Pharm: Anti-Arrhythmics Drugs Flashcards
What are the three mechanisms that can lead to tachyarrhythmias ?
Increased automaticity (SA, ectopic pacemaker etc)
Triggered activity
Re-entry (due to unidirectional block)
Increased or altered automaticity and Triggered activity are forms of altered impulse _________.
Formation
Re-entry is a form of altered impulse ________.
propagation
Bradyarrhytmias are due to __________ impulse formation and exhibit ___________ phase 4 depolarization
Decreased
Decreased
What are the mechanisms that lead to impaired conduction ?
Ischemic , anatomic or drug induced
To treat bradyarrhythmia with pharm you can give drugs that inhibit vagal tone or drugs that induce chronotropic effects of the heart. Which drug would you give to block vagal effects ?
Atropine
Which drugs would you give to induce chronotropic effects in the heart to treat bradyarrhythmia ?
B1-receptor agonists
Dopamine
Isoproterenol
How could you treat a bradyarrhythmia long term w/o drugs ?
Pacemaker
Altered automaticity leading to tachyarrhythmia results in _______ phase 4 depot on SA node AP.
increased
This is known as Sinus tachy.
The pharmacologic goal of treating tachyarrhythmia is
to eliminate increased automaticity
How do drugs eliminate automaticity when treating tachyarrhthmia ?
- Decrease the slope of phase 4 in pacemaker cells. (aka less steep phase 4, slower depolarization)
- Make diastolic potential more negative
- Make threshold potential less negative
Abnormal automaticity in atrial or ventricular myocytes is due to cells aquiring phase 4 depolarizations. What are two ways this can occur ?
Digitalis Toxicity
Increased Sympathetic tone
Triggered activity leads to what kind of non-typical depolarizations ?
Early After Depolarizations
Delayed after Depolarization
What is ‘triggered activity’ ?
A depolarization that forms after a single or multiple impulses following a preceeding depolarization
Early After Depolarization (EAD’s) occur due to conditions that prolong _______ interval.
QT
Due to their mechanism ,EAD predispose patients to what condition ?
Torsades De Pointes
What occurs to Phase 2 Ca++ influx in EAD’s ?
It is increased (leading to a longer Phase 2 –> Longer QT interval
What occurs to Na+influx in Phase 3 during EAD’s ?
It is increased, Longer Phase 3 –> Longer QT interval
DAD’s are theorized to occur due to …
Intracellular Ca++ overload
What are the specified goals of treating Triggered activity ?
Preventing EAD’s by shortening AP duration
Correct DAD’s by correcting conditions of calcium overload
What is required for Re-entry to occur ?
Unidirectional block Slowed conduction (retrograde)
What are the overall goals of treating reentry related tacchycardia ?
Extinguish the re-entry by impeding propagation in the slow conducting limb
Increase the refractory period of the tissue the re-entry is stimulating. (If it is total refractory it will not be able to fire)
Mechanism of Class I Antiarrhythmics
Na+ Channel Blockers
Mechanism of Class IA Antiarrhythmics
Block Na+ channels that lead to prolonged depolarization (increased refractory phase)
Mechanism of Class IB Antiarrhythmics
Shorten repolarization by blocking Na+ Channels
Mechanism of Class IC Antiarrhythmics
Blocks Na+ Channles (no real effect of AP)
Mechanism Class II Antiarrhythmics
Beta Receptor Blockers
MechanismClass III Antiarrhythmics
K+ Channel blockers, prolong the AP duration by not allowing depolarization
Mechanism Class IV Antiarrhythmics
Block Ca++ channels leading to decreased AP duration
List the Class IA drugs
Disopyramide(Minor), Quinidine , Procainamide
Pneumonic :Double Quarter Pounder
List the Class IB drugs
Lidocaine, Phenytoin, Mexelitine, Tocainide
(Pneumonic|: Lettuce, Pickle, Mayo, Tomato
List Class IC drugs
Flecainide, Propafone (Minor
Pneumonic: Fries Please
List Class II Drugs
Propanolol, Metoprolol and Esmolol
Propanolol is not Beta1 selective while the other two are.
List Class III drugs
Amiodarone, Sotalol, Bretylium, Ibutitide (minor) and Dofetitide (minor)
Note: One of the metabolites of Procainamide (1A) is N-Acetylprocainamide and has Class III actions.
