Antiarrhythmic Drugs

Cardiac Arrhythmias 
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity) 
– Conduction (conductivity) 
– Both

MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm

ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse

Types of Arrhythmias

• Sinus arrhythmias 
– Usually significant only 
– if they are severe or  prolonged 

• Atrial arrhythmias 
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart 

• Nodal arrhythmias 
– May involve tachycardia and increased workload of the heart or bradycardia from heart block 

• Ventricular arrhythmias 
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation 

Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR) 
• To maintain NSR after conversion from AF or flutter 
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation 
• When dangerous arrhythmias occur and may be fatal if not quickly terminated 
– For example: ventricular tachycardia may cause cardiac arrest 

Mechanism of Action 
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers) 
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells 
 

Non-barbiturate sedatives

1- Chloral hydrate is trichlorinated derivative of acetaldehyde that is converted to trichlorethanol in the body. It induces sleep in about 30 minutes and last up to 6 hr. it is irritant to GIT and produce unpleasant taste sensation.

2- Ramelteon melatonin receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. Ramelteon is an agonist at MT1 and MT2 melatonin receptors , useful in patients with chronic insomnia with no rebound insomnia and
withdrawal symptoms

3- Ethanol (alcohol) it has antianxiety sedative effects but its toxic potential out ways its benefits.
Ethanol is a CNS depressant producing sedation and hypnosis with increasing dose.

Absorption of alcohol taken orally is rapid, it is highly lipid soluble, presence of food delayed its absorption, maximal blood concentration depend on total dose, sex, strength of the solution, the time over which it is taken, the presence of food and speed of metabolism.

Alcohol in the systemic circulation is oxidized in the liver principally 90% by alcohol dehydrogenase to acetaldehyde and then by acetaldehyde dehydrogenase to products that enter the citric cycle. 

Alcohol metabolism by alcohol dehydrogenase follows first order kinetics in the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml, the enzymatic processes are saturated and elimination rate no longer increases with increasing
concentration but become steady at 10-15 ml/ 1 hr. in occasional drinkers. 

Thus alcohol is subject to dose dependant kinetics i.e. saturation or zero order kinetics.

Actions

- Ethanol acts on CNS in a manner similar to volatile anesthetic.
- It also enhances GABA so stimulating flux of chloride ions through ion channels.
- Other possible mode of action involve inhibition of Ca-channels and inhibition of excitatory NMDA receptors.
- Ethanol has non selective CNS depressant activity.
- It causes cutaneous vasodilatation, tachycardia and myocardial depression

Class IV Calcium Channel Blockers
• Block the movement of calcium into conductile and contractile myocardial cells 
• Treatment: treatment of supraventricular tachycardia 
– Diltiazem 
– Verapamil 

Adverse Effects 
• Adverse effects associated with vasodilation of blood vessels throughout the body. 
• CNS – dizziness, weakness, fatigue, depression and headache, 
• GI upset, nausea, and vomiting. 
• Hypotension CHF, shock arrhythmias, and edema 
 

Dissociation constants

Class II Beta Blockers 

Block SNS stimulation of beta receptors in the heart and decreasing risks of ventricular fibrillation
– Blockage of SA and ectopic pacemakers: decreases automaticity 
– Blockage of AV increases the refractory period
- Increase AV nodal conduction ´ 
- Increase PR interval
- Reduce adrenergic activity

Treatment: Supraventricular tachycardia (AF, flutter, paroxysmal supraventricular tachycardia 
– Acebutolol 
– Esmolol 
– Propanolol 

Contraindications and Cautions 

• Contraindicated in sinus bradycardia P < 45
• Cardiogenic shock,  asthma or respiratory depression which could be made worse by the blocking of Beta receptors. 
• Use cautiously in patients with diabetes and thyroid dysfunction, which could be altered by the blockade of Beta receptors 
• Renal and hepatic dysfunction could alter the metabolism and excretion of these drugs.
 

Calcium Channel Blocking Agents 

• Act on contractile and conductive tissues of the heart and on vascular smooth muscles 
• Prevent movement of extracellular calcium into the cell 
– Coronary and peripheral arteries dilate
– Myocardial contractility decreases 
– Depress conduction system

Therapeutic Actions
• Inhibit movement of calcium ions across the membranes of myocardial and arterial muscle cells. Altering the action potential and blocking muscle cell contraction 
• Depress myocardial contractility 
• Slow cardiac impulse formation in the conductive tissues 
• Cause a fall in BP