Pharmacology: Block 4: Drugs For Arrhythmias

Front 1

What happens at phase 0 of the cardiac myocyte?

Back 1

Upstroke: Na channels open (+70 mV), Na influx

Front 2

What happens at phase 1 of the cardiac myocyte?

Back 2

Early-fast repolarization: Na channels close, Ca, K channels open

Front 3

What happens at phase 2 of the cardiac myocyte?

Back 3

Plateau: Ca channels dominate (ECa = 119 mV), more K channels begin to open.

Front 4

What happens at phase 3 of the cardiac myocyte?

Back 4

Repolarization: K channels dominate EK = -88 mV

Front 5

What happens at phase 4 of the cardiac myocyte?

Back 5

Diastole: steady state equilibrium between pump activity and Ca influx. Usually see a slow depolarization

Front 6

What does verapamil do to phase 4 of the SA node action potential?

Back 6

It decreases the slope

Front 7

What are the three mechanisms by which arrhythmias occur?

Back 7

1. Abnormal impulse initiation
- Increases automaticity, ectopic focus

2. Abnormal impulse conduction
- Microscopic reentry
- Macroscopic reentry

3. Some combination of the above
- "R on T" phenomenon
- Early and delayed after depolarizations?

Front 8

What would you see on EKG in a patient with ectopic atrial tachycardia (EAT)?

Back 8

Unusual P-wave morphology in lead II. Tachycardia (~150 bpm)

Front 9

In what case would EAT trump the SA node action potential?

Back 9

If the phase 4 depolarization of the EAT were faster than the SA node depolarization.

Front 10

What do all of these have in common?

Digoxin
Adrenergic agonists
Anticholinergics

Back 10

They all can contribute to increased automaticity

Front 11

What are some examples of diseases that can cause arrhythmias via irritation?

Back 11

Pericarditis
Stretching (increased pressure)
Lung disease, pneumonia

Front 12

Bidirectional tachycardia (~150): diagnosis?

Back 12

Digoxin toxicity

Front 13

P-waves of at least three different morphologies + tachycardia = ?

Back 13

MAT (multifocal atrial tachycardia)

Front 14

If reentrant arrhythmias require "perfect timing," what is the general strategy of the treatment?

Back 14

Screw up the timing.

Front 15

Wolf-Parkinson-White

Back 15

Results from an accessory bypass track (bundle of Kent)

Will see "delta" waves on EKG, indicating ventricular pre-excitation. These can be seen as a part of the R wave upstroke.

Will also see widening of the R wave.

Mostly asymptomatic, but can cause sudden death.

Front 16

"R on T" phenomenon

Back 16

QRS of PVC falls on sinus T wave and starts a run of V tach.

Front 17

"Torsades de Pointes": lethal or non-lethal?

Back 17

Lethal

Front 18

What would you see on EKG in a patient with ectopic atrial tachycardia (EAT)?

Back 18

Unusual P-wave morphology in lead II. Tachycardia (~150 bpm)

Front 19

In what case would EAT trump the SA node action potential?

Back 19

If the phase 4 depolarization of the EAT were faster than the SA node depolarization.

Front 20

What do all of these have in common?

Digoxin
Adrenergic agonists
Anticholinergics

Back 20

They all can contribute to increased automaticity

Front 21

What are some examples of diseases that can cause arrhythmias via irritation?

Back 21

Pericarditis
Stretching (increased pressure)
Lung disease, pneumonia

Front 22

Bidirectional tachycardia (~150): diagnosis?

Back 22

Digoxin toxicity

Front 23

P-waves of at least three different morphologies + tachycardia = ?

Back 23

MAT (multifocal atrial tachycardia)

Front 24

If reentrant arrhythmias require "perfect timing," what is the general strategy of the treatment?

Back 24

Screw up the timing.

Front 25

Wolf-Parkinson-White

Back 25

Results from an accessory bypass track (bundle of Kent)

Will see "delta" waves on EKG, indicating ventricular pre-excitation. These can be seen as a part of the R wave upstroke.

Will also see widening of the R wave.

Mostly asymptomatic, but can cause sudden death.

Front 26

"R on T" phenomenon

Back 26

QRS of PVC falls on sinus T wave and starts a run of V tach.

Front 27

"Torsades de Pointes": lethal or non-lethal?

Back 27

Lethal

Front 28

Ventricular tachycardia, Ventricular fibrillation = ?

Back 28

Death

Front 29

General philosophy about treating arrhythmias?

Back 29

"When it's slow, make it fast. When it's fast, make it slow."

Front 30

Class I antiarrhythmics: M of A

Back 30

Na channel blockers.

