Antiarrhythmics: K+ and Ca+ Channel Blockers Flashcards
(44 cards)
What class are K+ channel blockers?
Class III
Which specific channels do the class III drugs block?
Inward rectifier K+ channels
What is the main role of K+ in the myocyte AP?
Cell depolarization (phase 3)
What is the net result of blocking the K+ channels?
Slows depolarization –> increases AP duration and effective refractory period-> prolongs QT interval
Which arrythmias are K+ channel blockers specific at suppressing?
Reentry arrythmias
What is the pneumonic for Class III drugs?
AIDS
Amiodarone, Ibutilide, Dofetilide, and Sotalol
Amiodarone
Mechanism Clinical Use Pharmacology Extracardiac Effects Toxicity
Class III
Mechanism: Prolongs ventricular AP (increases QT interval on ECG); potent Na+ channel blocker, and weak blocker of beta receptors and CA++ channels –> slows HR and AV node conduction too!
Clinical Use: Treatment and prevention of ventricular tachycardia (including ventricular fibrillation); also effective for atrial fib and flutter
Pharmacology: hep met –> elimination lastin 1-3 months d/t accumulation of drug in tissues; Substrate of CYP3A4 and inhibits several P450s –> causes increased levels of other drugs such as statins, digoxin, and warfarin
Extracardiac Effects: causes peripheral vasodilation
Toxicity: pulmonary fibrosis, hepatotoxicity, and thyroid disease! Also, bradycardia and heart block in pts with preexisting SA or AV node disease. Drug accumulates in the tissues
**contraindications for pts with heart block or SA node dysfunction d/t Class IV effects
Ibutilide
Mechanism Clinical Use Pharmacology Extracardiac Effects Toxicity
Class III
Mechanism: Prolongs ventricular AP (increases QT interval on ECG); slows inward Na+ activator which delays repolarization –> inhibits Na+ channel inactivation which increases ERP
Clinical Use: Acute conversion of atrial flutter and fibrillation to normal sinus rhythm (~20 min.)
Pharmacology: hep met.
Extracardiac Effects:
Toxicity: Excessive QT int. prolongation –> torsades de pointes
Dofetilide
Mechanism Clinical Use Pharmacology Extracardiac Effects Toxicity
Class III
Mechanism: Very selective K+ channel blocker; Prolongs ventricular AP (increases QT interval on ECG)
Clinical Use: Maintenance and restoration of normal sinus rhythm in atrial fibrillation; contraindicated in long QT, bradycardia, hypokalemia
Pharmacology: 100% bioavailability. Hep met via CYP3A4
Extracardiac Effects:
Toxicity: can cause life-threatening ventricular arrythmias (long QT int –> torsades de pointes)
Sotalol
Class II and Class III drug
See other card deck for answers
How do K+ channel blockers affect the QRS complex of the ECG?
There will be no change. K+ channel blockers will be affecting the depolarization phase which does not include the QRS complex.
What class are Ca2+ channel blockers?
Class IV drugs
Which type of channel do class IV drugs bind?
L-type Ca2+ channels located on the vascular smooth muscle, cardiac myocytes, and SA/AV nodes.
How do Ca2+ channel blockers affect smooth muscle?
These channels are responsible for regulating the influx of Ca2+ into muscle cells, which in turn stimulates smooth muscle contraction and cardiac myocyte contraction.
Blockers cause:
- sm. muscle relaxation (vasodilation)
- Decreased myocardial contractility
How do Ca2+ channel blockers affect cardiac myocytes?
In cardiac myocytes, Ca2+ influx is responsible for the slow depolarization (plateau) of the AP.
Blockers cause:
1. shortening phase 2 of AP
Reduce force of contraction (less Ca2+ to bind to troponin)
How do Ca2+ channel blockers affect nodal cells?
In nodal cells, L-type Ca2+ channels play an important role in pacemaker currents and in phase 0 of the AP.
Blockers cause:
- Decreased HR
- Decreased conduction velocity (particularly in AV node)
What are indications to use a Class IV drug?
- Hypertension (decreases systemic vascular resistance (TPR)) through smooth muscle relaxation)
- Angina
- Arrythmias
How does a Class IV drug treat HTN?
- lowers arterial BP
- primarily affects arterial vessels rather than venous vessels (b/c arteries have the greatest amt of smooth muscle)
How does a Class IV drug treat angina?
- Vasodilation reduces arterial pressure –> reduces ventricular afterload –> decreases myocardial O2 demand
- Decreased HR and contractility –> decreased myocardial O2 demand
- Dilates coronary arteries and prevent/reverse coronary vasospasm –> increasing O2 supply to the myocardium
How does a Class IV drug treat arrythmias?
- Decrease pacemaker depolarization rate –> good for ectopic foci that are causing aberrant AP firing
- Decrease conduction velocity and prolong depolarization at the AV node (helps block reentry mechanisms which cause SVT)
What are the subclasses of Class IV drugs? How do they differ?
Dihydropyridines and Non-dihydropyridines
They differ in specificity for cardiac vs. vascular L-type Ca2+ channels.
What L-type Ca2+ channels are dihydropyridines specific for?
Smooth muscle
What is the primary use of a dihydropyridine?
The primary use is to reduce systemic vascular resistance and arterial pressure –> used to treat HTN
Why aren’t dihydropyridines used to treat angina?
The vasodilator and pressure lowering effects can lead to reflex cardiac stimulation (tachycardia and increased contractility) –> dramatically increase myocardial O2 demand
