Cardio- Antiarrhythmic Drugs Flashcards
How are the forces different between the influx of sodium and the efflux of potassium, and what is the effect on the action potential
- Sodium is going with the electrical and chemical gradient (faster depolarization)
- Potassium is going with the chemical and against he electrical gradient (slower repolarization)
What is the target for esmolol
Short acting Beta-1 blocker
What is the mechanism of action for ibutilide
Slows the cardiac repolarization by blocking the rapid component fo the delayed potassium current
What are the effects of class 1A drugs on the action potentials
- Prolonged action potential duration
- Prolonged QRS and QT intervals of the EKG
What class of drug is amiodarone
Potassium channel blocker
Which patients populations are more likely to have an adverse reaction to flecainide
- Preexisting ventricular tachyarrhythias
- Previous MI
- Ventricular ectopic rhythms
Where does adenosine work in the heart
A1 adenosine receptor
Procainamide is used to treat which condition
Sustained ventricular tachycardia
What is the method of administration for esmolol
Continuous IV, with a rapid onset and termination
What are the pharmacokinetics for lidocaine
-Extensive first pass, so can only be administered IV
What are the clinal uses for sotalol
- Life threatening ventricular arrhythmias
- Maintaining sinus rhythm in pts with Afib
What are the clinical situations that mexiletine is used
- Ventricular arrhythmias
- Chronic pains due to diabetic neuropathy and nerve injury
IN the inactivated state of sodium channels, which gates are acting
H gates close, starting the refractory period
What are the cardiac adverse effects of lidocaine
May cause hypotension in patients with heart failure due to inhibition of the cardiac contractility
What class of drug is esmolol
Beta blocker
What class of drug is flecainide
Class 1C drug
What are the adverse cardiac effects of Procainamide
- QT interval elongation
- Induction of torsade de pointes
- Excessive inhibition of conduction
What is the mechanism that sympthetic effects are seen in the pacemaker cells of the heart
All resultsin the increases the levels of cAMP and PKA activity
- Epi/norepi binds to the B1 adrenergic receptors, increases the adenylate cyclase activity, which increases the cAMP levels and PKA
- T/L type calcium channels conductance increases from PKA activity
- Funny channels conductance increases with increased PKA
What is the drug class of ibutilide
Class 3 potassium channel blocker
Which class of drug is verapamil
Class 4 calcium channel blocker
What is the mechanism of action for adenosine
Activates the potassium curing and inhibits the calcium in funny channels, leading to hyperpolarization and suppression of action potentials
What are the effects of potassium blockers on Action potentials
- Prolonged action potential duration
- Prolonged QT interval
- Prolonged refractory period
What is the half life of esmolol and what is the metabolism
10 minutes due to hydrolysis by blood esterases
Class 1A sodium channel blockers preferentially affect which cells
Ectopic pacemaker cells with faster rhythms
What are the mechanims of action for class 4 drugs
- aka Cardioactive calcium channel blockers
- Decreases the slope of phase 0
- Increased L type Calcium channel threshold potential
- Prolonged refractory period in AV node
What receptors are affected by amiodarone
- Blocks potassium channels
- Blocks inactivated sodium channels
- Some calcium blocking activity
What are the clinical uses of esmolol
- Supraventricular arrhythmias
- arrhythmias due to thyrotoxicosis
- MI ischemia or acute MI with arrhythmias
What are the clinical uses for adenosine
-Conversion of paroxysmal SVT into normal sinus rhythm
What drug is given to patients that overdose on class 1 drugs and what is the reasoning
- Bicarbonate, which will try to raise the pH of the blood
- THis increase in pH will decrease the rate of protonation of the drugs and decrease their effect (because the activated form in protonated)
Most sodium blockers are acting during which state of sodium channels
Block the activated or inactivated sodium channels
What is the clinical uses for ibutilide
Convert atrial flutter and Afib to sinus
Which clinical situations is lidocaine used
Mono or polymorphic ventricular tachycardias, being very efficient in acute MI
What are the effects of beta blockers on the SA node
Decreased HR (Increased RR interval)
Class 1A drugs bind to which stare of sodium channels
Open (activated) sodium channels
What are the adverse effects of dofetilide
QT interval is Prolonged, with increased risk of ventricular arrhythmias
What are the pharmacokinetics of mexiletine
Oral drug
Class 1 drugs act in which location
Sodium channel blockers
What is the noncardiac effect of verapamil
Constipation
Which class of drug is Procainamide
Class 1A sodium blocker
What is the mechanism of action for dofetilide
Blocks rapid component of the delayed potassium current, so there is a slower HR
What class of drug is mexiletine
Class 1B drug
Which class of drug is disopyramide
Class 1A drug
What are the noncardiac adverse effects of quinidine
- Headache, dizziness, tinnitus
- GI side effects
- Thrombocytopenia, hepatitis, fever
What are the kinetics of class 1B drugs
Fast kinetics
What class of drug is propranolol
Beta blocker
What are the noncardiac adverse effects of disopyramide
Atropine like symptoms ( dry mouth, urinary retention, blurred vision, continuation)
-Exacerbation of glaucoma
What are the channels/affects of sotalol
- Class 2 (beta blocker)
- Class 3 (prolongs AP duration)
What is the clinical use of disopyramide
Recurrent ventricular arrhythmias
What are the adverse affects of propafenone
- Exacerbation of ventricular arrhythmias
- Metallic tase
- Constipation
Class 1C drugs prefer to bind to which channels
Open (activated) sodium channels
-Some potassium channels
Class 1B drugs bind to which channels and in which state
Bind to inactivated sodium channels, so therefore they prefer the depolarized cells
What is the clinical use for dofetilide
