Therapeutics I: CARDIO V Combined

Non-pharmacological options for arrhythmias? (four)

1. Pacemakers

2. Cardioversion

3. Catheter ablation

4. Surgery

What is an ICD?

Implantable cardioverter-defibrillator (ICD); can detect and treat potentially fatal arrythmias

Advantages of ICD? (three)

1. Widely used for reducing mortality in coronary artery disease

2. In heart failure with low ejection fraction

3. Advances in technology, dangers of long-term therapy with available drugs

Cardiac arrythmias with defined autonomic pathways? (four)

1. Arterioventricular reentry using accessory pathway

2. Arterioventricular node reentry

3. Atrial flutter

4. Ventricular tachycardia

Role of the SA node

Pacemaker/ where electrical impulse for heart arises from

Role of the AV node

Slow down impulses so that the atria can contract to fill the adjacent ventricles with blood

Pathway of electrical impulse through the heart

SA node -> AV node -> Bundle of His -> Purkinje fibers

Role of Bundle of His

Transmits cardiac impulse from AV node to the ventricular muscle

Role of Purkinje fibers

Help ventricles contract

What are the ions that establish the transmembrane potential of cardiac cells?

Na+

K+

Ca2+

Cl-

Which ions that establish the transmembrane potential of cardiac cells cannot freely diffuse across the lipid bilayer? (three)

Na+

Ca2+

Cl-

T/F: The transportation of ions across the membrane requires ion channels for diffusion.

True

Ohm's law equation

V = I*R

Three voltage gated channels?

Sodium channel

Potassium channel

Calcium channel

Resting membrane potential of the cardiomyocyte

-70 mV

At what threshold potential does a cardiomyocyte become depolarized?

-40 mV

What happens when a cardiomyocyte becomes depolarized?

Sodium channels open, Na+ ions permeate, depolarizing the membrane potential further to +40 mV

At what membrane potential do calcium channels activate?

+40 mV

When calcium channels are activated, what is simultaneously occurring? What phase is this?

Phase 1; while calcium channels are activated, sodium channels begin inactivating

Describe Phase 0

Depolarization stage: rapid depolarization occurs when sodium (Na+) channels open, allowing Na+ to enter the cell, leading to a sharp increase in membrane potential (to about +40 mV).

Describe Phase 1

Initial repolarization stage: sodium channels begin to inactivate, and some potassium channels open, causing a brief decrease in membrane potential.

Describe Phase 2

Plateau phase: Calcium channels open, allowing calcium ions to enter the cells. This balances the outward movement of potassium, resulting in a plateau of action potential.

Describe Phase 3

Repolarization phase: Potassium channels remain open, but the influx of calcium decreases. The membrane potential starts to repolarize as potassium ions exit the cell, moving back towards the resting potential.

Describe Phase 4

Resting membrane potential: The cell returns to its resting membrane potential of about -70 mV, ready for the next action potential.

What are the four main types of arrythmia?

1. Premature (extra) beats

2. Supraventricular

3. Ventricular arrythmias

4. Bradyarrythmias

Torsades is otherwise known as what?

Polymorphic ventricular tachycardia

Typical symptoms of long QT syndrome?

Dizziness

Transient loss of consciousness

What are the two forms of abnormal activity classified as a triggered automaticity

Early afterdepolarizations (EADs)

Delayed afterdepolarizations (DADs)

T/F: A triggered automaticity requires an abnormal action potential for its initiation.

False; requires a normal action potential

Factors that can precipitate or exacerbate arrythmias? (ten)

1. Ischemia

2. Hypoxia

3. Acidosis or alkalosis

4. Electrolyte imbalance

5. Excessive catecholamine exposure

6. Autonomic influences

7. Drug toxicity (digitalis)

8. Stretching

9. Scar, diseased tissue

10. Impulse formation or impulse conduction, or both

Procainamide belongs to what class of antiarrhythmics?

