Lecture 11 - Anti-hyperlipidemics

American Heart Association PREVENT Calculator

• Assesses risk in adults without established cardiovascular disease

• Estimates risk of cardiovascular disease, heart attack, stroke, and heart failure

• Evaluates cardiovascular risk in adults

  • aged 30 to 79 for 10-year projections

  • adults aged 30 to 59 for 30-year projections.

what’s including in risk calculating

• Age

  ▪ Sex

  ▪ Systolic Blood Pressure

  ▪ Blood Pressure Medication

  ▪ Total Cholesterol

  ▪ HDL Cholesterol

  ▪ Statin Medication

  ▪ Diabetes Status

  ▪ Current Smoker

  ▪ eGFR (estimated glomerular filtration rate)

  ▪ BMI (Body Mass Index)

lifestyle modifications

weightloss

>5% wt loss if overweight with dyslipidemia

▪ Obesity (BMI>30 kg/m2) or overweight (BMI 25-29.9 kg/m2) at higher risk for ASCVD

▪ Aim for BMI 18.5-24.9 kg/m2

diet

• Reduce saturated fat and trans fat

• Plant based or Mediterranean-like diet

• LIMIT

  • red meat, diary products w. whole milk, fried food

  • sugar

• cook with healthy oils

• MORE

  • fruit, veggies, whole rains, poultry, fish & nuts, more fiber

Physical activity

• at least 150 min/ weel of moderate physical activty

• 75 min/week of vigorous intense physicla activity —> resistance exercise

• muslce-strengthening activities

things to manage

• sleep for 7-9 hours

• stress

• smoking

• blood sugar & blood pressure

how do statins reduce plasma cholesterol

• reduce cholesterol synthesis & increase catabolism of LDL

• may increase HDL levels

• reduce relative cardiovascular risk by 20-30%

types of statins

• Atorvastatin(Lipitor)

  ▪ Fluvastatin (Lescol)

  ▪ Lovastatin (Altoprev, Mevacor)

  ▪ Pitavastatin (Livalo)

  ▪ Pravastatin (Pravachol)

  ▪ Rosuvastatin (Crestor)

  ▪ Simvastatin (Zocor

what med is greatest for LDL level reduction

statin

all statins are rec to be taken in evening EXCEPT

• atorvastatin, rosuvastatin, and pitavastatin

• can give these ANY TIME

contraindications of statins

• liver damage

• pregnancy

• co-admin w. strong CYP3A4 inhibitors (lovastatin & simvastatin)

avoid doses of Simvastatin 80 mg unless

• unless pt has already been taking for >12 months

why is statins contraindicated for use during pregnancy

• negative effect on cholesterol synthesis

• cholesterol is needed for fetal development

  • cell membranes & synthesis of steroids

• STOP treament immediately as soon as pregnant recognized

side effects of statins

Constipation

Increase in Liver Function Tests

Myopathy

• Increased risk with age, renal or hepatic dysfunction, low Vit D, higher statin doses, use with fenofibrates, other interacting drugs that increase statin levels

adverse reaction of statin

• rhabdomyolysis (muscle breaks down & release toxins to blood & kidney)

• liver damage

what should patients report

muscle aches, dark urine, severe abdominal pain, yellowing of skin or whites of eyes

statin monitoring parameters

• lipid profile (6 weeks after starting)

• LFTs

• CPK

Drug Interactions

many due to CYP3A4 & CYP2C9

Warfarin

Monitor INR, increased risk of bleeding

Fenofibrates (Gemfibrozil, Tricor)

increased risk of myopathies

Grapefruit Juice

CYP3A4 inhibition, increased levels of statins, increased risk of myopathies

and rhabdomyolysis

Simvastatin (Zocor)

also has many other interactions, including: clarithromycin, amlodipine, amiodarone, verapamil, others

▪ Lower Simvastatin dose or avoid using

Rosuvastatin (Crestor)

aluminum and magnesium antacids, give 2 or more hours after Crestor

Pravastatin (Pravachol):

fewer interactions because not metabolized significantly by CYP

enzymes

statins metabolism

• CYP2C9

  • Rosuvastatin-partially

• CYP3A4

  • simvastatin, atorvastatin, lovastatin

• OATP1B1

  • Pravastatin, lovastatin

what med can’t be taken with grapefruit juice

• atorvastatin

• lovastatin

• simvastatin

rec to avoid daily taking of juice & avoid taking med w/ juice

Zetia (Ezetimibe)

• MOA: Prevents absorption of cholesterol from small intestine

• lower ldl

• Side Effects: headache, diarrhea

• Also available as combo product Vytorin (simvastatin/ezetimibe)

  
  

zetia Drug Interactions:

• Fibrates - Zetia increases potential side effects of fibrates

  • Cyclosporine - can see increased Cyclosporine concentration or increased Zetia

  • Warfarin – increased effects of Warfarin

  • Bile Acid Sequestrants - Take 2 hours before or 4 hrs after bile acid sequestrant

fibric acid derivatives

MOA: Complex, exact mechanism unknown; inhibit triglyceride synthesis, stimulate catabolism of triglyceride rich lipoproteins

▪ Used to decrease triglycerides or increase HDL

▪ Fenofibrate (Tricor)

▪ Gemfibrozil (Lopid)

fibirc acid derivatives contraindications

Dose adjust in renal impairment

contraindications

• Hepatic impairment

  • Severe renal impairment

  • Gallbladder Disease

  • Concurrent Statin use (increased risk of myopathy)

  • Gemfibrozil contraindicated with Repaglinide (increased hypoglycemia)

side effects

Nausea/Vomiting

• Diarrhea-Gemfibrozil

• Constipation-Tricor

• Abdominal Pain

• Myopathy

• Incr. LFTs

how should gemfibrozil be taken

tid, 30 min before meals

fibric acid der intxn w. warfarin

may increase side effects of Warfarin (increase INR)