Download Medications To Control Hyperlipidemia Anticoagulants

Medications to Control
Hyperlipidemia
Coronary Heart Disease Risk
Factors
† Positive risk factors
„ Age: Male > 45 years
Female >55 years or women with premature
menopause not on estrogen replacement therapy
„ Family Hx of premature CHD(MI, CA) prior to55
years of age in father or brother, 65 for females
„ Smoker
„ HTN >140/90 or on HTN meds
„ Low HDL level:<35mg/dL
† Negative risk factors: HDL > 60mg/dL
(subtract one risk factor)
When do we start Medication
Therapy
† Dietary therapy
„ LDL 100-160dL and CHD risk factors
† Drug therapy
„ LDL 130-190mg/dL CHD risk factors
Three Basic Classes of Lipids
† Triglycerides
† Steroids
† Phospholipids
† Total cholesterol <200
† HDL less than 40 (want it >60)
† Triglycerides>150
Triglycerides (Neutral Fats)
†
†
†
†
Most common
Three fatty acids attached to glycerol
Energy source
90% of total lipids in the body
Steroids
† Steroid nucleus or ring
† Natural vital component of cellular
membranes
† Necessary for production of:
„ Vitamin D
„ Bile salts
„ Cortisol, estrogen, testosterone
† Body makes enough cholesterol
† Not necessary in diet
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Phospholipids
Cholesterol Metabolism
† Phosphorous group replaces one of
the fatty acids
† Essential to building cellular
membranes
† Lecithins
† Increased blood cholesterol equals
increased risk of cardiovascular
disease
† Plaque buildup occurs in the vessel
walls
Lipoproteins
† Cholesterol not soluble in the blood
† Inner core of lipid, outer core of
protein
† Water soluble and travels freely in the
blood
Low-density Lipoproteins (LDL)
† Highest amount of cholesterol
† Created in liver
† Build plasma membranes and
produce steroids
† Stored in tissues
† Contribute to plaque deposits and
CHD
† Aka bad cholesterol
Three Most Common Lipoproteins, Based on
Weight or Density:
† Low-density lipoproteins (LDL)
† High-density lipoproteins (HDL)
† Very low-density lipoproteins (VLDL)
High-Density Lipoproteins
(HDL)
† Picks up cholesterol
† Returns it to the liver
† Becomes part of bile and excreted in
feces
† Aka good cholesterol
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Very Low-Density Lipoproteins
(VLDL)
† Triglyceride carrier
† Converted to LDL in blood
† High levels are associated with
pancreatitis
National Cholesterol Education Program (NCEP)
Recommendations for Therapeutic Lifestyle
Changes
† Increase physical activity
† Maintain optimum weight
† Maintain a healthy diet
„ Reduce dietary saturated fats and
cholesterol
„ Increase soluble fiber in diet
Other Lifestyle Changes Include
HMG CoA Reductase Inhibitors
(Statins)
†
†
†
†
†
Tobacco cessation
Control of hypertension
Stress reduction
Limiting high sugar foods
Increasing Omega-3 fatty acids in the
diet
† Avoiding transfatty acids in the diet
† Drugs of first choice in reducing blood
lipid levels
† Reduce LDL, triglyceride, and VLDL
levels
† Raise HDL levels (good cholesterol)
Inhibit HMG CoA Reductase
Effect Not Permanent
† Critical enzyme in cholesterol
synthesis
† Liver produces less cholesterol
† More LDL receptors
† More LDL removed from blood
† Blood levels of LDL and cholesterol
reduced
† Take statins for the rest of life
† Or until controlled by lifestyle
changes
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Contra-I for Statins (HMG-CoA
reductase inhibitors)
†
†
†
†
Drug allergy
Pregnancy (X)
Liver disease
Elevated liver enzymes
Statin Adverse Effects
† Central Nervous
„ HA, dizziness, blurred vision,
fatigue,nightmare, insomnia
† Gastrointestinal
„ Constipation, cramps, diarrhea, nausea,
change in bowel function
† Skin rashes
The OMG side effect
Interactions with Statins
† Rhabdomylosis
† Oral anticoagulants
† Other antilipemic
† Oral antidiabetic
drugs
† Erythromycin,
† Gemfibrozil
† Insulin
† Niacin
† Grapefruit juice
„ Breakdown of muscle tissue (myoglobin)
„ Myoglobin is the oxygen carrying
pigment of muscle tissue
„ Protein in urine may lead to renal
damage.
† Report any unexplained muscle pain!
