Autonomic Nervous System

Drugs affecting the sympathetic nervous

system

I. Sympathomimetics (Sympathetic Agonists):

II. Sympatholytics (Sympathetic Antagonists):

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 Autonomic Nervous System

I. Sympathomimetics (Sympathetic Agonists):

Epinephrine

OTHERS Norepinephrine

Isoproterenol /
Phenylephrine
Isoprenaline
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 Autonomic Nervous System

Drugs affecting the sympathetic nervous

system
I. Sympathomimetics (Sympathetic Agonists):

 Epinephrine
Epinephrine interacts strongly with both

a-and -receptors.

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:The pharmacological action of epinephrine
 Epinephrine

1- Effect on Blood Vessels:

2- Effects on the Heart:

3- Effects on Smooth Muscle:

4- Metabolic effects:
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 Autonomic Nervous System

1- Effect on Blood Vessels:  Epinephrine

-Small doses of epinephrine,

constricts (α-receptors) some peripheral cutaneous blood
vessels while it
dilates the blood vessels of skeletal muslce.
The produced dilatation is beneficial for the fight or flight.
These effects cause minimal changes in the blood pressure.

-Large doses of epinephrine increase the arterial blood

pressure due to:
i) A generalized vasoconstriction.
ii) Increased cardiac output as a result of the inotropic and
chronotropic
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effects.
 Autonomic Nervous System

2- Effects on the Heart:  Epinephrine

Epinephrine produces changes in the cardiac function that

include:
I) Positive inotropic effect as a result of β1 receptors
stimulation
II) Positive chronotropic effect
III) Increased cardiac output.
iv) Increased coronary blood flow due to dilation of the
coronary arteries. (β2-effect) and increased cardiac work.

However, it increases cardiac oxygen demand which may

lead to angina.
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 Autonomic Nervous System

 Epinephrine
3- Effects on Smooth Muscle:

i) Epinephrine relaxes gastrointestinal smooth

muscle (α1 and β2receptor stimulation).

ii) Uterine contractions may be

• inhibited (β) or
• stimulated (α)
depending on menstrual phase or state of gestation.

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 Autonomic Nervous System

 Epinephrine
iii) In the bladder,
• the detrusor muscle relaxes (β),
• while the trigone and sphincter contract (α) by
epinephrine.

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 Autonomic Nervous System

 Epinephrine

iv) Epinephrine relaxes bronchial

smooth muscle (β2 effect),

thus it is effective in the treatment of

bronchial asthma.

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 Autonomic Nervous System

 Epinephrine
v) Epinephrine causes mydriasis by
contracting the radial muscle of the iris
(α-effect).

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 Autonomic Nervous System

4- Metabolic effects:  Epinephrine

Epinephrine produces:
i) An increase in glucose and lactate production
via liver and muscle glycogenolysis, respectively
(β2).
ii) Inhibition of insulin secretion and increase in
glucagon secretion (β2-effect).
iii) An increase in oxygen consumption.
iv) Release of fatty acids from adipose tissues via
β3-receptors.

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 Autonomic Nervous System

I. Sympathomimetics (Sympathetic Agonists):

Epinephrine

OTHERS Norepinephrine

Isoproterenol /
Phenylephrine
Isoprenaline
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 Autonomic Nervous System

 Norepinephrine

Norepinephrine is
• equipotent to epinephrine in its action on β1
receptors
• and equally or slightly less potent on α-receptors.
• It has a very little effect on β2-receptors.

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 Autonomic Nervous System
 Norepinephrine
i) Intravenous
infusion of
norepinephrine.

ii) The increased

peripheral vascular
resistance produces
a compensatory
vagal stimulation
reflex that slows the
heart rate.

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 Autonomic Nervous System

Pharmacokinetics of Epinephrine
and Norepinephrine
-Norepinephrine is given only by intravenous
infusion.
-The liver is an important site for the degradation
of epinephrine and norepinephrine.

The majority of the dose is metabolized by COMT

and MAO, and the metabolites are excreted the
urine.
COMT : Catechol-O-methyltransferase MAO : monoamine oxidase A

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Therapeutic Uses of Epinephrine and

Norepinephrine
a) Epinephrine is used:
1) To reduce bronchospasm in case of bronchial asthma.
2) As a physiological antidote to reverse the hypotension
associated with anaphylactic shock.
3) To prolong the duration of action of local anesthetics by
delaying their absorption, thereby, minimizing their
potential systemic toxicity.
4) To restore cardiac activity in cases of cardiac arrest via
direct intracardiac injection.
b) Norepinephrine is used for treatment of hypotension
due to general anesthesia.
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 Autonomic Nervous System