Class 1A

Procainamide MOA

Blocks sodium channels in myocardial cells, reducing autorhythmicity and slowing conduction.

Lidocaine belongs to what class of antiarrhythmics?

Class 1B

MOA of lidocaine

Blocks sodium channels, suppresses automaticity in the HIS Purkinje system and depolarization in the ventricles

Flecainide belongs to what class of antiarrythmics?

Class 1C

Flecainide MOA

Slows conduction in cardiac tissue by altering transport of ions across cell membranes; causes slight prolongation of refractory periods; decreases the rate of rise of the action potential without affecting its duration

Propranolol belongs to what class of antiarrhythmics?

Class II

MOA of propranolol

Beta antagonist, inhibits heart rate and hearts strength of contraction

Non-selective beta blocker

Propranolol is clinically applied where?

In atrial arrythmias, and prevention of recurrent infarction and sudden death

Flecainide is clinically applied where?

In supraventricular arrythmias in patients with normal heart

Contraindicated in ischemic conditions (post MI)

Amiodarone belongs to what class of antiarrhythmics?

Class 3

MOA of amiodarone?

Delay repolarization and increase the duration of the action potential

Dofetilide belongs to what class of antiarrhythmics?

Class 3

MOA of dofetilide?

Prolongs action potential, effective refractory period

Amiodarone is clinically applied where?

Serious ventricular arrhythmias and supraventricular arrhythmias

Dofetilide is clinically applied where?

Maintenance or restoration of sinus rhythm in Afib

Verapamil belongs to what class of antiarrhythmics?

Class 4

MOA of verapamil?

Calcium channel blocker

Slows SA node automaticity and AV node conduction velocity; decreases cardiac contractility, reduces blood pressure

Class 1 antiarrhythmics can be broadly described as what?

Sodium channel blockers

Describe Class 1A antiarrhythmics

Prolong the APD and dissociate from the channel with intermediate kinetics

Describe class 1B antiarrhythmics

Shorten the APD in some tissues of the heart and dissociate from the channel with rapid kinetics

Describe class 1C antiarrhythmics

Minimal effects on the APD and dissociate from the channel with slow kinetics

Describe class 2 antiarrhythmics

Action is sympatholytic; drugs with this action reduce -adrenergic activity in the heart

Describe class 3 antiarrhythmics

Action manifests as prolongation of the APD; most drugs with this action block the rapid component of the delayed rectifier potassium current, IKr.

Describe class 4 antiarrhythmics

Calcium channel blockers

This action slows conduction in regions where the action potential upstroke is calcium dependent, i.e. the SA and AV nodes

T/F: Drugs with local anesthetic action block sodium channels and reduce the sodium current.

True

T/F: Procainamide slows the upstroke of the action potential, slows conduction, prolongs the QRS duration of the ECG, and prolongs the APD.

True yea but read that a couple times

Quinidine belongs to what class of antiarrhythmics?

Class 1A

MOA of quinidine?

Blocks sodium channels

Slows impulse conduction

Delays repolarization

Blocks vagal input to the heart

Disopyramide belongs to what class of antiarrhythmics?

Class 1A

MOA of disopyramide

Sodium channel blocker; inhibits the fast sodium channels during depolarization phase. Prolongs APD, slows rate of depolarization.

Adverse effects associated with quinidine?

Cardiotoxic effects

Excessive QT-interval prolongation and induction of torsades de pointes.

Which of the following has cardiac antimuscarinic effects?

A. Quinidine

B. Propranolol

C. Verapamil

D. Disopyramide

D. Disopyramide

Mexiletine belongs to what class of antiarrhythmics?

Class 1B

T/F: The electrophysiologic and antiarrhythmic actions of mexiletine are similar to those of lidocaine.

True

Mexiletine is applied clinically where?

Ventricular arrhythmias

T/F: Amiodarone has strong adrenergic and calcium-channel blocking actions.

False; amiodarone has weak adrenergic and calcium-channel blocking actions.

