1. Epinephrine
By: Dr. Vahid Nikoui
Email: nikoui@razi.tums.ac.ir

2. •It is a catecholamine, a sympathomimetic monoamine derived from the
amino acids phenylalanine and tyrosine.
•The Latin roots ad-+renes and the Greek roots epi-+nephros both literally
mean "on/to the kidney" (referring to the adrenal gland, which secretes
epinephrine). Epinephrine is sometimes shortened to epi in medical
jargon.
•Epinephrine is now also used in EpiPen and Twinject. EpiPen is long
narrow auto-injectors that administer epinephrine, Twinject is similar but
contain two doses of epinephrine.

3. Adrenal Anatomy
• small, triangular glands loosely attached
to the kidneys
• divided into two morphologically and
distinct regions
- adrenal cortex (outer)
- adrenal medulla (inner)

5. Anatomy and Origin
• embryologically derived from
pheochromoblasts
• differentiate into modified neuronal cells
• more gland than nerve
• chromaffin cells
• acts like sympathetic ganglion

6. Function of the Adrenal Medulla
• an extension of the sympathetic nervous
system
• acts as a peripheral amplifier
• activated by same stimuli as the
sympathetic nervous system
(examples – exercise, cold, stress,
hemorrhage, etc.)

8. Biosynthesis of norepinephrine and epinephrine
HO NH2 HO NH2
NH2
Tyrosine Dopa
HO
CO2H
hydroxylase HO
CO2H
Decarboxylase HO
L-Tyrosine Levodopa Dopamine
OH
OH
HO NHMe
Dopamine HO NH2
N-methyl transferase
-hydroxylase HO (in Adrenal medulla) HO
Epinephrine
Norepinephrine (Adrenaline)
(Noradrenaline)

9. Metabolism involves two key enzymes:
MAO and COMT

10. Differences between Epinephrine
and Norepinephrine
 Epinephrine >> norepinephrine – in terms of
cardiac stimulation leading to greater cardiac
output ( stimulation).
 Epinephrine < norepinephrine – in terms of
constriction of blood vessels – leading to
increased peripheral resistance – increased
arterial pressure.
 Epinephrine >> norepinephrine – in terms of
increasing metabolism

11. Effects of Epinephrine
• metabolism
- glycogenolysis in liver and skeletal
muscle
• can lead to hyperglycemia
- mobilization of free fatty acids
- increased metabolic rate
• O2 consumption increases

12. Fight or Flight Response
 These catecholamine hormones facilitate immediate
physical reactions associated with a preparation for
violent muscular action. These include the following:
 Acceleration of heart and lung action and Inhibition of
stomach and intestinal action
 Constriction of blood vessels in many parts of the body
 Liberation of nutrients for muscular action
 Dilation of blood vessels for muscles
 Inhibition of tear glands and salivation
 Dilation of pupil
 Relaxation of bladder
 Inhibition of erection
(Gleitman, et al, 2004)

13. Pheochromocytoma
• a catecholamine-secreting tumour of
chromaffin cells of the adrenal medulla
adrenal pheochromocytoma (90%)
• paraganglioma – a catecholamine
secreting tumour of the sympathetic
paraganglia
extra-adrenal pheochromocytoma

14. Signs and Symptoms of Pheochromocytoma
• headache
• sweating classic triad
• palpitations
• chest pain
• anxiety
• glucose intolerance
• increased metabolic rate

17. Classes of G protein
Gs→ s→ AC → cAMP↑
Gi→ i→ AC → cAMP↓
G q→ q→ PLC → IP3+ DAG

18. Types of -adrenergic receptor
 -adrenergic receptors are adrenergic receptors
that respond to norepinephrine and to such blocking
agents as phenoxybenzamine.
 They are subdivided into two types:
 1, found in smooth muscle, heart, and liver, with
effects including vasoconstriction, intestinal
relaxation, uterine contraction and pupillary dilation,
 2, found in platelets, vascular smooth muscle,
nerve termini, and pancreatic islets, with effects
including platelet aggregation, vasoconstriction, and
inhibition of norepinephrine release and of insulin
secretion.

19. Types of β-adrenergic receptor
 -adrenergic receptors respond particularly to
epinephrine and to such blocking agents as
propranolol.
 There are three known types of beta receptor,
designated β1, β2 and β3.
 β1-Adrenergic receptors are located mainly in the
heart.
 β2-Adrenergic receptors are located mainly in the
lungs, gastrointestinal tract, liver, uterus, vascular
smooth muscle, and skeletal muscle.
 β3-receptors are located in fat cells.

