can also decrease VLDL production - cell wont use as much VLDL for synthesis -inhibits HMG-CoA reductase - inhibit cholesterolgenesis - increase expression of LDL receptor |
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Statin Uses /Pharmokinetics |
- lovastatin and sumvastatin - lactone prodrugs - hydrolyzed to active absorption - enhanced by food - high first pass extraction by liver - mostly excreted in bile - alone or in combo with resins, niacinm or ezetimibe (category X) not for pregnant women -ator and rosu statin good for severe hypercholesterolemia |
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Statin Toxicities |
Liver -medication discontinued if hepatoxicity present Myopathy -elevations in creatine kinase - intense myalgia - arms thighs, entire body - fatigue -increased myopathy with polymorphisms in gene encoding liver specific organic anion transporter |
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PCSK 9 inhibitors |
-monoclonal antibodies (mAbs) against PCSK9 protein -produced in ER undergoes autocatalytic process - diverts- LDLR from recycling and sends to lysosome - under control of SREBP pathway limit induction of LDL receptors |
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Bile Acid Sequestrant (resins) |
-works best with resins -cholestyramine- anion exchange resins -cholesevelam - newer - cross linked polymers - colestipol- anion exchange resins -inhibits bile reabsorption from terminal ileum from liver - highly positive charged - bind to negatively charged bile acids (large) - increased LDL clearance, LDL receptors increased - |
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Bile Acid Uses and toxic |
- with meals - to remove digitalis - bile salt accumulation and cholestasis - heterozygous FH - combined hyperlipoproteinamia Toxic - constipation, bloating, heartburn and diarrhea, cant absorb vitamin K or folic acid -- increased hepatic triglyceride synthesis |
