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117 Cards in this Set
- Front
- Back
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Steps of plaque formation
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LDL accumulates in subintimal space of artery
Monocytes attach Endothelial dysfunction Monocytes become macrophage. Ingest oxidized LDL and become FOAM Cells Fatty streaks-> Fibrous plaques |
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Properties of endothelial dysfunction
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Inability of arteries to dilate fully in response to stimuli
KEY event in artherosclerosis Predicts vascular events Caused by: toxins, HTN, smoking, DM |
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How is hyperlipoproteninemia classified according to Fredrickson-Levy-Lees?
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By lipoprotein type affected.
I. chylomicrons II. LDL IV. VLDL etc |
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Most common cause of hyperlipidemia?
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Elevated LDL
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Primary vs. secondary causes of dyslipidemia
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Primary: inborn errors in metabolism, mostly familial and genetic
Secondary: underlying health cause- diet, disease state, drugs |
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Causes of secondary dyslipidemia
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Diet
Obesity Physical inactivity Diabetes Hypothyroidism Nephrotic Syndrome Obstructive Liver disease Drugs: glucocorticoids, progestins, others |
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Why is HDL good cholesterol?
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Removes periph cholesterol from tissues and artery walls to reduce plaque formation
antioxidant: carries antiox enzymes anti-inflammation |
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Why is LDL bad cholesterol?
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Collects in arteries, gets oxidized and macrophaged to form foam cells
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Function of LPL?
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Lipoprotein lipase
Catalyzes breakdown of triglycerides to glycerol and free FA |
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2 ways to get cholesterol?
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From diet: cholesterol esters in LDL are hydrolyzed
From HMA-CoA reductase: cholesterol synthesis |
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Long acting statins?
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Atorvastatin
Rosuvastatin -Can be taken anytime. others qhs |
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Statin MOA
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Analog of HMG-CoA inhibit HMG-CoA reductase so less synthesis of cholesterol. Up regulation of LDL-receptors so less LDL in blood.
ALSO antioxidant, anti-coagulant, anti-inflammation, improves endothelial function, maintain plaque stability |
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Statin effects of lipoprotein levels
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Decrease LDL 20-50%
Decrease VLDL 25% Decrease TG 10-30% Increase HDL 5-10% |
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Statin Adverse effects
Contraindications |
RHABDOMYOLYSIS
Liver failure headache, GI upset Contra: pregnancy, liver disease |
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Most statins are prodrugs with active metabolites except:
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Fluvastatin
Pravastatin- also NOT met by CYP enyzmes. Good for pts on other CYP metabolized drugs |
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Ezetimibe
Class MOA |
Inhibits cholesterol absorption in small intestine- dietary AND biliary
Binds to NPC1L1-a reg channel that uptakes cholesterol (no effect on TGs) NOT a substrate for CYP (ok w/statins) |
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Ezetimibe effect on lipoprotein levels
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Decrease LDL 18%
Small effect on HDL and TG (<10%) Synergistic w/statin- Ezetimibe causes a compensatory increase in liver cholesterol synthesis that is avoided when given w/ statins |
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Ezetimibe adverse effects and contraindications
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-HA, diarrhea
-impaired liver function CONTRA: liver disease |
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Cholestyramine
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Bile acid-binding resin
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Colestipol
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Bile acid-binding resin
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Colesevelam
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Bile acid-binding resin
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Bile acid binding resin MOA
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Binds bile acid in intestine and promotes excretion (less reabsorption)= more cholesterol used to make more bile acids so less in blood
Also less liver cholesterol increases LDL receptors so less LDL in blood |
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Bile acid binding resins effect on lipoprotein levels
Indications |
Decrease LDL cholesterol 20%
Increase HDL modestly 5% For pts with isolated high LDL Not for pts with high TG or VLDL |
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Bile acid resins adverse effects, interactions, contraindications
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GI side effects
Interactions: reduce absorption of some drugs- warfarin, prava/fluva statin. Take resins at least 1 hr after contraindications- not for pts w/high TG |
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Gemfibrozil
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Fibric acid derivative
Fibrate short acting |
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Fenofibrate
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Fibrate
long acting |
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Fibrates MOA
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bind and activiate peroxisome proliferation activated receptor (PPAR) which changes lipid met. Increase LPL and apoAI/II
INCREASE HDL DECREASE TG synthesis |
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Fibrates effect on lipoprotein and indications
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DECREASE TG
INCREASE HDL Modest decrease LDL, VLDL For pts w/ high TGs, low HDL |
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Fibrates adverse effects and contraindications
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GI symptoms
MYOPATHY esp w/ statin Increase gallstone risk CONTRA: liver and kidney dysfunction |
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Nicotinic acid- AKA?
