Lecture 17 - Cardiac Pharmacology and Antiarrthymic Drugs Flashcards
1
Q
How does blood flow through the heart?
10 steps
A
- Blood enters right atrium from superior adn inferior venae cavae
- Blood in right atrium flows through right AV valve into the right ventricle
- Contraction of right ventricle forces pulmonary valve open
- Blood flows through pulmonary valve into pulmonary trunk
- Blood is distributed by right and left pulmonary arteries to the lungs where it unloads CO2 and loads O2
- Blood returns from the lungs via pulmonary veins to left atrium
- Blood in left atrium flows through the left AV valve into the left ventricle
- Contraciton of the left ventricle (simultaneous with step 3) forces aortic valve open
- Blood flows through aortic valve into ascending aorta
- Blood in aorta is distributed to every organ in the body to unload O2 and load CO2
2
Q
What is the sinoatrial (SA) node?
A
Part of the heart that normally generates electrical impulse that initiates contraction
- the ‘pacemaker’
- coordinates the contractions of both sides of the heart so each side pumps the same amount of blood
3
Q
How does the cardiac conduction system flow?
A
- SA node excites right atrium (RA)–> travels through Bachmann’s bundle to excite the left atrium (LA)
- Impulse travels through atrial myocardium in RA to the atrioventricular (AV) node
- Purkinje fibers (specialized for rapid transmission) distribute excitation through ventricular myocardium
4
Q
What is automaticity in the SA node?
A
Cells undergo spontaneous depolarization and an action potential is triggered
- Pacemaker cells do not require external stimulation to initiate action potential
5
Q
Describe the major currents in the phases of SA node action potential
SA Nodal Cells
A
- Phase 4: Pacemaker current, outward K+ current, HCN channels open at beggining –>T-type Ca2+ channels open –> L-type Ca2+ channels open
- Phase 0: Threshold potential passed, inward Ca2+ current, upstroke, ends when HCN and Ca2+ channels close and voltage-gated K+ channels open
- Phase 3: Repolarisation, outward K+ current
6
Q
Describe the phases in cardiac action potential in ventricle muscle cells
Ventricular Myocytes
A
- Phase 0: Conduction, depolarization, Na+ rapidly moves to the inside of the cell, reversal of membrane potential, -90 mV to -30 mV
- Phase 1: Refractory period, early phase repolarization, K+ moves to the outside of the cell
- Phase 2: Plateau phase, Ca2+ moves to the inside of the cell and is balanced by movement outward of K+ through delayed rectifier K+ channels
- Phase 3: RP, Ca2+ channels close but K+ channels stay open to return to -90 mV
- Phase 4: Automaticity, slow inward movement of Na+ and Ca2+, outward movemnt of K+ to automatically excite the membrane again
7
Q
What produces the P wave on an ECG?
A
Depolarization of the atria
8
Q
What does the PR interval measure?
A
The time it takes for an electrical impulse to pass from the SA node to the AV node
P to Q, section before the R spike
9
Q
What produces the QRS wave on an ECG?
A
Depolarization of the ventricles
10
Q
What produces the T wave on an ECG?
A
Repolarization of the ventricles
small bump after the big spike
11
Q
What does the QT interval measure?
A
The time it takes for the ventricles to depolarize and repolarize
12
Q
What is an electrocardiogram (ECG, EKG)?
A
Instrument that records the electrical activity of the heart from different body locations or leads and represents the activity in waveform
Invented by Willem Einthoven in 1903
13
Q
What is a heart arrythmia?
A
An irregular heartbeat (can be irregular, too fast, or too slow) and can originate anywhere in the heart
13
Q
What are heart arrhythmias caused by?
A
- Electrolyte (Na+, Ca2+, K+) disturbances
- Overstimulation of the heart
- Genetic defects (mostly ion channels)
- Drugs or chemicals
14
Q
What are the most common types of arrhythmias?
A
- Tachycardia
- Premature contractions
- Flutters and fibrillations
15
Q
What is different on ECG recordings for premature atrial beat?
A
Additional P wave with normal waveform
16
Q
What is different on ECG recordings for paroxyamal atrial tachycardia?
A
Rapid beats with each QRS complex preceded by a P wave
17
Q
What is different on ECG recordings for Atrial fibrillation
A
No define P waves present, random triggering of normal shaped QRS complexes
18
Q
What is different on ECG recordings for first-degree heart block?
A
Abnormally long PR intervals
19
Q
What is different on ECG recordings for ventricular fibrillation?
A
No define ECG waves, most serious condition
20
Q
What type of drugs are Class 1 Antiarrhythmic drugs?
