MEDICATIONS USED TO MEDICATIONS USED TO TREAT HIGH TREAT HIGH

CHOLESTEROLCHOLESTEROLANDAND

THEIR SIDE EFFECTSTHEIR SIDE EFFECTS

Cristi FroymanCristi FroymanBSP StudentBSP Student

University of SaskatchewanUniversity of SaskatchewanStueck Pharmacy Ltd.Stueck Pharmacy Ltd.Leader, SaskatchewanLeader, Saskatchewan

TOTAL BLOOD CHOLESTEROL:TOTAL BLOOD CHOLESTEROL:

Wax-like substance produced by liverWax-like substance produced by liver

Essential for the body to functionEssential for the body to function

Used to make cell membranes, vitamin D Used to make cell membranes, vitamin D and hormonesand hormones

If too high, plaque deposits build up on the If too high, plaque deposits build up on the artery wallsartery walls

Adapted from the Cypress Health Region’s Nutrition for Heart Health HandoutAdapted from the Cypress Health Region’s Nutrition for Heart Health Handout

Low-density Lipoprotein Low-density Lipoprotein (LDL) Cholesterol:(LDL) Cholesterol:

““Bad” or “Lousy” cholesterol Bad” or “Lousy” cholesterol Sticks to artery wallsSticks to artery walls High levels can increase the risk of High levels can increase the risk of

heart diseaseheart disease To help lower LDL:To help lower LDL:

– Eat a healthy diet, low in saturated and Eat a healthy diet, low in saturated and trans fats, and high in soluble fibertrans fats, and high in soluble fiber

– Maintain a healthy weight Maintain a healthy weight

Adapted from the Cypress Health Region’s Nutrition for Heart Health HandoutAdapted from the Cypress Health Region’s Nutrition for Heart Health Handout

High-density Lipoprotein High-density Lipoprotein (HDL) Cholesterol:(HDL) Cholesterol:

““Good” cholesterol or “Healthy”Good” cholesterol or “Healthy” Helps carry LDL-cholesterol away Helps carry LDL-cholesterol away

from the artery walls from the artery walls To help increase HDL:To help increase HDL:

– Participate in regular physical activityParticipate in regular physical activity– Do not smokeDo not smoke– Maintain a healthy weightMaintain a healthy weight

Adapted from the Cypress Health Region’s Nutrition for Heart Health HandoutAdapted from the Cypress Health Region’s Nutrition for Heart Health Handout

Triglycerides:Triglycerides: Not a type of cholesterolNot a type of cholesterol Storage form of fat in our bodiesStorage form of fat in our bodies High levels can lead to increased risk High levels can lead to increased risk

of heart disease and stroke of heart disease and stroke To help lower TG levels:To help lower TG levels:

– Limit sugar, alcohol and fatLimit sugar, alcohol and fat– Participate in regular physical activityParticipate in regular physical activity– Maintain a healthy weightMaintain a healthy weight– Do not smokeDo not smoke

Adapted from the Cypress Health Region’s Nutrition for Heart Health HandoutAdapted from the Cypress Health Region’s Nutrition for Heart Health Handout

LIPID TARGETS: LIPID TARGETS: Adapted from the Cypress Health Region’s Nutrition for Heart Health HandoutAdapted from the Cypress Health Region’s Nutrition for Heart Health Handout

Risk Risk CategoryCategory

TargetTarget ValuesValues

LDLLDL HDLHDL TGTG Total/HDLTotal/HDL

HighHigh <2.0*<2.0* >1.0>1.0 <1.7<1.7 <4.0<4.0

ModerateModerate <3.5<3.5 >1.0>1.0 <1.7<1.7 <5.0<5.0

LowLow <4.5<4.5 >1.0>1.0 <1.7<1.7 <6.0<6.0

RESINS: RESINS: 1, 21, 2

Cholestyramine (Cholestyramine (Questran®) Questran®)

Colestipol (Colestid®)Colestipol (Colestid®)

WHAT THEY DO:WHAT THEY DO:Attach to bile salts and Attach to bile salts and

cholesterol in the stomach and cholesterol in the stomach and intestineintestine

↓ ↓ bad cholesterolbad cholesterol

↑ ↑ good cholesterolgood cholesterol

May ↑ TG (blood fats)May ↑ TG (blood fats)

DRUG INTERACTIONS:DRUG INTERACTIONS:

Resins can also bind to other Resins can also bind to other drugs and fat-soluble vitamins, drugs and fat-soluble vitamins, decreasing their amount in the decreasing their amount in the bodybody