20. Receptors and signal transduction in the ANS
Adrenergic Receptors
1 2
1A 1B 1D 2A 2B 2C 1 2 3

21. Direct acting adrenergic receptor agonists:
1 receptors
NH 3
Phospho -
lipase C
 Phenylephrine (Neosynephrine)
 Methoxamine (Vasoxyl)
 Oxymetazoline (Visine) (+)
Gq
PIP 2
HO
COOH IP 3 Diacylglycerol
CH C H 2 NH C H3 2+
Increase Ca Activate Protein
Kinase C
OH
P henylephrine
Response

22. Direct acting adrenergic receptor agonists:
2 receptors
NH 3
 Clonidine (Catapres)
 Methyldopa (Aldomet)
 Guanabenz (Wytensin)
 Guanfacine (Tenex)
 Tizanidine (Zanaflex)
(-) Adenylate Cyclase
GI
Cl
N K+ (+) X
H
N ATP cAMP
COOH
N
H Reduce cAMP -Dependent
Cl Protein Kinase Activity
C lonidine
Response

23. Direct acting adrenergic receptor agonists:
receptors
NH 3
(+) Adenylate Cyclase
GS
ATP cAMP
COOH
Increase cAMP -Dependent
Protein Kinase Activity
Response

24. β3 adrenergic agonist
Amibegron (SR-58,611A)
It is the first orally active β3 agonist
developed that is capable of entering
the Central Nervous System, and has
antidepressant and anxiolytic effects.
Solabegron (GW-427,353)
It is being developed for the
treatment of overactive bladder and
irritable bowel syndrome. It has been
shown to produce visceral analgesia
by releasing somatostatin from
adipocytes.

25. Classification of Adrenergic Hormone Receptors
Second
Receptor Agonists G protein
Messenger
alpha1 ( 1) NE > E IP3/Ca2+; DAG Gq
alpha2 ( 2) E > NE cyclic AMP Gi
beta1 ( 1) E = NE cyclic AMP Gs
beta2 ( 2) E >> NE cyclic AMP Gs
E = epinephrine; NE = norepinephrine

26. Cardiovascular effects of adrenergic agonists in
man (injected iv)
A ( + )
NA ( >> )
Iso ( )

27. Indications
Cardiac Arrest
 Ventricular fibrillation
 Asystole

28. Indications
 Sever hypotension
 Anaphylaxis

29. Dosage
In cardiac arrest
1 mg (10 mL 1:10,000 solution)
If this fails, higher doses of epinephrine (up to 0.2 mg/kg) are acceptable but
not recommended (there is growing evidence that it may be harmful).
Precautions
Can precipitate myocardial ischemia
Avoid mixing with alkaline solutions
Can induce myocardial ectopy

30. EpiPen
EpiPen is a registered trademark for the most commonly used autoinjector of
epinephrine (aka adrenaline), used in medicine to treat anaphylactic shock.
http://www.epipen.com/howtouse_high.aspx

31. Anaphylaxis
Anaphylaxis is a severe and rapid multi-system allergic
reaction. The term comes from the Greek words ana
(against) and phyllus (protection). Anaphylaxis occurs when
a person is exposed to a trigger substance, called an
allergen, to which they have already become sensitized.
Minute amounts of allergens may cause a life-threatening
anaphylactic reaction. Anaphylaxis may occur after ingestion,
inhalation, skin contact or injection of an allergen. The most
severe type of anaphylaxis—anaphylactic shock—will
usually lead to death in minutes if left untreated.
Most common presentation is sudden cardiovascular
collapse.

32. Ephinephrine can be injected directly into the heart to stimulate it
after it as stopped beating due to drowning, suffocation, shock,
electrocution, and anesthesia.
The epinephrine dramatically restores the heart beat.
In cases of shock, norepinephrine has been used to restore and
maintain sufficient blood pressure and ensure adequate blood flow
to vital organs.
When local anesthetics are used to reduce or eliminate pain in a
specific area, epinephrine is frequently used in conjunction with
these agents to constrict the blood vessels at the area and prevent
drug diffusion from that area.

33. Thanks for Your Company