MOA |
Niacin= vit B3
Inhibits lipase, blocking fat breakdown in adipocytes= inhibit VLDL secretion= less LDL made |
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Niacin effect on lipoprotein levels and indication
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Improves ALL lipoproteins
MOST effective at HDL increases For pts w/most types of lipid adnormalities |
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Niacin adverse effects and contraindications
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Flushing- b/c of vasodilation & prostaglandin synthesis. Less if take w/ aspirin
Digestive upset CONTRA: gout liver disease |
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Fish Oil MOA, effects on lipids
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Decrease TGs up to 35%
MOA- unclear, reduce TG synthesis and increase FA oxidation. Also cardio protective: anti-arrhythmic and thrombotic Omega-3-fatty acids |
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Which drug classes decrease TGs?
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Fibrates
Niacin -fish oil |
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Which drug classes decrease LDL?
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Statins (best)
bile acid resins Ezetimibe/ absorption inhibitor Niacin |
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Which drug classes increase HDL?
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Niacin (best)
statins fibrates |
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Calculating LDL or TG
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TC=LDL + HDL + TG/5
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Foods that lower cholesterol
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Stanols/sterols: compete w/cholesterol for absorption. decrease cholesterol up to 15%.
oat bran fiber, flax seed, garlic, nuts, vegetables |
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Cholesterol screening guidelines
Nonfasting lipid levels |
-Start age 20 every 5 years
- age 2 if parents have premature CHD or TC>240 Nonfasting: TC>200 HDL<40 |
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9 step assessment of lipids
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1. Lipid levels: at least 2 for diagnosis
2. CHD risk 3. Assess risk factors 4. 10 year risk for CHD 5.Risk category and goals 6. TLC 7. Drug therapy 8. Metabolic syndrome 9. Treat high TG or low HDL |
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Classification for Total cholesterol and HDL
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<200 desirable
200-239 borderline >=240 High HDL <40 Low >60 high |
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Classification of LDL
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<100 Awesome.
100-129 near/above optimal 130-159 borderline high 160-189 high >=190 very high |
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Risk Factors for CHD framinghouse on ATPIII guidelines
(5) |
smoking
HTN (>=140/90) Low HDL <40 (>=60 is negative risk) Age M>=45 F>=55 FH: M<55 F<65 |
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Signs of Metabolic Syndrome
(5) |
Must have 3 of the following:
- abdominal obesity (M 40" F 35") -TG>=150 -HDL M<40 F<50 -BP >130/85 -Fasting glucose >=100/110? Treat w/ weight loss, exercise, no alcohol, low fat diet and other disease state treatment (HTN, DM, hypothyroid, prothrombotic state) |
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Cholesterol risk category: High
Define LDL goal Start TLC at Start DT at |
CHD or equivalent; >20% risk
Goal: 100 (70 option) TLC >=100 DT >= 100 |
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Cholesterol risk category: Moderately High
Define LDL goal Start TLC at Start DT at |
2+ risk factors; 10-20% risk
Goal: 130 (100 option) TLC >=130 DT >= 130 (100 option) |
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Cholesterol risk category: Moderate
Define LDL goal Start TLC at Start DT at |
2+ risk factors; <10% risk
Goal: 130 TLC >=130 DT >= 160 |
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Cholesterol risk category: Low
Define LDL goal Start TLC at Start DT at |
0-1 risk factor
Goal: 160 TLC >=160 DT >= 190 (160 option) |
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Classification of TG.
When do you treat TGs before LDL and with what? Why? When do you treat TGs as secondary goal? How? |
<150 Normal
150-199 Borderline. more exercise, weight reduction 200-499 High if LDL is reached, add niacin or fibrate or fish oil. or intensify LDL treatment >=500 VERY high Treat TGs first if >=500. Use very low fat diet (<15% fat calories), lose weight/exercise, Niacin, fibrate, Fish oil. High risk of PANCREATITIS Treat TG AFTER LDL goal is reached |
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How often F/U with new lipid therapy? Once at goal?
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4-8 weeks until goal
every year following |
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Pleiotropic effects of statins?
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Reduce oxidative stress
Reduce inflammation improve endothelial function stabilize plaques improve endothelial progenitor cell function ? |
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Monitoring for statins
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-FLP every 4-8weeks
-Liver function tests: 4-12 weeks for 6 months then as needed -Creatine Kinase -Myalgias, brown urine, side effects |
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How often to adjust statin dose?