Take other medications at least 1 Take other medications at least 1 hour before or 4 to 6 hours afterhour before or 4 to 6 hours after

SIDE EFFECTS:SIDE EFFECTS:

Not absorbed from the GITNot absorbed from the GIT

Mostly stomach relatedMostly stomach related

Titrate dose slowlyTitrate dose slowly

Common Side Effects:Common Side Effects:

Constipation (dose related) (10%)Constipation (dose related) (10%) Bloating and gas (resolves) (1-5%)Bloating and gas (resolves) (1-5%) Feelings of fullness (1-5%)Feelings of fullness (1-5%) Nausea (1-5%)Nausea (1-5%) ↑ ↑ triglycerides (blood fats)triglycerides (blood fats) ↑ ↑ liver enzymes (reversible)liver enzymes (reversible) Vitamin deficiencyVitamin deficiency

Constipation:Constipation:

High doses and in the elderlyHigh doses and in the elderly

Always take with liquidsAlways take with liquids

Fiber and fluidsFiber and fluids

Doctor may lower the dose or stop Doctor may lower the dose or stop medicationmedication

MONITORING:MONITORING: Liver functionLiver function

Triglycerides Triglycerides

INR (impaired vitamin K absorption) INR (impaired vitamin K absorption)

Electrolytes (increased chloride)Electrolytes (increased chloride)

HMG-CoA REDUCTASE HMG-CoA REDUCTASE INHIBITORS: (Statins)INHIBITORS: (Statins)1, 1,

33

Atorvastatin (LipitorAtorvastatin (LipitorTMTM)) Simvastatin (ZocorSimvastatin (Zocor®®)) Rosuvastatin (CrestorRosuvastatin (Crestor®®)) Fluvastatin (LescolFluvastatin (Lescol®)®) Lovastatin (MevacorLovastatin (Mevacor®)®) Pravastatin (PravacolPravastatin (Pravacol®®))

WHAT THEY DO:WHAT THEY DO: Block cholesterol synthesis in the liverBlock cholesterol synthesis in the liver Best medications to ↓ bad cholesterolBest medications to ↓ bad cholesterol ↓ ↓ the chance of having a heart attack or the chance of having a heart attack or

stroke by 26% stroke by 26% 44

↓ ↓ the chance of dying from a heart attack the chance of dying from a heart attack or stroke or stroke

Beneficial regardless of age, sex or healthBeneficial regardless of age, sex or health Maximum therapeutic benefit seen after 4 Maximum therapeutic benefit seen after 4

weeks of therapyweeks of therapy

SIDE EFFECTS:SIDE EFFECTS:Mild and transient Mild and transient

Side EffectSide Effect Number of Number of People out of 100People out of 100

HeadacheHeadache 7.77.7

DiarrheaDiarrhea 4.54.5

Nausea/VomitingNausea/Vomiting 3.33.3

Stomach Pain / CrampsStomach Pain / Cramps 3.33.3

Rash / ItchinessRash / Itchiness 3.03.0

GasGas 3.03.0

SIDE EFFECTS:SIDE EFFECTS:Mild and transientMild and transient

Side EffectsSide Effects Number of People Number of People out of 100out of 100

DizzinessDizziness 2.32.3

HeartburnHeartburn 2.22.2

Trouble SleepingTrouble Sleeping 1.91.9

Dry MouthDry Mouth 0.80.8

ConstipationConstipation 2.72.7

Liver Side Effects:Liver Side Effects: ↑↑ in liver enzymes: 1 to 2% incidencein liver enzymes: 1 to 2% incidence

Occurs within 3 to 12 monthsOccurs within 3 to 12 months

LFT’s at baseline, 3, 6 and 12 months, LFT’s at baseline, 3, 6 and 12 months, then yearly then yearly

People who drink a lot of alcohol and/or People who drink a lot of alcohol and/or have a history of liver disease need to be have a history of liver disease need to be monitored more carefullymonitored more carefully

Liver Side Effects:Liver Side Effects:

If liver enzymes rise to 3x ULN and If liver enzymes rise to 3x ULN and are sustained, the drug should be are sustained, the drug should be discontinued discontinued

Liver slowly returns to normal once Liver slowly returns to normal once drug stoppeddrug stopped

Muscle Side Effects:Muscle Side Effects:

Not common with statin mono-therapy Not common with statin mono-therapy

If muscle symptoms occur, they If muscle symptoms occur, they usually appear within weeks to usually appear within weeks to months after starting statinmonths after starting statin

