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Therapeutics Exam 4 Maynard
Therapeutics Exam 4 Maynard
37
Pharmacology
Graduate
09/19/2010

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Term
abnormal impulse generation - increased automaticity
Definition
the rate of spontaneous impulse generation of an abnormally automatic tissue exceeds the usual automaticity of the SA node, resulting in tachycardia
caused by early after depolarizations or delayed after depolarizations
Term
1) 2 pathways for impulse conduction
2) area of unidirectional block (prolong refractoriness) in one pathway
3) slow conduction in the other pathway
reentry begins with a critically timed premature beat
can occur at any level of the conduction system
various forms of heart disease or conduction abnormalities are often present prior to development of a reentrant loop - usually the result of ischemic or hypoxic damage leading to inflammation and fibrosis
Definition
3 conduction requirements for formation of a reentrant tachycardia - the indefinite propagation of electrical impulse and continued activation of previously refractory tissues
Term
atrial fibrillation
Definition
a supraventricular tachycardia characterized by uncoordinated and extremely rapid (400-600bpm) atrial activation with consequent deterioration of mechanical function
Term
acute atrial fibrillation
Definition
atrial fibrillation that has occurred in the last 48 hours
Term
paroxysmal atrial fibrillation
Definition
atrial fibrillation that lasts less than 7 days, begins and terminate suddenly
most common type of afib
Term
persistent atrial fibrillation
Definition
atrial fibrillation that continues for longer than 7 days, does not spontaneously stop on its own but can be treated with drugs
Term
permanent atrial fibrillation
Definition
atrial fibrillation that does not stop even with drug therapy
Term
lone atrial fibrillation
Definition
atrial fibrillation is the only issue, patient does not have any other disease states
Term
valvular disease
CAD
caffeine
alcohol
hyperthyroid
Definition
risk factors for atrial fibrillation
Term
[image]
irregular rhythm
no organized atrial activity
loss of "atrial kick" - P wave
symptoms vary
Definition
appearance of afib on an EKG
Term
some patients have minimal to no symptoms, while others experience severe symptoms at the onset of arrhythmias
most patietnts complain of palpitations/rapid heart beats and/or symptoms of worsening heart failure (shortness of breath and fatigue), lightheadedness and syncope
severe symptoms may include hypotension, pulmonary edema, chest pain, and hemodynamic instability requiring immediate medical attention
Definition
symptoms of afib
Term
embolic (cardiogenic) stroke in afib
embolic stroke may occur in afib via arterial embolization as a result of atrial stasis and mural thrombi occuring during fibrillation
Definition
risk of Afib
Term
EKG
CXR
thyroid, renal, hepatic function (to rule other things out)
chem-7 and CBC
2-D echocardiogram, transesophogeal echocardiogram (TEE)
Definition
diagnosis of afib
Term
rate control
rhythm control/maintenance of normal sinus rhythm (NSR)
stroke prevention
Definition
goals of therapy for afib
Term
non-DHP Ca channel blocker
beta blocker
digoxin
Definition
ventricular rate control in afib
patient has been in afib for >48hrs (chronic or paroxysmal afib)
LVEF > 40%
Term
beta blocker
digoxin
Definition
ventricular rate control in afib
patient has been in afib for >48hrs (chronic or paroxysmal afib)
LVEF < 40%
Term
nonDHP CCB
beta blockers
digoxin
Definition
ventricular rate control in afib
patient has been in afib for <48hrs (new or acute onset afib)
AVEF >40%
Term
digoxin
diltiazem
amiodarone
beta blocker - use with caution
Definition
ventricular rate control in afib
patient has been in afib for <48hrs (new or acute onset afib)
LVEF <40%
Term
beta blockers
Definition
MOA: decreases sympathetic stimulation of the AV node, slows AV nodal conduction, thereby decreasing impulses transmitted to the ventricles and the ventricular response rate
indications: indicated for acute and as maintenance rate control therapy in patients with normal LV function, should be considered first in states of high adrenergic tone (thyrotoxicosis, alcohol withdrawal), IV route should be used for acute management, controversial in patients with HF b/c of potential for exacerbation/worsening
adverse effects: CV - hypotension, bradycardia, AV block, HR exacerbation. metabolic - increase TG and decrease HD, glucose intolerance. pulmonary - bronchospasms. other - fatigue, depression, sexual dysfunction
monitoring - vital signs, HF symptoms (SOB, fatigue, weight gain), adverse effects
cautions/contraindications: CV - SBP<90-100, HR<60bpm, 2nd/3rd degree heart block, severe PVD, moderate-severe LV failure WITH fluid overload, WPW syndrome. pulmonary - severe bronchospastic airway disease
Term
nonDHP CCB
Definition
MOA: decreases intracellular influx of Ca in Ca dependent tissues (AV node), Slows AV nodal conduction thereby decreases impulses transmitted to the ventricles and the ventricular response rate
indications: first line rate control agent in patients with normal LV function, diltiazem is often the agent of choice b/c of adverse effects associated with verapamil
***should be avoided as a MAINTENANCE THERAPY in patients with impaired LV function***
adverse effects: CV - hypotension, bradycardia. GI - constipation. Other - fluid retention, HA, dizziness
