Antilipemic Drugs Flashcards
Two primary forms of lipids in the blood?
What are they used for?
Water-insoluble fats that must be bound to __________
Triglycerides and Cholesterol
Triglycerides (energy source stored in adipose)
Cholesterol (used to make steroid hormones, cell membranes, and bile acid)
Water-insoluble fats that must be bound to apolipoproteins, specialized lipid-carrying proteins
Apolipoproteins
specialized lipid-carrying proteins
Lipoprotein is the combination of?
Lipoprotein is the combination of triglyceride or cholesterol with apolipoprotein.
Lipoprotein
transport lipids via the blood
4 types of lipoprotein
Very-low-density lipoprotein
Intermediate-density lipoprotein
Low-density lipoprotein (LDL)
High-density lipoprotein (HDL)
Very-low-density lipoprotein
produced by?
transports? to?
Produced by the liver
Transports endogenous lipids to peripheral cells
Intermediate-density lipoprotein
Low-density lipoprotein (LDL)
bad cholesterol
High-density lipoprotein (HDL)
responsible for?
also known as?
produced in the?
formed when?
Responsible for “recycling” of cholesterol
Also known as “good cholesterol” (cardioprotective)
produced in the liver and intestines
formed when chylomicrons are broken down
Cholesterol and Coronary Heart Disease
The risk of coronary heart disease in patients with cholesterol levels of ____________ is 3 to 4 times greater than that in patients with levels less than _________
Incidence of CAD is lower in?
The risk of coronary heart disease in patients with cholesterol levels of 5.2 mmol/L is three to four times greater than that in patients with levels less than 4 mmol/L.
blood cholesterol level increases, incidence of death and disability related to CAD also increases
incidence of CAD is lower in premenopausal women
The goal of treatment is primary prevention and secondary prevention
Dyslipidemias and Treatment Guidelines
Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult
Framingham Risk Score
Heart Age Calculator
Medications to treat dyslipidemia
Drug choice based on the specific lipid profile of the patient (phenotyping)
Hyperlipidemias Treatment and Guidelines
All reasonable non-drug means of controlling blood cholesterol levels (e.g., diet, exercise)
Drug therapy based on the specific lipid profile of the patient (age, sex, menopausal status)
Antilipemics
4 established classes of drugs
Hydroxymethylglutaryl–coenzyme A (HMG–CoA) reductase inhibitors (statins)
Bile acid sequestrants
B vitamin niacin (vitamin B3, nicotinic acid)
Fibric acid derivatives (fibrates)
Cholesterol absorption inhibitor (Ezetrol®)
Antilipemics:
Statins
Indications
First-line therapy for hypercholesterolemia (elevated LDL-C)
Treatment of type IIa and IIb dyslipedemia which reduces LDL-C levels
Reduces plasma concentrations of LDL cholesterol by 30 to 40%
Decrease in plasma triglycerides by 10 to 30%
Increase in HDL cholesterol by 2 to 15% > reduces cardiac risk
Dose dependent
takes 6-8 weeks to work
Antilipemics: HMG-CoA Reductase Inhibitors (Statins)
FACT
2 medications
Most potent LDL reducers
atorvastatin (Lipitor®)- effective at lowering triglycerides than other statins
rosuvastatin calcium (Crestor®)- more potent on a per mg basis. Used to replace atorvastatin due to AE of it. Has fewer AEs, and improved lipid profile
Other:
pravastatin sodium- administered in its active form
simvastatin (Zocor®)- prodrug
fluvastatin sodium (Lescol®)
lovastatin- prodrug
HMG-CoA Reductase Inhibitors: (Also known as Atorvastatin/ statins)
Mechanism of Action
Lower blood cholesterol levels by decrease rate of cholesterol production
(to produce cholesterol, the liver needs HMG-CoA reductase. The statins inhibits this enzyme, which decreases cholesterol production)
When less cholesterol is produced, the liver increases the number LDL receptors to recycle LDL from circulation
—-Needed for synthesis of steroids, bile, cell membranes
inhibit HMG-CoA reductase
HMG-CoA Reductase Inhibitors:
Adverse Effects
Mild, transient gastrointestinal disturbances
Rash
Headache
Elevation in liver enzymes
Myopathy (muscle pain), possibly leading to rhabdomyolysis, a serious condition
memory loss, confusion, forgetfulness, increased risk for hyperglycemia and Type 2 diabetes
Statins: Do not use for patients with?