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4-8 weeks.
Statins are good for pts who need >25% LDL reduction |
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Ezetimibe monitoring parameters
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-LFTs
-FLP |
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Fibrates monitoring parameters
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Myalgias
LFTs Renal function GI symptoms |
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Other alternative cholesterol drugs
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vitamin E, C, beta carotene
Estrogen therapy Vit D Red rice yeast |
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Myocardial O2 Supply determinants
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Diastolic perfusion pressure
coronary vascular resistance: -O2 vasoconstrictor -adenosine dilator NO, endothelin, prostacyclin alpha and beta receptors Oxygen carrying capacity |
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Myocardial O2 Demand determinants
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Ventricular volume (preload)
Wall tension/stress Heart Rate Contractility |
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Diagnosis IHD
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-PE: history of chest pain, S4, risk factors
-EKG -Stress test: increase O2 demand, watch EKG -Coronary angiography: radio dye to see where blockage. >70% blockages= IHD |
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Stable angina is AKA and looks like:
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Angina of effort, classical angina, exertional angina
Inadequate O2 during exertion caused by plaque and/or endothelial dysfunction a DEMAND ischemia |
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Variant Angina
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aka Prinzmetal angina
Coronary artery spasm due to endothelial dysfunction occuring during rest and cyclic in nature a SUPPLY ischemia treat with CCB, nitrates, NOT beta blockers |
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Types of angina at rest
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Variant
Silent Unstable: a supply ischemia. thrombus-thrombolytics |
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Anti-angina drug classes
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nitrates
beta-blockers Ca2+ channel blockers Ranolazine (fatty acid oxidation inhibitor) |
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Nitrates MOA
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Release NO
activates GC= increase cGMP = active myosin light chain phosphotase = vasodilation -also opens K+ channels= hyperpolar= relaxation - Inhibits platelet aggregation |
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Nitrates cardio effects
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-vasodilation increases O2 supply
-heart decrease O2 demand, reduce pre and after load -coronary dilation can prevent vasospasm |
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Nitrates therapeutic indications
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-angina/MI
-Heart failure - HTN |
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Nitrates side effects
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HA
Flushing hypotension reflex tachycardia Tolerance: need 8-12 hour break in therapy |
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Beta blocker MOA in angina
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reduce O2 demand by decreasing HR and contractility
Inhibits cardiac remodeling NOT effective in variant angina |
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Ranolazine
MOA Indication Contraindication side effects |
-Inhibits late Na+ current reducing Ca2+ overload
-inhibits fatty acid oxidation so energy source in glucose and use less O2 for more ATP For chronic angina CONTRA: pts w/ prolonged QT intervals Side effects: arrythmias from prolonged QT segment |
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ABCDEs of Ischemic heart disease
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Aspirin and Antiangina therapy
Beta-blocker and Blood pressure Cigarettes and Cholesterol Diet and Diabetes Education and Exercise |
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Therapeutic plan for stable angina
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1-Reduce risk factors
2-aspirin 3-SL nitroglycerin 4- Beta blockers are FIRST LINE 5-CCBs (verapamil or diltiazem) if no BB 6-Combo BB and CCB 7-Long acting nitrates for prevention 8-ACE inhibitor for DM, HTN, CKD or LV dysfunction 9-New drugs 10-Stent 11-Bypass |
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Subjective signs of ACS
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Levine (hand across chest)
Sweating SOB Weakness N/V Syncope |
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Objective signs of ACS
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Mild Fever
increase/decrease BP high/low HR high respiratory rate |
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Diagnosis of Unstable vs. NSTEMI vs. STEMI
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UA; symptoms
NSTEMI: symptoms + enzymes STEMI: symptoms + enymes+ ST elevation |
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Dobutamine
Dipyridamole |
Drugs for pharmacologic stress test
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TIMI Risk Score criteria
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- Age >=65
- >3 coronary risk factors: DM, HTN, Smoking, high cholesterol, FH of CAD - Coronary stenosis >50% (cath lab or previous stent) - ST deviation ->2 angina events in 24 hours - Aspirin in last 7 days - Elevated cardiac markers |
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Heparin MOA
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Binds to ATIII so it's better at inactivating clotting factors 2a, 9a, 10, 11a and 12a
Pentasaccharide binding sequence on heparin binds to ATIII |
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Enoxaparin
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LMW heparin
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Dalteparin
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LMW heparin
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Tinzaparin
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LMW heparin
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Fondaprinux
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Factor X inhibitor
Synthetic pentasaccharide lower incidence of thrombocytopenia |
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Heparin monitoring and how to reverse too much
Adverse effects |
