Exam 2 - CV Flashcards
(94 cards)
Define dromotropism
- Ability to alter rate of electrical conduction. In heart, this is accomplished at the AV node.
Draw and describe AP of a cardiac myocyte
- Phase 0 (depolarization): fast opening of Na channels – Na influx = depolarization of membrane
- Phase 1 (early repolarization): Na channels close – some K channels open = K efflux = slight repolarization and beginning plateau phase
- Phase 2 (plateau): slow opening of Ca channels (L-type, long-lasting) with K channels open = Ca influx countered by K efflux.
- Phase 3 (rapid repolarization): Ca channels close, K channels open more = K rapidly effluxes causing return towards RMP
- Phase 4 (RMP): K channels open = inward/outward K flow are equal
see picture
Draw and describe the AP of a nodal cell of the cardiac conducting system
- Phase 4: slow influx of Na through funny Na channel = slow depolarization towards threshold. Note: T-type Ca channel opens briefly = Ca influx briefy providing final depolarization boost to the pacemaker potential.
- Phase 0: threshold met = slow Ca channels (L-type) open = Ca influx
- Phase 3: Ca channels inactivated – K channels open = K efflux = repolarization. These gradually close as phase 4 (slow depolarization) is approached.
* note: no phase 1 and 2
see picture
Describe the states of the cardiac Na channel
- Resting: activation gate close and inactivation gate open.
- Depolarization occurs and 2. Rapid opening of activation gate occurs = Na influx.
- Inactivation gates close and Na channels enter inactivated / closed state.
- With repolarization, the activation gate closes and inactivation gate opens.
What is the role of late Na current in cardiac function? Describe physiology. Clinical relevance.
- Na current peaks at onset of AP and importantly continues throughout systole with what is called a late component (I(sub)Na), partly responsible for maintaining the plateau of the AP in the myocytes (see AP in cardiac myocytes).
- This channel may be responsible for some pathologies in cardiac system and other NM disorders.
a. When enhanced: there is increased intracellular Na causing activation of Na/Ca exchanger = Na exit with Ca entry = intracellular Ca = overload of Ca = electrical instability, after depolarizations, arrhythmias, mechanical dysfunction (abnormal contraction/relaxation). Also seen in NM disorders (seizures, neuropathic pain, myotonia, paralysis) - If you can block these channels, you can prevent the pathologies from occurring.
Describe the difference(s) between nodal tissue depolarization and myocyte depolarization. Why do we care?
- Phase 0 in nodal cells is d/t Ca influx
- Phase 0 in myocytes is d/t Na influx
- Depending on where arrhythmias arise from, pharmacologic tx changes.
What is ERP/APD ratio? Why do I care?
- ERP: effective refractory period = duration of AP during which cell is not responsive to additional stimulus
- APD: AP duration = entire duration of AP
- Lower ratio = easier for tissue to be depolarized by abnormal impulses. Antiarrhythmic agent should prolong refractoriness relative to effect on AP duration, ie. increase ratio.
Which muscarinic receptors are found in the heart and what is the effect of activating them?
- M2 receptors
1. SA node: decrease HR (-ve chronotropy)
2. AV node: decrease conduction velocity
3. Atrial muscle: decrease atrial contraction
4. Ventricular muscle: decrease ventricular contraction (weak effect)
Beta 1 receptor. Location and response when activated?
- SA node: increase HR (chronotropy)
- AV node: increase conduction velocity (dromotropy)
- A and V muscle: increase FOC, conduction, CO and o2 consumption
- His: increase automaticity and conduction velocity
- Kidney: increase renin release
Beta 2 receptor. Location and response when activated?
- Blood vessels (all): vasodilation
- Uterus: relaxation
- Ciliary muscle: relaxation, flattening of lens
- Bronchioles: dilation
- SkM: increase glycogenolysis, increase contractility
- Liver: increase glycogenolysis
- Pancreas: increase insulin secretion
Alpha 1 receptor. Location and response when activated?
