Sympathomimetics

 

 

 

[PHW2:p197]

Parasympathetic nervous system

Preganglionic fibres arise from

CN III, VII, IX, X (3, 7, 9, 10)
* Eye, salivary gland, heart, bronchi, upper GI (up to splenic flexure), ureters

Sacral fibres (S2-4)
* Distal blowel, bladder and genitals

Preganglionic fibres synapse with ganglia which are close to the effector organ
* Release ACh
* Act via nAChRs

Postganglionic fibres also release AChRs and receptors are also nAChRs

 

Sympathetic nervous system

[PHW2:p188]

Preganglionic fibres arise from lateral horns of the spinal cord from T1-L2

Pathway:
* Lateral horn
--> Anterior primary rami
--> White rami communicans
--> Sympathetic chain or ganglia

Once in sympathetic chain, the preganglionic fibre could
* Synapse at the same level
* Go to an adjacent level and synpase there
* Pass anteriorly through a splanchnic nerve to synapse in a prevertebral ganglion

Preganglionic fibres release ACh, which acts on nAChRs

Post-ganglionic fibres (unmyelinated) go into the adjacent spinal nerve via the grey rami

Post-ganglionic fibres
* Release noradrenaline
--> Acts on adrenergic receptors

Two special cases of the sympathetic nervous system:

Adrenal medulla
* Pre-ganglionic fibres synapse directly with chromaffin cells
--> Release adrenaline into circulation

Sweat gland
* Post-ganglionic sympathetic fibres which innervate sweat glands release ACh (instead of NE) as the neurotransmitter

NB:

ALL pre-ganglionic ANS (sympathetic and parasympathetic) fibres are
* Myelinated
* Release ACh
* Act on nAChRs

 

 

 

[PHW2:p190-193]

Catecholamine

Naturally occurring catecholamine, synthetic agents, others

 

Naturally occurring catecholamine

adrenaline, noradrenaline, dopamine

 

 

[PHW2:p196]

Of the synthetic agents, only isoproterenol, dobutamine, dopexamine are classified as catecholamines because only they contant hydroxyl groups on 3- and 4- positions of the benzene ring

 

Methoxamine

[PHW2:p197]

A direct-acting amine with specific alpha 1 agonist actions.

Similar effects to phenylephrine

?More pronounced reflex bradycardia

No longer in production

 

Salmeterol

[PHW2:p200]

Long-acting beta2 agonist

15 times more potent than salbutamol at beta2, but 4 times LESS potent at beta1

Prevents release of histamine, leukotrienes, and prostaglandin D2 from mast cells

Some antiinflammatory actions

Other effects are similar to salbutamol

 

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[James] [???]

 

If OH group present on C3 and C4 (i.e. a catecholamine) --> metabolise by COMT

Increasing size of amine group substitution --> Increased beta and decreased alpha activity

OH present on both C3 and C4 --> Increased alpha and beta activity (e.g. adrenaline)

OH on C3 and C5 with long amino chain substitution --> Beta2 activity

No OH on C4 --> alpha selective (e.g. phenylephrine)

Alpha methyl group --> Increase alpha selectivity

Levorotatory forms more active