monitoring - vital signs, HF symptoms (SOB, fatigue, weight gain), adverse effects
Term
digoxin
Definition
MOA: increases vagal tone to the AV node, prolongs refractory period in the AV node thereby decreasing impulses transmitted to the ventricles and the ventricular response rate
indication: ideal maintenance therapy for rate control in atrial flutter or in AF patients with concomitant HF, ***digoxin dose should be reduced by 50% for concomitant amiodarone therapy***
adverse effects: digoxin toxicities are serious and may be fatal. CV - ventricular arrhythmias, heart block, bradycardia. GI - anorexia, N/V, abdominal pain (NOTE: these are often the first signs of toxicity). CNS: confusion, agitation, delirium, visual disturbances
patients are predisposed to digoxin toxicity by the following factors: hypokalemia, hypomagnesemia, interacting medications (amiodarone, thiazide and loop diuretics, verapamil), renal insufficiency
monitoring: Chem7/BMP, evaluation of serum K and renal functions at baseline, then q3-6 months, renal function should be monitored closely in patients also receiving diuretics, serum digoxin levels, ***hold AM dose in order to obtain an accurate serum level***
Term
The Cardiac Arrhythmia Suppression Trail (CAST)
CAST II - stopped prematurely b/c of a trend towards an increase in mortality in morcizine group
Definition
one of the most influential studies in antiarrhythmic therapy ever conducted
has directed treatments of tachycardias and drug development (shift away from Na blocking drugs and to K blocking drugs)
randomized patients post MI with EF < 55% after documentation of premature ventricular contraction
study interrupted by safety and monitoring board
preliminary results: flecainide (type 1 agent) compared to placebo associated with increased rate of total mortality and death due to arrhythmia (presumed drug induced pro-arrhythmia)
Term
amiodarone and dofetilide
Definition
To date, only ( ) and ( ) have been shown to NOT increase mortality with long term use.
Term
Atrial Fibrillation Follow-up Investigation on Rhythm Management - AFFIRM trail
Definition
AV nodal blocking drugs (digoxin, BB, nonDHP CCB) was compared to type I or type III antiarrhythmic drugs (mostly amiodarone, sotalol, and propafenone)
mortality not different between the 2 groups, but tended to be higher in the group given antiarrhythmic drugs to maintain sinus rhythm
Term
AFFIRM results
disadvantages of antiarrhythmic drugs
side effects such as proarrhythmic effects
drug interactions
long-term toxicities
AF often recurs after initial cardioversion b/c most patients have irreversible underlying heart and/or lung disease
Definition
Rhythm control/cardioversion with antiarrhythmic drugs is recommended only for patients with documented paroxysmal AF associated with intolerable symptoms because:
Term
flecainide
propafenone
sotalol
PD FADS
amiodarone
dofetilide
dronedarone
Definition
what antiarrhythmics can be given to a patient with no cardiovascular disease?
Term
amiodarone
dofetilide
Definition
what antiarrhythmic can be given to patients with cardiovascular disease - HF?
Term
sotalol
amiodarone
dofetilide
dronedarone
SADD
Definition
what antiarrhythmic can be given to patients with cardiovascular disease - CAD?
Term
amiodarone
dronedarone
Definition
what antiarrhythmics can be given to patients with cardiovascular disease - HTN with LVH?
Term
flecainide
propafenone
sotalol
dronedarone
Definition
what antiarrhythmic can be given to patients with cardiovascular disease - HTN without LVH?
Term
amiodarone
Definition
Class III antiarrhythmic - also causes Na channel, K channel, Ca channel blockage and behaves like a BB
indications: ***proven safe and effective for patients with HF***
half life of 15-100 days
adverse effects:
pulmonary fibrosis, monitoring parameter - CXR, pulmonary function test, monitoring frequency - baseline then q12 months as needed if symptoms develop, management - DISCONTINUE IMMEDIATELY, steroids may be needed
hypothyroidism: monitoring parameter - thyroid function test, monitoring frequency - baseline, then q6 months, management - thyroid hormone supplementation
hyperthyroidism: monitoring parameter - thyroid function test, monitoring frequency - baseline, then q6 months, management - antithyroid drugs
optic neuritis/neuropathy: monitoring parameter - ophthalmologic examination, monitoring frequency - baseline, then q12 months, management - discontinue immediately
corneal microdeposits: monitoring parameter - routine monitoring not necessary, management - no treatment necessary
elevation in hepatic transaminases (usually asymptomatic, hepatitis is rare): monitoring parameter - liver function test, monitoring frequency - baseline, then q6 months, management - lower the dose if possible or discontinue if severe
N/V/anorexia, abdominal pain: no specific monitoring parameters, management - lower the dose, take with food, take with divided doses
bradycardia/heart block: monitoring parameter - EKG, monitoring frequency - baseline then q3-6 months, management - lower the dose if possible or discontinue amiodarone if severe
tremors/ataxia/peripheral neuropathy: no monitoring parameter, management - lower the dose if possible, or discontinue if severe
photosensitivity/blue-gray skin discoloration: no monitoring parameter, management - advise patients to wear sunscreen while outdoors.
