Drugs that alter Cardiac Function Flashcards
Drugs That Modify Heart Function: Main Objectives
- Prevent/stop arrhythmias
- Maintain oxygenation of myocardium
- Reduce cardiac work
- Prevent thrombosis
- Treat pain associated with ischemia (lack of 02 reduced blood flow)
Antiarrhythmic Drugs
Class I, II, III, IV
Class I
Na+ channel blockers
Class II
B-adrenergic receptor antagonists
Class III
Drugs that prolong action potential by promoting closure of K+ channels
Class IV
Calcium channel antagonists
what do Class I drugs fo
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
Class IA Antiarrhythmics
- Lengthen duration of action potential
- Prolongs the refractory period
- Used for ventricular and supraventricular arrhythmias
side effect: Class IA Antiarrhythmics
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
Class IB Antiarrhythmics
• Shortens duration of action potential • Used for ventricular arrhythmias • Examples: LIDOCAINE - local anesthetic PHENYTOIN - antiepileptic • Side effects: may trigger epileptic seizures
Class IC Antiarrhythmics
- 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
Catecholamines (NE/E) & Cardiac Muscle
• 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
how do catecholamines affect action potential
increase the depolarisation rate = increase action potential rate - more peaks in same time
Class II antiarrhythmics
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
Class III antiarrhythmics
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
Class IV antiarrhythmics
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
Cardiac Glycosides
- inhibition of cardiac cell Na/K ATPase
=increased storage of Ca = increased force of heartbeat - 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
ACh and cardiac cells
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
NA+/K+ ATPase in cardiac muscle cells
drive Na+ out / K+ in
Ca2+ export driven by Na+ movement
drugs used to treat angina
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)
organic nitrates
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»_space; ischemic areas
NITROGLYCERIN
-treat congestive heart failure + angina
Side effects: hypotension + tachycardia
inhibits uterine sm contraction
tolerance develops over time - oxidative mitochondrial damage
drugs used to treat myocardial infarct
promote fibrinolysis (breakdown of fibrin in blood clots)
block platelet aggregation
lower blood pressure
drugs used to treat congestive heart failure (heart doesn’t pump blood as well as it should)
increase force of heart contraction
lower blood pressure (diuretics)
treat atherosclerosis
