Autonomic Nervous System (ANS)

Autonomic Nervous
System (ANS)
د.‏ م.‏ أ.‏
وحدة اليوزبكي
Department of Pharmacology- College of
Medicine- University of Mosul
Sympathetic (Adrenergic)
nervous system
2

Objectives
At end of this lecture, the students will be able
to:
1- Enumerate the classes of Adrenergic Agonists
drugs.
2- List the most widely used group (Direct acting
adrenergic agonists).
3- Discuss the most clinically used drugs in the direct
acting adrenergic agonists.
In a way, consistence with standards scientific
curriculum.

Classifications of Adrenergic Agonists according to
mechanism of action

Classifications of According to mechanism
of action
I- Direct acting adrenergic agonists:
Adrenaline (A), Noradrenaline (NA),
Isoproterenol (isoprenaline), Dopamine,
Phenylephrine, Methaxamine, Salbutamol,
Terbutalin, Clonidine, Xylometazoline,
Fenoldopam.

II- Indirect acting adrenergic agonists:
1- Amphetamine.
2- Tyramine.
III- Mixed-action adrenergic agonists.
1- Ephedrine.
2- Metaraminol.

I- Direct acting adrenergic agonists
(Sympathomimitics)
- These bind to
adrenergic
(postsynaptic)
receptors & causes
intracellular signals &
initiate action.
- As a group these
agents are widely used
clinically.

I- Direct acting adrenergic agonists
1- Epinephrine (Adrenaline) A:
- Natural catecholamine, commonly used in
therapy.
- In therapeutic low doses : β R effect
- At high dose : α R effect
Biotransformation:
C.A metabolized by COMT and MAO, and result in
production of metanephrine & vanillyl-mandelic
acid (VMA) in urine.
Note:
A destroyed by acid of stomach & so not effective
orally & usually given SC or IM injection.
-

Action of Adrenaline
1- C.V.S:
- Adrenaline causes increase HR & contraction of
heart which lead to increase CO and so to
increase systolic Bdp.
- But Adrenaline cause decrease PR , which
lead to slight decrease D Bdp.
(Adrenaline Lead to increase systolic Bdp
& Slight decrease D Bdp).

C.V.S effect of Adrenaline
(Epinephrine)
Summary:
(Adrenaline Lead to
increase systolic
Bd p & Slight decrease
diastolic Bdp).

2- Respiratory:
Bronchodilatation (β 2).
3-Metabolic:
a- hyperglycemia by increase
glycogenolysis in liver (β 2) & increase
release of glucagon (β 2) + decrease
release of insulin (α2).
b- Lipolysis: due to agonist effect on β R
of adipose tissue.

Clinical uses of Adrenaline
1- Acute asthma.
2- Anaphylactic shock
hypersensitivity reaction).
(1 st type
3- Anesthesia:
a- With LA (dilution of A 1:10000 parts), as A
lead to increase duration of LA by
vasoconstriction at the site of injection.
b- Topically (topical haemostatic agent).
4- Glaucoma (2% topically) due to decrease
production of aqueous humor by
vasoconstriction of ciliary body blood
vessels.

Side effects of Adrenaline
1- C.N.S: anxiety, fear, tension, headache,
tremor.
2- Hemorrhage: (due to increase cerebral
Bd p)
3- Cardiac dysarrhythmia: (with digoxin).
- Large dose lead to V.fibrillation (may be
fatal).
4- Pulmonary oedema.

5- Drug interaction with Adrenaline
a- Hyperthyroidism:
Adrenaline lead to hypertensive response due to
increase adrenergic R on vasculature of the
hyperthyroid patients.
b- Cocaine:
Cocaine lead to increase CV response of adrenaline
due to ability to prevent reuptake of C.A into
adrenergic neurons.

2- Nor epinephrine (NE) (Levarterenol,
(Nor adrenaline)
- It is the chemical mediator librated by
postganglionic sympathetic N.ending & act
directly on the effector cells.
- In therapeutic doses: α R effect and similar
β1R effect (on heart) but no β 2 R.

Action of Nor adrenaline (NA)
C.V.S :
NA increase PR due to intensive vasoconstriction
of most vascular bed
( including kidney via α 1R), which lead to increase
both S & D Bdp
(with increase mean Bdp). This lead to
compensatory vagal reflex by stimulation to the
baroreceptor reflex , which cause decrease
contraction of heart & decrease HR ( called reflex
bradycardia).

C.V.S effect of Nor adrenaline
Summary:
NA cause intensive
vasoconstriction
which lead to
increase PR, and so
to:
increase both S & D
Bd pressure, and this
lead to:
reflex bradycardia
(Nor epinephrine)

Notes:
1- Due to powerful vasoconstrictor effect of
NA:
a- Lead to reflex bradycardia. -
b- NA not used as vasoconstrictor in LA
solution.
-
2- The main function of NA appear to be
maintenance of normal sympathetic tone
and adjustment of circulatory dynamic.

3- Isoproterenol (Isoprenoline):
- Direct acting synthetic C.A.
- It is extremely potent β R agonist (β 1,
β 2).
PK: Given sublingually, pranterally & as aerosol.
Uses: Usually to stimulate heart in
emergency
cases.
SE: as Adrenaline.

Action of Isoproterenol (Isoprenoline)
1- C.V.S: (Like A)
Lead to increase systolic Bdp & Slight
decrease D Bd p).--- ?
2- Pulmonary:
β2R:Rapid & profound bronchodilatation.
3- Other effects:
- β R: increase Bd sugar & increase lipolysis
(not significant clinically).

4- Dopamine
-It is immediate metabolic precursor of N.A
occurs naturally in C.N.S in basal ganglia
(function as N.T) and in adrenal medulla.
-
- Dopamine activates:
1- β1 Receptors (and at higher dose
activate also a R.),
2- D1 & D2 R occur in peripheral mesenteric
& renal vascular bed lead to vasodilatation.

Actions of Dopamine
1- C.V.S: Dopamine lead to increase force &
rate of contraction of heart (β1 effect).
2- Renal and visceral: Dilatation of renal &
splanchnic arterioles (D1,D2 agonist effect),
which lead to increase blood flow to kidney &
other viscera.
Uses:
Dopamine drug of choice (over A) in shock as A
cause decrease renal blood supply & may
cause renal shutdown.
Overdose:
Nausea, hypertension, arrhythmia.

5- Fenoldopam
D1 Receptor agonist: selectively cause
peripheral arteriolar vasodilatation in
vascular bed.
-
Uses: in severe hypertension (IV or
continuous infusion).
SE:
Decrease K, tachycardia, headache,
flushing.
-