Phl211 Sns 13th Lecture Sf

7/28/2019 Phl211 Sns 13th Lecture Sf

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Pharmacology-1 PHL 211

Thirteenth Lecture By

Abdelkader Ashour, Ph.D. Phone: 4677212 Email: [email protected]



Drugs Acting on the

Sympathetic NervousSystem



Autonomic Nervous System



Sympathetic Nervous System (SNS), Overview

SNS regulates the expenditure of energy and is operative when the organism is

confronted with stressful situations, such as danger, intense emotion, or severe

illness

SNS is referred to as “Fight-or-flight” system

SNS promotes adjustments during exercise

Blood flow to organs is reduced, flow to muscles is increased

SNS prepares the body for emergency situations Heart rate increases and breathing is rapid and deep

The neurohormones (neurotransmitters) of the SNS are epinephrine (EP) and

norepinephrine (NE), in addition to ACh

ACh serves as the chemical transmitter at ganglionic synapses between pre- and post-

ganglionic neurons, NE is the mediator at synapses of the postganglionic neuron with

the effector organ

EP is secreted by the adrenal medulla. NE is secreted mainly at nerve endings of

sympathetic (also called adrenergic) nerve fibers



Drugs Acting on the Sympathetic NervousSystem, Responses to sympathetic activation

1. Pupils dilate (contraction of radial muscles)2. Bronchioles dilate, enabling alveolar oxygen uptake to be increased.

This is not due to a direct innervation by sympathetic nerves. Instead, adrenaline

released from the adrenal glands cause the dilation

3. Increased heart rate and force of contraction

4. Blood vessels (especially in the skin and viscera) constrict5. Skeletal muscle blood vessels dilate so muscles can get more blood

6. GIT and urinary bladder: relaxation of the walls and constriction of sphincters

7. Salivary secretion: vicid (remember; in response to PSNS, it is watery and copious)

8. Increased sweating9. Blood sugar rises (increased glycogenolysis and gluconeogenesis)

10. Hair becomes erected on skin

11. Increased lypolysis in adipose tissues

12. Ejaculation (remember; in response to PSNS, erection occurs)



NoradrenergicNeurotransmission

Tyrosine is transported into the noradrenergic

ending by a sodium-dependent carrier (A)

Tyrosine is converted to dopamine, which istransported into the vesicle by a carrier (B)

that can be blocked by reserpine.

The same carrier (B) transports NE and

several other amines into these granules

Dopamine is converted to NE in the vesicle

by dopamine-b-hydroxylaseRelease of transmitter occurs when an action

potential opens voltage-sensitive Ca2+

channels and increases intracellular Ca2+

Fusion of vesicles with the surface membrane

results in expulsion of NE, cotransmitters, and

dopamine-b-hydroxylase. Release can beblocked by drugs such as guanethidine and

bretylium

After release, NE diffuses out of the cleft or is

transported into the cytoplasm of the terminal

(uptake 1, blocked by cocaine, tricyclic

antidepressants) or into the postjunctional cell(uptake 2)



Biosynthesis of Catecholamines



Termination of catecholamine action

Catecholamines are metabolised (inactivated) mainly by two enzymes:

monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)

MAO occurs within cells, bound to the surface membrane of mitochondria

It is abundant in noradrenergic nerve terminals but is also present in many other

places, such as liver and intestinal epithelium

MAO can also oxidise other monoamines, such as dopamine and 5-HT

It is inhibited by various drugs, which are used mainly for their effects on the CNS

Within sympathetic neurons, MAO controls the content of dopamine and NE

The final product formed by the sequential action of MAO and COMT is partly

conjugated to sulfate or glucuronide derivatives, which are excreted in the urine,but most of it is converted to vanillylmandelic acid and excreted in the urine in

this form

In the periphery, neither MAO nor COMT is primarily responsible for the

termination of transmitter action, most of the released NE being quickly

recaptured by uptake 1. Circulating catecholamines are usually inactivated by a

combination of uptake 1, uptake 2 and COMT

COMT is absent from noradrenergic neurons but present in the adrenal medulla

and many other cells and tissues



Adrenergic Receptors (Adrenoceptors)

Adrenergic nerve fibers have either alpha (a) or beta (b) receptors.

Adrenergic drugs may act on a receptors only, b receptors only, or on both

a and b receptors

Agonists at adrenoceptors (direct sympathomimetics) mimic the actions of

the naturally occurring catecholamines (norepinephrine and epinephrine),

and are used for various therapeutic effects.

For example, phenylephrine acts chiefly on a receptors; isoproterenol acts

chiefly on b receptors; and epinephrine acts on both a and b receptors

The a and b receptors can be further divided into a1- and a2-adrenergic

receptors and b1-, b2- and b3-adrenergic receptors



Distribution of Adrenergic Receptors

a2

a1

Ejaculation

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Phl211 Sns 13th Lecture Sf