Raise the action potential threshold, so phase 4 is lengthened --> dec in automaticity

Front 31

Quinidine: general

Back 31

Class IA antiarrhythmic

Not first line b/c of Afib associated mortality

Front 32

Quinidine: dosing

Back 32

Loading dose, then 2-3 times daily

No IV

Front 33

Quinidine: AE

Back 33

Prolongs QT interval (K blockade) --> predisposing to Torsade de Pointes

Diarrhea, tinnitus, visual changes

Can be pro-arrhythmic

Increases levels of digoxin

Front 34

Quinidine: drug interactions

Back 34

Increases levels of digoxin (often used together)

Front 35

Procainamide: class

Back 35

Class IA antiarrhythmic

Front 36

Procainamide: route

Back 36

PO or IV

Front 37

Procainamide: metabolism

Back 37

Hepatic: PCA --> NAPA --> elimination

Front 38

Procainamide: AE

Back 38

Prolongs QT (NAPA is a potent K blocker)

Agranulocytosis (0.01%)

Drug induced lupus (slow acetylators)

Pro-arrhythmic

Front 39

Procainamide: what population of people have high levels of metabolites?

Back 39

Fast acetylators will have increased NAPA levels and therefore be at more of a risk for prolonged QT

Front 40

Disopyramide: class

Back 40

Class IA antiarrhythmic

Front 41

Disopyramide: route

Back 41

PO only

Front 42

Disopyramide: AE

Back 42

Prolongs QT

Major AE is negative inotropy:

- Not helpful in patients with CHF

- Useful in patients with hypertrophic cardiomyopathy (too much ventricular function)

- Also anticholinergic (causes vasoconstriction, makes CHF worse)

Front 43

Disopyramide: drug interactions

Back 43

Phenobarbital, phenytoin increase the hepatic metabolism of disopyramide.

Front 44

Name the three class IA antiarrhythmics

Back 44

Procainamide
Quinidine
Disopyramide

Front 45

Class IA antiarrhythmics: Uses

Back 45

Afib, Aflutter, SVT, VT

Front 46

Class IA antiarrhythmics: general effects on the action potential

Back 46

- Decrease conduction velocity
- Change the refractory period (K blockade)

Front 47

Lidocaine: route

Back 47

Given as an IV load followed by an infusion.

Front 48

Lidocaine: especially useful with what?

Back 48

MI. Lidocaine blocks depolarized (sick) cells better.

Front 49

Lidocaine: shortcomings

Back 49

Vd and clearance decreased in CHF

Clearance falls after 24 hrs.

Front 50

Lidocaine: AE

Back 50

CNS toxicity:

Tremor, slurred speech, metallic taste, seizures

Front 51

Lidocaine: M of A

Back 51

Voltage-dependant Na blocker. Blocks rhythms made by the ischemic heart.

Front 52

Lidocaine: drug interactions

Back 52

Watch out for use with CHF patients and with administration of cimetidine (H2 histamine blocker)

Front 53

Flecainide: class

Back 53

Class IC antiarrhythmic

Front 54

Flecainide: route

Back 54

PO only

Front 55

Flecainide: use

Back 55

Primarily for SVT:

- Suppresses PVCs
- But it kills people with a history of MI and PVCs.

Front 56

Flecainide: half-life

Back 56

Long (20 hrs)

Front 57

Use dependence: definition

Back 57

Drug binds to the transient form of the channel in its active or inactive state.

Works better with faster heart rates

Front 58

Reverse use dependence: definition

Back 58

Binds to the resting (more durable) form of the channel.

Works better with slower heart rates.

Front 59

Propafenone: class

Back 59

Class IC antiarrhythmic

Front 60

Propafenone: dosing, half-life

Back 60

Short half-life, requires 2-3x daily dosing

Front 61

Propafenone: beta blocking activity

Back 61

1/40 of that of propranolol

Front 62

Propafenone: AE

Back 62

Hypersensitivity reactions, lupus-like syndromes, agranulocytopenia, CNS disturbances: dizziness, lightheadedness, GI upset, metallic taste, bronchospasm

Front 63

Class IC antiarrhythmics: major contraindication

Back 63

CAD

Front 64

QT prolongation predisposes to what

Back 64

Torsades de Pointes

Front 65

Class II Antiarrhythmics: alternate name?

Back 65

Beta blockers

Front 66

Class II Antiarrhythmics: M of A

Back 66

Decrease the phase 4 depol rate (this phase is sensative to adrenergic tone). This reduces cardiac automaticity.

Front 67

Class II Antiarrhythmics: Effects on the heart

Back 67

Reduces the pacemaker rate, decreases AV conduction, increases AV refractoriness.

Front 68

Class II Antiarrhythmics: effects on mortality

Back 68

Decrease mortality with MI

Front 69

Class II Antiarrhythmics: AE

Back 69

Bronchospasm, bradycardia, depression (due to lipid solubility of some beta blockers)

Front 70

Class II Antiarrhythmics: dosing

Back 70

once or twice daily

Front 71

Class III Antiarrhythmics: M of A

Back 71

Delayed repolarization via K channel blockade.

