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165 Cards in this Set
- Front
- Back
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In general, what can appropriate lifestyle changes in combination with drug therapy decline the progression of?
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coronary plaque, regression of preexisiting lesions, reduction in mortality due to CHD
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what is CHD most commonly associated with?
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high total cholesterol, and significantly, high LDL
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What is associated with decreased risk of heart disease?
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high levels of HDL
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What is the primary goal in lowering cholesterol? (in cholesterol therapy) generally
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lower LDL
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Who are candidates for drug therapy in the treatment of hypercholesterolemia?
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pts with LDL levels higher than 160mg/dL and with one other risk (htn, smoking, diabetes, family hx)
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What is the goal LDL for a pt with risk factors?
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less than 130mg/dL
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What else besides high LDL levels is associated with CHD?
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hypertriacylglycerolemia
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What are diet and exercise the primary modes of therapy for?
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hypertriacylglycerolemia
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What drugs are the most effective in lowering triacylglycerols?
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niacin and fibrates
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What is a secondary benefit of statin drugs?
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lower triacylglycerdies
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What is another name for statins?
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HMG CoA reductase inhibitors
(they lower LDL) |
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What drugs inhibit the first enzymatic step of cholesterol synthesis?
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statins
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What are some names of statins?
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Fluvastatin
Lovastatin Atorvastatin Pravastatin Simavastatin Rosuvastatin (they inihibit cholesterol synthesis) |
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These are the most potent LDL lowering drugs
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AR
Atorvostatin and Rosuvastatin |
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What happens to LDL receptors when the intracellular depletes?
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they increase their surface LDL specific receptors
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What role does the cell play in lowering plasma cholesterol ?
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LDL receptors bind and internalize LDL. So they lower plasma cholesterol by lowering LDL synthesis and by increased catabolism of LDL
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What are the two MOAs of statins?
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Inhibition of HMG CoA reductase
Increase in LDL receptors |
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T or F: statins are effective in lowering all types of hyperlipidemia?
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true
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Who is at risk for less effective mechanism of statins?
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pts who are homozygous for familial hypercholesterolemia. (because they LACK LDL receptors)
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What percentage of pts still present with coronary events after on statin therapy?
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1/4
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What should be monitored while taking statins?
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liver function (serum transaminase levels)
plasma creatine kinase levels (bc of myopathy and rhabdomyolysis) PT levels (may increase warfarin levels) |
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What are some side effects of statins?
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liver biochemical abnormalities
myopathy and rhabdomyolysis increase wafarin levels |
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What are the contradindications of statins?
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MOMMYS and NURSING mommys
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What is the role of niacin and how does it work?
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increasing HDL
It inhibits the lipolysis in adipose tissue, and decreases in liver triacylglycerol synthesis |
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What is the side effect of niaciin?
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flushing with warmth and pruritus
Take ASA prior to taking niacin sustained release formation of niacin prevents adverse effects |
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what is a side effect of niacin? Who should watch out?
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niacin inhibits tubular secretion of uric acid, predisposes to hyperuricemia and gout
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What do fibrates do?
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lower triacylgyclerols
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Name two fibrates and the difference between them
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fenofribrate and gemfibrozil
Fenofibrate is more effective |
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What drug causes gallstones?
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fibrates
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Besides causing potential gallstones, what other side effects of fibrates?
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myositis
myopathy rhabdomyolysis compete with coumarin binding sites |
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What should be monitored with fibrates?
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PT times
muscle weakness and tenderness should be evaluated |
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What are the contraindications of fibrates?
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severe hepatic or renal dysfunction
preexisting gallbladder disease |
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What is the role of bile acid resins?
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lower LDL level (less than statins though)
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How do bile acid binding resins?
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They bind bile acids/salts in the sm intestine and this resin/bile complex is excreted in the feces. This stops the bile acids from going to the liver. So the liver has to make bile acids from cholesterol..so the intracellular cholesterol conc decreases which causes the liver to increase uptake of LDL particles(fall in LDL)
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Name three bile acid binding resins
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Cholestyramine, colestipol, and colesevelam
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Cholestyramine also relieves what?