cautions/contraindications: iodine allergy, 2nd/3rd degree heart block, bradycardia, prolonged QT interval, hepatic or pulmonary disease
drug interactions: digoxin - increased concentration and effect with AV/SA node depression, **decrease digoxin dose by 50% when using with amiodarone**, warfarin - decreased metabolism of warfarin and increased effect **decrease warfarin dose by 50% when using with amiodarone**, quinidine/procainamide/disopyramide - increased antiarrhythmic concentrations and increased risk of torsades de pointes, nonDHP CCB - bradycardia and AV block, BB - bradycardia and AV block, phenytoin - increased phenytoin concentration and effect
Term
dronedarone
Definition
bioavailability low but can be increased up to 50% if taken with food
half life = 13-19 hours
indication: ***not safe in CHF NYHA class IV patients, those with recent CHF hospitalization***
adverse effects: CV - new/worsening CHF, bradycarida, hypotension, QT prolongation. GI - N/V, diarrhea, abdominal pain. skin - rash. renal - increase SrCr
contraindications: heart failure, 2nd/3rd degree heart block, bradycardia, prolonged QT interval, severe hepatic disease, drug interactions, pregnancy/nursing
Term
dofetilide
Definition
MOA: class III antiarrhythmic, ***pure K channel blockade***
indications: conversion and maintenance of sinus rhythm in highly symptomatic patients with AF/A flutter, proven safe and effective in patients with HF, dose is dependent on CrCl and QT interval
***eliminated renally (glomerular filtration and tubular secretion)***
adverse effects: CV - hypotension, bradycardia, QT prolongation, torsades de pointes. CNS - syncope, dizziness, headache
monitoring: vital signs, BP and HR (baseline, q shift, 1-2 days after initiation, q follow up), EKG, ***QT interval at baseline and 2-3 hours after each dose while hospitalized during initiation***
cautions/contraindications: prolonged QT interval, CrCl<20ml/min, 1st/2nd degree heart block, bradycardia
drug interactions: inhibition of renal tubular secretion - HCTZ (also lowers K), megace, trimethoprim, ***cimetidine (3A4 inhibition)***, ketoconazole (3A4 inhibition), prochorperazine. increased absorption - verapamil. use with caution with medications that inhibit CYP450 or cause hypokalemia
***patients must be admitted to the hospital, other antiarrhythmic therapy should be stopped for a minimum of 3 half lives, patients must be off amiodarone for at least 3 months or until levels are less than 0.3mcg/ml, patients should be anticoagulated, patients must be monitored, patients should be hospitalized for 3 days or 12 hours after conversion to normal sinus rhythm, whichever is longer
Term
sotalol
Definition
MOA: class III antiarrhythmic
efficacy: SWORD - significantly increased mortality when used in patients with HF
indications: ***no evidence that it converts patients to NSR***, ***must be hospitalized to initiate***
renally eliminated
adverse effects: CV - bradycardia, hypotension, AV block, HF exacerbation, QT prolongation, arrhythmia. pulmonary - bronchospasm. GI - N/V, diarrhea. CNS - dizziness, fatigue
monitoring: vitals, SrCr and K at baseling and q follow up visit (at least 6 months), adverse effects
precautions/contraindications: bronchospastic disease, ***renal failure***, ***heart failure***, prolonged QT interval, 2nd/3rd degree heart block
Term
if AFib is >48h, anticoagulate for 3 weeks prior and 4 weeks after conversion
if immediate cardioversion is required, anticoagulate immediately with heparin or LMWH
if cardioversion is emergent and TEE cannot be obtained, start UFH ASAP followed by 4 weeks of anticoagulation with warfarin to INR2-3
***full atrial contraction does not occur immediately after cardioversion; maximum contractile force returns over a period of 3-4 weeks***
TEE negative for presence of thrombus may indicate that 3 weeks of anticoagulation before cardioversion is not needed
Definition
what anticoagulation has to be done before cardioversion?
Term
cardiac ablation: 90-98% effective, useful for - afib, atrial flutter, AV reentrant tachycardia, WPW syndrome, atrial tachycardia
DC electric cardioversion: most effective within 24 hours of onset, TEE must be performed, electric shock provided to the heart, disrupts irregular electrical activity, re-synchronizes electrical conductance, useful in afib or atrial flutter
Definition
non-pharm strategies for cardioversion
Term
patients in afib for <48h will not need anticoagulation, but duration of afib is often unknown at the time of patient presentation
CHADS2: CHF, HTN, age > 75, DM, TIA/stroke = 2
0 points = aspirin 81-325mg
1 point = aspirin81-325mg or warfarin
2 or > = warfarin
Definition
stroke prevention guidelines for patients with afib
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