Do not use for patients with elevated liver enzymes or liver disease
contra- allergy and pregnancy, high alcohol intake
previous myopathy/ rhabdomyolysis
Rhabdomyolysis
How to reverse it?
Instruct patients to report?
RF
Breakdown of muscle protein, accompanied by myoglobinuria (urinary elimination of muscle protein- myoglobin). This may strain the kidney and result in acute kidney injury.
Early detection- usually reversible with discontinuation of the statin drug
Instruct patients to immediately report any signs of toxicity, including muscle soreness or changes in urine colour (tea-coloured).
RF of myopathy- age older than 65, Asian descent hypothyroidism, immunosuppressant….
Myoglobinuria
Define
Can lead to?
urinary elimination of the muscle protein myoglobin
Can lead to acute kidney injury and even death
HMG-CoA Reductase Inhibitors:
Interactions
Oral anticoagulants
Drugs metabolized by CYP3A4
[erythromycin
azole antifungals
quinidine sulphate
verapamil hydrochloride
diltiazem hydrochloride
Human immunodeficiency virus (HIV) and hepatitis C protease inhibitors
amiodarone hydrochloride
Grapefruit juice
cyclosporine
clarithromycin
amlodipine]
atorvastatin calcium (Lipitor®) and rosuvastatin (Crestor®)
Mechanism of action
Dosing?
FACT
Lowers total and LDL-C 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
Two of the most commonly used drugs in this class of cholesterol-lowering drugs
rosuvastatin
Lowers total and LDL-C cholesterol levels as well as triglyceride levels. Can modestly raise HDL levels.
Use of 40 mg is contraindicated in the Asian population or in pts with myopathy/ rhabdomyolysis
Bile Acid Sequestrants
1 medication
cholestyramine resin (Olestyr®)
Other:
colestipol hydrochloride
colesevelam
Also called bile acid–binding resins and ion-exchange resins
Bile Acid Sequestrants: (bile acid-binding resins/ ion-exchange resins)
Mechanism of Action?
Bile acids are necessary for?
The more the bile acids are excreted, the more the liver converts?
Commonly used as?
Bind bile and prevent the resorption of bile acids from small intestine (bile acids are necessary for the absorption of cholesterol from the SI and are synthesized from cholesterol in the liver; the natural way the liver excretes cholesterol from the body). The more bile acids are excreted in the feces, the more the liver converts cholesterol to bile acids. This reduces the level of cholesterol in the liver and the circulation. LDL is released to compensate and it bind to receptors and is taken up by the liver- reducing circulating LDL in the blood
Lower cholesterol, (esp. LDL-C) by increasing the destruction of LDL
Bile acids are necessary for absorption of cholesterol.
The more the bile acids are excreted, the more the liver converts cholesterol to bile acids, reducing cholesterol in liver and circulation
Commonly used as an adjunct to statin therapy
Bile Acid Sequestrants: Indications
Type II hyperlipoproteinemia
Relief of pruritus associated with partial biliary obstruction (cholestyramine)
May be used along with statins
Bile Acid Sequestrants: Adverse Effects
Constipation
Heartburn, nausea, belching, bloating
—These adverse effects tend to disappear over time.
—-Increasing dietary fibre intake or taking a fibre 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.
Take other drugs at least 1 hr before or 4-6 hrs after bile sequestrants
Bile Acid Sequestrants: 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).
Bile Acid Sequestrants: cholestyramine resin (Olestyr®)
Contraindications?
Contraindications: known hypersensitivity, phenylketonuria or complete biliary obstruction
Pregnancy and lactation considerations
Treatment of loose bowel movements
Caution when administering dry powder
interfere with the distribution of fat soluble vitamins
used for constipating effect, given for loose BMs
Niacin (Niaspan®, nicotinic acid)
Type of vitamin?
Vitamin B3
Niacin (Niaspan®, nicotinic acid)
Mechanism of action
Benefits?
Often given as?
Lipid-lowering properties require much higher doses than when used as a vitamin.
