Cardia Contractility Pathway

SA node
-Pacemaker / Action potential initiator
-Propagate action potential to left atrium
SA Node to (fast) AV node to (slow) AV bundle to purkinje fibers to ventricular walls
(base to apex)
Cardiac action potential (Non pacemaker cells)
-Ex: Purkinje fibers
5 phases 0 to 4 (0,1,2,3,4)
ECG:
R and S waves = P0 and P1
P2 = plateau
ST segment = S to onset of T wave
P3 = fast repolarization
SA/Pacemaker
-3 Phases
-P4 some but not all K+ channels close allowing few of Na + to open
P atrial depolarization / atrial contraction
QRS Complex Ventricular depolarization
T wave ventricular repolarization / ventricular relaxation
PR Interval
-from P to onset of QRS complex
-0.12 to 0.20 seconds
-measures travel of impulses from SA to purkinje fibers
PR Segment
-portion of PR interval
-endpoint of P wave to onset of QRS complex
-isoelectricity
-equal atrial systole and ventricular diastole
QRS Complex
-contraction of ventricle
QT interval
-ventricular depolarization + repolarization
ST segment
-endpoint of S wave up to onset of T wave
-isolelectricity
-atrial diastole + ventricular systole
~~~All anti-arrhythmic drugs can be pro-arrhythmic
~~~Digoxin causes tachyarrythmia (tachycardia resting heart rate over 100
beats)
A review:
-P4 of Non-pacemaker cells is straight resting membrane potential
-P4 of PC is slow depolarization (slow upwards)
Arrhythmia
-SA node problem
-Parasympathetic
-Bradycardia = form of arrhythmia
-Result into:
-too fast (tachycardia)
- too slow (bradycardia)
-Formation of impulse = pacemaker (SA node)
-Normal SA node firing dominate NPC

- arrhythmia may result from ectopic pacemaker / NPC (when there is

cardiopathology)
-inactive, latent activity of NPC
Triggered Automaticity
-EAD or early afterdepolarization
-late P2 or early P3; interruption in cardiac action potential
Anterograde impulse transfer of SA node to ventricles (normal)
-re-entry may be a problem
Re-entry abnormal conduction wherein excitatory impulse is circulated in the
unexcitable regions of the heart
-results into tachycardia
Purkinje fibers termination of impulses by collision
-apex to walls of heart
Retrograde impulse ventricle to atria
-Unidirectional impulses
-Extrasystoles
Ventricular fibrillation severe, may lead to cardiac arrest
Class I (Na+)

Class II ()
Class III (K+)
Class IIII (Ca+2)

IA DQP
IB TMLP
IC MFPE
All blockers except Sotalol
Sotalol + Class 3

~~~Nondihydropyridines Verapamil
-To some extent Diltiazem also
-Blood vessels are unrelated
Antiarrhythmic drugs 4 classes
Class 1 (Fast sodium channel blockers)
-Block fast gated
-Depress P4, or P4 automaticity
-Depress P0 (depolarization)
-P0 afected
1a
-moderate P0 depression
-Prolong repolarization (non-selective Na + channel blocking)
-Longer time to complete P0
-Prolong P0 and P3 = prolong action potential duration
Quinidine
Toxicity
-Polymorphic QRS complex (Torsades de pointes arrhythmia)
-Tinnitus, headache, dizziness (Cinchonism)
-Immunologic = Hypersensitivity reaction (Allergen)
-Idiosyncratic = genetically determined reaction

Procainamide
-secondary or tertiary choice for ventricular tachycardia/ fibrillation
Toxicity

Syncope ganglionic blocking effect

-vasodilating effect
-orthosatic hypotension
Hydralazine; Procainamide Lupus erythematosus
Disopyramide
-Anticholinergic effect higher than Quinidine and Procainamide
-Atropine like effects
1
Lidocaine
-IV only or will become subtherapeutic due to first pass effect
Class 2
-Prototype: Propranolol
-Esmolol t1/2 of 10 minutes
Class 3
-Prolong / delay repolarization
Delay K+ efflux
Amiodarone
-Toxicity
Hypothyroidism
Hyperthyroidism

Wolff-Chaikoff Effect

Negative Feedback Mechanism

-Inhibit TSH by hypothalamus
Betrylium
-same MOA as Guanethedine and Gunanabenz
Promethazine antihistamine
A review:
-Ca+2 channel blockers
-Non-dihydropyridines only
-Cardioselective drugs
-Verapamil
-Some extent, Diltiazem
-Intermediate effect on heart and blood vessels
Class 4
-Non-dihydropyridines
-Verapamil
-Most common adverse: constipation

Class 5
Digoxin / Digitalis Glycosides
-Vagal stimulation
-Increase sensitivity of Ach to muscarinic receptors especially in atria
- Lower heart rate higher refractoriness; the reason why Digoxin is for atrial
fibrillation
Toxicity: Ectopic pacemaker
-Higher beats in ventricles

-Ventricular tachyarrhythmia
Miscellaneous:
Sites:
1. Vascular smooth muscles / Blood vessels
2. SA / AV nodes
Vascular Smooth Muscles
-A2 (Adenosine 2 receptors)
-Gs coupled
-Adenylyl cyclase
-CAMP
-K+ opening hyperpolarization
-Vasodilation / Relaxation of blood vessels
Adenosine in SA / AV nodes
-A1 receptors
-Gi coupled
-Lower Adenylyl cyclase
-Lower CAMP negative chronotropy/dromotropy
MLC kinase -------- Adenosine
Actin
MLC -------- MLC-PO4 -------- contraction
(relaxed)
cGMP dephosphorylation
kinase transfers phosphate group/s
automaticity spontaneous depolarization
Methylxanthines + Adenosine = Subtherapeutic effect
Dipyridamole + Adenosine
~~~Mg+2 follows K+1
~~~Lower K+1 equals lower Mg+2