Cardiovascular Pharm-1 Flashcards
Excitability
The ability for a cell to respond to an external electrical stimulus (usually in the form of an action potential)
Automaticity
The ability for a cell or region of cells to initiate an action potential (SA nodes etc, pacemaker shit same as excite )
Conductivity
ability to receive n transmit AP (all cardiac tissue can conduct AP but some more specialized, mean SA node go thru inter atrial conductive path to av node to his n spreading out in right n left branches, other areas cardiac muscle can also conduct but usually conductivity here less, if scar, ishemia, some areas muscle can become more conductive rep phys or functional conduct pathway not previous present can lead to arrythmia generation and propogation)
Dromotropism
The ability to alter the rate of electrical conduction (most drugs we use have neg dromo, dec conduction velocity through AV node)
Refractoriness
The inability of a cell to receive and transmit an action potential
Drugs that block K+ channel
prolong phase 3 AP longer duration, k+ cant leave cell to repolarize it
What happens when drugs block second conformation of the NA+ channel (activated state activation gate and inactivation gate open)
Slow down upslope, DECREASE v max of pahse 0 -due to fast na channel
What happens when drugs block third conformation (inactivated closed) of the NA+ channel (inactivation gate closed activation gate open) (late slow inactivated currents)
shorten the AP. Important in CVD and ichemia b/c in these conditions AP is prolonged (bad)
Conditions that cause increased late NA+ chennel activity (and thus inceased intra cell CA and early depol arrythmias etc)
Ishcemic heart disease
Heart faiure (diastolic)
Aryythmias (atrial fib and ventricuklar)
PAD
neuromuscuklar: seisures and neuropathic pain,myotonnia muscle paralysisq
consequence of increased later na+ channels
increased intacell NA
Na+ exit with Ca2+ entry (NCX\
increased intracell CA+
cellular Ca+ overload
cellular Ca overload consequences
Electrical instability
After-depolarizations
Arrhythmias
Mechanical dysfunction
Abnormal contraction & relaxation
(e.g., diastolic tension)
- Differences between cardiac conduction tissues (nodal) and cardiac muscle:
Phase 0 of AP in nodal tissues is controlled by Ca2+ entry - Phase 0 of AP in non- nodal cardiac tissue is controlled by Na+ entry This difference is of importance in pharmacological handing of arrhythmias originating from these different tissues.
Drugs that affect CA affect what most?
Nodal tissue manifests in decrease HR
Drugs that block NA channels
target arrthymias that involve ventricular muscle
ERP/APD ratio
ERP (normally 0-3 phase 0 repsonse to stimulus)
smaller the ratio greater chance for depol and arryhtmia, cuz ERP is less so can depol more often
many drugs increase ERP/APD ratio makes tissue less repsonsive to abnormal imoulses
RRP
after pase 3 can repsond to sufficient stimulus
Disorders of Impulse Formation
no change in original pacemaker site (ex all originate from same location like SA NODE)
change in original pacemaker site (ectopic foci) (Af, AF, …)
early and delayed after-depolarizations
*Most common site of generation is SA node
Disorders impulse conduction
AV Nodal Block
Ventricular Re-entry
AV Nodal Re-entry (PSVT, PAT, WPW)
No change in original pacemaker site
ex sinus tachacardia, originate in SA node, all P waves followed by QRS
Change in original pacemaker site
ex ectopic foci, ex premature beats, atrial tachycardia,
atrial fibrillation, etc., not all P waves followed by QRS in atrial tach since depol occurs during qrs repol still refract
EAD
The key abnormality if the marked prolongation of the cardiac AP, such as occurs as a result of slow heart rate, hypokalemia or drugs that prolong APD.
When this occurs, phase 3 repolarization may be interrupted by an early
afterdepolarization.
Triggered activities
abnormal upstrokes only occur after an initial normal, or “triggering” upstroke, and so are termed triggered rhythms. includes EAD and DAD
where are EAD most common?
EADs are induced more readily in Purkinje cells than in epicardial or endocardial cells. can pccur from MI pr ischemia
torsades de pointes (TdP) relationship to EAD
EADs triggering functional reentry across the ventricular wall (transmural re-entry) causes torsades de pointes (TdP), a common polymorphic ventricular tachycardia seen commonly as a result of long QT interval (congenital or acquired). associated with hypokalemia. type of vent tach
Which conditions can result in DAD?
myocardial ischemia, adrenergic stress, digitalis intoxication,heart failure
DAD
Under conditions of intracellular or sarcoplasmic
reticulum Ca2+ overload,
a normal action potential may be
followed by a delayed afterdepolarization (DAD). If
this DAD reaches threshold, a secondary triggered
beat or beats may occur.
DAD-mediated triggered beats are more frequent
when the underlying heart rate is rapid.
primary AV block
increased P-R interval more than 200ms or .2 s but symetric all p waves equally prolonged, #p waves= #qrs
secondary av block
progressively longer P-R interval until finally P wave not followed by QRS
tertiary AV block
AV dissociation, atria and vent beat according to own rhytmm. have impulses from atria that dont pass through AV node, more P waves than QRS, enlarged QRS slow so think originating from ventricled
reentry
reentry represents one of the most common mechanisms of tachycardias. The condition for this mechanism is the existence of conduction routes with different conduction velocity. This difference may be functional or organic.
MOA re entry
A premature atrial impulse finds the fast pathway refractory, allowing conduction only down the slow pathway (left). By the time the impulse reaches the His bundle, the fast pathway may have recovered, allowing retrograde conduction back up to the atria—the resultant “circus movement” gives rise to slow-fast atrioventricular nodal re-entrant tachycardia (right).
consequences of arrythmias
Compromise of Mechanical Performance
dec efficiency = dec SV = decCO
Proarrhythmic/Arrhythmogenic
e.g. conversion of v. tachycardia to v. fibrillation
Thrombogenesis
atrial flutter and fibrillation contribute to increased stroke incidence
atrial flutter (ex reentry)
t
