Reversal action of adrenaline on blood pressure in dog Experimental Pharmacology(Virtual lab)

1. Reversal Action Of
Adrenaline on
Blood pressure
By Dr Sameh AM Abdelghany

2. Physiology Review
• The autonomic nervous system
(ANS) is that division of the
nervous system concerned with
regulation of involuntary
functions.
• It consists of 2 divisions,
sympathetic and
parasympathetic, controlled by
higher CNS centers.

3. Sympathetic Parasympathetic
Autonomic nerve:
 Origin
 Pre-gang fiber
 Post-gang fiber
 Ganglia
Thoracic part: T 1-12
Lumbar part: L 1-3
Short
Long
Outside organs
Cranial part: III, VII, IX, X
Sacral part: S 2,3,4
Long
Short
Inside organs (é few
exceptions)
Chemical
transmitters:
 1ry:
 2ry:
 Co-transmitters
NA, A
Dopamine
ATP, NPY, Substance-P, etc.
Ach
–
The same
Receptors:
 Main:
 Other:
Alpha: α1, α2
Beta: β1, β2, β3
Dopaminergic: D1, D2
Imidazoline: I1, I2
Muscarinic: M1, M2, M3, m4,
m5
Nicotinic: Nn, Nm
–
Autonomic tone
Predominates on:
- Heart (vent ms) → ↑ contraction
Predominates on:
- Heart (S-A node) → ↓ rate

6. Chemical transmitters in the
ANS
 Primary transmitters:
I. Adrenaline and noradrenaline(NA)
II. Acetylcholine

7. Adrenaline and noradrenaline(NA)
Synthesis and storage:
1. In nerve terminals, most of catecholamines
are in the form of NA because the enzyme N-
methyl transferase is not present
2. In adrenal medulla, most of catecholamines
are in the form of adrenaline.

8. Sites of release:
 all sympathetic system except:
I. Sympathetic ganglia
II. Postganglionic sympathathetic
fibers to sweat glands.

9. Fate:
 all sympathetic system except:
I. Re-uptake (80%):
 Neuronal uptake (uptake 1)
 Tissue uptake (uptake 2)
 Granular uptake (uptake 3)
II. Metabolism (20%):
 Monoamine oxidase (MAO)
enzyme
 Catechol-O-methyl transferase
(COMT)

11. Autonomic receptors
1. Adrenergic receptors.
2. Cholinergic receptors.

12. Adrenergic receptors
Type Tissue Second
messenger
Actions
1  Most vascular smooth ms
 Pupillary dilator muscle
 Pilomotor smooth muscle
 Liver (in some species)
IP3, DAG  Contracts (vasoconst)
 Contracts (mydriasis)
 Contracts (erects hair)
 Glycogenolysis
2  Adrenergic and cholinergic
nerve terminals
 Platelets
 Some vascular smooth ms
 Fat cells
 Pancreatic B cells
 cAMP  Inhibits transmitter
release
 Stimulates aggregation
 Contracts
 Inhibits lipolysis
 Inhibits insulin release

13. Type Tissue Second
messenger
Actions
1  Heart
 Juxtaglomerular cells
cAMP  Incease rate and force
 Stimulates renin release
2  Respiratory, uterine, and
vascular smooth muscle
 Liver (human)
 Somatic motor nerve terminals
(voluntary muscle)
 Pancreas
cAMP  Relaxes
 Stimulates glycogenolysis
 Causes tremor
 Increase insulin release
3  Fat cells  cAMP  Stimulates lipolysis
D1  Renal and other splanchnic
blood vessels
cAMP  Relaxes (reduces
resistance)
D2  Nerve terminals  cAMP  Inhibits adenylyl cyclase

14. Organ Alpha(α) Beta(β)
Eye Mydriasis (α1) -
Heart - ++ all cardiac properties(β1)
Bronchi - Bronchodilatation (β2)
GIT Cont. Sphincters (α1) Relax wall (β2)
UT Cont. Sphincters (α1) Relax wall (β2)
Uterus Cont. (α1) Relax (β2)
Bl.vessel V.C esp skin-mm(α1) V.D esp skeletal- coronary(β2)
Insulin release decrease(α2) Increase (β2)
Others - ++ NM transmisssion - Glycogenlysis (β2)
- Lipolysis(β3)
- ++ Renin release(β1)
- ++ K uptake(β2)

15. Alpha Adrenergic receptors
agonists & antagonists
I. Alpha adrenoceptor agonists:
 Alpha 1 and alpha 2: EP and NE.
 Alpha 1: phenylephrine and methoxamine.
 Alpha 2: clonidine.
II. Alpha adrenoceptor antagonists:
 Alpha 1 and alpha 2: phentolmaine
 Alpha 1: prazosin.
 Alpha 2: yohmbine.

