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

TCI -Target Controlled Infusion

TCI is an infusion system which allows the anaesthetist to select the target blood concentration required for a particular effect and then to control depth of anaesthesia by adjusting the requested target concentration

Mechanism

Instead of setting ml/h or a dose rate (mg/kg/h), the pump can be programmed to target a required blood concentration.

• Effect site concentration targeting is now included for certain pharmacokinetic models.

• The pump will automatically calculate how much is needed as induction and maintenance to maintain that concentration.

Anti-Histamines:
 
The effect of histamine can be opposed in three ways:
1. Physiological antagonism: by using a drug to oppose the effect (e.g adrenaline). Histamine constricts bronchi,
causes vasodilatation which increases capillary permeability. Adrenaline opposes this effect by a mechanism unrelated to histamine.
2. By preventing histamine from reaching its site of action (receptors), By competition with H1-H2 receptors (Drug antagonisms).
3. By preventing the release of histamine. (adrenal steroids and sodium-cromoglycate can suppress the effect on the tissues)

Types of Anti-histamine drugs

Selected H1 antagonist drugs

First-generation H1 receptor antagonists:

Chlorpheniramine (Histadin) & Dexchlorpheniramine 
Diphenhydramine (Allermine)
Promethazine (Phenergan) -  strong CNS depressants
Cyproheptadine (Periactin)

ACTION
These drugs bind to both central and peripheral H1 receptors and can cause CNS depression or stimulation.

- They usually cause CNS depression (drowsiness,sedation) with usual therapeutic doses
- Cause CNS stimulation (anxiety, agitation) 
with excessive doses, especially in children. 
They also have Anticholinergic effects (e.g. dry mouth, urinary retention, constipation, blurred vision).

Second-generation H1 receptor antagonists (non-sedating) agents

Terfenadine
Fexofenadine
Loratadine
Acravistine and Cetirizine
Astemizol

Action

They cause less CNS epression because they are selective for peripheral H1 receptors and do not cross the blood brain barrier.

Indications for use

The drugs can relieve symptoms but don’t relieve hypersensitivity.

1) Allergic rhinitis. Some relief of sneezing, rhinorrhea, nasal airway obstruction and conjunctivitis are with the use of antihistamine.
2) Anaphylaxis. Antihistamine is helpful in treating urticaria and pruritus.
3) Allergic conjunctivitis. This condition, which is characterized by redness, itching and tearing of the eyes.
4) Drug allergies. Antihistamines may be given to prevent or treat reactions to drugs (e.g, before a dignostic test that
uses an iodine preparation).
5) Transfusions of blood and blood products.
6) Dermatologic conditions. Antihistamines are the drug of choice for treatment of allergic contact dermatitis and
acute Urticaria. Urticaria often occurs because the skin has many mast cells to release histamine.
7) Miscellaneous. Some antihistamines are commonly used for non-allergic disorder such as motion sickness, nausea, vomiting, sleep, cough or add to cough mixtures.

Contraindication

hypersensitivity to the drugs, narrow-angle glaucoma, prostatic hypertroph, stenosing peptic ulcer, bladder neck obstruction, during pregnancy and lactating women

Adverse effects:

Drowsiness and sedation
Anticholinergic
Some antihistamines may cause dizziness, fatigue, hypotention, headache, epigastric distress and photosensitivity
Serious adverse reaction including cardiac arrest & death, have been reported in patients receiving high dose astemizole

H2-receptor antagonists

 Cimetidine (Tagamate), Ranitidine (Zantac), Fomatidine, Nizatidine. 

Mechanism of action

Numerous factors influence acid secretion by the stomach, including food, physiological condition and drugs. H2 receptor blockers reduce basal acid-secretion by about 95% and food stimulated acid-secretion by about 70%. Both conc. and vol. of H ions will decrease.

Pharmacokinetics:
1) They are all well absorbed after oral dose.
2) Antacids decrease their absorption in about 10-20%

Uses
Cimetidine -  reduction of gastric secretion is beneficial, these are in main duodenal ulcer, benign gastric ulcer, stomach ulcer and reflux eosophagitis.

Rantidine -used as alternative for duodenal ulcer

Adverse effects:
headache, dizziness, constipation, diarrhoea, tiredness and muscular pain. 

Levofloxacin

Levofloxacin is effective against a number of gram-positive and gram-negative bacteria. Because of its broad spectrum of action, levofloxacin is frequently prescribed in hospitals for pulmonary infections

 Beta - Adrenergic Blocking Agents 
 
 Mechanisms of Action  
 
- Initial decrease in cardiac output, followed by reduction in peripheral vascular resistance. 
- Other actions include decrease plasma renin activity, resetting of baroreceptors,  release of vasodilator prostaglandins, and blockade of prejunctional beta-receptors.  

Advantages 

- Documented reduction in cardiovascular morbidity and mortality. 
- Cardioprotection: primary and secondary prevention against coronary artery events (i.e. ischemia, infarction, arrhythmias, death). 
- Relatively not expensive. 

Considerations 

- Beta blockers are used with caution in patients with bronchospasm. 
- Contraindicated in more than grade I AV, heart block. 
- Do not discontinue abruptly. 

 Side Effects
- Bronchospasm and obstructive airway disease. 
- Bradycardia  
- Metabolic effects (raise triglyerides levels and decrease HDL cholesterol; may worsen insulin sensitivity and cause glucose intolerance). Increased incidence of diabetes mellitus.  
- Coldness of extremities.  
- Fatigue. 
- Mask symptoms of hypoglycemia. 
- Impotence. 

Indications 

- First line treatment for hypertension as an alternative to diuretics. 
- Hypertension associated with coronary artery disease.
- Hyperkinetic circulation and high cardiac output hypertension (e.g., young hypertensives). 
- Hypertension associated with supraventricular tachycardia, migraine, essential tremors, or hypertrophic cardiomyopathy. 

Beta adrenergic blocker Drugs

Atenolol 25-100
Metoprolol 50-200 
Bisoprolol 2.5-10 

Dextromethorphan  
O-methylated dextrorphan,  Excellent oral antitussive,  No analgesic effect,  No GI effects,  No respiratory depression