Effective, inexpensive, often used in combination with other lipid-lowering drugs
Often given as adjunct to statins
Niacin: Mechanism of Action
inhibit lipolysis in adipose tissue
decrease esterification of triglycerides in the liver
increase the activity of lipoprotein lipase
Reduces the metabolism or catabolism of cholesterol and triglycerides
Resultant effect: decreased triglyceride levels, decreased LDL and increased HDL levels
May also stimulate fibrinolytic system to break down fibrin clots
Niacin: Indications
Effective in lowering triglyceride, total serum cholesterol, apolipoprotein B and
LDL cholesterol levels
Increases HDL levels
Therapeutic effects noticed after 1-4 days of therapy
Maximum effects in 3-5 weeks of continuous therapy
Niacin Contraindications
Contraindicated in peptic ulcer disease, hypertension, active hemorrhagic process
liver disease, allergy
Niacin:
Adverse Effects
Contraindication
Flushing (caused by histamine release)
Pruritus
Gastrointestinal distress
start on low dosage, take with meals
small dose of aspirin (NSAID) may be taken 30 minutes before nicotinic acid to minimize cutaneous flushing
contra- statins- increase risk for myopathy, allergy, peptic ulcer, liver disease, hemorrhage, hypotension, lactating women, gout
Fibric Acid Derivatives
Also known as?
1 medication
Also known as fibrates
gemfibrozil- decreases synthesis of Apo-B and lowers the VLDL level, increase HDL level, lower plasma triglyceride levels
Other:
bezafibrate
fenofibrate
Fibric Acid Derivatives: Mechanism of Action
Activates lipoprotein lipase, which breaks down cholesterol
Suppress the release of free fatty acid from adipose tissue
Inhibit the synthesis of triglycerides in the liver
Increase the secretion of cholesterol in bile
can induce changes in blood coagulation; decrease in platelet adhesion
(can increase plasma fibrinolysis the process that causes fibrin (clots) to be broken down
decrease triglyceride levels and increase HDL levels; treats dyslipidemia
Fibric Acid Derivatives: Indications
Treatment of types III, IV, and V hyperlipidemias
The fibric acid derivatives bezafibrate, gemfibrozil, and fenofibrate decrease the triglyceride level and increase the HDL cholesterol level by as much as 25%.
Fibric Acid Derivatives: Contraindications
Known drug allergy
Severe liver or kidney disease
Cirrhosis
Gallbladder disease
use birth control- childbearing year and d/c in pregnant women
Fibric Acid Derivatives: Adverse Effects
Abdominal discomfort, diarrhea, nausea
Blurred vision, headache
Increased risk of gallstones
Prolonged prothrombin time
Increased enzyme levels perhaps shown by liver studies
Fibric Acid Derivatives: Interactions
Gemfibrozil enhances the action of oral anticoagulants (warfarin)
All are given with a statin, which increases risk of myositis, myalgia, and rhabdomyolysis.
Fibric Acid Derivatives: Laboratory test reactions:
Decreased hemoglobin level, hematocrit value, and white blood cell count
Increased aspartate aminotransferase, activated clotting time, lactate dehydrogenase level, and bilirubin level
Cholesterol Absorption Inhibitor
1 medication
ezetimibe (Ezetrol)
Cholesterol Absorption Inhibitor
ezetimibe (Ezetrol)
Mechanism of action
Selectively inhibits absorption of cholesterol and related sterols from the small intestine
Results in reduced total cholesterol, LDL cholesterol, apolipoprotein B, and triglyceride levels
Also increases HDL cholesterol levels
Often combined with a statin drug
Can be used as monotherapy
Levels are increased by fibric acid derivatives- concurrent use is not recommended
contra- allergy, active liver disease
Herbal Product: Garlic
Indications?
Adverse effects?
Interactions?
May enhance?
Used as an antispasmodic, antiseptic, antibacterial, antiviral, antihypertensive, antiplatelet, and lipid reducer
Adverse effects: dermatitis, vomiting, diarrhea, anorexia, flatulence, antiplatelet activity
Possible interactions with warfarin, diazepam, and protease inhibitors
May enhance bleeding when taken with nonsteroidal anti-inflammatory drugs (NSAIDs)
Herbal Product: Flax
Types used?
Indication?
Adverse effect?
Interactions?
Both the seed and oil of the plant are used.
