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41 Cards in this Set
- Front
- Back
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What causes peripheral arterial diseases?
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-Caused by atherosclerosis
-Causes intermittent claudication -Markedly increased risk of cardiovascular morbidity and mortality |
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What drugs are used for PADs?
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-Antiplatelet agents (aspirin, clopidogrel)
-lipid lowering agents -ACE-I |
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What happens to the distal portion of an artery that is plagued with a plaque?
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Reduced blood flow and pressure to the distal portion, and in addition, the chronic hypoxia causes dysfunction of the endothelium and so the endothelial cells won't release vasodilators such as nitric oxide (for localized vasodilation). So you get ischemia.
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What are the differences in the capillary in normal vs chronic hypoxia?
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Normal- the RBCs deform to fit in the capillary and the platelets pass on by.
Chronic Hypoxia- RBCs don't deform very well, they become stiff, so it's harder for them to move through. Also, there is plately adhesion. This will impair blood flow and perfusion. |
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End results of peripheral arterial disease?
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reduced blood flow and reduced o2 delivery to the tissues. this causes pain with walking (increased o2 demand of skeletal muscle.)
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What would happen if you gave a vasodilator? Would it makes things better?
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Since this isn't a localized dilation, and all the arteries will dilate, this will not makes things better.
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What drugs are used to treat claudication?
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-Cilostazol
-Pentoxifylline They are ONLY used for claudication and won't effect morbidity and mortality. They will only help the pain that occurs from walking. |
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What does cilostazol do?
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inhibits phosphodiesterase III (which normally breaks down cAMP). This will increase cAMP in the platelets, preventing platelet aggregation. This also increases cAMP in the vasculature, causing vasodilation. This will somehow help with intermittent claudication. Takes a few weeks.
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Cilostazol is contraindicated in what? and why?
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heart failure. makes it worse.
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What does pentoxifylline do?
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-increases RBC flexibility; decreases fibrinogen which decreases blood viscosity. These both will increase blood flow and increase tissue oxygenation.8
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Everyone likes pentoxifylline, right?
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no. causes NVD, dizziness, headache. it's not liked well because of the adverse effects as well as the questionable efficacy.
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First line for claudication is...
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cilostazol (except for those with heart failure). Pentoxyifylline is the alternative.
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What is Raynaud's Disease? what do you use to treat this?
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vasospasm of the small arteries in the skin of the hands and feet with intermittent pallor or cyanosis. This is treated with vasodilators.
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Which classes of vasodilators are used for Raynaud's Disease?
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Those that are most specific for vasodilation of the arteries...
Calcium channel blockers (DHPs) alpha antagonists direct vasodilators- nitrates (high amnt) ACE-I |
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Causes of Elevated pulmonary vascular resistance?
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idiopathic, genetic, diseases, toxins. this leads to pulm HTN, then RIGHT sided heart failure.
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When you think of the pulmonary vasculature, is it a high or low pressure bed?
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Low pressure, high volume. You're taking 100% cardiac output and sending it just to the lungs. But when you have this disease, it becomes a high pressure bed.
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What doe endothelin do?
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decreases prostacyclin and decreases nitric oxide. this means it vasoconstricts and increases cell proliferation. the more smooth muscle, the more smooth muscle that needs to be constricted, which means an increase in PVR.
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What does prostacyclin and NO do?
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vasodilate and decrease proliferation of cells. there is also an inhibition of platelet proliferation.
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What happens if there's an increase of calcium in smooth muscle cells?
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too much vasoconstriction and too much proliferation.
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End result of pulmonary arterial hypertension is?
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proliferation of the intima, media and adventitia, excess smooth muscle tone (vasoconstriction), and thrombosis in situ.
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Who typically gets pulmonary hypertension? Young/old, male/female?
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Young females. And if you don't treat it, you's gonna die.
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What are the tx goals for PAH
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-prevent thromboembolism (using anticoagulants)
-Reduce pulmonary vascular resistance and remodeling of the pulmonary arteries to increase CO, exercise capacity and reduce mortality |
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how do you treat the too much Ca in the cell with PAH?
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ccb
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how do you treat too much endothelin in PAH?
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endothelin antagonist.
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how do you treat the lack of PGI2 in PAH?
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give PGI2. this will Dilate pulmonary vasculature
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how do you treat not enough NO in PAH
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PDE-5 inhibitor. this will Dilate pulmonary vasculature
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Which ccbs do you use?
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nifedipine, amlodipine, diltiazem. if the person has right sided heart failure and you give a ccb, what happens to the contractility of the right ventricle? it decreases. so you don't give verapamil which has the most negative ionotrophic effect on the heart.
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Responses to ccbs
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Decreases pulmonary vascular resistance in only 10-15% of patients
Doses are 2-3 times higher than what is used for systemic hypertension People that respond to CCBs may have long term survival -Acute vasoreactivity test -Try CCBs only in patients that respond to IV epoprostenol, inhaled NO or IV adenosine (b/c they're short acting) -Long term treatment with CCB in patients that exhibit a sustained response |
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What do you need in an acute vasoreactivity test to start using CCBs?
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need a good change in pulmonary arterial pressure and no bad change in cardiac output using short acting epoprostenol, NO, or adenosine. If they react well, then you can use oral CCBs, then if that's good, you can continue using CCBs.
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Name the prostacyclin analogues
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Epoprostenol (IV)
Traprostinil (subq, IV) Iloprost (inhale) |
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MoA of prostacyclin analogues
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-Prostacyclin (PGI2)
-Dilates pulmonary vessels -Decrease pulmonary vascular resistance -Probably a small degree of systemic vasodilation -Inhibits platelet aggregation -Antiproliferative effects |
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Describe epoprostenol
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-half life is 6 minutes
-central venous catheter -infections/cath comes out -works! |
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Treprostinil
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-half life 4 hours
-SQ infusion or central venous cath -SQ- injection site pain -no much benefit shown |
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Iliprost-
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-half life 20-30 minutes
-inhalation -10-12 minutes, 6-9x a day -not shown to help mortality. |
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Name the endothelin Receptor Antagonists
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-Bosentan
-Ambisentan *both taken orally. |
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MoA of endothelin Receptor antagonists?
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-Blocks Endothelin A and B receptors
-Plasma levels of Endothelin are increased in patients with pulmonary hypertension and correlates with disease severity |
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What do you get if you have too much endothelin?
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Vasoconstriction
Fibrosis Hypertrophy and hyperplasia Increases vascular permeability |
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Adverse effects of bosentan
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Elevations in liver aminotransferases
-Incidence 11% (that's pretty high) Decrease in hemoglobin and hematocrit Expected to be teratogenic in humans Induces CYP3A4, CYP2C9, and CYP2C19 -Decrease concentration of some drugs, such as hormonal contraceptives |
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Name a Phosphodiesterase Type 5 Inhibitor
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Sildenafil
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MoA of sildenafil
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Large concentration of PDE-5 in pulmonary vasculature
PDE-5 gene expression and activity are increased in pulmonary arterial hypertension Sildenafil inhibits PDE-5, which normally breaks down cGMP, a product of NO ( which is a vasodilator) |
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Which drug do you give for the worst of the worst cases of PAH?
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epoprostenol.
if it's not that bad, use oral drugs. If it's worse, use an parenteral. |