Does flecainide prolong the action potential and/or the QT interval?

A. Yes

B. No

B. No

Despite blocking certain potassium channels, it does not prolong the action potential or the QT interval.

Sotalol belongs to what class of antiarrhythmics?

Class 2 and Class 3

T/F: Verapamil selectively blocks activated L-type calcium channels.

False; Verapamil blocks both activated and inactivated L-type calcium channels.

T/F: Verapamil can suppress both early and delayed afterdepolarizations.

True

Dronedarone ___________ sinus rate and prolongs AV nodal conduction and refractoriness.

A. reduces

B. increases

A. Reduces

Describe a supraventricular arrhythmia

Originates from ABOVE the bundle of His

Types of supraventricular arrhythmias? (four)

1. Afib

2. Aflutter

3. Paroxysmal supraventricular tachycardia

4. Autonomic atrial tachycardia

Describe a ventricular arrhythmia

Originates from BELOW the bundle of His

Types of ventricular arrhythmias? (three)

1. Premature ventricular complexes

2. Ventricular tachycardia

3. Ventricular fibrillation

Define atrial fibrillation

A supraventricular arrhythmia with uncoordinated atrial activation and consequently ineffective atrial contraction

Afib is defined by what kind of heartrate? Bpm?

Chaotic, rapid (300-500 bpm); irregular atrial rhythm

Conditions which predispose a person to Afib?

Advanced age

Smoking

Physical activity

Alcohol

Obesity

Height

Blood pressure (HTN)

Resting heart rate

Diabetes

Cardiovascular conditions which predispose a person to Afib?

HF

CAD

VHD

Cardiac surgery

Acute cases which can precipitate Afib?

Thyrotoxicosis

Surgery

Alcohol withdrawal

Sepsis

Excessive physical exertion

T/F: Afib is a progressive disease.

True

Describe AF Stage 2

Evidence of structural or electrical findings further predisposing a patient to AF

(atrial enlargement, frequent atrial ectopy)

Describe AF Stage 3

Has diagnosed AF

Paroxysmal, persistent, long-standing persistent, or successful AF ablation

Describe AF Stage 4

Permanent AF

Testing used to diagnose AF?

12-lead ECG (gold standard)

Holter/event monitor (paroxysmal)

Afib graph looks like what?

Extra spiky

Aflutter graph looks like what?

More squiggly in the middle

What are the FDA-cleared Direct to Consumer monitor types? (four)

Apple Watch

Fitbit sense

Samsung Galaxy Watch 3

Withings ScanWatch

Clinical characteristics of AF?

Palpitations, exertional fatigue, lightheadedness, exercise intolerance, dyspnea

Syncope is possible but uncommon

What are the 4As of AF management?

Access to All Aspects of Care for All

What does SOS stand for in AF management?

Stroke risk

Optimize (modifiable risk factors)

Symptom management

What does HEAD 2 TOES stand for in AF management?

Heart failure, exercise, arterial hypertension, diabetes, tobacco, obesity, ethanol, sleep

These are the most common/pertinent risk factors for AF

Primary prevention recommendations (LRFM) for management of AF?

Patients at increased risk of AF should receive comprehensive guideline-directed LRFM for AF, targeting obesity, physical inactivity, unhealthy alcohol consumption, smoking, diabetes, and hypertension.

What is the recommended percentage weight loss for secondary prevention in AF management?

Target of 10%

What is the recommended weekly physical fitness guideline for secondary prevention in AF management?

210 minutes/wk

Which risk score assessment do we prefer for assessing AF risk?

CHADS-VASc

T/F: For stroke management in Afib, we prefer DOACs over warfarin.

True

DOACs include? (four)

Apixaban

Dabigatran

Edoxaban

Rivaroxaban

T/F: ASA alone or with clopidogrel is an acceptable alternative to DOAC or warfarin in stroke management of AF.

False; only in the presence of another indication