Statins
†
†
†
†
†
Atrovastatin (Lipitor)dose anytime
Fluvastatin (Lescol)
Lovastatin (Mevacor)
Pravastatin (Pravachol)
Simvastatin (Zocor)
† Can lead to
rhabdomyolysis
Administration
† Give all statins orally
† Give in the evening
† Monitor for muscle injury
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Bile Acid Sequestrants
Bile Acid sequestrants
Contra-I
† Bile acid resins bind cholesterol in the
intestines so it can’t be reabsorbed
† Cholesterol eliminated in feces
† Reduces LDL levels
† 2nd line drugs to statins
† Lower LDL 15-30%
† Increase HDL 3-8%
† Drug allergy
† Biliary or bowel obstruction
Bile Acid Sequestrants
Adverse Effects
Bile Acid sequestrants
Interactions (messy powders)
† GI/Usymptoms
† Interaction due to absorption of other
drugs
† (Take 1 hour before and 4-6 hrs after
these drugs)
† These drugs affect the absorption of
fat soluble vitamin (DEAK of Cards)
†
„ Heartburn, nausea, belching, and
bloating. (take with meals to reduce
effects)
„ Constipation (instruct to increase dietary
fiber)
„ May cause mild increases in the
triglyceride levels.
„ Other: bleeding, tinnitus, burnt odor of
urine.
Bile Acid Sequestrants
Administration
† Choestyramine(Questran)
† Colesevelam(Welchol)
† Colestipol (Colestid)
† More frequent side effects than
statins
† Sometimes given in combination with
statins
† Can prevent absorption of other
medications
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Nicotinic Acid
† Aka niacin - water-soluble B-complex
vitamin
† High dosages needed to produce
antilipidemic effects
† Primary use is to decrease VLDL levels
† Secondary effect is to decrease LDL levels
10-20% and triglycerides 30-70%
† Increases HDL levels 20-35%
† Side effects limit use
† Often used in combination with a statin or
bile acid sequestrant
Niacin Contra-I
†
†
†
†
Liver disease
Hypertension
Peptic ulcer
Active hemorrhagic process
Niacin
† In large doses, it may produce
vasodilation that is limited to the
cutaneous vessels. Re: prostalandins
† Niacin also causes the release of
Histamine: increase GI mobility and
acid secretion.
† Niacin may also stimulate the break
down of fibrin clost.
Niacin Adverse Effects
†
†
†
†
Flushing, hyperpigmentation
Pruritus
GI distress
Blurred vision, glucose intolerance, dry
eyes, hepatotoxicity
† Taking aspirin 30 min before niacin can
minimize flushing
† Titrate up doses of Niacin for pt to tolerate
Fibric Acid Agents/Fibrates
† Activate lipoprotein lipase(breakdown of cholesterol)
† Most effective agent in reducing VLDL
and triglyceride levels
† Increases HDL 25% but very little
effect on LDL levels
† Replaced by the statins
Fibric Acid agents
Contra-I
† Severe Liver or Kidney disease
† Gallbladder disease
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Fibric Acid Agents
Adverse Effects
Fibric Acid Sequestrants
Drug interactions
† GI: nausea,vomiting, diarrhea,
gallstones, acute appendicitis
† GU: impotence, decreased urine
output, hematuria, UTI
† Other: drowsiness, rash, pruritus,
alopecia, eczema, vertigo, HA
† Gemfibrozil: enhance the action of
oral anticoagulants
† Risk of Rhabdomyolysis if taken with
statins
† Decrease Hb level, Hct, WBC
† Increase AST, ACT, bilirubin levels
Fibric Acid Agent
† Gemfibrozil (Lopid)
† Clofibrate (Atromid-S)
† Fenofibrate(Tricor)
Ezetimibe
† Blocks absorption of dietary
cholesterol
† LDL and triglycerides are reduced
† Slight increase in HDL
† Well tolerated by patients
Newer Approaches to Treating
Hyperlipidemia
† Ezetimibe (Zetia)
† Fixed-dose combination therapy
Fixed-Dose Combination
Therapy
†
†
†
†
Allows for lower doses of each agent
Potentially fewer side effects
Better patient compliance
Synergistic effect
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New Trend in Treatment of CHD
† Combine an antihypertensive with an
antihyperlipidemic
† Targeted at the many patients with
both hypertension and elevated
cholesterol
Hemostasis - Process of
Stopping the Flow of Blood
† Internally and externally
† Prevent bleeding from wounds which
could lead to shock or even death
Three Basic Steps to
Hemostasis
† Injured vessel constricts to slow
blood flow
† Platelets adhere to injured area and
aggregate, plugging damaged vessel
† Coagulation cascade occurs thus
forming insoluble fibrin strands which
slows blood flow more
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Major steps in the coagulation cascade
Coagulation Cascade - Series of
Complex Steps
† Injured cells release prothrombin
activator
† Prothrombin activator changes
prothrombin to thrombin
† Thrombin changes fibrinogen to fibrin
† Fibrin forms an insoluble web over
injured area which stops blood flow
Mechanism of action of anticoagulants
Coagulation-Modifier Drugs
† Anticoagulants
† Thrombolytics
† Hemostatics
Disorders Commonly Treated with Coagulation-modifying Drugs
Anticoagulants
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Anticoagulants
Anticoagulants - Prevent the
Formation of Clots
† Inhibiting specific clotting factors in
the coagulation cascade
† Diminishing the clotting action of
platelets
† Both ways increase the time to form
clots
Antiplatelet Agents
Thrombolytics
† Dissolve life-threatening clots
Thrombolytics
Hemostatics
† Promote formation of clots
† Inhibit removal of fibrin
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Anticoagulants Prevent the Formation
and Enlargement of Clots
† Examples - heparin (Heplock), warfarin
(Coumadin)
† Mechanism of action - inhibit specific
clotting factors which interfere with
coagulation cascade in order to prevent
formation or enlargement of clot
† Primary use - thromboembolic disease;
prevent formation of clots in veins
† Adverse effects - abnormal bleeding
Coumadin
† Monitoring:
„ Prothombin time (PT) report INR
† Goal INR for AF 2-3
† Goal INR for Mech Valves 3-4.5
† Adverse effects
„ Hemorrhage-antidote is vitamin K
† Fetal harm.
