This document discusses drugs that affect the sympathetic nervous system. It begins by describing the autonomic nervous system and sympathetic division. Sympathomimetic drugs mimic the effects of endogenous agonists like epinephrine and norepinephrine. These drugs can directly activate adrenergic receptors or act indirectly. Examples of direct-acting agonists include epinephrine and dopamine. Epinephrine increases heart rate and contractility while constricting some vessels and dilating others. It also has effects in the lungs, kidneys, liver, and adipose tissue. Beta-adrenoceptors are coupled to G proteins to increase cAMP and calcium entry, enhancing contraction. These drugs have therapeutic uses but also side effects like anxiety

1. Dr. Haji Bahadar, PharmD, PhD
Assistant professor of Pharmacology,
Khyber Medical University Peshawar
Drugs affecting sympathetic nervous
system

3. Autonomic nervous system
 The autonomic nervous system (ANS) is
the part of the peripheral nervous system
controlling visceral functions.
• Sympathetic division = Thoracolumbar
division
Preganglionic neurons of the sympathetic division originate in
the thoracic (T1 to T12) and upper lumbar (L1 to L3)
spinal cord

6. Sympathomimetic drugs
Sympathomimetic drugs (also known as adrenergic drugs)
mimic the effects of endogenous agonists of
the sympathetic nervous system. The primary endogenous
agonists of the sympathetic nervous system are
the catecholamines (i.e., epinephrine [adrenaline], norepine
phrine [noradrenaline], and dopamine), which function as
both neurotransmitters and hormones

8. Nutritional sources of
tyrosine
meat, nuts and eggs,
Dairy
products such as
cheese also contain
high amounts of
tyrosine

9. Cholinergic and adrenergic neurons
 Cholinergic neurons: the neurons in which the
transmission is mediated by acetylcholine, the
neuron is termed cholinergic.
 Adrenergic neurons: When norepinephrine and
epinephrine are the neurotransmitters, the fiber is
termed adrenergic.

10. Adrenergic agonists and antagonists
The adrenergic drugs affect receptors that are
stimulated by norepinephrine (noradrenaline) or
epinephrine (adrenaline). These receptors are known
as adrenergic receptors or adrenoceptors. Adrenergic
drugs that activate adrenergic receptors are termed
sympathomimetics, and drugs that block the activation
of adrenergic receptors are termed sympatholytics.
Some sympathomimetics directly activate adrenergic
receptors (direct-acting agonists), while others act
indirectly by enhancing release or blocking reuptake of
norepinephrine (indirect-acting agonists).

12. Salbutamol

14. Indirect-Acting
Sympathomimetics

15. Direct-acting adrenergic agonists
Direct-acting agonists bind to adrenergic
receptors on effector organs.
Pharmacological actions of Epinephrine
Cardiovascular:
 Heart: Epinephrine increases the contractility of the
myocardium (positive inotrope: β1 action) and increases
its rate of contraction (positive chronotrope: β1 action).
 Blood vessels: Epinephrine constricts arterioles in the
skin, mucous membranes, and viscera (α effects), and it
dilates vessels going to the liver and skeletal muscle (β2
effects).

16.  Respiratory: Epinephrine causes powerful
bronchodilation by acting directly on bronchial
smooth muscle (β2 action). It also inhibits the
release of allergy mediators such as histamines from
mast cells.
 Kidney: Epinephrine activates β1 receptors of the
kidney to cause renin release. Renin is an enzyme
involved in the production of angiotensin II, a potent
vasoconstrictor
 Liver: Epinephrine has a significant hyperglycemic
effect because of increased glycogenolysis in the liver
(β2 effect), increased release of glucagon (β2
effect), and a decreased release of insulin (α2
effect).
 Adipose tissue: Epinephrine initiates lipolysis through
agonist activity on the β receptors of adipose tissue

17. Molecular mechanism??
 Beta-adrenoceptors are coupled to Gs-
proteins, which activate adenylyl cyclase to
form cAMP from ATP. Increased cAMP
activates a cAMP-dependent protein kinase
(PK-A) that phosphorylates L-type calcium
channels, which causes increased calcium
entry into the cells. Increased calcium entry
during action potentials leads to enhanced
release of calcium by the sarcoplasmic
reticulum in the heart; these actions
increase inotropy (contractility).

19. Smooth muscles: These receptors, like
those in the heart, are coupled to
a Gs-protein, which stimulates the
formation of cAMP. Although
increased cAMP enhances cardiac
myocyte contraction (see above), in
vascular smooth muscle an increase in
cAMP leads to smooth muscle
relaxation. The reason for this is that
cAMP inhibits myosin light chain
kinase that is responsible for
phosphorylating smooth muscle myosin.
Therefore, increases in intracellular
cAMP caused by β2-agonists inhibits
myosin light chain kinase thereby
producing less contractile force (i.e.,
promoting relaxation).

20. Therapeutic uses
 Bronchospasm
 Anaphylactic shock
 Cardiac arrest
 Vasoconstriction at the site of injection: Local
anesthetic solutions may contain low concentrations
(for example, 1:100,000 parts) of epinephrine
Adverse effects
Common side effects of adrenergic drugs, like
epinephrine, include: anxiety. restlessness or
wakefulness. dizziness.

22. Dopamine
Cardiovascular: Dopamine exerts a stimulatory effect on
the β1 receptors of the heart, having both positive
inotropic and chronotropic effects.
Renal and visceral: Dopamine dilates renal and
splanchnic(visceral) arterioles by activating
dopaminergic receptors, thereby increasing blood flow
to the kidneys and other viscera.

23. Therapeutic uses:
Dopamine is the drug of choice for cardiogenic
and septic shock and is given by continuous
infusion. It raises blood pressure by stimulating the
β1 receptors on the heart to increase cardiac
output and α1 receptors on blood vessels to
increase total peripheral resistance. In addition, it
enhances perfusion to the kidney.
 Fenoldopam: Fenoldopam is an agonist of
peripheral dopamine D1 receptors. It is used as a
rapid-acting vasodilator to treat severe
hypertension in hospitalized patients.