potassium channel blockers/ adenosine - anti-arrythmia drugs

potassium channel blocker drug names (5)

sotalol, amiodarone, dronedarone, dofetilide, ibutilide

open state class III selective block of K drugs (3) and what does this channel normally do

sotalol, dofetilide, ibutilide

the delayed rectifier K channels for K efflux, driver of repolarization

what channel do amiodarone and dronedarone block

non-selective class III block of outward delayed rectifier and inward rectifier K channels

amiodarone and dronedarone primarily increases what

ERP

dofetilide and ibutilide increase what two things

ERP/APD

amiodarone and dronedarone have what type of pharmacology

complex; they have properties of the other VW Classes (closed-state block of Na+ channels, blocks Ca++ channels, blocks B receptors) and is a ligand for thyroid hormone receptors

sotalol oral formulation therapeutic use

oral formulation of hydrochloride salt for conversion & maintenance of atrial fibrillation in patients who have structural heart disease without severe systolic dysfunction

sotalol IV formulation therapeutic use

treatment of life-threatening ventricular arrythmias

is sotalol racemic? what activity

yes; “S” is a non selective B blocker; enantiomers equapotent as K channel blockers

all K channels blockers have what warning in common

Risk of Torsades de Pointes (unstable ventricular tachycardia)

sotalols risk oftorsades de pointes is enhanced with what drugs

class 1C or class II coadmin

sotalol adverse effects (4)

risk of hypotension

bradycardia

cardiac failure

worsening bronchospasms

sotalol ddi’s?

none

amiodarone therapeutic use / dosage form

Oral and intravenous formulations for treating life-threatening ventricular arrhythmias in hemodynamically unstable patients or cardiac arrest settings

amiodarone is second line for what

Second-line agent for treating of atrial fibrillation in patients with left ventricular dysfunction or heart failure, where other agents (e.g., b-blockers, Ca++ channel blockers) may not be suitable or sufficient

amiodarone half life and why

58 days; very lipid soluble, stored in fat, diffuses out slowly, bad if pt isn’t tolerating med bc stays stored

amiodarone is oxidized by what cyp to what with what activity

CYP3A4 to des-ethyl amiodarone; activity and half life similar to amiodarone

amiodarone BBB

pulmonary, hepatic, and cardiac toxicity

potentially fatal pulmonary fibrosis/ drug induced liver injury

amiodarone’s risk of torsades de pointes in comparison to other class III drugs, and when is risked enhnced

lower in comparison

enhanced risk with class 1C/ class II coadmin

amiodarone has multiple potential adverse effects such as

visual impairment, thyroid abnormalities, bradycardia, peripheral neuropathy, photosensitivity and skin discoloration

amiodarone ddi when other antiarrhythmics/drugs r coadmin (ddi #1)

can prolong QT interval

amiodarone ddi #2: is a substrate for what cyps

CYP3A and CYP2C8, so inhibitors and inducers affect amiodarone exposure

amiodarone ddi #3: inhibits what

P-glycoprotein, CYP1A2, CYP2C9, CYP2D6, CYP3A -> can increase exposure of other drugs

dronedarone dosage form/ therapeutic use

Oral formulation for maintenance of sinus rhythm in patients with chronic atrial

fibrillation without heart failure or significant left ventricular dysfunction

dronedarone compared to amiodarone in preventing AF recurrences/safety profile

dronedarone less effective in prevention of AF recurrence

dronedarone has better safety profile/ less side effects

dronedarone can oxidized by what enzyme, to what, activity of metabolite

CYP2D6 oxidation to des-butyl dronedarone; 1/10 activity and similar half life to dronedarone

what warnings/contraindications/ddi’s of amiodarone does dronedarone NOT share

no warnings for pulmonary fibrosis / thyroid adverse effects (weaker off target thyroid binding); rest similar including ddi’s

dofetilide therapeutic use / dosage form

oral formulation for conversion and/or maintenance of sinus rhythm in atrial fibrillation

dofetilide metabolite / activity

dofetilide N-oxide metabolite is class I na channel blocker but doesn’t contribute to efficacy

dofetilide risk of torsades de pointes is directly related to what

plasma level of drug

what monitoring is required for first few days on dofetilide

cardiac monitoring and kidny function assessment

dofetilide ddi’s are possible with drugs that impair what/ inhibit what

drugs that impair kidney function/ inhibit CYP3A4 (parent excreted in kidney, liver makes/excretes metabolite)

ibutilide therapeutic uses

Intravenous formulation of fumarate salt for rapid conversion sinus rhythm in atrial fibrillation (similar to esmolol)

ibutilide also activates what

besides being an open state class III selective blocker of delayed rectifier K channels it ALSO activates slow inward Na currents

ibutilide experiences rapid what

oxidative metabolism to heptyl side chain —→ inactive

ibutilide warning

torsades de pointes risk

adenosine therapeutic use / dosage form

Intravenous formulation for the acute treatment of paroxysmal supraventricular tachycardia (PVST)

adenosine moa

Agonist of adenosine Type 1 G-protein coupled receptors (A1R)

adenosine activating A1R receptor leads to what activation and where

activation of acetylcholine-senstive K current in the sinoatrial and AV nodes

adenosine half life

10 seconds, v short but good b/c does a lot

adenosine warning / contra (3)

1) transient asystole (heart block)

2) dyspnea

3) atrial fib

sotalol

amiodarone (des-ethyl amiodarone just has an H instead of one ethyl on the N)

dronedarone

dofetilide (metabolite dolfetilide N-oxide just has an extra O on the N so positive charge)

ibutilide

adenosine