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43 Cards in this Set
- Front
- Back
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When does coronary blood flow occur?
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When heart is at rest.
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Can we affect oxygen supply or oxygen demand easier?
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Oxygen demand
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What is preload?
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Pressure generated by blood coming back from veins into right side of the heart.
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What is afterload?
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The tension or stress developed in the wall of the left ventricle during contraction.Load against which heart contracts to eject blood.
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True/False: Wall tension of the heart can be affected by nitrates.
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True
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What are the two types of problems with ischemic heart disease?
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1. Blood clot
2. Transient ischemia or angina |
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What is typical angina caused by?
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Its usually due to atherosclerosis limiting the flow and is related to exertion.
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What is variant angina due to?
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Acute vasospasms
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What are the two types of Typical Angina?
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1. Stable
2. Unstable (plaque rupture) |
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What are the seven pharmacological agents for Ischemic Heart Disease?
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1. Amyl Nitrite
2. Nitroglycerin 3. Isosorbide dinitrate 4. Isosorbide-5-mononitrate 5. Inhaled nitric oxide 6. Beta blockers 7. Calcium channel blockers |
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Amyl Nitrite:
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ONO
Inhalation/Infrequently used |
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Nitroglycerin:
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ONO2
Sublingual Peak: 4 minutes t1/2: 1-3 minutes oral sustained release tablets BID-QID Patches |
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What is important to remember about nitroglycerin patches?
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Slow release. HAVE to keep in mind that the patches have to be removed for 8-12 hours every day or a tolerance will develop.
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Isosorbide dinitrate:
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Sublingual -
Peak: 6 minutes t1/2: 45 minutes Oral - Peak: 60-90 minutes Lasts: 3-6 hours Extended release |
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Isosorbide-5-mononitrate:
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Oral -
t1/2: 3-6 hours dinitrate metabolite Sustained release |
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Inhaled Nitric Oxide:
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used selectively for pulmonary vasodilation in hypoxic neonates.
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Mechanism of action of Nitrites and Nitrates:
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They cause release of NO and/or nitrothiols. This activates cytosolic guanylate cyclase to form cGMP. cGMP activates protein kinase which phosphorylates proteins. Removes phosphate from myocin which relaxes VSM and also increase movement of calcium out of cell which further relaxes VSM. (Decrease in myosin light chain kinase causes dephosphorylation of myosin which relaxes vessels.
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What group do nitrates have to interact with to become effective and activate cGMP?
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thiols/sulfur groups
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What are seven physiological responses of nitrates?
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1. Affects veins more than arteries and reduced preload (low doses)
2. Dilation of coronary vessels (Larger vessels) 3. Decreased TPR and cardiac output (higher doses) 4. Reduced oxygen demand (decrease pre and afterload) 5. Decreased platelet adhesion 6. Reflex tachycardia 7. Balance oxygen supply with demand |
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How do we develop tolerance to nitrates?
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Frequent administration or continuous exposure leads to tolerance
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How is the nitrates bioactivation with sulfhydryl groups affected during tolerance?
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1. Continued use depletes sulfhydryl groups
2. No cross tolerance with NO 3. Sulfhydryl-reducing agents (N-Acetylcysteine) reverse tolerance |
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How does the formation of free radicals contribute to tolerance?
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Free radicals inactivate enzymes of activation
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What is the free radical hypothesis?
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O2+NO=ONOO (peroxynitrate)
Interferes with endothelium |
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True/False: Activation of counter-regulatory mechanisms (Ang II) can contribute to tolerance?
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True
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What are six side effects to Nitrates?
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1. Headache
2. Postural Hypotension 3. Reflex tachycardia 4. Overdose - elevated methemoglobin 5. Oral agents - nausea 6. Patches - skin reactions |
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Which two medications were involved in the African American Heart Failure Trial?
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Isosorbide dinitrate and Hydralazine (fixed combo of 20mg Isos and 37.5mg Hydr)
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Why are African Americans more susceptible to heart failure with standard treatments?
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Blacks have less active renin-Ang system. Lower bioavailability of nitric oxide
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Describe the process of developing an erection.
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Cells in corpus cavernosum produce NO on sexual arousal. NO stimulates cGMP which relaxes smooth muscle of cavernosum and arteries leading to engorgement of cavernosum and erection.
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How does cGMP get metabolized?
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Phosphodiesterase 5 (PDE 5)
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How can we prolong erections?
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Blocking PDE 5 can lead to elevated levels of cGMP and erections.
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True/False: PDE 5 inhibitors cause erection by themselves.
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False
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Name three medications for erectile dysfunction.
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1. Sildenafil
2. Tadalafil 3. Vardenafil |
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What is a contraindications of using erectile dysfunction medications?
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They potentiate actions of nitrates and NO donors. Do not use within 24 hours of each other. May induce ischemia.
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How long before intercourse do you have to take Sildenafil?
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30 minutes prior
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What are the side effects of Sildenafil?
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1. Headache
2. Flushing 3. Dyspepsia 4. Priapism 5. Visual Disturbance (Color perception) 6. hearing loss (PDE6 in retina and inner ear) |
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How long before intercourse do you have to take Tadalafil?
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60 minutes prior
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True/False: There is a lower dose oral daily tablet of Tadalafil indicated for Erectile Dysfunction.
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True
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Mechanism of action of Tadalafil:
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PDE5 selective
Longer duration of interaction with nitrates >36 hours because has slower onset and 36 hour duration |
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What are the side effects of Tadalafil?
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1. Headache
2. Flushing 3. Dyspepsia 4. Priapism |
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What is the onset of action and duration for Vardenafil?
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45-60 minutes
Duration similar to Sildenafil |
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True/False: Vardenafil has both PDE5 and PDE6 activity.
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True
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Which side effects are we concerned about with PDE6 activity?
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Hearing and Retina
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What are the side effects of Vardenafil?
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1. Headache
2. Flushing 3. Dyspepsia 4. Priapism 5. Visual disturbances |