Converts atrial fib to sinus rhythm and then maintaining it after
What are the effects of beta blockers on AV node
-Decreased AV conductance (increased PR interval)
What class of drug is diltiazem
Class 4 calcium channel blocker
Which rate of dissociation leads to more sodium channel blockage
Slow dissociation rates
What is unique about the cells lidocaine targets and its effect
Binds to damaged tissue cells and makes them electrically silent , with no effect on normal tissue due to the fast kinetics
What are the adverse cardiac effects of amiodarone
- AV block and bradycardia
- Induction of torsade de pointes (low compared to other Class 3)
What is the metabolism of dofetilide and how does this affect therapeutic window
Eliminated by the kidneys, so the levels have to be very closely monitored
Which drugs need to be monitored with amiodarone
Inhibitor of CYP, so effects metabolism of many drugs
-Metabolized by CYP3A4, so cimetidine (inhibitor) or refaptin (activator)
Why will a sodium channel blocker not affect the slow action potential cells
Aka the pacemaker cells in the SA and AV node
-Because there are not sodium channel present there
What is the drug class of sotalol
- class 2 Beta blocker
- Class 3 Potassium blocker
What are the contraindications for propranolol
- Stress induced arrhythmias
- Reentrant arrhythmias that involved AV node
- Afib and flutter
- Arrhythmias associated with MI
What are the clinical uses of amiodarone
- Treatment of ventricular arrhythmias
- Atrial fibrillation
What is the class of drug for propafenone
Class 1C drug
What are the clinical uses for class 4 drugs
- Prevention of paroxysmal SVT
- Rate control for Atrial flutter and fibrillation
What are the effects of class 4 drugs
Slows the SA node depolarization, leading to bradycardia
Prolonged AP duration and conduction time in the AV node
Which form of sodium channel blockers binds to channels
Cationic form
What are the contraindications for beta blockers
- Asthma
- Peripheral vascular disease
- Raynaud’s syndrome
- Type 1 DM
- Depressed CO
What are the clinical uses for propafenone
- Prevents paroxysmal atrial flutter and SVT without structural diseases
- Sustained ventricular arrhythmias
In the activated state of sodium channels, which set of gates are open
-M gates open in depolarization
What are the adverse cardiac effects of class 4 drugs
- Negative inotropy
- AV block
- SA arrest
- Hypotension
Class 1A sodium channel blockers interact with with channel s
Sodium and potassium are both blocked
What are the kinetics of Class 1C
Slow
Class 4 drugs block which channels
Activated and inactivated L type Calcium channels
Which class of drug is lidocaine
Class 1B drugs
What are the adverse effects of sotalol
- Depression of cardiac function
- Torsade de pointes
What are the effects of class 1C on AP, and the ECG
- No change in the AP duration or QT interval
- Prolonged QRS
What are the numbers of normal sinus rhythm and risk of death while on Quinidine
2x as likely to have normal rhythm
2-3x likely to have risk of death
Which potassium channels are responsible for the regulation of action potentials
Voltage gated determine the refractory period
What are the extracardiac adverse effects of Procainamide
- Ganglion blocking properties and reduces peripheral vascular resistance leading to hypotension
- SLE
- Nausea
What are the noncardiac adverse effects of lidocaine
Paresthesias, tremors, slurred speech, convulsions
What is the clinical uses for Quinidine
Restoring rhythm in atrial flutter/fibrillation with normal hearts
Which potassium channels are open in the resting state
Inward rectifying K+ channels but no current due to equilibrium with the electric and concentration gradients
What is the effect on action potentials with regards to class 1B drugs
- Shortens action protentials (because does not affect potassium channels)
- Does not prolong the action potential or the QT duration
What are the cardiac adverse effects of disopyramide
- QT interval prolongation
- Induction of torsade de pointes
- Syncope and heart failure due to excessive depression of cardiac condition
What are the adverse cardiac effects of quinidine
- QT interval prolongation
- Induction of torsade de pointes
- Excessive slowing of conduction
How does esmolol and sotalol differ
Esmolol (beta blocker)
Sotalol (potassium blocker with some beta blocker)
-Because sotalol is a potassium blocker, it will effect the length of the action potential, therefore the QT is prolonged
What are the targets for flecainide
Sodium and potassium channels
Which drugs uses are contraindicated with propafenone
-CYP2D6 or CYP 34A inhibitors (risk of proarrhythmias)
What are the clinical uses for flecainide
Patients with normal hearts who have:
- Supraventricular arrhythmias (aka atrial flutter, paroxysmal SVT)
- Sustained ventricular tachycardia
Which class of drug is quinidine
Class 1A drug
What is the effect of sympathetic activity
- Increased slope due to activity on funny channel and T type Calcium channels
- Reduced threshold for L type Calcium channels
What are the noncardiac effects of amiodarone
- Fatal pulmonary fibrosis
- Hepatitis
- photodermatitis (blue grey skin on sun exposed areas)
- Optical neuritis
- may cause thyroid issues
What are the adverse effects of adenosine
- Shortness of breath
- Bronchoconstriction
- Chest burning
- AV block
- Hypotension
What is the metabolism aspect of ibutilide
Administered IV, and is rapidly cleared by hepatic metabolism
What are the pharmacokinetics of amiodarone
Metabolized by CYP3A4
-Long half life (effects seen 1-3 months after discontinuing)
What are the adverse effects of beta blockers
Decreased CO
Impaired liver glucose metabolization
Increased VLDL and decreased HDL
Sedation, depression
What is a contraindication for Procainamide
-accumulates in renal dysfunction, need to measure both drug and active metabolite
What are the adverse effects of ibutilide
- QT prolongation and increased risk of ventricular arrhythmias
- Require continuous EKG monitoring until the QT returns to baseline
What is the dissociation kinetics of class 1A
Intermediate kinetics
