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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
Slowed Repolarization


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
- Location
- Enzyme
- 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


Dofetilide toxicity

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

100% bioavailable
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


Ibutilide pharmacokinetics

Hepatic metabolism


Ibutilide toxicity

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?

Smooth muscle
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.


Adenosine MOA

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

heart block


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.


Main causes of Digitalis toxicity

Renal impairment, especially in elderly + narrow TI