Pharm - Antiarrhythmics Flashcards
What are the Vaughn Williams classes
IA IB IC II III IV
3 Class IA drugs
- Disoyramide
- Procainamide
- Quinidine
3 Class IB drugs
- Lidocaine
- Mexiletine
- Phenytoin
2 class IC drugs
- Flecainide
- Propafenone
1 Class II drug
beta blockers
5 Class III drugs
- Amiodarone
- Dofetilide
- Ibutilide
- Sotalol
- Dronedarone
2 Class IV drugs
- dihydropyridine calcium channel blockers
- non-dihydropyridine calcium channel blockers
Class IA MoA
- Moderate Na+ channel - K+ to a lesser extent
- slow conduction velocity
- prolong refractoriness
- decrease automatic property of na-dependent conduction tissue
Class IB MoA
Weak Na+ channel antagonists
- decrease conduction velocity
- decrease refractory period
- decrease automaticity
Class IC MoA
Extremely potent Na+ channel blockers
- greatly slows conduction velocity
- decreases automaticity
- no change to refractory period
Class II MoA
beta blockers
- anti-adrenergic blockers (SA and AV nodes)
- decrease conduction velocity
- increase refractory period
- decrease automaticity
Class III Moa
Block K+ channels
- prolongs refractoriness in atrial and ventricular tissue
- delays repolarization
- no affect on conduction velocity or automaticity
Class IV MoA
Calcium channel blockers
- slow conduction velocity
- prolong refractory period
- decrease automaticity
Disopyramide ADR
- hypotension (serious)
- cardiac failure (serious)
- anticholinergic (dry mouth, urinary hesitation, constipation) most common
- EKG changes (widen QT interval)
- proarrhythmic action
Lidocaine ADR
- CNS toxicity (most common)
- Cardiovascular toxicity
- GI: n/v anorexia
Mexiletine ADR
- GI: n/v heartburn, take with food
- CNS
- Cardiovascular: heart failure and hypotension
- Dermatitis: face and trunk
- Proarrhythmic action: avoid in lesser arrhythmias like asymptomatic PVC
Flecainide ADR
- Cardiac toxicity (pro arrhythmic, conduction abnormalities, hemodynamics like negative inotropic effects)
- dizziness, blurred vision, HA, nausea
- neurotoxicity (dizzy, visual changes, psychosis, hallucinations, seizures)
Flecainide
- conduction abnormalities
- prolongs depolarization
- slows conduction in AV node/His-Purkinji
- prolonged PR interval (slows dronotropy)
- increased QRS
- first and second degree heart block
- No effect on QT
Felcainide: what is main downside to hemodynamic changes
decreased inotrope can cause or worsen heart failure
Propafenone ADR
- GI – dysgusia, nausea: take with food
- CNS
- Cardiovascular: beta blocker effects (negative inotropic activity, bradycardia, slow AV conduction, prolong PR and QRS intervals etc.)
List the 7 big ADR associated with beta blockers
- Exacerbation of heart failure
- Negative chronotropic effect
- beta blocker withdrawal
- increased airway resistance
- facilitation of hypoglycemia
- fatigue
- sexual dysfunction
beta blocker ADR
- Exacerbation of heart failure
- Exacerbate heart failure in pts in acute decompensated situation
- Cause heart failure in pt with preexisting myocardial dysfunction with borderline compensation
- These pts’ cardiac output depends on sympathetic drive which is taken away by β-blockers
beta blocker ADR
- Negative chronotropic effects
- slowing heart rate which can be problem with pts who have sick sinus syndrome
- depressing conduction through AV node, potentially causing heart block. This is a problem in pts with complete or partial AV conduction problems
beta blocker ADR
- β-blocker withdrawal
- Receptor upregulation due to continued blocking, when stop β-blocker, now have too much response to circulating catecholamines stimulation
- Acute withdraw: can lead to morbidity and mortality, I pts with known CAD, can exacerbate ischemic sx (precipitation of acute MI)
- Gradual tapering off β-blocker should be considered
beta blocker ADR
- Increased airway resistance
Nonselective β-blockers prevent bronchodilation (bronchial β2 receptors) → increased airway resistance in pt with bronchospasm dz
beta blocker ADR
- Facilitation of hypoglycemia
- Epinephrine increases glucose production, helps prevent hypoglycemia.
- β-blocker can increase risk of hypoglycemia because blocks release of glycogen from the liver when glucose is needed.
