Chap 27 Antilipemic Drugs Flashcards
Triglycerides and Cholesterol***
Two primary forms of lipids in the blood
Water-insoluble fats that must be bound to apolipoproteins, specialized lipid-carrying proteins
Lipoprotein is the combination of triglyceride or cholesterol with apolipoprotein.
Lipoproteins
Very-low-density lipoprotein (VLDL)**
Produced by the liver
Transports endogenous lipids to the cells
Low-density lipoprotein (LDL)**
BAD CHOLESTEROL LOWER THE BETTER
Optimal: <100 mg/dL
very high: 190 mg/dL
High-density lipoprotein (HDL)**
GOOD CHOLESTEROL HIGHER THE BETTER
<40 mg/dL major risk for heart disease
Responsible for “recycling” of cholesterol
Also known as “good cholesterol”
TOTAL CHOLESTEROL
BEST:200 mg/dL or below
Borderline: 200-239
High: 240 or above
ARTERIOSCLEROSIS**
[ARTERIO] - Artery
[SCLEROSIS] - Hardening
Definition - hardening from plaque “ atheromatous plaque”
Hyperlipidemias and Treatment Guidelines
National Cholesterol Education Program Adult Treatment Panel III of the National Institutes of Health
Antilipemic drugs
Drugs used to lower lipid levels
Used as an adjunct to diet therapy
Drug choice based on the specific lipid profile of the patient (phenotyping)
All reasonable nondrug means of controlling blood cholesterol levels (e.g., diet, exercise) should be tried for at least 6 months and found to fail before drug therapy is considered.
Antilipemics
ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (2013)
Hydroxymethylglutaryl–coenzyme A (HMG–CoA) reductase inhibitors (HMGs, or statins*)
Bile acid sequestrants**
B vitamin niacin** (vitamin B3, nicotinic acid)
Fibric acid derivatives (fibrates)**
Cholesterol absorption inhibitor (Zetia)**
Combination drugs (Vytorin)**
Newer Agents
Mipomersen:* once-weekly subcutaneous injection*
Microsomal triglyceride transfer protein inhibitor
Lomitapide (Juxtapid)**
Proprotein convertase subtilisin kexin 9 *(PCSK9) *inhibitors
Alirocumab (Praluent)**
Evolocumab (Repatha)**
Antilipemics: HMG-CoA Reductase Inhibitors (Statins)**
Statins**
Patients with clinical atherosclerotic cardiovascular disease (CVD)
Patients with LDL cholesterol levels >190 mg/dL
Patients with diabetes* age 40 to 75 years with LDL levels of 70 to 189 mg/dL and* without evidence of CVD*
Patients without evidence of CVD or diabetes but who have LDL levels between 70 and 189 mg/dL and a 10-year risk of CVD > 7.5%
Antilipemics: HMG-CoA Reductase Inhibitors (Statins)
Most potent LDL reducers
Lovastatin* (Mevacor)
Pravastatin (Pravachol)
Simvastatin (Zocor)
Atorvastatin (Lipitor)
Fluvastatin (Lescol)
Rosuvastatin (Crestor)
Pitavastatin (Livalo)
HMG-CoA Reductase Inhibitors: Mechanism of Action*
Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol
Lower the rate of cholesterol production
HMG-CoA Reductase Inhibitors: Indications
First-line drug therapy for hypercholesterolemia
Treatment of types IIa and IIb hyperlipidemias
Reduces LDL levels by up to 50%
Increases HDL levels by 2% to 15%
Reduces triglycerides by 10% to 30%
HMG-CoA Reductase Inhibitors: Adverse* Effects
Mild, transient gastrointestinal (GI) disturbances
Rash
Headache*
Myopathy (muscle pain), possibly leading to the serious condition rhabdomyolysis
Elevations in liver enzymes or liver disease
Rhabdomyloysis
Breakdown of muscle protein
Myoglobinuria: urinary elimination of the muscle protein myoglobin
Can lead to acute renal failure and even death
When recognized reasonably early, rhabdomyolysis is usually reversible with discontinuation of the statin drug.
Instruct patients to immediately report any signs of toxicity, including muscle soreness or changes in urine color.
HMG-CoA Reductase Inhibitors: Interactions*
Oral anticoagulants*
Drugs metabolized by Cytochrome P-450*
Erythromycin
Azole antifungals**
Verapamil
Diltiazem
Human immunodeficiency virus protease inhibitors
Amiodarone**
Grapefruit juice**
Atorvastatin (Lipitor) **
One of the most commonly used drugs in this class of cholesterol-lowering drugs
Lowers total and LDL cholesterol levels as well as triglyceride levels and raises “good” cholesterol, the HDL component
Dosed once daily**, usually with the evening meal or at bedtime to correlate with diurnal rhythm
Simvastatin (Zocor)**
One of the first statins to become generic and one of the most commonly used drugs in this class
Used to primarily lower total and LDL cholesterol levels as well as triglyceride levels
Can moderately raise levels of HDL
Many drug interactions which may require dosing adjustments
Bile Acid Sequestrants **
Cholestyramine (Questran)**
Colestipol (Colestid)**
Tablet form
Colesevelam (Welchol)**
Also called bile acid–binding resins and
ion-exchange resins
Powdered form may not be convenient or well tolerated
Bile Acid Sequestrants: Mechanism of Action
Considered second line choice after statins
Prevent resorption of bile acids from small intestine**
Bile acids are necessary for absorption
of cholesterol.
Bile Acid Sequestrants: Adverse Effects
Constipation**
Heartburn, nausea, belching, bloating
These adverse effects tend to disappear over time.
