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 
 

Lithium carbonate: 1st choice (controls mania in bipolar disorders); delay before onset of therapeutic benefit; no psychotropic effects in normal humans

i. Mechanism: blocks enzymes in inositol phosphate signaling pathway; no consistent effects of lithium on NE, 5-HT, and DA
ii. Side effects: severe CNS (ataxia, delirium, coma, convulsions) and CV (cardiac dysrhythmias)

Inhalational Anesthetics

The depth of general anesthesia is directly proportional to the partial pressure of the anesthetic agent in the brain. These agents enter the body through the lungs, dissolve in alveolar blood and are transported to the brain and other tissues.

A. Rate of induction and rate of recovery from anesthesia:

1. The more soluble the agent is in blood, the more drug it takes to saturate the blood and the more time it takes to raise the partial pressure and the depth of anesthesia.

2. The less soluble the agent is in blood, the less drug it takes to saturate the blood and the less time it takes to raise the partial pressure and depth of anesthesia.

B. MAC (minimum alveolar concentration)

The MAC is the concentration of the anesthetic agent that represents the ED₅₀ for these agents. It is the alveolar concentration in which 50% of the patients will respond to a surgical incision.

The lower the MAC the more potent the general anesthetic agent.

C. Inhalation Anesthetic Agents 

• Nitrous Oxide
• Ether
• Halothane
• Enflurane
• Isoflurane

Neurotransmitters can be classified into:
1. Biogenic amines:
ACh, NA, DA, 5-HT, Histamine
2. Amino acids:
Excitatory (glutamate & asparate)
Inhibitory (GABA& glycine)
3. Others:
Adenosine, melatonin

Acid-Peptic disorders

This group of diseases include peptic ulcer, gastroesophageal reflux and Zollinger-Ellison syndrome.

Pathophysiology of acid-peptic disorders

Peptic ulcer disease is thought to result from an imbalance between cell– destructive effects of hydrochloric acid and pepsin on the one side, and cell-protective effects of mucus and bicarbonate on the other side. Pepsin is a proteolytic enzyme activated in gastric acid (above pH of 4, pepsin is inactive); also it can digest the stomach wall. A bacterium, Helicobacter pylori, is now accepted to be involved in the pathogenesis of peptic ulcer.

In gastroesophageal reflux the acidic contents of the stomach enter into the oesophagus causing a burning sensation in the region of the heart; hence the common name heartburn or other names such as indigestion and dyspepsia.

However, Zollinger-Ellison syndrome is caused by a tumor of gastrin secreting cells of the pancreas characterized by excessive secretion of gastrin that stimulates gastric acid secretion.

These disorders can be treated by the following classes of drugs:

A. Gastric acid neutralizers (antacids)
B. Gastric acid secretion inhibitors (antisecretory drugs)
C. Mucosal protective agents
D. Drugs that exert antimicrobial action against H.pylori

Class I Sodium Channel Blockers 

• Block movement of sodium into cells of the cardiac conducting system
• Results in a stabilizing effect and decreased formation and conduction of electrical impulses 
• Have a local anesthetic effect
• Are declining in use due to proarrhythmic effects and increased mortality rates 

• Na channel blockers - Class 1 drugs are divided into 3 subgroups 
• 1A. 1B, 1C based on subtle differences in their mechanism of action. 
• Blockade of these channels will prevent depolarization. 
• Spread of action potential across myocardium will slow and areas of  pacemaker activity is suppressed.

Class IA Sodium Channel Blockers 

• Treatment of: symptomatic premature ventricular contractions, supraventricular tachycardia, and ventricular tachycardia, prevention of ventricular fibrillation
– Quinidine (Cardioquin, Quinaglute) 
– Procainamide (Pronestyl, Procanbid) 
– Disopyramide (Norpace) 

• Quinidine – prototype 
• Low therapeutic index
• High incidence of adverse effects 

Class IB Sodium Channel Blockers 

• Treatment of: symptomatic premature ventricular contractions and ventricular tachycardia, prevention of ventricular  fibrillation
– Lidocaine (Xylocaine) 
– Mexiletine (Mexitil) 
– Tocainide (Tonocard) 
– Phenytoin (Dilantin) 

Side Effects: Lidocaine 
• Drowsiness • Paresthesias  • Muscle twitching • Convulsions  • Changes in mental status (disorientation, confusion) • Hypersensitivity reactions (edema, uticaria, anaphylaxis) 

Side Effects: Phenytoin (Dilantin)
• Gingival hyperplasia 
• Nystagmus 
• Ataxia, slurring of speech 
• Tremors 
• Drowsiness 
• Confusion 

• Lidocaine – prototype 
• Must be given by injection 
• Used as a local anesthetic 
• Drug of choice for treating serious ventricular arrhythmias associated with acute myocardial infarction, cardiac surgery, cardiac catheterization and electrical conversion 

Class IC Sodium Channel Blockers
• Treatment of: life-threatening ventricular tachycardia or fibrillation and supraventricular tachycardia unresponsive to other  drugs 

– Flecainide 
– Propafenone 

Adverse Effects 
• CNS - dizziness, drowsiness, fatigue, twitching, mouth numbness, slurred speech vision changes, and tremors that can progress to convulsions.
• GI - changes in taste, nausea, and vomiting. CV - arrhythmias including heart blocks, hypotension, vasodilation, and potential for cardiac arrest. 
• Other Rash, hypersensitivity reactions loss of hair and potential bone marrow depression. 

Drug-Drug Interactions
• Increased risk for arrhythmias if combined with other drugs that are know to cause arrhythmias- digoxin and beta blockers 
• Increased risk of bleeding if combined with oral anticoagulants. 

Drug Food Interactions
• Quinidine needs an acidic urine for excretion. Increased levels lead to toxicity 
• Avoid foods that alkalinize the urine- citrus juices, vegetables, antacid, milk products