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pruritus caused by accumulation of bile acids with biliary obstruction
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What are some side effects of bile acid binding resins?
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GI problems
constipation dcd absorption of fat soluble vitamins (ADEK) farting they interfere with intestinal absorption of many drugs |
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What is Ezetimibe?
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cholesterol absorption inhibitor
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how do cholesterol absorption inhibitors work?
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stop dietary and biliary cholesterol absorption in the sm intestine. decrease delivery of cholesterol to the liver. reduction of cholesterol in the liver. increase of cholesterol clearance from the blood.
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what is angina caused by? in general
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coronary blood flow insufficinet to meet oxygen demands of myocardium
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what can cause an imbalance between oxygen delivery and utilization?
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-spasm of vascular smooth muscle
-obstruction of the vessels to the heart -exertion (these do NOT cause death) |
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what are the three angina drugs?
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nitrates, ccb, bb
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what type of angina is relieved with nitro and rest?
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stable
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describe unstable angina
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increasing frequency and precipitated with progressively less effort.
unrelated to exercise occurs at rest not relieved with nitro or rest |
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What two drugs can be used to help prinzmetals angina?
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vasodilators: nitro and ccbs
prinzmetal: occurs at rest, due to coronary artery spasm |
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What two actions do nitrates have?
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-dilate veins , results in pooling of blood (decrease preload and VR)
-dilate coronary vessels (brings more oxygen to the heart) |
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What do nitrates do initially? generally
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cause a rapid reduction in myocardial oxygen demand
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What is the MOA of nitrates?
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conversion to NO > activates guanylate cyclase > increases cyclic GMP > vascular smooth muscle relaxation
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How do the drugs in angina differ?
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onset of action and rate of elimination
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What is the most effective drug in relieving ongoing angina?
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sublingual or spray form of nitroglycerin
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What drug decreases myocardial oxygen consumption by decreasing cardiac work?
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Nitroglycerin
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What is the onset for nitrates?
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one minute for nitroglycerin and one hour for isosorbide mononitrate
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What is the first pass metabolism for nitrates?
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liver (take sublingually or patch to avoid this)
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What are the side effects of nitrates?
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headache
flushing postural hypertension |
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What should sildenafil not be taken with?
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sildenafil (viagra)
NOT with nitrates or Six hours in between them |
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What drug is tolerance concerned with?
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nitrates
Should have a nitrate-free interval every day of 10-12 hours, usually at night |
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Where should the tolerance interval be for pts with variant angina?
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nitrate-free interval should occur in late afternoon because variant angina is worse in the morning
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What do Bblocker do to the heart? (how do they work)
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decrease the oxygen demand by lowering
- heart rate - contractility |
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Name the non cardioselective Bblocker
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propanolol
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T or F; some bblockers are always selective
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false,
at high doses, all bblockers are nonselective (inhibit b2 receptors too) |
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What is a drug with ISA (name) and what class is it in?
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pindolol
bblockers has intrinsic sympathomimetic activity (Should be AVOIDED) |
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What is the first line of therapy for angina?
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bblockers if they are not contratindicated
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What is the purpose of bblockers besides decreasing contractility?
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lowering hr to 50-60
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What are the contraindications of bblockers?
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asthma, diabetes, severe bradycardia, peripheral vascular disease or copd
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What class of drugs should not be stopped all together at once?
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bblockers
they should be tapered off over 5-10 days so that no rebound angina or hypertension is experienced |
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What do ccbs do for the heart? generally
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vasodilate that causes a
decrease smooth muscle tone and decrease in resistance |
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What class of drugs is Verapamil in? and what does it affect?
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CCBs
it affects the myocardium |
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What class is Nifedipine in? and what does it affect?
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CCBs
affects smooth muscle in peripheral vasculature It's also a dihydopyridine |
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T or F; All CCBs lower blood pressure
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true
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What is variant angina treated with?