Adverse Effects of Epinephrine

and Norepinephrine
1) Both epinephrine and norepinephrine can
cause severe hypertension with possible
cerebral hemorrhage and pulmonary edema.
2) Anxiety and headache are less serious side
effects.
3) Cardiac arrythmias, especially in the presence
of digitalis and certain anesthetic agents.
4) Extravasation of intravenous infusion of
norepinephrine can cause ischemia and tissue
necrosis.
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 Autonomic Nervous System

I. Sympathomimetics (Sympathetic Agonists):

Epinephrine

OTHERS Norepinephrine

Isoproterenol /
Phenylephrine
Isoprenaline
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 Isoproterenol / Isoprenaline
Isoproterenol is a synthetic sympathomimetic drug
that acts almost entirely on β-receptors with
practically no effect on α-receptors.
Pharmacological Effects

1) Increases the force and rate of the myocardial

contraction leading to increased cardiac
output.
2) Relaxation of bronchial smooth muscles and
gastrointestinal tract.
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 Autonomic Nervous System

Isoproterenol Therapeutic Uses

• Isoproterenol is used as a bronchodilator and as a cardiac
stimulant.

• It is available in solution for nebulization, injection or

sublingual tablets.

Isoproterenol Adverse Effects

-These are similar to the adverse effects of
epinephrine.
-Overdosage can induce fatal ventricular arrhythmias.

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 Autonomic Nervous System

I. Sympathomimetics (Sympathetic Agonists):

Epinephrine

OTHERS Norepinephrine

Isoproterenol /
Phenylephrine
Isoprenaline
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 Autonomic Nervous System

 Phenylephrine

Pharmacological Effects
1) Phenylephrine is a synthetic direct-acting
sympathomimetic agent stimulating α-
receptors. Its effects are similar to those of
norepinephrine, but it is less potent and has a
longer duration of action.
2)Vasoconstriction, increased blood pressure, and
reflex bradycardia are the main effects that
occur with parenteral administration.
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 Autonomic Nervous System

Phenylephrine Therapeutic Uses

Phenylephrine is used:
1. As a nasal decongestent and mydriatic.
2. As a pressor agent to prevent hypotension
during spinal anesthesia.
3. To provide local vasoconstriction with local
anesthetics to prolong duration and decrease
toxicity.

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 Autonomic Nervous System

Phenylephrine Adverse Effects

1. Large doses cause cardiac arrhythmias.
2. Ophthalmic solutions as well as intranasal
solution can be systemically absorbed causing
some cardiac arrhythmias.
3. Rebound nasal congestion can occur with its
chronic use as a nasal decongestant if used by
children.
4. It should be given only for 3 days as it may affect
the sense of smell.

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 Autonomic Nervous System

I. Sympathomimetics (Sympathetic Agonists):

Epinephrine

OTHERS Norepinephrine

Isoproterenol /
Phenylephrine
Isoprenaline
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 Other Examples of Sympathomimetic Drugs

β2- Stimulant Drugs:

1. The adrenergic agents that are primarily β2 agonists
have a relaxing effect on bronchial and uterine smooth
muscle ( in pregnancy) and show little effect on cardiac
β1 receptors.

2. These agents are used therapeutically for the treatment

of bronchial asthma or bronchospasm in patients with
cardiovascular diseases.
They are also useful in the treatment of threatened
abortion.
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 Autonomic Nervous System

 Other Examples of Sympathomimetic Drugs

3. These agents differ from isoproterenol in that they are

effective orally and have a longer duration of action and
do not penetrate blood brain barrier.
4. They can be administered by inhalation or parentrally.

5. Examples of β2-stimulants:
a. Salbutamol .
b. Terbutaline .
c. Salmetrol. It has a longer duration of action.

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 Autonomic Nervous System

Drugs affecting the sympathetic nervous

system

I. Sympathomimetics (Sympathetic Agonists):

II. Sympatholytics (Sympathetic Antagonists):

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 Autonomic Nervous System

Drugs affecting
the sympathetic nervous system
II. Sympatholytics (Sympathetic Antagonists):
The drugs of this class are also called anti-adrenergic
agents or adrenergic blocking agents. Activity of the
sympathetic nervous system could be inhibited or
antagonized by one of two ways:
1. The use of drugs that block either (α) or (β) adrenergic
receptors.
2. The use of drugs that inhibit or interfere with the function
of adrenergic neurons. These are called the adrenergic
neuron blockers.

