Transcript 13th Lecture Updated

Pharmacology-1 PHL 211
Thirteenth Lecture
By
Abdelkader Ashour, Ph.D.
Phone: 4677212
Email: [email protected]
Drugs Acting on the
Sympathetic Nervous
System
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 postganglionic 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 Nervous
System, 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) constrict
5. 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 sweating
9. 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)
Noradrenergic
Neurotransmission
Tyrosine is transported into the noradrenergic
ending by a sodium-dependent carrier (A)
Tyrosine is converted to dopamine, which is
transported 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-hydroxylase
Release 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 be
blocked 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
 COMT is absent from noradrenergic neurons but present in the adrenal medulla
and many other cells and tissues
 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
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
a1
Ejaculation
a2