Coumadin
† Suppresses by antagonizing vitamin K
and blocks synthesis of factors
VII,IX,X and prothrombin
† Effects take a few days
† Long term prophylaxis of venous
thrombosis, mechanical heart valves,
atrial fibrillation
Antiplatelet Agents Prolong
Bleeding Time by Interfering with
Platelet Aggregation
† Example - ticlopidine (Ticlid)
† Mechanism of actions
„ Aspirin: inhibits thromboxane2, which prevents
aggregation of platelets
„ ADP receptor blockers: interfere with platelet
plasma membrane, which prevents platelet
aggregation
„ Glycoprotein IIb/IIIa inhibitors: glycoprotein
IIb/IIIa enzyme inhibited which prevents
platelet aggregation
Heparin
Heparin
† Suppresses the formation of fibrin in
veins, Inactivates clotting factors
thrombin and Xa
† Anticoagulant effect develops quickly
† Uses: prevent venous thrombosis, PE,
Evolving stroke, DVT, CABG, MI ,
renal dialysis
† Monitoring: Activated partial
thromboplastin time (aPTT)
† Normal aPTT 40 seconds
† Therapeutic levels 60-80seconds
† Adverse Effects Bleeding!!!
„ Antidote is protamine sulfate
„ May cause thrombocytopenia
„ May be used during pregnancy
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Antiplatelet Agents Prolong Bleeding
Time by Interfering with Platelet
Aggregation (cont’d)
† Primary uses - prevent clot formation in
arteries
† Adverse effects - abnormal bleeding;
reduce number of neutrophils
Aspirin
Antiplatelet drug
COX inhibitor First generation NSAID
† Suppresses platelet aggregation by
inhibition of COX-1 and COX 2
† Decreases prostaglandin synthesis
† Reduces inflammation, fever, and
pain
ASA
Plavix(clopidogrel)
† USEs: Pain ,fever, inflammation, prevention
of thrombus in arteries (coronary arteries),
PREVENTS MI and STROKE
† Adverse effects: bleeding, gastric ulcers,
renal impairment,
† Reyes syndrome in children
† Hypersensitivities in patients with allegies.
† Adenosine Diphosphate receptor
antagonist, ADP receptor blocker
† ANTI PLATELET DRUG
† How does it work: blocks enzyme so
that platelets are unable to
aggregate.
† Uses: prevention of stroke and MI.
Integrilin(eptifibatide)
† “SUPER ASPIRIN”
† How does it work: interferes with final
step in platelet aggregation
† Uses: acute coronary syndrome, used
during angioplasty
† Adverse effects: ICB, GI bleed,
Hematuria, gum bleeding,
thrombocytopenia, anaphylaxis.
Thrombolytics Are Used to
Dissolve Existing Clots
† Example - alteplase (Activase)
† Mechanism of action - convert plasminogen to plasmin
which causes fibrin to degrade, then preexisting clot
dissolves
† Primary uses - acute MI, pulmonary embolism, acute
ischemic CVA, DVT, arterial thrombosis, coronary
thrombosis, clear thrombi in arteriovenous cannulas
and blocked IV catheters
† Adverse effects - abnormal bleeding; contraindicated
in patients with active bleeding or recent trauma
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Thrombolytics
Alteplase(tPA)
† Converts plasminogen to plasmin
† Plasmin is an enzyme that digests the
fibrin matrix of clots
† USES: Acute MI, PE, ischemic stroke
† Adverse Effects: bleeding, intracranial
hemorrhage.
Hemostatics Are Used to
Promote the Formation of Clot
† Example - aminocaproic (Amicar)
† Mechanism of action - prevent fibrin
from dissolving, which enhances
stability of the clot
† Primary use - prevent and treat
excessive bleeding from surgical sites
† Adverse effects - none listed
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