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 α- Adrenergic ●
A. Phenoxybenzamine (Dibenzyline)
Receptors Blocking
●
B. Phentolamine (Regitine) and
Tolazoline (Priscol):
Agents ●
C. Prazosin:
(α-Blockers)

β-Adrenergic ●
Non-Selective β-Blockers
Blocking Agents
●
Cardio-selective β-
(β-Blockers) Blockers:

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 Autonomic Nervous System

 α- Adrenergic Receptors Blocking Agents

:(α-Blockers)

A. Phenoxybenzamine (Dibenzyline):
Phenoxybenzamine produces an irreversible
blockade of α1 and α2 adrenergic receptors.

This blockage is not overcome by giving more

norepinephrine.

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 Autonomic Nervous System
α- Adrenergic Receptors Blocking Agents
:(α-Blockers)

B. Phentolamine (Regitine) and Tolazoline (Priscol):

It is a reversible and non-selectively blocker α-adrenergic
receptors.
1. These two drugs differ mainly in their duration of action.
2. By blocking sympathetic tone to blood vessels, they cause
vasodilatation.
3. They cause only small decrease in supine blood pressure,
but produce a sharp decrease during compensatory
vasoconstriction on standing because reflex sympathetic
central of capacitance vessels (veins) is blocked.

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 Autonomic Nervous System
α- Adrenergic Receptors Blocking Agents
:(α-Blockers)

4. This results in orthostatic (postural)

hypotension.
5. A reflex tachycardia may occur.
The produced tachycardia is also due to blocking
α2-adrenergic receptors; this blockade increases
the release of norepinephrine which stimulate
cardiac β1 adrenergic receptors.

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 Autonomic Nervous System
α- Adrenergic Receptors Blocking Agents
C. Prazosin: :(α-Blockers)
It is a relatively specific α1-adrenergic receptor
antagonist.
It causes less tachycardia than the nonselective α-
blockers.
Therapeutic uses:
1) Control of acute hypertensive episodes.
2)Relieve vasospasm and in the treatment of Raynaud's
disease

Raynaud's disease
(peripheral vasoconstriction of the
extremities).

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 Autonomic Nervous System
α- Adrenergic Receptors Blocking Agents
:(α-Blockers)
C. Prazosin:
Adverse effects:
1) Postural hypotension due to a lack of compensatory
sympathetic vasoconstriction.
2) Reflex tachycardia may take place (less with prazosin).
They must be used with caution in patients with coronary
disease.
3) Phentolamine and tolazoline should be used with caution
in patients with peptic ulcer since they stimulate GI tract
to produce abdominal pain and diarrhea.
4) Nasal stiffness.

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 Autonomic Nervous System
β-Adrenergic Blocking Agents
(β-Blockers):

– These drugs inhibit the effects mediated by

epinephrine via β-adrenergic receptors.

– According to whether they block one or

bothβ1 andβ2 receptors, these drugs are
classified into non-selective and selective β-
blockers.
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 :β-Blockers
Cardio-selective

Atenolol Metopralol

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 Autonomic Nervous System

1) Non-Selective β-Blockers
A. Propranolol
Pharmacological effects:
1) Propranolol decreases heart rate and cardiac
contractility, hence reducing the cardiac output.
2) It decreases cardiac work and oxygen consumption.
3) Bronchospasm due to blocking of β2-receptors.
(Especially in the asthmatic patients).
4) It reduces renin secretion.
5) Anti-arrhythmic activity.
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 Autonomic Nervous System
Therapeutic uses:
A. Propranolol
Propranolol is used for:
1) Treatment of hypertension.
2) Prophylaxis in cases of angina pectoris since it
reduces cardiac work and oxygen consumption.
3) Prophylaxis in cardiac arrhythmia

N. B: Angina pectoris is a
group of symptoms related
to decreased blood flow to
cardiac muscle due to
narrowing of coronary
arteries; thus reducing
oxygen delivery.
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 Autonomic Nervous System
A. Propranolol
Adverse effects and precautions:
1) Propranolol can induce heart failure, especially in
patients with compromised myocardial function.

2) Because propranolol blocks β2-receptors:

i. It must be used with caution in asthmatics because it may
cause bronchospasm
ii. It must be used with caution in diabetics because it can
increase insulin-induced hypoglycemia and block
hypoglycemia-induced tachycardia.

3) Allergic reaction such as skin rash and fever.

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 Autonomic Nervous System

B. Labetalol:
It is a reversible antagonist of α1 and β1 and β2
adrenergic receptors.
So its pharmacological effects are similar to
combination of propranolol and prazosin.
It is effective in the treatment of
pheochromocytoma, which is a tumor of adrenal
gland.

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 Autonomic Nervous System

2) Cardio-selective β-Blockers:

Atenolol, Metopralol :
They are selective β1-adrenergic
antagonists, which are sued for the
treatment of cardiac disorders in
patients with bronchial asthma.

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