List Class IV drugs
Verapamil Diltiazem (notice how these are non-DHP CCB’s. These have more effect on the heart)
List the miscellaneous drugs used for Arrhythmia
Adenosine, digoxin, magnesium
What are the overall effects of Class I drugs (Na Channel Blockers)
Decreased automaticity
decreased conduction velocity
can prevent reentry arrhythmias
Indication for class IA drugs
wide variety of reentrant & ectopic supraventricular & ventricular tachycardias
Where do class IA drugs mainly have their effects in treating automaticity?
Purkinje Fibers and Ectopic pacemakers (actually have little effect of SA node automaticity)
Is it possible for Class IA drugs to convert a-flutter and A-fib to normal sinus rhythm ?
YES !
How do Class IA drugs treat reentrant arrhythmias ?
Produce bidirectinal blocks (decreases conduction)
increase refractory period ! (UNIQUE TO 1A !!!)
(Note:Later on he says that Class III drug affect the refractory quality of the perkinje and ventricular muscle fibers, so maybe Class IA only affect atrial ?)
What may Class IA drugs predispose a patient to ?
Torsades De pointes
What is the protoype Class IA drug ?
Quinidine
Quinidine (IA) has strong anti-muscarinic effects. How will this alter SA node automaticity and AV node conduction ?
Increase both SA and AV node automaticity
What can you pre-treat with prior to giving quinidine to ensure minial vasolytic effects ?
Digoxin, BB’s or Verapamil (a CCB)
Quinidine Side Effects
Diarrhea (most common, 1/3 of all patients)
Torsades de pointes
Cinchonism
What is cinchonism ?
Side effect caused by quinidine resulting in : tinnitus, headache, vertigo, disturbed vision (is usually dose related)
What are the drug interactions related to Quinidine
Increases digoxin levels by decreasing it’s clearance
Procainamide (IA) is like quinidine except..
it is not as anti-muscarinic, meaning that it will not increase the ventricular rate as much as quinidine us would
It also has marked decrease in ability to prolong the QT interval, thus less likelyhood of Torsade de Pointes
Adverse effects of Procainamide
Lupus Like Syndrome :arthralgias, rash, fever, connective tiss. inflammatio (is reversible with discontinuation)
Active metabolite N-Acteylprocainamide works like a Class III drug which may lead to QT prolongation and TdP.
When is disopyramide contraindicated ?
Patients w/ heart failure due to negative inotropic effects
Not really used much anymore
Class IB drugs are most commonly used to …
Supress Ventricular Arrhythmia (esp if associated w/ ischemia or digitalis)
Class IB drugs act to inhibit re-entrant arrhythmias by ..
Decreasing conduction velocity
How do IB drugs decrease automaticity of ectopic pacemakers ?
Raising the threshold potential so that depolarization is more difficult.
Class IB side effects
Seizures
Confusion
dizziness
Which of the IB drugs are an oral anolog of lidocaine (IB) ?
Mexiletine
Adverse effects of Mexiletine
Tremor, nausea and seizure
When is Phenytoin going to be used exclusively ?
Digitalis induced arrhythmia (delayed afterdepolarizations)
Class IC drugs are indicated for …
Atrial fib, supraventricular arrhythmia in patients with otherwise healthy hearts
Class IC drugs can be proarrhythmic by increasing what ?
QRS comples
Indications for Class II
Suppressing arrhythmias induced by excessive catecholamines (stress: exercise, emotional), including triggered arrhythmias
A.fib/Flutters
Re-entrant rhythms involving the AV node
Class II drugs are the only to show
decreased mortality by preventing recurrent infarction and sudden death in patients recovering form acute MI !
Which Beta Blocker has Class III interactions ?
Sotalol
Which of the beta-blockers have a less complete BB effects ?
Acebutolol, Pindolol
HAVE Intrinsic Sympathomimetic Activity (ISA)
What is an adverse effect of Class II drugs ?
Beta blockers cause AV block and thus sinus bradycardia
Class III drugs block K+ currents. This leads to
Prolonged AP and refractory period.
Prolonged QT interval
Due to their effect on the QT interval, Class III drugs predispose patients to
TdP
amiodarone is effective when used for
A.fib/flutter
Bypass tract mediated parosysmal SVT
V. Tach,
Amiodarone is First line drug for ..
