Part 24: Beta-Blockers and Sympatholytics Flashcards
at a cellular level, cardiac contraction and the movement of blood between the chambers of the heart and eventually out into circulation is achieved by what is known as _____
excitation-contraction coupling
AP are generated by the ____ node and propogated by the _____ system in the heart
SA; electrical conduction
once an AP reaches the cardiac muscle cells in the atria and ventricles, the membrane depolarization causes ____ channels to open, which causes more depolarization and the openinf od ____ channels
Na; Ca
the influx of Ca interacts with receptors on the _____ to cause _____ to be released. This process is called _____
SR; stored Ca; calcium induced Ca release
the large concentration of Ca in the cytoplasm of the cardiac myoscytes interacts with _____ to cause cardiac muscle contraction
contractile fibers (myofilaments)
what happens when all of the heart cells contract together?
the whole heart contracts and pumps blood out of the chambers in a coordinated way
t/f the larger the amount of intracellular Ca, the larger the cardiac contraction
t
when the sympatholytic nervous system is activated, the release of _____ activates B1 adrenergic receptors in the heart
catecholamines (NE and Epi)
B1 receptors are G____ coupled and their activation leads to increased concentrations of ____ and ____
S; cAMP and PKA
what is the effect of Ca and contraction of heart cells when activated by B1?
increased intracellular Ca through the channels, resulting in a forceful cardiac contraction
sympathetic activation causes the SA node to fire AP _____(faster or slower)
faster
sympathetic activation makes the heart pump ____ and ___ (harder and faster or weaker and slower)? Does this increase of decrease cardiac output?
faster and harder ; increased cardiac output and increased BP
what are 3 ways to target the sympathetic activation of the heart?
- centrally target the sympathetic nervous system in the brain
- target the B adrenergic receptors
- target the Ca channels
what is the MOA of clonidine?
centrally acting antihypertensive agent that acts as an agonist at Alpha 2 adrenergic receptors in the brain to reduce sympthetic input to the heart
the alpha 2 receptor is primarily expressed on ____ neurons and acts as a ____ receptor
presynaptic ; auto
stimulation of the alpha 2 receptor by an endogenous NT like NE or Epi regulates the release of _____ and regulates the propogation of _____ between neurons and ultimately modulates the sympathetic effects in target tissues
additional NT; signals
clonidine stimulates Alpha 2 receptors in the ____ neurons, particulary in the _____, activating G___ coupled signalling cascade
central; medulla; i
when clonidine activates the Gi signalling cascade, it ____(raises/lowers) the amount of NE being released from the central neurons, which ____ (increases/decreases) sympathetic tone
lowers; decreases
what does a decrease in sympathetic tone do bronchodilation, vasoconstriction, and cardiac output?
less bronchiodilation, less vasoconstriction, reduced CO
clonidine acts in the ____, which is the part of the brain responsible for regulating cardiac function
medulla
t/f clondine may act on off target alpha 2 receptors (not in the medulla) and this can cause off target effects
t
what are the most commonly observed side effects of clonidine?
headache, hypotension, dizziness, fatigue, nausea and othe rcentral nervous effects
the actions of clonidine on the CNS may be beneficial for patients with ____
ADHD
how is it belived that clonidine may help with ADHD?
modulating NE release from adrenergic neurons may help to restore some balance between neuronal circuits in teh prefrontal cortex to help with attention
t/f clonidine may also be helpful in the management of pain and drug use disorder (opioids and nicotine)
t
why cant normotensive patients use clonidine for pain, ADHD and substance abuse disorders?
bc clonidine can cause hypotension even in pts with high BP, so its too dangerous for normotensive patiensts
t/f due to its ability to cause too much BP reduction, often resulting in hypotension, clonidine is often not used unless several other options have been tried and failed
t
what is the effect of clonidine on the vascular smooth muscle?
decreases peripheral resistance
what is the effect of clonidine on the heart?
decrease HR and contractility
beta blockers block the B1 receptors in the heart ____ (competively or non-competively)
competitively
most of the differences between different drugs of the beta blocker class are related to differences in ____
receptor selectivity
how do beta blockers lower BP?
prevent release of PKA which causes release of Ca which causes heart contraction, which increases BP
why is it important that beta blockers bind competively to the B1 receptor?
bc we still need sympathetic activation to work when its needed, like when we are exercising
why can epi still increase BP when a patient is on a beta blocker?
epi is also an agonist of the alpha 1 receptors that also cause vasoconstriction to increase BP
whn a pt is given Epi while on a beta blocker, ____ can increase, but ____ should not increase
BP; heart rate/contractility
blocking alpha 1 receptors in the _____ and B1 receptors in the ____ has an additive antihypertensive effect
BV; heart
give an example of a mixed A1/B1/B2 drug used for hypertensive (greatest affinity for a1 and b1)
carvediol
patients with what conditions should not take carediol?
asthma and COPD bc it may block B2 and reduce the bronchodilation needed in the lungs; as well those with orthostatic hypotension shouldnt take it due to the blocking of a1
of the a1, b1, b2 receptors, what is the order from greatest to least affinity of carvediol?
b1>a1>b2
carvediol binds ____ (reversibly/irreversibly) to the adrenergic receptors
reversibly
what is teh prototypic beta blocker?
propranolol
why is propranolol not commoly used anymore?
its not selective, so it can affect the B2 in the lungs and we dont like that
____ is an example of a cardioselectibe B blocker
metoprolol
t/f the selectivity of metoprolol is dose-dependent; if the dose is high enough, it can start to target the B2 receptors
t
the affinity of metoprolol for B1 is estimated to be _____X greater than for the B2 receptor
2-6
why is the term “cardioselective” beta blocker misleading?
there are B1 receptors in areas of the body other than the heart and these drugs can target these peripheral receptors as well
B1 receptors are also found in the kidneys, where their activation leads to the secretion of ____
renin
what is the effect of beta blockers blockign the B1 receptors in the kidneys?
reduced renin, reduced aldosterone so decreased blood volume and less vasoconstriction = more bp lowering
_____ is an example of a Ca channel blocker that acts in BOTH the vascular smooth muscle and cardiac cells
diltiazem
what is the effect of diltiazem blocking the Ca channels in teh SA node of the heart?
decrease in AP genration and lowers heart rate
what is the effect of diltiazem blocking the Ca channels in the atrial and ventricular myocytes
reduced force of contraction
t/f diltizem prevents the compensatory increase in heart rate
t
t/f non-DHP Ca blockers like diltiazem are typically not the 1st line for hypertension but may be used if other treatments have failed
t