A
Sodium channel blockers
21
Q
Class 1 antiarrhythmic drug - main mechanism of action
A
- Blocks Na ion influx during depolarization of nerves and excitable membranes
- prolongs depolarization and conduction during phase 0
22
Q
Class 1A Antiarrhythmias
Quinidine
A
- Rarely used
- Cardiac depressant, produces anticholinergic and alpha-blocking effects
- slightly block K+ channels
23
Q
Class 1A Antiarrhythmias
Procainamide
A
- Produces less anticholinergic and alpha-blocking actions than quinidine
- slightly blocks K+ channels
24
# Class 1A Antiarrhythmias
Disopyramide
- produces decreased conduction and prolonged refractory period
- slightly block K+ channels
25
# Class 1B Antiarrhythmias
Lidocaine
- Prevents ventricular arrhythmias, depresses automaticity
- Side effects: sleepiness, confusion, numbness
- Little effect on K+ channels
25
# Class 1C Antiarrhythmias
Flecanide and propafenone
- Used to treat arrythmias that are unresponsive to other drugs
- slightly block K+ channels
25
Hydroxychloroquine
- Dose-related cardiac sodium and potassium channel blocking effect
- Delayed repolarization and slow intraventricular conduction
- Results in bradycardia, hypotension, ventricular dysrhythmias, widened QRS, and prolonged QT interval
| Used to treat malaria
26
How do class 1A - 1C antiarrhythmics effect ventricular action potential graphs?
1A: Moderate Na+ channel block (smaller slope on phase 0), prolonged repolarization (phase 1-3 farther from y-axis and closer to x-axis)
1B: Mild Na+ channel block (slgithly smaller slope), shortened repolarization (Phase 2 and 3 closer to x-axis and y-axis)
1C: Marked Na+ channel block (much smaller slope on phase 0), no change in repolarization
27
What effects do sympathetic neurons have on cardiac myocytes?
Release norepinephrine which activate beta1 receptors in atria, ventricles, and conduction system
- Causes increased heart rate, faster conduction through AV node, increased contractility, faster relaxation after contraction
28
What effects do parasympathetic neurons have on cardiac myocytes?
Parasympathetic neurons release ACH which activates muscarinic M2-receptors on the cardiac myocytes of SA and AV nodes
- Causes decreased heart rate, ventrical innervation is minimal
29
What type of drugs are Class 2 Antiarrhythmic drugs?
Beta-blockers
30
# Class 2 Antiarrhythmic Drugs
Beta-blocker - example drugs
- Propranolol: Possesses beta-blocking and depressant effects
- Esmolol: mainly affects beta-1 receptors in the heart
31
# Class 2 Antiarrhythmic Drugs
Beta-blockers - Indication
Used for supraventricular arrhythmias and ventricular arrhythmias that are caused by sympathetic overstimulation
32
# Class 2 Antiarrhythmic Drugs
Beta-blockers - Effects
Decrease heart rate, AV cconduction, and automaticity of the SA and AV nodes and the atrial and ventricular muscle
- Reverese the tonic sypathetic stimulation of cardiac beta1-adrenergic receptors
- Decrease the slope of phase 4 depolarization
33
What does AV conduction depend on?
Dependent on distinct types of myocardial tissue and includes atrial inputs into the AV node, the various components of the AV node, and the His-Purkinje conduction system
34
What type of drugs are Class 3 antiarrhythmics?
Potassium channel blockers
35
# Class 3 Antiarrhythmic Drugs
Class 3 Potassium channel blockers - Mechanism of action
- Blocks K+ channels
- Interferes with the efflux of K+ during repolarization phases 1-3
36
# Class 3 Antiarrhythmic Drugs
Amiodarone
Used for most supraventricular and ventricular arrhymias
37
# Class 3 Antiarrhythmic Drugs
Sotalol
Treats ventricular arrhythmias and atrial fibrillation
38
Effects of Class 3 drugs on ventricular action potential graph
- Extended line after phase 1
- Balance of Ca2+ (depolarizing) and K+ (hyperpolarizing) currents
- Block or repolarizing K+ currents
- Prolonged repolarization
39
What type of drug are Class 4 Antiarrhythmic Drugs?
