Vasodilators and Angina (Exam III) Flashcards
Between arteries and veins, which has the greater amount of muscular tone?
Arteries
What are the 3 structures that create Arteriolar Tone?
- Arteries
- Arterioles
- Precapillary Sphincters
What is the primary purpose of precapillary sphincters? Give an example.
Shunting of Blood
ex. SNS activation causing blood to be shunted from GI tract to skeletal muscle.
Contraction of what helps the facilitation of venous blood back to the heart?
Skeletal Muscle
What are the two functions of the venous system?
- Return blood back to the heart
- Reservoir for blood volume
How much of total blood volume is contained in the venous system?
How about the splanchnic bed specifically?
Venous system = 70% blood volume
Splanchnic Bed = 20-30% blood volume
What is the compliance of veins compared to arteries?
Veins have 30x greater compliance (i.e. ability to stretch)
How does the venous system protect cardiac output from dropping?
The Venous system serves as a reservoir to counteract changes in blood volume (Preload)
Describe the process of a blood vessel contraction starting with Ca⁺⁺ entering the cell.
- Ca2+ enters the cell.
- The SR releases Ca2+
- Ca2+-Calmodulin complex forms
- Ca2+-Calmodulin potentiates MLCK
What important secondary messenger is inhibitory to smooth muscle contraction?
cAMP
What is the reason for pain in angina pectoris?
What drug provides immediate relief for this?
Accumulation of metabolites (lactic acid) due anaerobic metabolism in myocardial ischemia.
Nitroglycerin
What drugs are prophylactic for angina pectoris?
β-blockers and CCB’s
Describe classic angina.
What usually brings about this form of angina?
“Exertional Angina” which is characterized by ischemia from ↑ oxygen requirement (usually exercise)
What is Variant Angina?
What other names exist for this condition?
What causes this angina? How prevalent is it?
- Myocardial Ischemia secondary to ↓O₂ delivery from coronary vasospasm.
- Vasospastic or Prinzmetal angina.
- Idiopathic and transient. (only 2% of angina cases)
What form of angina is a medical emergency?
When is this angina felt?
Unstable Angina
Pain is felt at rest.
What pharmacologic therapy is best for variant angina?
CCBs
Which two factors most greatly influence the oxygen requirements of the heart?
- Heart Rate
- Contractility
Where do we see an initial best response from nitrates and nitrites?
Where would we see a response with increased dosages?
Where would we see an effects, but less than the two aforementioned responses?
Large Veins
Large Arteries
Arterioles and precapillary sphincters
What is the mechanism of action of nitroglycerin?
What is the bioavailability of nitroglycerin?
How is nitroglycerin metabolized?
Where is nitroglycerin excreted?
- Nitric Oxide (NO) release in vascular smooth muscle.
- 15-20% bioavailability (sublingual or IV route needed)
- Nitrate Reductase in the liver
- Kidneys
What is the mechanism of action of Nitric Oxide in causing smooth muscle relaxation?
- NO released from endothelial cells
- ↑ Guanylyl cyclase (GC)
- GTP → cGMP (by GC)
- cGMP → Myosin-LC
- Relaxation
Name a PDE-5 (Phosphodiesterase-5) Inhibitor.
How do PDE-5 Inhibitors work?
Sildenafil
PDE-5 Inhibitors block Phosphodiesterase-5 from converting cGMP to GMP.
cGMP potentiates relaxation.
What is the T1/2 of nitroglycerin?
How does this compare to dinitroglycerin?
Trinitroglycerin T1/2: 2-8 mins
Dinitroglycerin T1/2: 3 hours
Are there any mononitro forms of nitroglycerin available? What are there benefits?
Isosorbide dinitrate
100% bioavailability
What are the “good” actions of nitroglycerin?
↑ venous capacitance
↓ preload, CO, overall heart size
What is the biggest side effect of nitroglycerin?
What dangerous side effects need to be monitored for with nitroglycerin use?
- Headaches
- Reflex Tachycardia
- Methemoglobinemia - Nitrate-Hgb binding (preventing O₂ binding)
Describe the relevance of someone working in a nitrate factory.
Continuous nitrate exposure can cause tolerance to nitrates. 8-hour off periods are needed.
What hematological toxicity of nitrates can occur with patients?
Why is this dangerous?
Conversely, when can this be an antidote for a certain condition?
methemoglobinemia
Hgb molecules on RBCs develop low affinity for O₂ and can develop pseudocyanosis at very high levels.
Antidote for cyanide poisoning due to affinity for cyanide.
Which drug is the prototypical dihydropyridine calcium channel blocker?
Which two other CCB’s should be known?
- Nicardipine
- Verapamil and Diltiazem
What specific type of Ca⁺⁺ channel do CCB’s most commonly bind to when eliciting their effects?
L-type Ca⁺⁺ channels causing decreased opening frequency.
Which two CCB’s can be used for cardiac effects?
Which one is completely cardio-specific?
Diltiazem (smooth muscle & cardiac) and Verapamil (cardio-specific)
What 3 major effects would Ca⁺⁺ channel blockade have on the heart?
- ↓ Contractility
- ↓ SA node rate
- ↓ AV node conduction
What major uses do CCB’s have?
Treating HTN and angina.
How do β-blockers treat angina?
↓ CO = ↓ cardiac demand
Name β-blockers in order of best-to-worst for treatment of angina.
- 3rd gen Vasodilatory (Nebivolol)
- 2nd gen β1selective (Metoprolol)
- 1st gen non-selective (Propanolol)
How do pFOX inhibitors work?
↓ FOX (Fatty Acid) metabolism, ↑ glucose metabolism
Fatty acid metabolism requires ↑O₂ vs glucose.
Which vasodilators are contraindicated for angina and why?
- Hydralazine & Minoxidil (reflex ↑HR)
- Nitroprusside (↑ toxicity)
- Fenoldepam (reflex ↑HR)
Modifying which 3 risk factors affects coronary artery disease (and thus angina) the most?
Smoking, HTN, and HLD.
What should be known about utilization of nitrates with or without β-blockers and CCB’s in the treatment of angina?
Nitrates work better when paired with BB’s or CCB’s.
What receptors are in the epicardial coronary arteries?
α-1 and β-1
What receptors are in the microarteries of the heart?
β2 primarily (a little bit of α-2)
Why would a β-1 selective drug be much better for heart failure?
β2 receptors dilate micro
