Anti- Arrhytmic Drugs Pt. 2 Flashcards
AUTONOMIC REGULATION OF HEART RATE
-Nodal tissue innervation
- Parasympathetic nervous system (Muscarinic M 2
receptors)
- Sympathetic nervous system (Adrenergic β 1
receptors)
-SNS: Increases HR
• Increase ICa(L), Increase I k , Increase I f
-PNS: Decreases HR
• Decrease I Ca(L) , Decrease I K ,, Decrease I f, Produces I k(Ach)
Mode of action
CLASS II: β-BLOCKERS
- Decrease SA and AV nodal activity
- Decrease slope of phase 4 (diastolic currents) of action potential in pacemakers
- Increase the refractory period of the AV node and can prevent recurrent SVT: restore sinus rhythm
- Reduce ventricular rate in Afib
- Many dysrhythmias are due to sympathetic activation
CLASS II: β-BLOCKERS
Examples
- Propranolol (non-selective), with minor class I activity
- Metoprolol (β 1 -selective)
-Esmolol (β1 -selective: used in acute SVT via IV route: very short-acting)
Clinical uses of Class II
- to reduce mortality after MI
- to prevent recurrence of tachyarrhythmias (paroxysmal afib) induced by increased symp. activity
- in managing hyperthyroidism while control of anti thyroid drugs is being established
CLASS III: K+ CHANNEL BLOCKERS
Mode of Action
- Block K+ channels, including the outward
(delayed) rectifier current - Significantly prolong APD
- Greater refractory period may interrupt
reentrant arrhythmias and suppress
ectopic beats - Especially active in Purkinje and ventricular
fibers
CLASS III: K+ CHANNEL BLOCKERS
Pro-arrhythmic adverse effects
-Prolonged APD (prolonged QT interval) may
lead to torsade de pointes (polymorphic form of VT)
- Increased risk with antipsychotics,
especially K+ hypokaelemia, hypercalcaemia or hereditary prolonged QT
- Important to monitor electrolyte levels,
CLASS III: K+ CHANNEL BLOCKERS
Examples
- Amiodarone
- dronedarone
- Sotalol
-AMIODARONE Pk PD
- Very effective
- Extensively bound to tissues
- Long half-life: 10-100 days
- Accumulates in the body during repeated dosing
- Loading dose needs to be used and needs to be
given IV
AMIODARONE: ADVERSE EFFECTS
- Photosensitive skin rashes
- Slate-grey/bluish discoloration of the skin
- Thyroid abnormalities
- Pulmonary fibrosis (late in onset but may be
irreversible) - Corneal deposits
- Neurological and GI disturbances, including hepatitis
- Cardiovascular effects
•Bradycardia, heart block, heart failure
• Torsades de pointes and VT are very unusual
Dronedarone
Clinical uses + AE
Lacks iodine: designed to be less lipophilic
than amiodarone to reduce thyroid and pulmonary toxicity
Improved survival in high-risk patients with Afib
Increased mortality in patients with severe CHF
-Sotalol
Use: life-threatening VT
Also non-selective β-blocker
Less effective than amiodarone in prevention of
chronic VTs
Can cause torsades de pointes
Used in paroxysmal Supraventricular dysrhythmias and suppresses ventricular ectopic beats and short runs of ventricular tacchycardia
Amiodarone clinical use
Tachycardia ass. W/ Wolff-Parkinson- White syndrome. Also effective in many other supraventricular and ventricular tachyarrhythmias but has serious AE.
CLASS IV: CALCIUM CHANNEL BLOCKERS
Ex.
Verapamil
CLASS IV: CALCIUM CHANNEL BLOCKERS
Decrease which phases
Decrease phases 0 and 4 in the SA and AV nodes
- Slow conduction in the SA and AV node
- Increase ERP
- Terminate SVT by causing partial AV block and increasing AV nodal refractoriness (increased PR interval)
Decrease phase 2 in fast-response fibers
-Shorten the plateau of the AP
-Decrease contractility
-Reduce after-depolarization: suppresses premature ectopic beats
Verapamil
Uses+ roA
- Main drug in this class
- Uses: prevention of paroxysmal SVT, Afib (reduce
ventricular rate) - Oral preparations
- IV: previously used to terminate SVT: dangerous and
very rarely needed
-> Adenosine is safer for this
Verapamil CI
-Wolff-Parkinson-White-Syndrome
- VTs
Verapamil AE
Constipation (verapamil), dizziness, flushing,
hypotension, AV block, edema
Important drug interactions
With verapamil
-Additive AV block with β-blockers and digoxin
- Verapamil displaces digoxin from tissue-binding sites check digoxin levels and reduces its renal elimination thus predisposing to digoxin toxicity
- Co-prescription with digoxin: reduce digoxin dose and
-ANTI-ARRHYTHMIC DRUGS NOT CLASSIFIED
Atropine -> Sinus bradycardia
Adenosine -> SVT
Digoxin -> Afib
-ATROPINE
Mechanism of Action
Muscarinic receptor antagonist
- Inhibits the effects of excessive vagal activation on the heart, which is manifested as sinus bradycardia and AV nodal block
Atropine Clinical use + roA
Clinical Use: Temporarily reverts sinus bradycardia to a normal sinus rate and reverses AV nodal block
Mode of administration: IV
Atropine
AE
anti-cholinergic
- Tachycardia, pupil dilation, dry mouth, urinary retention, inhibition of sweating (anhidrosis), blurred vision, constipation.
‘(DUMBBELLS?)
Adenosine MoA
Produced endogenously
Mode of action:
- Adenosine receptor (A1)
- Gi-coupled decrease in cAMP
- Increases K outward current (I KAch) and decreases Ca inward current
- Hyperpolarization
- Decreases SA and AV nodal activity
Adenosine Clinical use
Clinical use: SVT termination (IV)
- Shorter-lived effect than verapamil, thus safer
- Effects only last 20-30s after a bolus, metabolized quickly
Adenosine
Short-lived adverse effects:
chest pain, SOB (shortness of breath), dizziness,
nausea, flushing
-Clinically important interactions w/ Adenosine
Theophylline and other xanthines (caffeine) block adenosine receptors and thus inhibit the actions of adenosine
Dipyridamole blocks the nucleoside uptake mechanism potentiating adenosine and prolonging its adverse effects
Ivabradine is NOT anti-arrhythmic
MoA
Selective inhibitor of I f channels
Prolongs slow depolarization phase
Decreases SA node firing
Reduces oxygen demands
Ivabradine clinical uses
-Chronic stable angina
- Chronic heart failure for patients
•In sinus rhythm; HR ≥70bpm
•LVEF≤35%
•Who are either on a maximum tolerated dose of beta-blocker or have a contraindication to a beta-blocker
Ivabradine AE
bradycardia, visual disturbances, hypertension,
long QT, atrial fibrillation