Insulin
Insulin is only given parenterally (subcutaneous or IV) Various preparations have different durations of action 
 

Mechanism

bind transmembrane insulin receptor
activate tyrosine kinase
phosphorylate specific substrates in each tissue type
liver
↑ glycogenesis
store glucose as glycogen
muscle
↑ glycogen and protein synthesis
↑ K+ uptake 
fat
increase triglyceride storage

Clinical use

type I DM
type II DM
life-threatening hyperkalemia
increases intracellular K+
stress-induced hyperglycemia
 

Toxicity
hypoglycemia
hypersensitivity reaction (very rare)

Insulin Synthesis
first generated as preproinsulin with an A chain and B chain connected by a C peptide. 
c-peptide is cleaved from proinsulin after packaging into vesicles leaving behind the A and B chains

 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 

Piroxicam:

Half‐life of 45 hrs. Once‐daily dosing. Delay onset of  action.

High doses inhibits PMN migration, decrease oxygen  radical production, inhibits lymphocyte function. 

used to relieve the symptoms of  arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic,non-selective  cyclooxygenase (COX) inhibitor

The risk of adverse side efects is nearly ten times higher than with other NSAIDs. Peptic ulcer (9.5 higher)

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 
 

Gabapentin (Neurontin): newer; for generalized tonic-clonic seizures and partial seizures (partial and complex)

Mechanism: unknown but know doesn’t mimic GABA inhibition or block Ca currents

Side effects: dizziness, ataxia, fatigue; drug well-tolerated and no significant drug interactions

Enflurane (Ethrane) MAC 1.68, Blood/gas solubility ratio 1.9
- Extremely stable chemically.
- Less potent and less soluble in blood than is halothane.
- Respiratory depression is similar to that seen with halothane.
- Cardiac output is not depressed as much as with halothane, and the heart is not sensitized to catecholamines to the same degree.
- Enflurane produces better muscle relaxation than does halothane.
- Metabolism of this agent is very low. Inorganic fluoride is a product of metabolism, but is not sufficient to cause renal problems.
- Enflurane differs from halothane and the other inhalational anesthetic agents by causing seizures at doses slightly higher than those that induce anesthesia. 
- Nausea appears to occur somewhat more often following Enflurane than it does following halothane.