Drugs for cardiac arrhythmias 3

Question 1

Amiodarone: Pks
Absorption
Distribution
Response
Onset of action
Metabolims

Answer 1

Oral absorption is slow with bioavailability of 20-55%
* Wide distribution in fat muscles and liver
* Therapeutic response may take 3 weeks, with peak effect reached in 1-5 months
* Antiarrhythmic effect persist for 10 – 150 days after withdrawal of long-term treatment
* Onset of action: IV 10-15 minutes
* Extensive hepatic metabolism with biliary excretion (renal excretion negligible)

Question 2

Contra-indications for Amiodarone

Answer 2

Contraindications
* Cardiac bradycardia / block, hyperthyroidism, sensitivity to iodine, hypokalemia
* Pregnancy and lactation

Question 3

Caution for amiodarone

Answer 3

Heart failure, hepatic impairment

Question 4

Drug interactions for amiodarone

Answer 4

Drug interactions (may interact with other drugs for months after discontinuation of treatment)
* Other antiarrhythmics, b-blockers, digoxin, drugs causing QT prolongation, phenytoin, simvastatin, warfarin, grapefruit juice

Question 5

Adverse effects for Amiodarone

Answer 5

May take several weeks to appear and continue of months after discontinuation of treatment
* Torsades de Pointes
* Hyper/hypothyroidism (thyroid function monitoring necessary)
* Neurotoxicity (including peripheral neuropathies)
* Photosensitivity (warn to avoid exposure to sunlight)
* GI
* Uncommon: pulmonary fibrosis & hypersensitivity pneumonitis

Question 6

MoA of Propranolol

Answer 6

MoA:
* Inhibit sympathetic activation of cardiac automaticity and conduction,
* Slow the heart rate,
* Decrease the AV node conduction velocity, and
* Increase the AV node refractory period,
* Little effect on ventricular conduction and repolarization.

Question 7

Indications for Propranolol

Answer 7

Indications:
* Prevent and treat supraventricular dysrhythmias
* Reduce ventricular ectopic depolarizations and sudden death in patients with myocardial infarction.

Question 8

MoA for Verapamil

Answer 8

MoA:
* Decrease the AV node conduction velocity and
* Increase the AV node refractory period,
* Smaller effect on the SA node and heart rate,
* Little effect on the ventricular conduction velocity and refractory period.

Question 9

Indications for Verapamil

Answer 9

Indications:
* Controlling or converting certain supraventricular dysrhythmias, not effective in treating ventricular dysrhythmias.
* Control the ventricular rate in patients with atrial fibrillation

Question 10

RoA for Verapamil

Answer 10

Verapamil can be administered intravenously to terminate paroxysmal supraventricular tachycardia (PSTV), and it is given orally for chronic treatment

Question 11

Adverse effects for Verapamil

Answer 11

Adverse effects:
Exacerbate wide QRS complex VT and should not be given to patients with this dysrhythmia.

Question 12

Dihydropyridine drugs have less effects on which tissues

Answer 12

Note: dihydropyridine drugs (-dipine) have less effect on cardiac tissue and no role in the treatment of dysrhythmias.

Question 13

List the miscellaneous antiarrhythmics

Answer 13

• Adenosine
• Digoxin
• Magnesium sulphate
• Ivabradine & ranolazine

Question 14

ADENOSINE
1. Indication
2. RoA
3. Half life
4. Adverse effects
5. Only use when?

Answer 14

• Acute management of paroxysmal supraventricular tachycardias – convert to sinus rhythm
• Administer as rapid IV bolus
• Half-life <10 seconds
• Adverse effects: dyspnoea, flushing, chest pain are an indication the bolus has reached the heart
• Adverse effects are short lived <1 minute: bradycardia, prolonged hypotension
• Only use when cardiac monitoring and resuscitation is available

Question 15

Manangenment of dysrhythmias

Answer 15

Atrial fibrillation and flutter
* Torsades de Pointes

Question 16

Explain the pathology of atrial fibrillation and flutter

Answer 16

Pathology: disorganized form of re-entry in which atrial cells are continuously re-excited by re-entrant stimuli as soon as they are repolarized - AV node is continuously bombarded with atrial impulses, some of which are conducted to the ventricles, so that the ventricular rate is often rapid and irregular.

Question 17

Explain the 2 general approaches to pharmacologic therapy

Answer 17

Two general approaches to pharmacologic therapy:
* Ventricular rate control is essential for all patients to avoid symptoms and development of cardiomyopathy and is the first objective in treating acute atrial fibrillation: β -blockers and calcium channel blockers, which slow AV node conduction velocity and increase its refractory period, so that fewer atrial impulses are transmitted to the ventricles.
* Preventing recurrences and maintaining normal sinus rhythm (rhythm control): amiodarone
* Anticoagulant (warfarin) to prevent thromboembolism and stroke

Question 18

Explain the Torsades de pointes

Answer 18

Polymorphic ventricular tachycardia (VT), associated with
QTc prolongation, which is the heart rate adjusted lengthening of the QT interval.

Question 19

The Torsades de pointes

Answer 19

Induced by:
* Drugs (including tricyclic antidepressants and antipsychotic agents )
* Electrolyte abnormalities that prolong the QT interval and predispose cardiac cells to afterdepolarizations
* Congenital prolonged QT syndrome.

Question 20

Explain the treatment for Torsades de pointes

Answer 20

Treatments:
* Withdrawal of the causative agent,
* Correction of any electrolyte abnormalities, such as hypokalemia,
* Intravenous administration of magnesium sulfate IV ,
and
* Cardiac overdrive pacing.
* These treatments act in part by shortening the QT
interval.