Tx. of vent. arr. during cardiac resuscitation
Amiodarone is go for treating arrhythmias in patients with vent. sys. dysfunction because
less pro-arrhythmic complications than with many other agents
Mechanism of Amiodarone action
Prolong AP duration & refractoriness of all cardiac fibers: blocks K+ rectifier current
Amiodarone has effects in all classes. Explain Class I, II and IV effects
Significant Na+ channel blocker effect as well (Class I).
Weakly blocks Beta-rec.’s & Ca++ channels (Class 2 & 4)
Prolong PR, QRS & QT intervals
Additional firing suppression provided by these effects likely account for the absence of Torsades typically seen with agents that produce long QT intervals
What are the extracardiac effects of amiodarone ?
peripheral vasodilation (noncompetitive alpha-blocker & blocks Ca++ influx in vascular smooth muscle) perhaps beneficial, rarely requires discontinuation
Why will amiodarone accumulate in most organs ?
Highly lipophilic
in plasma, highly bound to proteins
Where is amiodarone inactivated ?
In the liver
Why is amiodarone difficult to discontinue ?
VERY SLOW ELIMINATION… prolonged effects event after it has been stopped
Drug interactions of amiodarone
Increased action of Dig. & warfarin, avoid other drugs with negative chronotropic/inotropic effects (Beta-blockers, verapamil, diltiazem)
What occurs with prolonged high dose treatmet with amiodarone ?
Toxicities with the most serious being PULMONARY FIBROSIS
Others include : Corneal micro-deposits
Hypo and hyperthroid problems
Sotalol (III) is used for
supraventricular & ventricular arrhythmias
what are the major side effects associated with sotolol >
bradycardia, AV block, CHF, bronchospasm (these are those associated with BB’s as well)
When is Bretylium tosylate indicated ?
for life-threatening v. tach or v. fib when all other resuscitation attempts fail
How does Bretylium tosylate work ?
initially increased release of NE at nerve terminals followed by decreased release.
Overall there is a decrease in catecholamines .R aises threshold for vent. fibrillation
Side effect of Bretylium tosylate ?
Orthostatic hypotension
Dofetilitide is a new AA drug and is unique in that it is a …
PURE K+ channel blocker –> Delays depolarization
When is Dofetilide used ?
Conversion of A-fib & A-flutter sinus rhythm, maintenance of rhythm after conversion
Adverse effect of Dofetilide
TdP
When are the Class IV drugs used
reentrant arrhythmias whose circuit involves AV node. Also decreased ventricular rate in A-flutter, A-fib
Side effects of Class IV drugs
Similar effects as Betablockers (can cause bradycardia, HF, AV block)
May cause hypotension
Adenosine is the DOC for …
termination of PSVT with reentrant circuits involving the AV node, including WPW syndrome
How does Adenosine achieve its therapeutic action ?
Activates K+ rectifier current in SA & AV nodes
decreases Ca++ influx
Leads to hyperpolarization and inhibition of Ca++ dependent depolarization (decreases SA automaticity and AV conduction)
What is Adenosines affect of cAMP levels and what will this cause ?
inhibits intracellular adenylate cyclase–>cAMP-mediated effects which occur with sympathetic stimulation
This leads to decreased inward pacemaker current (If channels)
and decreases Ca influx
Why must Adenosine be given as an IV bolus as close to the heart as possible ?
Extremely short plasma t1/2 (< 10 seconds)
Rapidly cleared from the blood and thus has minimal adverse effects
What are the side effects related to Adenosine
Transient asystole: common but lasts < 5 sec & is, in fact, the therapeutic goal
Rarely precipitates A-fib
Drug interactions of Adenosine
Methylxanthines block adenosine receptors
Caffeine and Theophyline
When is digoxin used ?
Commonly used for CHF complicated by A. Fib
Not really used much anymore due to narrow therapeutic range and side effects.
Digoxin MOA
Decreases AV nodal conduction by direct depressant effect on AV node and by acting in the CNS to increase vagal impulses to the AV node.
Leads to prolonged PR interval
Decreases SA node automaticity by increasing’ing vagal activity and decreasing sympathetic activity at the node
Digoxin has a propensity to cause arrythmias. How do you treat these ?
Treat dig.-induced arrhythmias with digoxin-immune F-ab (digoxin antibody fragments), lidocaine or phenytoin
When is MgSO4 indicated ?
IV admin. prevents recurrent episodes of torsades de pointes