- Radial (dilator) muscle of eye: contraction (mydriasis)
- Arterioles (skin and viscera): contraction
- Veins: contraction (increase venous return and pre-load)
- Bladder trigone/sphincter: contraction
- Vas deferens: ejaculation
- Liver: increase glycogenolysis
- Kidney: decrease renin
Receptors responsible for the main source of arteriole resistance?
- alpha-1. Increases TPR, DBP and afterload
Alpha 2 receptor. Location and response when activated?
- Prejunctional nerve terminal: decrease NT release and NE synthesis
- Platelets: aggregation
- Pancreas: decrease insulin secretion
Mechanisms of arrhythmias
- Disorders of impulse formation
a. No change in original pace-maker: eg. sinus tach
b. Change in original pace-maker site: ectopic foci, a tach and a fib
c. Triggered activities: refers to abnml upstrokes after initial normal or “triggering” upstrokes
i. EADs (early after-depolarizations): marked prolongation of the cardiac AP (d/t slow heart rate, hypokalemia, drugs) leads to early after-depolarization, which can lead to an abnormal rhythm (eg. TdP)
ii. DADs (delayed after-depolarizations): conditions of SR Ca2+ overload (MI, adrenergic stress, digitalis intoxication, heart failure) may cause a nml AP to be followed by DAD. If it reaches threshold, a secondary triggered beat(s) may occur. - Disorders of impulse conduction
a. AV-nodal blocks
b. Re-entry: existence of conduction routes with different conduction velocity (functional d/t MI, drugs, electrolytes OR organic d/t congenital abnormality or scarring)
i. AV nodal re-entrant tachycardia (AVNRT): requires two conduction pathways present in the heart – one slow and one fast. Slow pathway has short refractory period. Fast refractory period with long refractory period. If an atrial premature beat originates and takes the slow pathway and loops back around into the fast pathway (ie. when not in refractory period), then a fast loop circuit is created.
ii. Examples of re-entry arrhythmias = aflutter (every x atrial beats, one goes down to v), AVNRT, accessory-pathway mediated SVT and ventricular re-entry.
Types of arrhythmias
- Supraventricular: sinus tach, sinus brady, aflutter, afib, PAT/PSVT, AV nodal tach
- Ventricular: v tach, v fib
What is an AVNRT?
- Disorder of impulse conduction in heart. Stands for AV nodal re-entrant tachycardia.
- Requires two conduction pathways present in the heart – one slow and one fast. Slow pathway has short refractory period. Fast refractory period with long refractory period. If an atrial premature beat originates and takes the slow pathway and loops back around into the fast pathway (ie. when not in refractory period), then a fast loop circuit is created.
Compare and contrast EAD vs DAD.
- These refer to mechanisms for arrhythmia generation
i. EADs (early after-depolarizations): marked prolongation of the cardiac AP (d/t slow heart rate, hypokalemia, drugs) leads to early after-depolarization, which can lead to an abnormal rhythm (eg. TdP)
ii. DADs (delayed after-depolarizations): conditions of SR Ca2+ overload (MI, adrenergic stress, digitalis intoxication, heart failure) may cause a nml AP to be followed by DAD. If it reaches threshold, a secondary triggered beat(s) may occur.
Consequences of arrhythmias
- Compromise mechanical performance: affect SV, decrease CO
- Pro-arrhythmic/arrhythmogenic: vtach converts to vfib
- Thrombogenesis: thrombi form in heart, follow flow to cause vessel occlusion in periphery. Aflutter and fib are commonly associated with thrombi
4 mechanisms to decrease spontaneous activity in the heart
- Decrease the phase 4 slope
- Increase threshold for AP
- Increase maximum diastolic potential: membrane potential is decreased further away from resting
- Increase AP duration
Mechanisms by which drug can increase refractoriness of AP
- Na channel blockers.
- Action-potential prolonging drugs: eg. K channel blocker
Classes of antiarrhythmic drugs. General mechanism for class (and subclass if any), drug names and indication.