It takes days to weeks for muscle pain, It takes days to weeks for muscle pain, weakness, and serum CK weakness, and serum CK concentrations to return to normal concentrations to return to normal after stopping the statinafter stopping the statin

Myalgia:Myalgia:

Muscle painMuscle pain

TendernessTenderness

Weakness Weakness

Serum CK may or may not be high Serum CK may or may not be high

2 to 11 % incidence 2 to 11 % incidence 55

Myositis:Myositis:

Inflammation / swelling of the Inflammation / swelling of the musclesmuscles

Serum CK levels > 10 x ULNSerum CK levels > 10 x ULN

0.5 % incidence0.5 % incidence 55

Rhabdomyolysis:Rhabdomyolysis:

Skeletal muscle breakdown / death Skeletal muscle breakdown / death Toxic muscle cell components released Toxic muscle cell components released

into the bloodinto the blood– Can lead to kidney problems, high Can lead to kidney problems, high

potassium levels and cardiac arrestpotassium levels and cardiac arrest Very Rare: occurs in approximatelyVery Rare: occurs in approximately

0.2/1 million statin prescriptions 0.2/1 million statin prescriptions 66

< 0.1 % incidence < 0.1 % incidence 55

Death occurs in ~ 10 % of cases Death occurs in ~ 10 % of cases 77

Risk Factors for Muscle Side Effects:Risk Factors for Muscle Side Effects:

Higher dosesHigher doses Liver problemsLiver problems Kidney problemsKidney problems Alcohol abuse Alcohol abuse Advanced age (> 80 yrs old)Advanced age (> 80 yrs old) Women > menWomen > men Frailty, small body frameFrailty, small body frame Untreated low thyroid levelsUntreated low thyroid levels Multiple medicationsMultiple medications Grapefruit juice intakeGrapefruit juice intake

NICOTINIC ACID: NICOTINIC ACID: 1, 81, 8

NiacinNiacin (Vitamin B(Vitamin B33) )

WHAT IT DOES:WHAT IT DOES:

Slows down the rate and Slows down the rate and production of bad cholesterol in production of bad cholesterol in the liverthe liver

↓ ↓ TG’s and bad cholesterol TG’s and bad cholesterol

Best medication to ↑ good Best medication to ↑ good cholesterolcholesterol

SIDE EFFECTS:SIDE EFFECTS:

Hot flushesHot flushes

Itchy / dry skinItchy / dry skin

Skin discoloration (reversible)Skin discoloration (reversible)

Reactivation of peptic ulcerReactivation of peptic ulcer

SIDE EFFECTS:SIDE EFFECTS: Stomach problemsStomach problems

↑ ↑ sugar, uric acid and liver enzymes sugar, uric acid and liver enzymes (SR product) in the blood(SR product) in the blood

Blood sugar and liver function should Blood sugar and liver function should

be monitored at 3, 6 and 12 months, be monitored at 3, 6 and 12 months, then yearlythen yearly

Flushing:Flushing:

Starts in the face but it may spread Starts in the face but it may spread to the arms, chest, legs and feetto the arms, chest, legs and feet

Also feel hot, itchy and may have Also feel hot, itchy and may have stomach upsetstomach upset

Starts within 20 minutes and lasts up Starts within 20 minutes and lasts up to 60 minutesto 60 minutes

Flushing:Flushing:

Tolerance develops after 2 weeksTolerance develops after 2 weeks

Do not miss a dose!Do not miss a dose!

Avoid hot drinks, hot showers, Avoid hot drinks, hot showers, spicy food or alcohol for 1–2 spicy food or alcohol for 1–2 hours after a dosehours after a dose

Flushing:Flushing:

Regular aspirin (325 mg) daily in Regular aspirin (325 mg) daily in the first few weeks of treatment the first few weeks of treatment or when increasing the dose may or when increasing the dose may be helpful (if no CI’s!)be helpful (if no CI’s!)

