PPT 12: angina Flashcards
What are the two functions of the venous system?
- Conduct blood back to the heart
- Reservoir for blood volume (contain 70% of total blood volume, 20-30% in splanchnic bed)
What is the benefit of the venous system having larger volume of blood compared to arterial?
Maintains filling of heart despite significant variation in blood volume
What are effects from increased venous tone (venous constriction)
increases all the following:
venous return to right ventricle → EDV (end diastolic volume) → stretch of cardiac myocytes → force of contraction (Starling’s law) → stroke volume → cardiac output → blood pressure
what are the effects of decreased venous tone (venodilation)
increased capacitance
decreased all the following:
venous return to right ventricle → EDV (end diastolic volume) → stretch of cardiac myocyte → force of contraction (starling’s law) → stroke volume → cardiac output → BP
What is angina caused by
accumulation of metabolites due to myocardia ischemia
What drug is given for immediate relief of angina?
nitroglycerin
What drugs are good for angina prophylaxis?
calcium channel blockers and beta blockers
Which type of angina is classic angina
“angina of effort”
O2 requirement increases with activity, but coronary blood flow not enough, leads to O2 debt and ischemia with toxic metabolites
what type of angina is also known as Prinzmetal angina or vasospastic?
Variant angina
O2 delivery decreased due to coronary vasospasm
What type of angina is also known as “angina at rest”?
Unstable angina
microvascular disease s/t small patelet clots and atherosclerotic plaque
Which type of angina is an emergency?
unstable angina
Which type of angina is most rare?
variant
What is treatment of classic angina?
reduction of demand through beta blockers, calcium channel blockers
what is treatment of variant angina?
primarily calcium channel blockers to prevent , vasodilators/nitrates
Coronary blood flow is _______ related to perfusion pressure, _______ related to duration of diastole, and ________ related to coronary vascular bed resistance
directly, directly, indirectly
Which blood vessels have the best response to nitrates and nitrites?
large veins
What is the mechanism of action of nitroglycerin?
NO release in vascular smooth muscle
What is the ADME of nitroglycerin
A: low bioavailability (10-20%), subligual or IV route
M: high 1st pass metabolism (nitrate reductase in liver)
E: kidneys
How does NO lead to vasodilation?
NO activates guanylyl cyclase, which converts GTP to cGMP. cGMP dephosphorylates Myosin-LC leading to relaxation
What Nitrate/Nitrite was used, and abused, by inhaling to reduce BP (and short high)
Amyl Nitrite (“poppers”)
What are the good effects from Nitrates and Nitrites?
Increased venous capacitance
decreased ventricular preload
decreased heart size
decreased cardiac output
What are the bad effects of nitrates and nitrites?
Headache (most common), orthostatic hypotension, syncope, reflex tachycardia, hemoglobin interactions (methehemoglobin = low affinity for oxygen)
What are the 3 types of vascular tone?
- Arteriolar tone
- Arteries, arterioles
- Precapillary sphincters
- Capillary tone
- Venous tone
Describe how Ca++ contributes to blood vessel contraction
- Ca++ binds to calmodulin (protein) → activates MLCK → MLC-P interacts with actin to contract
- cAMP inhibits MLCK
What are the different drugs that induce relaxation of vascular tone?
Ca++ channel blockers (prevent contraction)
K+ channel blockers (prevent depolarization)
B2 agonists (increase cAMP)
Nitrates (increase cGMP)
How do Ca++ channel blockers treat angina?
- L-type channel most dominant in cardiac and smooth muscle
- Drug binds to depolarized membranes
- Decreased opening frequency with drug binding
- relaxation and reduced BP in smooth muscle
- Heart: ↓ contractility, ↓ SA node pacemaker rate, ↓ AV node conduction velocity
How are Beta Blockers used for angina treatment?
Not vasodilators - decrease oxygen demand
↓ HR
↓ BP
↓ Contractility
- more B2 receptors in micro-arteries → dilation
How do pFOX inhibitors treat angina?
- Decreased oxygen requirement in cardiac metabolism
- ↓ FOX, ↑ glucose utilization (more efficient)
What are the contraindicated vasodilators for angina? Why are they contraindicated?
- Hydralazine, Minoxidil - May increase angina (increased SNS output)
- Sodium Nitroprusside - Hypertensive emergencies; High toxicity – better agents for angina (May be useful for vasospastic angina)
- Fenoldepam - Reflex tachycardia
What risk factors contribute to angina symptoms?
- Smoking
- Hypertension
- Hyperlipidemia
What are the non-pharmaceutical interventions for angina?
- Surgical revascularization (CABG)
- Cardiac catheter
- Stent