- Class I:
- MOA: block fast inward Na channels in conductive tissues of heart, therefore decrease max depolarization rate, reduce automaticity, delays conduction, increases ERP/APD.
- Indication: Digitalis or MI-induced arrhythmias
a. 1a: quinidine, procainamide, disopyramide
- MOA: moderate binding to Na channels (moderate phase 0 depo effect), K channel blockage (delayed phase 3 repo, prolonged QRS and QT), Ca channel blocked at high doses (depresses phase 2 and nodal phase 0)
b. 1b: lidocaine, mexiletine
- MOA: weak binding to Na channels (weak phase 0 depo effect), blocks late Na channel (accelerated phase 3 repolarization = shortened APD and QT)
c. 1c: propafenone, flecainide
- MOA: strongest binding to Na channels (strong effect on phase 0 depo, lengthens QRS and APD, QT unchanged, lengthened PR d/t depressed AV node conduction)
- Class II: beta-adrenergic antagonists
- MOA: decrease SA node automaticity (phase 4), AV node conduction, ventricular contractility
- Indication: SVT and PSVT, only drug to prevent sudden cardiac death in patients with prior MI - Class III: dronedarone, amiodarone, sotalol, ibutilide, dofetilide
- MOA: effects on all cardiac target receptors except for adenosine. Main effect = prolong phase 3 repolarization (increase QT)
- Indication: useful for ventricular re-entry/fib arrhythmia - Class IV (aka non-DHP CCBs): verapamil, diltiazem
- MOA: cardiac Ca channel antagonists, similar to class II with primary effects on nodal phase 0 depo. It depresses SA node automaticity, AV node conduction and ventricular contractility
Quinidine. Class, MOA, indications, adverse effects
- Class Ia antiarrhythmic
- MOA: block rapid inward Na channel, so decreases vmax of phase 0, slows conduction, effects greatest with fast HR. Dose-dependent actions: blocks K (increase APD), blocks alpha (decrease BP), blocks M (increase HR in intact subjects)
- Indications: patients that are refractory to: convert symptomatic afib or flutter, prevent recurrences of afib or flutter, treat life-threatening documental ventricular arrhythmias
- Adverse effects: DIARRHEA, nausea, vomiting, CINCHONISM (tinnitus, hearing loss, blurred vision), HOTN, PROARRHYTHMIC (TDP: K blocked prolongs AP = increased probability for EADs)
Procainamide. Class, MOA, indications, adverse effects, other notes
- Class Ia antiarrhythmic
- MOA: blocks rapid inward Na channel, so slows conduction, automaticity, excitability. Blocks K channels to increase APD and refractoriness.
- Indications: acute tx of re-entrant SVT, afib, aflutter associated with WPW (pre-excitation syndrome) and treat documented life-threatening ventricular arrhythmias (IV loading takes 20 mins though)
- Adverse effects: arrhythmia aggravation; contraindicated in long QT syndrome, history of TDP and hypokalemia); heart block and sinus node dysfunction. Can cause SLE-like syndrome (arthralgia, fever, weakness, pericarditis, skin lesions, anemia, etc.), GI nausea and vomiting very common, decreased kidney functions
- Other: little vagolytic activity compared to quinidine.
Lidocaine. Class, MOA, indications, adverse effects, other notes
- Class 1b antiarrhythmic
- MOA: blocks open and inactivated Na channels, reducing Vmax – this leads to shortened cardiac AP (effect in ischemic tissue). Lowers slope of phase 4 altering threshold for excitability. If abnormal conduction system exists, effect variable (slow ventricular rate, potentiates infranodal block)
- Indications: Second choice behind amiodarone for life-threatening or symptomatic arrhythmias
- Adverse effects: tinnitus, seizure with rapid bolus. High dose = CNS effects. Be careful in use in HF patient where decreased clearance and high concentrations can build up.
- Other: has extensive first-pass metabolism (requires IV use), need multiple loading doses and Md infusion