Calcium channel blockers
40
# Class 4 Antiarrythmic Drugs
Class 4 - Effects
- On SA node: Slow depolarization and decrease in heart rate
- On AV node: Slow conduction
- Affects contraction of cardiac and smooth muscle
- Reduced myocardial contractility (less calcium enters cells)
- Causes vasodilation
41
# Class 4 Antiarrhythmic Drugs
Verapamil
Acts on the SA and AV nodes of the heart
- non-dihydropyridine
42
# Class 4 Antiarrhythmic Drugs
Diltiazem
Potent vasodilator that works on SA and AV nodes
- non-dihydropyridine
43
How does Adenosine work as an antiarrhythmic?
- anti beta-adrenergic affects
- used in emergency and acute situations
- decreased activity of calcium ions in the SA and AV nodes which slows heart rate and AV conduction
- terminates episodes of paraxysmal supraventricular tachycardia
- antagonized by caffeine
44
# Vaughn-Williams Classification of Antiarrhythmic Drugs
Class 1A
Mechanism - moderate block of Na channels
Effects - moderate decrease in phase 0 depolarization, QRS and QT intervals prolonged
Examples - Quinidine, procainamide, disopyramide
45
# Vaughn-Williams Classification of Antiarrhythmic Drugs
Class 1B
Mechanism - Mild block of Na channels
Effects - Mild decrease in phase 0 depolarization, decreased ventricular automaticity
Examples - Lidocaine, mexiletine
46
# Vaughn-Williams Classification of Antiarrhythmic Drugs
Class 1C
Mechanism - Marked block of Na channels
Effects - Marked decrease in phase 0 depolarization, prolongation of QRS interval
Examples - Flecainide, propafenone
47
# Vaughn-Williams Classification of Antiarrhythmic Drugs
Class 2
Mechanism - Blockade of adrenergic beta-1 receptors
Effects - Decrease in heart rate, AV conduction, and ventricular atoumaticity, increased PR interval
Examples - Propranolol, acebutolol, esmolol
48
# Vaughn-Williams Classification of Antiarrhythmic Drugs
Class 3
Mechanism - Blockade of K channels
Effects - Prolongation of ventricular repolarization (phases 1-3), prolongation of QT interval
Examples - Amiodarone, dofetilide, ibutilide, sotalol
49
# Vaughn-Williams Classification of Antiarrhythmic Drugs
Class 4
Mechanism - Blockade of Ca channels in SA and AV nodes
Effects - Decrease in heart rate and AV conduction, increase in PR interval
Examples - Diltiazem, verapamil
50
What is chronic heart failure (CHF)?
The contractile ability of the heart to pump blood is decreased so that the
heart pumps out less blood than it receives
- Blood accumulates inside the chambers, causing enlargement of the heart
- less blood circulating in the blood vessels to supply the body organs.
51
What are the causes of chronic heart failure?
Coronary heart disease, high blood pressure, heart attack, heart valve disorders
52
What drugs are used to treat chronic heart failure?
- Cardiac glycosides
- Vasodilators
- Diuretics
- Beta-blockers
53
# Cardiac Glycoside
Digoxin - Effects
- Increases force of myocardial contractions
- stimulates the vagus nerve (parasympathetic effect) which slows activity of SA and AV nodes
54
# Cardiac Glycosides
Digoxin - Mechanism of action
Inhibits Na/K adenosine triphosphatase
- causes Na+ ions to increase inside muscle --> decreases exchange of Ca2+ --> increased formation of actinomyosin
| Narrow theraputic window and increases risk of death
55
How does vasodilator therapy treat chronic heart failure?
- dilate blood vessels --> lowers peripheral resistance and blood pressure --> decreases cardiac work and oxygen consumption, increases cardiac output
56
# Vasodilator Therapy
Angiotensin-converting enzyme (ACE) inhbitors - Mechanism
- Reduces the formation of angiotensin II
- Decreases the activation of bradykinin (endogenous vasodilator)
| Preffered treatment, dilates both arteries and veins
57
# Vasodilator Therapy
Angiotensin receptor blockers (ARBs)
Blocks the action of angiotensin II
| Preffered treatment, dilates both arteries and veins
58
# Diuretic Therapy of CHF
Loop diuretics - Mechanism
- Most potent, used to treat severe heart failure or impaired renal function
- effects last 4 to 8 hours
- Blocks NKCC2
- Causes hypokalemia
59
# Diuretic Therapy of CHF
Thiazide diuretics - Mechanism
- Blocks sodium reabsorption
- used in mild cases of CHF
- may cause hypokalemia
60
# Diuretic Therapy of CHF
Aldosterone antagonists
| Potassium-sparing diuretics (Spironolactone)
- Weak diuretics, act on collecting ducts of the nephron
- Increases Na excretion and retain K
- reduces mortality
- used in combo with loop diuretics to counterbalance the loss of K