Increasing dietary fiber intake or taking a fiber supplement such as psyllium (Metamucil and others), as well as increasing fluid intake, may relieve constipation and bloating.
May also cause mild increases in triglyceride levels
Bile Acid Sequestrants: Considerations
Overdose can cause obstruction because the bile acid sequestrants are not absorbed.
Treatment of overdose includes restoring gut motility.
Drug interactions**
All drugs must be taken at least 1 hour before or 4 to 6 hours after the administration of bile acid sequestrants.
High doses of a bile acid sequestrant decrease the absorption of fat-soluble vitamins (A, D, E, and K).
Niacin *(Nicotinic Acid)
Vitamin B3**
Lipid-lowering properties require* much higher* doses* than when used as a vitamin.
Effective, inexpensive, often used in combination with other lipid-lowering drugs
Niacin: Mechanism of Action
Thought to increase activity of lipase, which breaks down lipids
Reduces the metabolism or catabolism of cholesterol and triglycerides
Niacin: Indications
Effective in *lowering triglyceride, total serum cholesterol, and LDL** levels
Increases HDL levels**
Effective in the treatment of types IIa, IIb, III, IV, and V hyperlipidemias
Niacin: Adverse Effects**
Flushing (caused by histamine release)**
Small dose aspirin or NSAIDS 30 minutes before Niacin may help cutaneous flushing**
Pruritus
GI distress
Fibrates**
Group of lipid-lowering meds along w/ statins and niacin
*Effective at lowering triglyceride levels**
less effective at controlling cholesterol
Fibric Acid Derivatives
Primarily affect the triglyceride levels but may also lower the total cholesterol and LDL levels and raise the HDL
Also known as fibrates
Gemfibrozil (Lopid)**
Fenofibrate (Tricor)**
Fibric Acid Derivatives: Mechanism of Action
Believed to work by activating lipase, which breaks down cholesterol
Also suppress the release of free fatty acid from adipose tissue, inhibit synthesis of triglycerides in the liver, and increase secretion of cholesterol in the bile
Fibric Acid Derivatives: Contraindications**
Known drug allergy**
Severe liver or kidney disease**
Cirrhosis**
Gallbladder disease**
Fibric Acid Derivatives: Adverse Effects**
Abdominal discomfort, diarrhea, nausea
Blurred vision, headache
Increased risk of gallstones
Prolonged prothrombin time
Liver studies may show increased enzyme levels.
Fibric Acid Derivatives: Interactions*
Oral anticoagulants
Statins*
Risk of myositis, myalgias, and rhabdomyolysis is increased.
Laboratory test reactions
Decreased hemoglobin level, hematocrit value, and white blood cell count
Increased activated clotting time, lactate dehydrogenase level, and bilirubin level
Miscellaneous Antilipemic Drugs: Cholesterol Absorption Inhibitor
Ezetimibe (Zetia)**
Inhibits absorption of cholesterol and related sterols from the small intestine
Results in reduced total cholesterol, LDL, and triglyceride levels
Also increases HDL levels
Often combined with a statin drug
Can be used as monotherapy
Alirocumab (Praluent)**
Approved in 2015
Given subcutaneously every 2 to 4 weeks
Very expensive
Adverse effects: diarrhea, increased liver function tests, influenza, hypersensitivity reactions, injection site reaction, myalgia, cough
Herbal Product: Garlic *
Used as an antispasmodic, antihypertensive, antiplatelet, lipid reducer
Adverse effects: dermatitis, vomiting, diarrhea, flatulence, antiplatelet activity
Possible interactions with warfarin, diazepam
May enhance bleeding when taken with nonsteroidal antiinflammatory drugs (NSAIDs)*
Herbal Product: Flax*
Both the seed and oil of the plant are used.
Uses: atherosclerosis, hypercholesterolemia, GI distress, menopausal symptoms
May cause diarrhea and allergic reactions
Possible interactions: antidiabetic drugs, anticoagulant drugs
Herbal Product: Omega-3 Fatty Acids
Fish oil** products
Used to reduce cholesterol
May cause rash, belching, allergic reactions
*Potential interactions with anticoagulant** drugs
Nursing Implications**
Before beginning therapy, obtain a thorough health and medication history.
*Assess dietary patterns, exercise level, weight, height, vital signs, tobacco and alcohol use, and family history.**
Assess for contraindications**, conditions that require cautious use, and drug interactions.
Contraindications* include biliary obstruction, liver dysfunction, and active liver disease.**
Obtain baseline liver function studies.
Patients on long-term therapy** may need *supplemental fat-soluble vitamins (A, D, E, K).
Refer to guidelines regarding administration times and meals.
Counsel patient concerning diet and nutrition on an ongoing basis.
Instruct patient on proper procedure for taking the medications.
Powder forms must be taken with a liquid, mixed thoroughly with food or fluids (4-6 oz of fluid)**
Never take the powder dry
Other medications* should be taken 1 hour before or 4 to 6 hours after meals to avoid interference with absorption.
To minimize adverse effects** of niacin, *start on low initial dose and gradually increase it, and take with meals.**
Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to minimize cutaneous flushing.**
Provide teaching regarding use of NSAIDs and aspirin.**
Inform patients** that these drugs may take several weeks (6-8 weeks) to show effectiveness.
Instruct patients to report persistent GI upset, constipation, abnormal or unusual bleeding, and yellow discoloration of the skin.
Monitor* for adverse effects, *including increased liver enzyme studies.**
Monitor for therapeutic effects:
Reduced cholesterol and triglyceride levels