Taking niacin with food may help Taking niacin with food may help to decrease stomach upset and to decrease stomach upset and flushingflushing

FIBRATES:FIBRATES:1, 91, 9

Gemfibrozil (LopidGemfibrozil (Lopid®)®)

Fenofibrate (Lipidil™ EZ)Fenofibrate (Lipidil™ EZ)

Bezafibrate (BezalipBezafibrate (Bezalip® SR)® SR)

WHAT THEY DO:WHAT THEY DO: Inhibit fat breakdown in the Inhibit fat breakdown in the

tissues so less fat is taken up by tissues so less fat is taken up by the liver from the blood; the liver from the blood; therefore less TG’s are madetherefore less TG’s are made

↓ ↓ TG (blood fat)TG (blood fat)

↑ ↑ good cholesterolgood cholesterol

SIDE EFFECTS:SIDE EFFECTS:NauseaNauseaStomach pain / gasStomach pain / gasMuscle pain (reversible)Muscle pain (reversible)Gall stonesGall stones↑ ↑ liver enzymes (reversible)liver enzymes (reversible)Mild Hgb, Hct, and WBC decrease Mild Hgb, Hct, and WBC decrease

(stabilize with long term use)(stabilize with long term use)

SIDE EFFECTS:SIDE EFFECTS:

CBC’s, LFT’s and renal function at 3, CBC’s, LFT’s and renal function at 3, 6 and 12 months, then yearly 6 and 12 months, then yearly

Fibrates are usually not given with Fibrates are usually not given with statins because the combination statins because the combination increases the risk of developing increases the risk of developing muscle problemsmuscle problems

CHOLESTEROL ABSORPTION CHOLESTEROL ABSORPTION INHIBITORS: INHIBITORS: 1, 101, 10

Ezetimibe (EzetrolEzetimibe (Ezetrol®)®)

WHAT IT DOES:WHAT IT DOES:

Blocks the absorption of Blocks the absorption of cholesterol from the intestinecholesterol from the intestine

Less cholesterol is taken to Less cholesterol is taken to the liver, forcing the body to the liver, forcing the body to take it from the bloodtake it from the blood

Advantages…Advantages…

Better tolerated than resinsBetter tolerated than resins

Less drug interactions than Less drug interactions than statinsstatins

Does not affect the absorption of Does not affect the absorption of fat-soluble vitaminsfat-soluble vitamins

SIDE EFFECTS:SIDE EFFECTS: Back pain (4.1% vs. 3.9% placebo)Back pain (4.1% vs. 3.9% placebo) Joint pain (3.8% vs. 3.4%)Joint pain (3.8% vs. 3.4%) Muscle pain (5.0% vs. 4.6%)Muscle pain (5.0% vs. 4.6%) Diarrhea (3.7% vs. 3.0%)Diarrhea (3.7% vs. 3.0%) Stomach pain (3.0% vs. 2.8%)Stomach pain (3.0% vs. 2.8%) Fatigue (2.2% vs. 1.8%)Fatigue (2.2% vs. 1.8%) Dizziness (2.7% vs. 1.2%)Dizziness (2.7% vs. 1.2%) Headache (8.0% vs. 5.4%)Headache (8.0% vs. 5.4%)

Muscle Side Effects:Muscle Side Effects:

In clinical trials, the number of In clinical trials, the number of people who developed muscle people who developed muscle disease or rhabdomyolysis was disease or rhabdomyolysis was similar with the control group similar with the control group

Most people who developed Most people who developed muscle pain had also had it muscle pain had also had it before while taking a statinbefore while taking a statin

Rare Side Effects:Rare Side Effects:

Increased liver enzymes Increased liver enzymes (0.5% vs placebo 0.3%)(0.5% vs placebo 0.3%)

It has not been proven that It has not been proven that Ezetrol causes hepatitis or Ezetrol causes hepatitis or pancreatitispancreatitis

Comparison of Effects of Comparison of Effects of Cholesterol Lowering Drugs: Cholesterol Lowering Drugs: 11

LDLLDL HDLHDL TGTG

ResinsResins ↓↓↓↓ ↑↑ ↑↑

StatinsStatins ↓↓↓↓↓↓ ↑↑ ↓↔↓ ↓↓↔↓ ↓

NiacinNiacin ↓↓↓↓ ↑↑↑↑ ↓↓↓↓

FibratesFibrates ↓↔↓↓↔↓ ↑↑↑↑ ↓↓↓↓↓↓

EzetimibeEzetimibe ↓↓↓↓ ↑↔↑↔ ↓↓

Comparison of Effects of Comparison of Effects of Cholesterol Lowering Drugs: Cholesterol Lowering Drugs: 11

*Atorvastatin and rosuvastatin *Atorvastatin and rosuvastatin have the greatest TG-lowering have the greatest TG-lowering effect effect

*Bezafibrate and fenofibrate ↓ *Bezafibrate and fenofibrate ↓ bad cholesterol > gemfibrozilbad cholesterol > gemfibrozil

