Drugs that alter Cardiac Function

Question 1

Drugs That Modify Heart Function: Main Objectives

Answer 1

• Prevent/stop arrhythmias
• Maintain oxygenation of myocardium
• Reduce cardiac work
• Prevent thrombosis
• Treat pain associated with ischemia (lack of 02 reduced blood flow)

Question 2

Antiarrhythmic Drugs

Answer 2

Class I, II, III, IV

Question 3

Class I

Answer 3

Na+ channel blockers

Question 4

Class II

Answer 4

B-adrenergic receptor antagonists

Question 5

Class III

Answer 5

Drugs that prolong action potential by promoting closure of K+ channels

Question 6

Class IV

Answer 6

Calcium channel antagonists

Question 7

what do Class I drugs fo

Answer 7

Inhibit Phase 0 = USE DEPENDENT

• Block Na+ channels in open or refractory state
• Primarily effective against tachycardias
• Have little or no effect on normally functioning Na+ channels

Question 8

Class IA Antiarrhythmics

Answer 8

• Lengthen duration of action potential
• Prolongs the refractory period
• Used for ventricular and supraventricular arrhythmias

Question 9

side effect: Class IA Antiarrhythmics

Answer 9

may trigger additional arrhythmias by inducing after-depolarization; increased risk of “torsades de pointes”-a type of ventricular tachycardia; 
should not be given to patients with Lupus erythematosus; worsens myasthenia gravis symptoms
Less frequently used than other class I drugs

Question 10

Class IB Antiarrhythmics

Answer 10

• Shortens duration of action potential
• Used for ventricular arrhythmias
• Examples: 
LIDOCAINE - local anesthetic 
PHENYTOIN - antiepileptic
• Side effects: may trigger epileptic seizures

Question 11

Class IC Antiarrhythmics

Answer 11

• No effect on duration of action potential
• Used for prophylaxis of paroxysmal atrial fibrillation, especially those caused by re-entrant circuits
• Effective in treating ventricular tachycardias

Side effects: increases risk of death caused by ventricular fibrillations triggered by a heart attack

Question 12

Catecholamines (NE/E) & Cardiac Muscle

Answer 12

• Bind to B1 receptors in all types of cardiac cells
= increased synthesis of cAMP = activates (PKA)

• PKA facilitates the opening of L type Ca2+ channels, increasing depolarization rate and decreasing the time between action potentials
- increases level of Ca2+ storage in SR
= increase in heart rate and force of contraction

Question 13

how do catecholamines affect action potential

Answer 13

increase the depolarisation rate = increase action potential rate - more peaks in same time

Question 14

Class II antiarrhythmics

Answer 14

decrease depolarisation rate = decrease action potential

B1 blockers - B-adrenergic antagonists
used for supraventricular and ventricular arrhythmias - result from overproduction of catecholamines + used for heart block

PROPRANOLOL

Side effects:
worsens congestive heart failure
promotes bronchoconstriction through effects on B2 R
bradycardia

Question 15

Class III antiarrhythmics

Answer 15

target = pacemaker cell
delay opening of K+ channels
prolongs action potential
used for supraventricular and ventricular arrhythmias
*involved in re-entrant effect/ectopic pacemaker activity

SOTALOL (D-isomer = K channel blocker)

Side effects: increased risk of torsades de pointes

Question 16

Class IV antiarrhythmics

Answer 16

Ca2+ channel blocker
reduces cardiac contractile force / alter rate
act on L-type channels in all cardiac cells: slows conduction between SA/AV nodes

indirectly on heart - relaxes arterioles - reduces BP

used to prevent recurrence of supraventricular tachycardia
+ treat angina

VERAPAMIL

Side effects: cardiodepression, hypotension, AV node block
taken with K+ lowering directics => cardiac arrhythmias

Question 17

Cardiac Glycosides

Answer 17

1. inhibition of cardiac cell Na/K ATPase
   =increased storage of Ca = increased force of heartbeat
2. increase release of ACh from vagus nerve
   = slower heart rate + decreased AV conduction

used to treat atrial fibrillation + congestive heart disease

DIGOXIN

Side effects: AV block, arrhythmias, nausea/vomiting from overstimulation of parasympathetic nervous system

Question 18

ACh and cardiac cells

Answer 18

ACh released by vagus nerve (reduce HR)
nodal/atrial cells = M2 receptors/ absent in ventricular cells

activation of M2Rs = opposite effect of B1Rs
- open GIRK (G-protein activated inwardly rectifying K+ channels) => hyperpolarises cardiac cells -> arrhythmias

Question 19

NA+/K+ ATPase in cardiac muscle cells

Answer 19

drive Na+ out / K+ in

Ca2+ export driven by Na+ movement

Question 20

drugs used to treat angina

Answer 20

pain = reduced blood flow to heart

organic nitrates
potassium channel activators
calcium antagonists
(vasodilative - reduce effort by heart to pump blood)

B-adrenergic receptor antagonists
(reduce 02 demand by reducing HR)

Question 21

organic nitrates

Answer 21

generate NO - potent vasodilator
NO increases cGMP - activates cGMP dependent kinase =relaxing smooth muscle
- reduces both venous/arterial pressure - increasing blood flow to coronary arteries + heart
- increases collateral blood flow&raquo_space; ischemic areas

NITROGLYCERIN
-treat congestive heart failure + angina

Side effects: hypotension + tachycardia
inhibits uterine sm contraction
tolerance develops over time - oxidative mitochondrial damage

Question 22

drugs used to treat myocardial infarct

Answer 22

promote fibrinolysis (breakdown of fibrin in blood clots)

block platelet aggregation

lower blood pressure

Question 23

drugs used to treat congestive heart failure (heart doesn’t pump blood as well as it should)

Answer 23

increase force of heart contraction

lower blood pressure (diuretics)

treat atherosclerosis