Monitor aPTT
Reversed with protamine sulfate Toxicity is bleeding and HIT (heparin induced thrombocytopenia)- new thrombus or current one gets worse |
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Advantages of LMWH
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more bioavailability
Lab monitoring not needed Less toxicity |
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lepirudin
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direct thrombin inhibitor
parenteral |
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bivalirudin
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direct thrombin inhibitor
parenteral |
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argatroban
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direct thrombin inhibitor
parenteral |
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dabigatran
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direct thrombin inhibitor
oral NEW. for artial fibrillation to prevent stroke |
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Warfarin
MOA Indications Monitoring Contraindications |
-Inhibits synthesis of Vit K clotting factors 2, 7, 9, 10 by inhibiting vit K epoxide reductase
For thromboembolic diseases (ACS, DVT, Pulm. emb, atrial fib, and chronic angina) Monitor INR Give Vit K or frozen plasma for toxicity CONTR: Pregnant |
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Ticlopidine
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ADP receptor inhibitor
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Clopidogrel
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ADP receptor inhibitor
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Prasugrel
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ADP receptor inhibitor
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Abciximab
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GP IIB/IIIA Inhibitor
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Eptifibatide
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GP IIB/IIIA Inhibitor
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Tirofiban
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GP IIB/IIIA Inhibitor
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Aspirin
MOA |
Irreversible COX inhibitor.
decreases thromboxane(TxA2) = no activation of Gq = decrease plastaglandin (PLA2)= less activation of GPII/IIb = less interaction w/fibrin= less platelet aggregation |
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ADP receptor inhibitor MOA
Side effects |
Irreversible binding to P2Y12 ADP receptor= no Gi activation= higher cAMP= less platelet activation= less GP II/IIb expression= less platelet aggregation
Neutropenia, bleeding |
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GP IIb/IIIa Inhibitors MOA
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Inhibit fibrinogen from binding to GPIIb/IIIa and cross linking platelets.
Parenteral admin only |
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Dipyridamole
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Inhibits phosphodiesterase. increases cAMP= decrease platelet aggregation
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Mechanism of Thrombolytic drugs
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Activate plasminogen to plasmin so breaks down fibrin cross links.
-Tissue plasminogen activator converts plasminogen to plasmin -streptokinase and urokinase form complexs with w/ plasminogen that releases plasmin. Streptokinase is not specific for fibrin bound plasminogen. |
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t-PA
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tissue plasminogen activator
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Alteplase
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human recombinant t-PA, short half-life 5 min
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Reteplase
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human recomb. t-PA less fibrin specific
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Tenecteplase
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human recomb t-PA longer half life more fibrin specific than tPA
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Valsartan dose
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40-160mg q12h
ARB |
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Spironolactone dose
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12.5-50mg qd
aldosterone antagonist |
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Carvedilol dose
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3.125-25 q12h
alpha, beta 1 &2 blocker |
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Metoprolol dose
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25-100mg q12h
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Atenolol
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25-100mg qd
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Enalapril dose
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2.5-25mg q12h
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Lisinopril dose
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5-40mg qd
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Ramipril dose
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2.5-20mg qd
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Clopidogrel dose
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300-600mg x1 for USA/MI
75mg NSTEM for 1 year Drug eluting stent at least 1 year Bare metal stent at least 1 month; up to 1 year STEMI at least 14 days up to 1 year |
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Aspirin Dose
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Day 1 hospital: 4 crushed/chewed (324)
UA/NSTEMI 162-325 Bare metal stent: 162-325 for 1 month Drug eluting: 325 for 3-6 months then 75-162 daily |
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Cilostazol
MOA |
reversible PDE III inhibitor; increases cAMP and inhibits platelet aggregation and causes vasodilation.
For PAD |
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Pentoxifylline
MOA |
methylxanthine derivative
decreases blood viscosity increases deformability of blood cells For intermittent claudication |
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Diagnosis of PAD
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ABI <0.9
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Who should have ABI?
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-pts w/ PAD & claudication or severe ischemic resting pain
-age 70+ -age 50+ w/ history of smoking or DM -any age w/ DM + one atherosclerotic risk factor (smoking, lipids, HTN) -abnormal lower extremity pulse -known atherosclorosis of any artery |