REFERENCES:REFERENCES: 1) e-Therapeutics. Cardiovascular Disorders: Dyslipidemias 1) e-Therapeutics. Cardiovascular Disorders: Dyslipidemias

[Online]. [cited 2007 Jan 18]; Available from: URL: [Online]. [cited 2007 Jan 18]; Available from: URL: https://www.e-therapeutics.cahttps://www.e-therapeutics.ca

2) Compendium of Pharmaceuticals and Specialties. 2) Compendium of Pharmaceuticals and Specialties. Cholestyramine CPhA Monograph [online version (e-CPS)]. Cholestyramine CPhA Monograph [online version (e-CPS)]. CPhACPhA, 2007. [cited 2007 Jan 18]; Available from: URL: , 2007. [cited 2007 Jan 18]; Available from: URL: https://www.e-therapeutics.cahttps://www.e-therapeutics.ca

3) Compendium of Pharmaceuticals and Specialties. HMG-3) Compendium of Pharmaceuticals and Specialties. HMG-CoA Reductase Inhibitors CPhA Monograph [online version (e-CoA Reductase Inhibitors CPhA Monograph [online version (e-CPS)]. CPS)]. CPhACPhA, 2007. [cited 2007 Jan 18]; Available from: URL: , 2007. [cited 2007 Jan 18]; Available from: URL: https://www.e-therapeutics.cahttps://www.e-therapeutics.ca

4) Silva, M.A., Swanson, A.C., Gandhi, P.J., et al. Statin-4) Silva, M.A., Swanson, A.C., Gandhi, P.J., et al. Statin-related adverse events: a meta-analysis. related adverse events: a meta-analysis. Clinical Clinical TherapeuticsTherapeutics. 28(1):26-35, 2006 Jan.. 28(1):26-35, 2006 Jan.

5) Miller, M.L., Rosenson, R.L. Muscle injury associated with 5) Miller, M.L., Rosenson, R.L. Muscle injury associated with lipid lowering drugs [online]. lipid lowering drugs [online]. 2007 UpToDate®.2007 UpToDate®. [cited 2007 [cited 2007 Jan 19]; Available from: URL: Jan 19]; Available from: URL: http://http://www.utdol.com/utd/store/index.dowww.utdol.com/utd/store/index.do

REFERENCES:REFERENCES: 6) Koller, H., Neuhaus, O., Schroeter, M. et al. Myopathies 6) Koller, H., Neuhaus, O., Schroeter, M. et al. Myopathies

under therapy with lipid-lowering agents. under therapy with lipid-lowering agents. NervenarztNervenarzt. . 76(2):212-7, 2005 Feb.76(2):212-7, 2005 Feb.

7) Law, M., Rudnicka, A.R. Statin safety: a systematic 7) Law, M., Rudnicka, A.R. Statin safety: a systematic review. review. Am J CardiolAm J Cardiol. 97(8A):52C-60C, 2006 Apr 17.. 97(8A):52C-60C, 2006 Apr 17.

8) Compendium of Pharmaceuticals and Specialties. 8) Compendium of Pharmaceuticals and Specialties. Niacin/Niacinamide CPhA Monograph [online version (e-Niacin/Niacinamide CPhA Monograph [online version (e-CPS)]. CPhA, 2007. [cited 2007 Jan 18]; Available from: URL: CPS)]. CPhA, 2007. [cited 2007 Jan 18]; Available from: URL: https://www.e-therapeutics.cahttps://www.e-therapeutics.ca

9) Compendium of Pharmaceuticals and Specialties. Lopid 9) Compendium of Pharmaceuticals and Specialties. Lopid Product Monograph [online version (e-CPS)]. CPhA, 2007. Product Monograph [online version (e-CPS)]. CPhA, 2007. [cited 2007 Jan 18]; Available from: URL: [cited 2007 Jan 18]; Available from: URL: https://www.e-therapeutics.cahttps://www.e-therapeutics.ca

10) Compendium of Pharmaceuticals and Specialties. 10) Compendium of Pharmaceuticals and Specialties. Ezetrol Product Monograph [online version (e-CPS)]. CPhA, Ezetrol Product Monograph [online version (e-CPS)]. CPhA, 2007. [cited 2007 Jan 18]; Available from: URL: 2007. [cited 2007 Jan 18]; Available from: URL: https://www.e-therapeutics.cahttps://www.e-therapeutics.ca