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nitro and ccbs (vasodilators)
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What effects does a dihydropyridine have on the heart? (for angina)
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nifedipine.
vasodilates. minimal effect on hr and cardiac conduction |
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What are some side effects of nifedipine?
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flushing, headache, hypotension, peripheral edema (duh, it works on the peripheral vasculature) constipation, may cause reflex tachycardia
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What CCB should be avoided in coronary artery disease?
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nifedipine (short acting dihyrdopyridines)
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What CCB decreases the heart rate?
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Verapamil (slows cardiac conduction)
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Which CCB causes inotropic effects?
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Verapamil,
Diltiazem does too, but not to as great as an extent |
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What is a side effect of Verapamil
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Verapamil=CCB
constipation |
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What is contraindicated with Verapamil?
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preexisting depressed cardiac function and AV conduction abnormalities
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What is Diltiazem and what can it be used for?
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CCB
slows heart rate but to a lesser extent than verapamil useful in patients with variant angina |
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What are CCBs first line for?
second line? |
vasospastic angina
2nd-stable angina |
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What is Ranexa?
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New angina drug
use as adjunct after BBs, CCBs, nitrates lowers HBA1c |
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What does increased peripheral vascular smooth muscle tone, incd arteriolar resistance, and reduced capacitance in veins cause?
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HTN
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What results in HTN?
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increased peripheral resistance which leads to increased arteriolar resistance and reduced capacitance in veins
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What percentage of ppl have essential hypertension?
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90%
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What is the most common abnormality of hemostasis?>
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thrombosis-unwanted clot within a blood vessel
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What are examples of thrombotic disorders?
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MI, DVT, PE, acute ischemic stroke
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what is used to treat thrombotic disorders?
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anticoags and fibrinolytics
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what is treated with factor VIII?
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hemophilia
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What can a vit K deficiency cause?
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bleeding disorder,
failure of hemostasis |
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What are arterial thromboses comprised of?
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happen in medium sized vessels caused by atherosclerosis.
platelet rich |
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What are venous thromboses made of?
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triggered by blood stasis and inactivation of coag cascade.
rich in fibrin (fewer platelets) |
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What is prostacyclin and where is it produced?
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Prostacyclin and nitric oxide are inhibitors of platelet aggregation. They are synthesized by endothelial cells
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What can cause less synthesis of prostacyclin?
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damage to endothelial cells (cut)
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Describe the role of thrombin and thromboxane in the beginning of platelet aggregation.
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Platelets have receptors on their surface for thrombin and thromboxane. In an intact (not cut) normal vessel, thrombin and thromboxane are low in circulation. When the platelet receptors are occupied, they trigger reactions that relase intracellular granules of the platelets. This stimulated aggregation
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What plays a major role in platelet adhesion?
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exposing of Collagen.
Collagen is covered by endothelium. When the endothelium is injured, the collagen is exposed and platelets cover it. triggers chemical rxns that result in platelet activation |
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Describe platelet activation.
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Receptors on platelets are activated by collagen. > Morphological changes in platelets > release of the granules containing mediators > The mediators bind to receptors of the surrounding resting platelets
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What are the chemical (signaling) mediators released by the platelets? And what is this in response to?
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Mediators: ADP, serotonin, thromboxane a2, thrombin, PAF
This happens when there is a morphological change in the platelet in response to exposed collagen |
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After activation, activation of the GP IIb/IIIa receptors starts. What role do they play? generally
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platelet-platelet interaction and thrombus formation.
They do this by binding fibrinogen. Fibrinogen binds to 2 platelets simultaneously and causes them to attach (aggregate) |
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What activates thrombin?
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stimulation of coag cascade by tissue factors released from the injured site and by mediators on the surface of the platelets
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What is thrombins role in platelet aggregation?
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Thrombin catalyzes the hydrolysis of fibrinogen to fibrin
MAKES FIBRIN fibrin goes into the clot and stabilizes it. forms a hemostatic platelet fibrin plug |
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What is the major player in fibrinolysis?
