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 

ANTICHOLINERGIC DRUGS
Blocks the action of Ach on autonomic effectors.

Classification
Natural Alkaloids - Atropine. Hyoscine

Semi-synthetic deriuvatives:- Homatropine, Homatropine methylbromide, Atropine methonitrate.

Synthetic compounds 

(a) Mydriatics - Cyclopentolate. Tropicamide.
(b) Antisecretory - Antispasmodics - Propantha1ine. Oxy-phenonium, Pirenzipine.
c) Antiparkinsonism- Benzotopine, Ethopropazine, Trihexyphenidyl, Procyclidine, Biperiden 
Other drugs with anticholinergic properties • Tricyclic Antidepressants • Phenothiazines • Antihistaminics • Disopyramide

MUSCARINIC RECEPTORS SUBTYPES & ANTAGONISTS 
• M 1 Antagonists – Pirenzepine, Telenzepine, dicyclomine, trihexyphenidyl 
• M 2 Antagonists – Gallamine, methoctramine 
• M 3 Antagonists – Darifenacin, solifenacin, oxybutynin, tolterodine

Pharmacological Actions
CNS - stimulation of medullary centres like vagal. respiratory. vasomotor and inhibition of vestibular excitation and has anti-motion sickness properties.
CVS - tachycardia.
Eye - mydriasis
Smooth muscles - relaxation of the muscles receiving parnsympathetic motor innervation.
Glands - decreased secretion of sweat and salivary glands
Body Temperature - is increased as there is stimulation of  temperature regulating centre.
Respiratory System- Bronchodilatation & decrease in secretions. For COPD or Asthma - antimuscarinic drugs are effective
GIT - Pirenzepine & Telenzepine - decrease gastric secretion with lesser side effects.

GENERAL ANESTHETICS

General anesthesia often involves more than one drug to get different, favourable effects.
Premedication is often used to:
1. Treat anxiety - Benzodiazapenes
2. Reduce pain - Opiod anaglesics such as morphine
3. Produce muscle paralysis -E.g. Tubocurare
4. Reduce secretions
Induction of anesthesia is often done via intravenous anesthetics, which are quick and easy to administer.
Maintenance of anesthesia involves inhalation agents.

Prototype Agents:
Volatile Anesthetics:
•    Nitrous Oxide
•    Ether
•    Halothane
•    Enflurane
•    Isoflurane

Injectable Anesthetics:
•    Thiopental 
•    Ketamine
•    Etomidate
•    Propofol 
•    Midazolam
 

Carbamazepine (Tegretol): most common; for generalized tonic-clonic and all partial seizures; especially active in temporal lobe epilepsies

Mechanism: ↓ reactivation of Na channels (↑ refractory period, blocks high frequency cell firing, ↓ seizure spread)

Side effects: induces hepatic microsomal enzymes (can enhance metabolism of other drugs)

Thiazide diuretics

Chlorothiazide, Hydrochlorothiazide

Mechanism(s) of Action

1.    Block facilitated Na/Cl co-transport in the early distal tubule. This is a relatively minor Na absorption mechanism and the result is modest diuresis 

2.    Potassium wasting effect 

a.    Blood volume reduction leads to increased production of aldosterone 
b.    Increased distal Na load secondary to diuretic effect 
c.    a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting

3.    Increase distal Ca re-absorption (direct effect) 

o    causes an increase in plasma calcium.This is unimportant NORMALLY but makes thiazides VERY inappropriate choice for hypercalcemic patients.

4.    Anti-diuretic effect in nephrogenic diabetes insipidus patients secondary to depletion of Na and Water. 

Toxicity
 
•    Electrolyte imbalance (particularly hypokalemia) ,Agranulocytosis , Allergic reactions 
•    Hyperuricemia , Thrombocytopenia 
 

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