Extends phase 3.

Amiodarone also decreases conduction velocity and phase 4 depolarization.

Front 72

Amiodarone: class

Back 72

Class III Antiarrhythmic

"Amiodarone is the most effective antiarrhythmic"

Front 73

Amiodarone: what does it do?

Back 73

Slows HR and AV node conduction.

Inhibits manny channel types:

K (IKr)
Na (inactive)
Ca (weak)
Beta-adrenergic receptors (weak)

Front 74

Amiodarone: route

Back 74

Available PO or IV. IV administration causes hypotension

Front 75

Amiodarone: drug interactions

Back 75

Competes with carrier proteins:

Increases digoxin concentrations

Increases warfarin concentrations

Also: quinidine, procainamide, flecainide, beta-blockers, CCBs, mexiletine

Front 76

Amiodarone: pharmacokinetics

Back 76

HUGE Vd (resides in lipid stores). So if you put someone on amiodarone for 1 year, it will be stored up in the body for a long time...

Very long half-life

Hard to get rid of

Front 77

Amiodarone: AE

Back 77

FATAL pulmonary fibrosis (1%)

Skin: photosensitivity, blue-man syndrome

Eye: Corneal deposits

GI: increased LFTs

Endo: Blocks T4 to T3 conversion

Lots of drug interactions

Front 78

Dofetilide: class

Back 78

Class III Antiarrhythmic

Front 79

Dofetilide: route

Back 79

Only PO

Front 80

Dofetilide: use

Back 80

Only for atrial arrhythmias.

Front 81

Dofetilide: AE

Back 81

HIGH incidence of Torsades de Points. Thus initiation of dofetilide requires hospitalization and trained physician.

Front 82

Dofetilide: M of A

Back 82

Pure K channel blocker

Class III Anti-arrhythmic

Front 83

Dofetilide: clearance

Back 83

80% renal clearance (keep an eye on Cr clearance)

Front 84

Dofetilide: drug interactions

Back 84

Agents that interfere with renal cation exchange should be avoided:

Verapamil, cimetidine, hydrochlorothiazide, itraconazole, ketoconazole, prochlorperazine, and trimethoprim.

Front 85

Sotalol: class

Back 85

Class III Antiarrhythmic

Front 86

Sotalol: what is it, route

Back 86

Class III Antiarrhythmic

PO only

Front 87

Sotalol: use/activity

Back 87

Class III Antiarrhythmic

Has beta-blocking activity (L-enantiomer)

Used for ventricular tachycardia

Front 88

Sotalol: AE

Back 88

Class III Antiarrhythmic

Moderate incidence of Torsades de Pointes

Use with caution in CHF

Front 89

Which class of antiarrhythmics requires the most caution?

Back 89

Class III (amiodarone toka)

Front 90

Class IV antiarrhythmics: M of A

Back 90

Block the slow inward Ca current of phase 4 --> slow heart rate.

Also slow AV node repolarization

Front 91

Class IV antiarrhythmics: generally used for, not used for?

Back 91

Used to slow HR and inhibit reentry

Not used for ventricular arrhythmias.

Front 92

Class IV antiarrhythmics: alternate name?

Back 92

Calcium channel blockers.

Front 93

Class IV antiarrhythmics: elimination?

Back 93

Hepatic

Front 94

Class IV antiarrhythmics: AE

Back 94

Hypotension due to smooth muscle relaxation

Constipation

Front 95

Class IV antiarrhythmics: drug interactions

Back 95

Digoxin levels may increase
Theophylline levels increase

Front 96

Digoxin: General M of A

Back 96

Effects mediated via central and peripheral augmentation of vagal tone.

Front 97

Digoxin: AE

Back 97

Anorexia, nausea, vomiting, changes in color vision (Van Gogh), arrhythmias (bidirectional VT)

Front 98

Adenosine: what does it do?

Back 98

AV nodal blockade.

Front 99

Adenosine: what types of patients are highly sensitive?

Back 99

Heart transplant patients - they are denervated.

Front 100

Adenosine: what can adenosine help you figure out about arrhythmias?

Back 100

It can help you figure out if it is coming from the atria or the ventricles b/c it causes a AV nodal blockade.

Front 101

Adenosine: AE

Back 101

Chest pain and dyspnea (short-lived)

Proarrhythmic: decreased atrial refractoriness can lead to Afib.

Front 102

Adenosine: half-life

Back 102

Short

Front 103

Atropine: what type of drug

Back 103

Muscarinic antagonist

Front 104

Atropine: use for CV

Back 104

Used for bradyarrhythmias

Front 105

Atropine: route

Back 105

IV only

Front 106

Atropine: not effective in treating arrhythmias if?

Back 106

If the block is below the AV node.

Front 107

Amiodarone toxicity can present like what?

Back 107

Like pneumonia