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plasmin.
plasmin limits the growth of the clot and dissolves the fibrin network as wounds heal |
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The last step of the coag cascade depends on...
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GP receptors (most importantly GP IIb/IIIa)
they bind fibrinogen, remember? and adhere another platelet |
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What causes platelet cross linking and adherence to another?
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fibrinogen that has binded to the GP IIb/IIIa receptor
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How do platelet aggregation inhibitors work? (in general, what do they block?)
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they either :
-inhibit cyclooxygenase1(COX1) -block GP IIb/IIIa receptors -block ADP receptors |
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Describe the cascade that aspirin interupts.
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activation of phospholipases > liberate arachidonic acid > arachidonic acid is converted to thromboxane a2 > promotes clumping
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What step does aspirin interrupt?
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inhibits thromboxane a2 synthesis (from arachidonic acid) in platelets by acetylation
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What regimens is aspirin used in? What is the daily dose?
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prophylatic treatment of TIA, MI, and decreases mortality in pre and post MI
Daily dose: 81-165mg |
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What problems can aspirin cause?
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decreased clot time sooo hemorrhagic stroke and GI bleeds,
especially at higher doses |
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What can antagonize the platelet inhibition of aspirin?
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ibuprofen
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Selective COX2 inhibitors play what role in clots? (in aspirin section)
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they may contribute to cardiovascular events by shifting the chemical rxn (in the aspirin pathway) to thromboxane a2 (instead of prostacyclin)
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Name some platelet aggregation inhibitors.
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Aspirin
Ticlopidine and clopidogrel Abciximab Eptifibatide and tirofiban Dypyridamole |
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What drugs interfere with the binding of ADP to its receptors on platelets?
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Ticlopidine and clopidogrel (Plavix)
(interfering with ADP then inhibits GP IIb/IIIa activation) |
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What drugs are useful in stent insertion during MI?
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Ticlopidine and clopidogrel
(also used for cerebrovascular cardiovascular and peripheral vascular disease) |
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What drug can cause neutropenia?
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ticlopidine
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what is an adverse effect of ticlopidine and clopidogrel?
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thrombocytopenic purpura
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What is the name of the antibody used in platelet inhibition?
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abciximab
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What does abciximab do? (MOA)
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binds directly to the GP IIb/IIIa receptor
stops clot formation given IV !!!! as alternative to percutaneous coronary intervention |
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What two drugs have similar MOA to abciximab?
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Eptifibatide and tirofiban
(block GP IIb/IIIa receptor) given IV also |
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What platelet aggregation inhibitor is used with aspirin as a prophylatic treatment for angina?
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Dipyridamole
(coronary vasodilator) |
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What is Factor Xa?
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factor in the coagulation process(both extrinsic and intrinsic) that CONVERTS PROTHROMBIN TO THROMBIN.
(thrombin makes fibrin) |
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What two anticoagulants are there? general idea
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inhibit action of coag factors (heparin)
or inhibit the Synthesis of coag factors (warfarin) |
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What is heparin used for?
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used acutely to interfere with the formation of thrombi, prevention of venous thrombosis and thrombotic disorders (PE and MI)
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What is unfractionated heparin?
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has a wide range of molecular weights
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What is Heparins MOA?
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binding to antithrombin III, with subsequent inactivation of coag factors
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How do heparin and LMWHs limit the formation of thrombi?
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prevent fibrin formation
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What drug is used to treat pregnant women with prosthetic heart valves?
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heparin
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What anticoag does not cross the placenta?
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heparin (thrombin inhibitor)
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What anti coags are useful in outpatient therapy?
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LMWHs
enoxaparin and dalteparin |
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What drug is used in dialysis machines?
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heparin
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Why is intramuscular injection of LMWHs contraindicated?
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hematoma formation
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How is heparin administered?
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IV bolus and then continuous admin for 7-10 days after so that the aPTT is 1.5-2.5 fold of normal
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What is not necessary to get for LMWHs?