Uses: atherosclerosis, hypercholesterolemia, hypertriglyceridemia, gastrointestinal distress, menopausal symptoms, bladder inflammation, others
May cause diarrhea and allergic reactions
Possible interactions: antihyperglycemic drugs, anticoagulant drugs
Herbal Product: Omega-3Fatty Acids
Type?
Indication?
Adverse effects?
Interactions?
Contraindicated?
Fish oil products
Used to reduce cholesterol
May cause rash, belching, allergic reactions
Potential interactions with anticoagulant drugs
Contraindicated in pregnancy
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.
Obtain results of baseline liver function studies.
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.
Provide teaching regarding the use of NSAIDs and aspirin.
Inform patients that these medications may take several weeks to show effectiveness.
Instruct patients to report persistent gastrointestinal 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
Antilipemic drugs contraindications?
Patients on long-term therapy may need supplemental?
How to take powder forms?
Other medications should be taken_____ before or 4___ to ___ hours after meals to avoid interference with ______.
To minimize adverse effects of ____, start on a low initial dose and gradually increase it, and have the patient take the medication with meals.
Small doses of ___ or ____ may be taken 30 minutes before ____ to minimize cutaneous flushing.
Contraindications include biliary obstruction, liver dysfunction, and active liver dysfunction
Patients on long-term therapy may need supplemental fat-soluble vitamins (A, D, E, K).
Powder forms must be taken with a liquid, mixed thoroughly but not stirred, and never taken 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 a low initial dose and gradually increase it, and have the patient take the medication with meals.
Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to minimize cutaneous flushing.
cholesterol
chylomicrons
HMG-CoA
Lipoprotein
triglycerides
a fat-soluble steroid alcohol, widely distributed in the body (bile, blood, brain tissue, liver, kidneys, adrenal gland, myelin sheath)
carry fat to tissues, primarily in the liver
cholesterol-lowering drugs, act by inhibiting the rate-limiting step in cholesterol synthesis (statins)
conjugated protein synthesized in the liver that contains varying amounts of triglycerides, cholesterol, and other lipids
consist of fatty acids and a type of alcohol known as glycerol
Lipid abnormalities (lipids and lipoprotein forms…)
foam cells
what causes atherosclerosis
Where does lipid metabolism occur?
atherosclerotic plaque which leads to CAD
lesion of atherosclerosis
repeated; injury to artery wall such as smoking, elevated BP, diabetes, elevated cholesterol. Ongoing inflammatory response has a central role in the formation of plaque referred to as atherogenesis.
Liver
Risk factors for CAD
males 40 years or older
females 50 years or older or postmenopausal
family history, premature CAD
cigarette smoking
BP 140/90
low HDL
diabetes
To know
Cholestyramine- test for PKU; pts with PKU cannot process amino acid phenylalanine (a protein component). High levels result in behavioural, cognitive, and learning dysfunction (child). for adults to monitor PKU monthly (dissolve it for 1 minute). Give 1 hour before or 4-6 hrs after other meds. Take with meals
statins- not for pts with liver disease, who drink alcohol because of potential liver dysfunction- assess liver tests. Take with 120-180 mL of water or with meals. Monitor liver and kidney function every 3-6 months.
nicotinic- contra in active bleeding. flushing of face may occur, take the drug with meals. Monitor liver, kidney , and PThrombin. Take with meals.
antilipemic- may require supplementation of vitamins, GI problems, and liver dysfunction.
low fat, low cholesterol diet (diet rich in raw veggies, fruit, and bran) Incase fluids.
Never take dry form of
powder/ granule , oral-based form of antilipemic- must be mixed with carbonated liquids
Lipids and lipoprotein
participate in the formation of A plaque which leads to CAD
when plaque forms in the BVs that supply the heart with oxygen and nutrients, the lumen will decrease and 02 and nutrients supplied will also be reduced
How to lessen AE of nitric acid
Monitor this when giving nitric acid
Report muscle pain when taking
contraindication of antilipemics
what drug puts a pt at a higher risk for developing rhabdomyolysis?
cholestyramine (Bile a cid sequestrant) nursing interventions?
lab tests for statins
administer a small dose of aspirin or an NSAID 30 minutes before niacin dose
cutaneous flushing
statins
liver cirrhosis
fibric acid derivatives
take with meals, take fibre supplements, increase fluids, not take with other drugs
total cholesterol, triglycerides, liver function tests, HDL &LDL levels
