Pharmacology Chapter 28 Lipids318

8/12/2019 Pharmacology Chapter 28 Lipids318

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Chapter 28 LipidsNU 361 ACCB

Spring 2013


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Objectives

Identify core drug knowledge for medications that

affect lipid levels

Relate the interaction of core drug knowledge to core

patient values for drugs that affect lipid levels

Determine key points for patient and family

education for drugs that affect lipid levels


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Pathophysiology

Hyperlipidemia elevation of blood lipid levels.

risk factor for the following disorders Atherosclerosis

Coronary artery disease

Thromboses

HTN

When the amount of cholesterol within cells builds up, thenumber of these receptors on cell surfaces is reduced,

preventing all of the lipids from entering the cells.


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What are the types of Lipoproteins?

5 Types of Lipoproteins:

Chylomicrons

Synthesized in smallintestine

VLDL

carry triglyceride to fat &muscle cells

Synthesized in liver

IDL (intermediate-density

lipoprotein) Main source of LDL

LDL Bad cholesterol

HDL Good cholesterol

Ideal cholesterol levels: Total cholesterol: less than 200

mg/dL

LDL: 100 mg/dL HDL: 40 to 59 mg/dL

Patients with narrowedarteries from atheroscleroticcardiovascular disease aremore likely to have

hypertension


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Lifestyle and Reduction of Low-Density Lipoprotein

Levels

The National Cholesterol Education Program (NCEP)

ATP III (Adult Treatment Plan)

Recommendations for reducing LDL levels. Therapeutic Lifestyle changes

Diet

Weight loss

Increased physical activity ATP IV will be released later this year


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Antihyperlipidemics


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Introducing the Statin family!

Lovastatin

Simvastatin

Atorvastatin

Fluvastatin

Prevastatin

Rosuvastatin

Pitavastatin Cerivastatin (recently removed from the market)

52 deaths related to rhabdomyolysis


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Introducing the Statins family! Statins

Lower LDL cholesterol by 20% to 55% when given at their maximumrecommended dose. Adverse effects CYP 3A4 inhibitors

Raise HDL levels between 5% and 15% Lower triglycerides between 7% and 33% Positive effect on vascular endothelium

Increases bioavailability of NO Promotes vasodilation Stabilize plaque

Decrease risk of stroke Decrease mortality from CAD Lowering serum lipid levels

decreases risk of atherosclerosis, HTN and cardiac disease. Increased effectiveness when used with ACEi, ARBs

Prototype drug: lovastatin (Mevacor)


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Identify core drug knowledge for

medications that affect lipid levels


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Lovastatin: Core Drug Knowledge Pharmacotherapeutics

Primary hypercholesterolemia and combinedhyperlipidemia

Hypercholesterolemia = Cholesterol of > 200 mg/Dl Hyperlipidemia = LDL >160 mg/Dl, triglycerides > 150 and

HDL < 40 mg/Dl

Prevention of vascular events and thrombus formation Available in rapid release and extended release forms

Immediate release is best absorbed after a meal

Extended release absorption is affected by taking it withfood

Available in generic as well as trade name


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Lovastatin: Core Drug Knowledge

Pharmacokinetics Very high first pass metabolism

Concentration of drug is greatly reduced before it reachessystemic circulation

Only 5% reaches general circulation

Metabolized by P-450 3A4 Administering other drugs that use this pathway will

decrease metabolism of statins and increase their circulatingblood levels

May result in toxicity Excreted primarily through the GI tract

10% in urine


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Pharmacodynamics Inhibits HMG-CoA reductase

enzyme that catalyzes the early rate-limiting step in

cholesterol biosynthesis Decrease uptake of modified lipoproteins by vascular cells Increase in HDL 2-9.5% Decrease

LDL 21-40% Total cholesterol 16-29% decrease VLDL Plasma triglycerides 6-30%


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Metabolism CYP 450


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Contraindications and precautions

Active liver disease

Check liver function tests

Pregnancy category X

Prescribing or co administering the drug with meds that

inhibit the P450 site

EES

Grapefruit

High dose therapy has a risk for myopathy and

rhabdomyolysis


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Precautions

Pre existing ALS

Older adults with complex co morbidities

Renal insufficience

Patients with familial hypercholesterolemia are at risk

Reduced efficacy of lovastatin Increased risk in liver enzyme


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Precautions

Combined therapy with other drugs that lower

cholesterol

Niacin

Increases HDL, decreases triglycerides

Gemfibrozil (Lopid)


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Adverse effects Myalgias 1/20 patients experience muscle pain or weakness

joint aches Weakness Increase in creatine phosphokinase (CPK) elevations

Rhabdomyolysis Leakage of myoglobin into blood and urine

Urine becomes brown

Can lead to renal failure and death CPK > 10,000 U/L indicates

Liver damage AST, ALT

Low dose ASA is more likely to have a fatal side effect thantaking statins


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Drug interactions

Itraconazole

Erythromycin

Grapefruit juice Any drugs or foods that

are metabolized throughCYP450

CYP450 system


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Relate the interaction of core drug

knowledge to core patient values for

drugs that affect lipid levels


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Lovastatin: Core Patient Variables

Health status Assess cholesterol levels and past medical history

Life span and gender Pregnancy category X

Lifestyle, diet, and habits Treat elevated cholesterol with diet and exercise first.


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Lovastatin: Nursing Diagnoses and Outcomes

Risk for Injury to skeletal muscles related to adverseeffects of drug therapy Desired outcome:The patient will not incur serious

skeletal muscle injury while on drug therapy.


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Lovastatin: Planning and Interventions

Maximizing therapeutic effects

Most effective when administered in the evening

Immediate-release administered after evening meal

Extended-release administered at bedtime Minimizing adverse effects

Liver function test

(AST and ALT) results evaluate before starting therapy

Monitory following therapy Evaluate the patient carefully for muscle soreness, tenderness,

or pain and CK levels.

Combining statins with niacin or a fibrate or other lipidlowering drug increases the risk for rhabdomyolysis


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Determine key points for patient and

family education for drugs that affect

lipid levels


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Lovastatin: Teaching, Assessment, and Evaluations

Patient and family education Stress the importance of following a low-cholesterol and

low-saturated-fat diet.

Instruct patients to report any unexplained muscle pain,tenderness, or weakness.

Photosensitivity may occur Pregnancy category X Exercise

Ongoing assessment and evaluation The patient should have liver function tests and CK

measurement performed periodically throughout drugtherapy.


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Statin Therapy


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Drugs Significantly Different from Lovastatin: Fibric

Acid Derivatives: Combination therapy

Lower triglyceride levels Increase HDL cholesterol. Often used in combination with statins

increased risk of myopathy. Contraindications

hepatic or severe renal dysfunction, Serious adverse effects include abnormal liver function

tests, rhabdomyolysis, and hyperglycemia.


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Drugs Significantly Different from Lovastatin: Nicotinic

Acid

Nicotinic acid (niacin or vitamin B3) Used to treat hyperlipidemia Street drug use

Reduces levels of triglycerides and LDL cholesterol levels and raiseslevels of HDL cholesterol.

Triglycerides and VLDL levels are reduced by 25% to 30% in 1 to 4days.

LDL level reductions may be seen in 5 to 7 days, with the maximaleffect seen in 3 to 5 weeks.


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Pharmacology Chapter 28 Lipids318