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aPTT levels
should be 1.5-2.5 fold normal for heparin |
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What side effect of heparins is lower in LMWHs pts?
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thomboembolic problems
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What can be used to stop hemorrhage as a result of heparin? besides stopping the use of heparin
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protamine sulfate
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Why may heparin cause hypersensitivity reactions?
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because its from an animal source
may be antigenic |
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Describe the two types of Thrombocytopenia.
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Type 1- more common, mild decrease in platelets, occurs within the first 5 days of tx
Type 2- rare, IgG mediated rxn causing platelet aggregation of the platelets left, occurs w.in the 5-14th day of tx, platelet counts drop to 50% or more Stop Heparin, can start lepirudin |
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How does lepirudin work?
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one molecule of lepirudin binds to one molecule of thrombin
Little effect on platelet aggregation IV given |
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What is used in the tx of heparin induced thrombocytopenia?
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lepirudin
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What can exacerbate lepirudin?
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tx with streptokinase or alteplase
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What drug is an anti FactorXa?
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Danaparoid
administered subcutaneously (with enoxparin and daltparin) |
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What should the PT be in a vit k antagonist?
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(warfarin)
1.5-2.5 fold of normal BUT even controlling this does not prevent bleeding in 20% of pts |
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What is inhibiting vit K useful?
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because some of the protein factors in coagulation need vit k to be synthesized in the liver
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What does warfarin inhibit?
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Vit K epoxide reductase
it's an enzyme |
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How can warfarin be reversed?
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administering vit K
(still takes 24 hrs) |
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How is warfarin administerd?
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orally
99% bound to plasma albumin |
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What drugs can compete for spot on albumin with warfarin?
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sulfonamides (have a great affinity for albumin)
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Which drug should never be used with pregnancy?
Heparin or warfarin? |
Warfarin
teratogenic, abortion |
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What drugs have first dose syncope
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alpha 1 blockers and ACE inhibitors
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What are some thrombolytic drugs?
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Streptokinase and alteplase
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Is thrombolytic therapy always successful?
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no, not successful in 20% of patients with infarcted arteries
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Is intracoronary delivery of a thrombolytic useful?
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yes, it is the best way to treat MI, but cardiac caths usually are not possible within the 2-6 hr window for thrombolytics, so they are given IV
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What is the major side effect for thrombolytics?
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hemorrhage (may have unsuspected ulcer that may hemorrhage)
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What drug class is contraindicated in pts with healing wounds or metastatic ca?
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thrombolytics
because they destroy fibrin...and fibrin will be in the healing wound and the area of cancer where the body is trying to heal the cancer |
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What are the two mechanisms for controlling blood pressure? (generally, beginning of chap 19_
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CO and peripheral resistance are controlled by:
the baroreflexes(sympathetic nervous system) and RAAS system |
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What is the body's most potent circulating vasoconstrictor?
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Angiotensin II
it stimulates aldosterone secretion (incd Na reabsorption) incd blood volume |
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What do black patients respond well to?
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DC
diuretics and calcium channel blockers |
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What is the most common reason for failure of htn?
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pt compliance
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What drug class can cause decreased libido and impotence?
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BBlockers
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what drug is first line in htn?
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diuretics
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What is the initial effect of thiazide diuretics?
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initially cause Na and H20 excretion
long term (plasma vol goes to normal and resistance decreases) |
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What are some side effects of thiazide diuretics?
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hypokalemia
hypomagnesemia hyperuricemia |
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What is the difference between loop diuretics and thiazide diuretics?
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loop diuretics increase the ca2+ content of urine
(thiazide dcd) |
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What are two selective bblockers?
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metoprolol and atenolol
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When are ACE inhibitors indicated?
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when BB and diuretics are contraindicated
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What are the contraindications of thiazides
? |
gout
sulfa allergy creatinine clearance of <50 ml/min |
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What are some examples of kidney function in disease? specifically edematous states?
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heart failure
ascites (hepatic) nephrotic syndrome premenstrual edema |