- Epinephrine induces early warning signs of neuroglycopenia
- β-blocker can decrease the perception of hypoglycemia (except sweating)
beta blocker ADR
- fatigue
β-blocker reduces hearts ability to respond to increased activity
Sotalol ADR
- Cardiovascular
- Prolonged QT
- Bradycardia
- Torsades de Pointes
- New ventricular arrhythmias
- New/worse heart failure
- Proarrhythmia
Amiodarone ADR - list 7 main
- Pulmonary
- Thyroid
- Cardiac toxicity
- Hepatotoxicity/GI
- Ocular Chanes
- Skin reactions
- Neuro
Amiodarone
- Pulmonary ADR
- Related to cumulative dose
- Chronic interstitial pneumonitis is most common
- Also organizing pneumonia, ARDS, solitary pulmonary mass
- Nonproductive cough and dyspnea in affected pts
- Pleuritic pain, weight loss, fever, malaise
Amiodarone
- Thyroid ADR
- Hypothyroidism
- Can occur anytime, not dose related
- Hyperthyroidism
- Occurs early and suddenly
- Thyrotoxic sx
- Type I: related to iodine load = lots of thyroid hormone produced
- Type II: destruction of thyroid cells leads to release of thyroid hormone
Amiodarone
- Cardiac toxicity ADR
- Ca2+ channel blocking activity
- Sinus bradycardia
- AV nodal block
- K+ channel blocking activity
- Prolongation of QT interval and repolarization
- Ventricular arrhythmias
- Torsades de Pointes – more common with other factors that prolong QT interval
Amiodarone
- GI/Hepatoxicity ADR
- Jaundice or hepatitis
- Test AST and ALT (2X elevation = stop drug)
- GI: n/v/d, anorexia, constipation
Amiodarone
- Ocular Changes ADR
- Corneal microdeposits: “cat whiskers” on cornea, not usually a problem
- Optic neuropathy: Big time problem – optic nerve injury = unilateral or bilateral visual loss/blindness
Amiodarone
- skin change ADRs
- Photosensitivity
- Blue-gray slate colored skin
Amiodarone
- neuro ADR
Many forms: tremor, ataxia, peripheral neuropathy, paresthesias, sleep disturbance
Dronedarone ADR
- GI: abd pain, n/d, rash
- Hepatic damage
- CV: 2X heart failure risk with given to pt with mod-to-severe left ventricular systolic dysfunction who are recently decompensated
- Pulmonary toxicity
- Skin reactions (eczema, rash, photosensitivity)
- Thyroid issues seen in amiodarone
Ibutilide ADR
- Cardiac toxicity (Hypotension, sinus-tachy, supraventricular tachycardia, sinus bradycardia, AV block, BBB)
- Proarrhythmias
Disopyramide drug interactions
Contraindicated with concurrent use of drugs that prolong QT interval (quinolone abx, etc.)
Flecainide drug interactions
Contraindicated with ritonavir (HIV drug)
Sotalol drug interactions
QT prolonging drugs (macrolides, Zofran, etc.) bc sotalol also prolongs QT interval
Amiodarone drug interactions
- Digoxin
- Warfarin
- Statins, esp. simvastatin
- Azoles
- quinolone abx
- QT prolonging drugs
Amiodarone and Digoxin
- effect
- action
- Amiodarone can increase digoxin levels
- Decrease digoxin by 25-50% empirically
Amiodarone and Warfarin
- effect
- action
- Amiodarone can change Warfarin metabolism, increasing levels
- Can increase INR to dangerous levels
- Decrease warfarin by 25-50% empirically
- Titrate to INR goal
Dronedarone drug interactions
QT prolonging drugs
Monitoring tests and frequency for pts on Amiodarone
- PFT/CXR – baseline and if sx
- Thyroid panel – baseline, q 3-6 mo
- Liver panel – baseline, q 3-6 mo
- Eye exam – baseline, q 12 mo
- Interacting drug plasma level (esp warfarin) – baseline, PRN (INR weekly first 3-4 weeks)
- Clinical evaluation – baseline, q 3 mo
5 Agents that increase risk of Torsades de Pointes
- Disopyramide
- Sotalol
- Dofetilide
- Amiodarone
- Ibutilide
Risks of proarrhythmias with antiarrhythmic drugs
- Potential to cause premature ventricular contractions, induce/aggravate VT, torsades de pointes, V-fib, conduction disturbances, bradycardia
- Risks vary according to type of arrhythmia being treated, presence of structural heart disease, QT interval, pre-existing conduction disturbances, sinus node dysfunction, patient age, heart failure, left and right ventricular function
What pt is risk for induced arrhythmia due to antiarrhythmic drug highest
pt with depressed LV function
What is most recognized form of drug proarrhythmias
torsades de pointes
Class I and risk of proarrhythmias
risk is higher with structural heart dz, esp coronary heart disease and/or left ventricular dysfn
Class II and risk of proarrhythmias
bradycardia is biggest risk (except Sotalol which has class III properties at higher doses)
Class III and risk of proarrhythmias
prolong repolarization → torsades de pointes and ventricular tachycardia
