AUTONOMIC NERVOUS SYSTEM-PART-VII

DIRECT ACTING ALPHA, BETA AGONISTS

These drugs acting on the adrenergic receptors directly. They mimic the actions of noradrenaline.

1.Epinephrine(Adrenaline)

Epinephrine act on alpha-1,alpha-2;and beta-1,beta-2 receptors in a proportionate manner.

In low dosage, it is effective to stimulate the beta-receptors and at high doses, it is effective on alpha receptors. But the alpha stimulation is predominant and persistent at high doses.

Effects of Epinephrine

1.It increases heart contractility(inotropic);heart rate(chronotropic);vasoconstrictions of arterioles in the skin,viscera,and mucus membrane (apha-1);

2.Bronchodilation due to stimulation of beta-2 receptors.

3. Increased glycogenolysis and release of glucagon and a reduced release in insulin leads to hyperglycemia.

Uses

1. To relieve bronchospasm as a secondary symptom in Asthma and Anaphylactic shock.

2.Used in anaphylactic shock and cardiac arrest to increase the electrical conductivity through the pacemaker AV and SA nodes and Purkinje fibers (Dronotropic effects)

3.In conjunction with local anesthetics to prolong the local effects by local vasoconstriction effects.

4. To achieve hemostasis.

Side effects

1.Arrhythmias

2.Hypertension

3.Palpitations

4.Dizziness, anxiety, headache

5.Myocardial Infarction due to heavy workload on the heart.

6.Pulmonary edema.

Epinephrine Reversal 

Interestingly if epinephrine is given alone it increases the systemic blood pressure due to its alpha vasoconstriction effects. If given along with an alpha-blocker such as phenoxybenzamine it will lower the blood pressure due to its beta smooth muscle-relaxing effects. This action is technically known as Adrenaline Reversal.

2.Nor Epinephrine-Nor Adrenaline 

Noradrenaline the main prototype nerve transmitter stimulates alpha-1,alpha-2, and beta-1 receptors with a stronger affinity for alpha receptors than for beta receptors.

Its main physiologic effects are vasoconstriction, Reflux bradycardia

It is one of the last line agents in the treatment of shock.

Side effects

1.Tissue hypoxia secondary to potent vasoconstriction

2.Decreased perfusion to the kidneys

3.Tissue necrosis due to extravasation during I.V. administration.

4.Arrhythmia

3.Dopamine

This drug is synthesized in the CNS, sympathetic ganglia and adrenal medulla.

Dopamine act on alpha-1,beta-1, and beta-2 receptors with a greater affinity towards dopamine and beta receptors. It also acts on its own receptors D-1 and D-2 receptors located in the peripheral mesenteric and renal vascular beds.

Dopamine at its low dose stimulates dopamine receptors, at moderate dose beta receptors and at high dose alpha-1 receptors. Dopamine is highly polar, hydrophilic, and does not cross the blood-brain barrier.

Uses

1. Treatment of shock-It raises blood pressure by increasing the heart rate by stimulating the beta-1 receptors

2. In acute renal failure, dopamine is used to increase renal blood flow.

3.Treatment of acute congestive heart failure.

Administered through I.V.

Side effects

1.Decreased renal perfusion a higher doses

2.Arrhythmias

3.Tachycardia

4.Hypertension

5. Tissue necrosis may occur if dopamine extravasates during I.V.infusion. 

 

 

AUTONOMIC NERVOUS SYSTEM-PART-VI-Continued...

DIREC ACTING BETA SELECTIVE AGONISTS

These drugs are stimulating selectively at beta receptors of the postganglionic adrenergic nervous system.

Beta-1 receptors are mostly situated on the postsynaptic membrane and beta-2 receptors are found both in pre and postsynaptic membrane.

Beta receptors are present in heart muscle and their stimulation may cause an increase in heartbeat, rate, and rhythm by an increase in both inotropic and chronotropic effects.

Beta-1stimulation leads to increased lipolysis.

Beta-2 receptor stimulation works through adenylate cyclase to dilate the vasculature in bronchial as well as skeletal muscles.

The uterus, ciliary and detrusor muscles are relaxed.

Glucagon release is increased.

Both b-1 and b-2 receptor stimulation leads to reduced intestinal tone and motility.

1.Dobutamine

It is a dopamine derivative

Primarily act on the beta-1 receptor with a secondary effect on beta-2 receptor

The physiological effects of dobutamine are increased heart rate, and contractility(beta-1);

Smooth muscle relaxation (beta-2)

Use

Treatment of unstable CHF and shock.

Route

Intra venously

Side effects

1.Arrhythmias

2.Hypertension

3.Headaches

4.Palpitations

5.Angina

6.Nausea.

2.Isoproterenol

It acts equally on both b-1 and b-2.

Physiological effects

1.Increases both cardiac inotropic and chronotropic effects(b-1)

2.Increases peripheral vascular resistance(b-2)

3.Relaxes smooth muscles(b-2)

Use

It is appropriate to use isoproterenol in 

1.Stimulate heart rate in heart block and bradycardia

2. To treat asthma but now it becomes older.

I.V route is preferable

Side effects

1.Arrhythmias

2.Palpitation

3.Tachycardia

4.Headache

3.Albuterol, Metaproterenol, and Terbutaline

Mainly on b-2 receptors causes smooth muscle relaxations

But on concentration may affect b-1

Albuterol and metaproterenol can be given by inhalation

Terbutaline by oral or s.c

Uses

1.Asthma

2.Chronic Obstructive Pulmonary Disease

3.Bronchitis

4.Uterine relaxation in premature labour-Terbutaline and ritodrine

Side effects

Similar to the above