AUTONOMIC NERVOUS SYSTEM-PART-VI

ADRENERGIC AGONISTS

Those drugs similar to endogenous catecholamines acting on the adrenergic postganglionic receptors and stimulate them are known as Adrenergic Stimulants or Adrenergic Agonists. Since anatomically most of the sympathetic postganglionic major nerve transmitter is noradrenaline except a few it is also known as Sympathetic Stimulants or Sympathomimetics.

They can be classified as direct or indirect as well as receptors specified such as a1,a2,b1,b2.

A comprehensive classification is as follows:-

1.Peripheral excitatory action on certain smooth muscles such as blood vessels of the skin, kidney, mucous membranes, salivary, and sweat glands.

2.Peripheral inhibitory actions on certain other types of smooth muscles such as an intestinal wall, bronchial tree, and in blood vessels of skeletal muscles.

3.Cardiac excitatory actions

4.Metabolic actions

5.Endocrine actions

6.CNS actions

7.Presynaptic actions.

Chemistry of noradrenaline

Norepinephrine or noradrenaline is an isomer of adrenaline in which the methyl radical is replaced by a hydrogen ion as seen in the following structure. The basic structure of all sympathomimetic drugs is based on the structure of the compound phenylethylamine. A phenyl radical (a benzene ring attached with a phenolic hydroxyl group) attached with an ethylamine side chain.

Noradrenaline as seen in the above structure is demethylated adrenaline (nor means demethyl). It is more potent than adrenaline and highly unstable. All these compounds are derivatives of catecholamines or hydroxy phenylethylamines

Physiological Functions of Adrenergic Receptors

To a comprehensive study of how different adrenergic agonists differing in their action at the specific target tissues the following details will elucidate that.

The different adrenergic receptors are present in different concentration at different sites as follows:

1. Bronchial smooth muscles are largely concentrated with b-2 receptors and hence only beta-2 agonists like isoproterenol and ephedrine have to influence on these muscles

2. Cutaneous blood vessels are concentrated with receptors and hence alpha agonists like adrenaline, noradrenaline has an influence on these muscles.

3. The blood vessels supplied to skeletal muscles are concentrated with both alpha and beta-2 receptors and hence both agonists have an influence on these muscles accordingly, such as stimulation of beta-2 receptor causes vasodilation whereas stimulating alpha receptor causes vasoconstriction.

In skeletal muscle, the threshold concentration for activation of beta-2 receptors by epinephrine is lower than the concentration needed to stimulate alpha receptors but at a high concentration of epinephrine, the alpha stimulation predominates.

1.Alpha(a)Selective Direct Acting Agonists

A.Alpha-1 Receptors

i.Phenylephrine

Its primary action is on blood vessel smooth muscle where alpha-1 receptors are present and causes vasoconstrictions and consequently raises blood pressure results in reflex bradycardia

Use-

1.As a nasal decongestant

2. To treat hypotension.  

3.Eye tests(mydriasis)

4. To terminate paroxysmal atrial tachycardia

Side effects

1.Rebound mucosal swelling

2.Hypotensive headache

ii.Methoxamine

Similar to phenylephrine this drug acts specifically on the alpha-1 receptor.

Use

1.Treatment of hypotension

2.Paroxysmal Atrial Tachycardia(PAT)

B.Alpha-2 Receptors

In this category, there are two drugs that act specifically on alpha two receptors.

Remember that stimulating alpha-2 receptors will stop the further secretion of noradrenaline from the presynaptic fiber and hence there is a reduction in the sympathetic outflow

I. Clonidine

Clonidine stimulates the adrenergic alpha-2 receptors of the CNS and thereby causes a reduced sympathetic outflow from the brain.

Uses

1.Treatment of hypotension

2.Withdrawal symptoms of benzodiazepines and opiates

3.Treatment of diarrhea in DM with autonomic neuropathy.

Side effects

1.Sedation

2.Dry mouth

3.Sexual dysfunction

4.Orthostatic hypotension