Flashcards in K+ and Ca++ Blockers Deck (39):
Class III drugs have what activity (be specific)? What is the effect?
Inward rectifier K+ channel blocker
Amiodarone site of action
Primarily: K+ channel blocker
Also: potent Na+ channel blocker, weak beta blocker, weak Ca channel blocker
What are the effects of amiodarone (cardiac and extracardiac)?
Prolongs the action potential
Extracardiac: peripheral vasodilation
Basic toxicity of Amiodarone (4)
Bradycardia & heart block in pts with preexisting SA or AV node dis.
Accumulates in tissues (heart, lung, liver, skin, tears)
Effects up to 3 months post discontinuation.
Blocks peripheral T4 (thyroxine) to T3 (triiodothyronine)
Metabolism of Amiodarone
- Drug interactions
Hepatic metabolism with CYP3A4
Major metabolite is bioactive
Inhibits several P450s, interfering with statins, digoxin, and warfarin
Therapeutic use of Amiodarone
Ventricular tachycardia, including V-fib.
Effective for atrial fibrillation and flutter - off label use
More severe adverse effects of Amiodarone (4)
- abnormal liver function, hypersensitivity hepatitis
- skin deposits -> photodermatitis (grey-blue skin w/ sun exposure)
- Corneal microdeposits (in nearly all patients) -> halos in peripherals, rarely optic neuritis -> blindness
- Hypo and hyperthyroidism
Dofetilide drug class and cardiac effects
Class III, a very selective K+ channel blocker (unlike Amiodarone)
- Prolongs refractory period in His-Purkinje and ventricles -> increased QT interval
Can cause life-threatening ventricular arrhythmias
Dofetilide therapeutic uses
Maintenance and restoration of NSR in a-fib
Contraindications for Dofetilide
Long QT, bradycardia, hypokalemia
Pharmacokinetics of Dofetilide
Hepatic metabolism via CYP3A4
Ibutilide Class and Cardiac Effects
Class III (K+ channel inhibitor) -> prolongs repolarization
Also a slow inward Na+ activator -> delays repolarization -> inhibits Na+ channel inactivation -> increased ERP
Ibutilide therapeutic use
ACUTE conversion of a-fib or flutter to NSR
More effective in flutter w/ mean time to termination = 20 min
Excessive QT prolongation -> Torsades de pointes
Life-threatening polymorphic ventricular arrhythmias
General effects and side effects of Class III Drugs
Proarrhythmic AND antiarrhythmic
Prolonging QT can -> torsades de pointes
Class IV drugs binding site
L-type Ca channels located on vascular smooth muscle, cardiac myocytes, and SA/AV nodes
What does the channel that is the target of class IV drugs do normally?
L-type Ca channels regulate influx of calcium into smooth muscle cells -> smooth muscle and myocyte contraction
Effects of Class IV drugs (4)
- Vascular smooth muscle relaxation (vasodilation)
- Decreased myocardial contractility
- In cardiac myocytes: shortens phase 2 (plateau), reduces force of contraction because there is lass Ca available to bind troponin
- In nodal cells: blocks phase 0 depolarization -> dec HR, dec conduction velocity, especially in AV node
Therapeutic indications for class IV drugs and why
HTN: decreases TPR via smooth muscle relaxation -> decreased arterial blood pressure, primarily affects arterial vessels
Angina: Vasodilation and dec HR -> dec O2 demand, also dilates coronary arteries -> inc O2 supply to myocardium
Arrhythmias: dec pacemaker depolarization rate=good for ectopic foci, dec conduction velocity, prolonged repolarization -> block reentry
How do subclasses of Class IV drugs differ? What are the classes?
Differ in specificity for cardiac vs. vascular L-type channels
Dihydropyridines and Non-Dihydropyridines
Dihydropyridines are selective for ________. Recognizable by what naming convention?
Ends in "pine"
Dihydropyridine uses and what it doesn't work for (why?)
Used for hypertension: reduces systemic vascular resistance and arterial pressure.
Not used for angina: vasodilation -> compensatory increase in heart rate and contractility -> increased O2 demand (bad reflex loop)
Which drugs make up the class IV non-Dihydropyridines? (2)
Verapamil and Diltiazem
Rank the dihydropyridine subclass vs the two non-dihydropyridines in order of most selective for myocardium to most selective for vascular smooth muscle
Verapamil - Diltiazem - Dihydropyridines
How does Verapamil work? What are its cardiac effects and indications?
Relatively selective for the myocardium
Reverses coronary vasospasm. Decreases contractility, HR, and velocity of conduction -> decreased O2 demand
Indications: angina and arrhythmias
What is Diltiazem's cardiac vs. vascular L-type Ca channel specificity?
Intermediate between Verapimil (myocardium) and Dihydropyridines (vascular) --> cardiac depressant and vasodilator actions
Diltiazem and the hydropyridines both --> vasodilation. Why can Diltiazem be used with angina when hydropyridines can't?
Diltiazem also acts as a cardiac depressant, not only a vasodilator. Therefore, there is less risk of reflex cardiac stimulation caused by hypotension.
Side effects of dihydropyridines
Flushing, HA, excessive hypotension, edema, reflex tachycardia
Side effects of non-dihydropyridines
Excessive bradycardia, impaired electrical conduction e.g. AV block, depressed contractility
Contraindications to calcium channel blockers
Preexisting bradycardia, conduction defects, heart failure caused by systolic dysfunction - especially for non-dihydropyridines, but also for dihydropyridines.
Ca channel block -> suppresses nodal APs + inward K+ channel activation -> hyperpolarization
Adenosine therapeutic uses
SVT. Not effective for a-fib or flutter.
Contraindication to adenosine
Digitalis (digoxin) MOA
Inhibits Na/K ATPase -> inc Na in cell -> reversed action of Na/Ca pump -> inc Ca in cell -> improved contractility. Also activates vagal efferents to heart.
Uses for Digoxin
Primarily HF. Also for reducing vent rate driven by high atrial rate (a-fib or flutter)
Digitalis toxicity: EKG
EKG: arrhythmias, "Salvador Dali's mustache" checkmark in ST segment, flattened T waves.