16. Beta Adrenergic receptors
agonists & antagonists
I. Beta adrenoceptor agonists:
 Beta1, beta2, beta3: isoproterenol and EP.
 Beta 1: dobutamine
 Beta 2: salbutamol, terbutaline
II. Beta adrenoceptor antagonists:
 Beta1, beta2: propranolol
 Beta 1: Atenolol
 Beta 2: butoxamine

17. Sympathomimetics
 Definition:
o These are drugs, which produce pharmacological
actions and effects similar to sympathetic
stimulation.

18. Sympathomimetics
Catecholamines
Natural e.g NE, EP
Synthetic e.g Isoprenaline
Non-Catecholamines

19. Classification
According to mechanism of action:
i. Direct acting: e.g. E, NE, and
dopamine
ii. Indirect acting: e.g. amphetamine
iii. Both direct and indirect: e.g.
ephedrine

20. According to selectivity:
i. Drugs acting mainly on α1 receptors:
e.g. NE, phenylepherine
ii. Drugs acting mainly on β receptors:
a. On β1 mainly: e.g. dobutamine
b. On β2 mainly: e.g. salbutamol and
turbutaline
c. On both β1 and β2: e.g. isoprenaline
iii. Drugs acting on α and β receptors:
e.g. adrenaline, ephedrine
iv. Drugs acting on α, β, and dopamine
receptors: dopamine

21. Adrenaline (Epinephrine)
Chemistry:
• Natural alkaloid synthesized by
adrenal medulla.

22.  Pharmacokinetics
Absorption:
• Slow (due to its local VC) and poor (because it is
polar) from all sites.
• Slowly absorbed if given SC and rapidly after
IM,IV
Distribution:
• all tissues except CNS (catecholamine).

23. Fate:
• Re-uptake: (80%)...(neuronal,
tissue, and granular).
• Metabolism: (15%) by MAO and
COMT.
• 5% Excreted in urine in the form
of VMA (4-8 mg/ day).

24.  Pharmacodynamics
Mechanism of action:
 stimulates all α1, α2, β1, β2, β3 receptors.

25. Pharmacological effects:
CVS:
a) Heart: ↑ all cardiac properties
(β1).
b) BV:
• VC of skin, visceral and brain BV
(α1)
• VD of sk ms BV (β2)

26. c) BP:
• Small dose → ↓ BP (β2 is more
sensitive than α1).
• Large dose → biphasic response:
i. Initial ↑: due to predominant
α1 action.
ii. Delayed ↓: due to predominant
β2 action (β2 is more sensitive to
small doses of adrenaline).
• Hypertensive effect reversed by
α-blocker

27. Respiratory system:
• Airway:
i. Bronchodilatation (β2).
ii. Bronchial decongestion due to
VC of bronchial BV (α1).

28. GIT and urinary system:
• Wall: relaxation (β2).
• Sphincters: contraction (α1).

29. Metabolic effects:
 Liver → ↑ glycogenolysis (β2).
 Kidney → ↑ renin secretion (β1)
 Fat cells → ↑ lipolysis ( β3)

30. Exocrine glands:
 Sweat glands: sympathetic
sweating (forehead and palms)
(α1).
Atiallergic action:
 It is the physiological antidote of
histamine on BP and bronchi

31. Eye:
• Local adrenaline: no effects
(destroyed by alkalinity of the
tears).
• Local dibivalyl adrenaline:
↓ IOP (due to VC of ciliary BV → ↓
aqueous humor secretion)

32. Local actions:
• Decongestant -hemostatic
• Delay absorption of drugs given
SC

33.  Therapeutic uses
Acute bronchial asthma
Acute anaphylactic shock
a)Stimulation of bronchial β2 receptors → ↑ cAMP
→ bronchodilatation.
b)Stimulation of bronchial α1 receptors → VC of
bronchial BV →↓ br secretions.
c)↑ BP (due to ↑ COP “β1” + ↑ PR “α1”).
d)↓ histamine release from mast cells (β2).

34. Local uses:
1. In acute epistaxis (nasal bleeding)
to produce VC of nasal BV.
2. Dibivalyl adrenaline is used as eye
drops for treatment of glaucoma.
3. Injected locally with local
anesthetics:
i. To prolong the duration of local
anesthetics due to local VC.
ii. To minimize bleeding due to local
VC.

35.  Side effects
1. Severe hypertension and cerebral hemorrhage.
2. Tachycardia, palpitations, and ventricular
fibrillation.
3. Acute heart failure.
4. Gangrene of fingers when used with local
anesthetics in high conc (due to VC).

36.  Contraindications
1. Heart diseases.
2. Hypertension.
3. Hyperthyroidism
4. During general anesthesia with halothane or
cyclopropane because they increase the
sensitivity of the sympathetic receptors.
5. With local anesthesia in fingers and toes

37. NOREPINEPHRINE
(NORADRENALINE)
► Source and Chemistry as
adrenaline
► Pharmacokinetics as adrenaline
►Pharmacodynamics
 Mechanism of Action:
• directly stimulates both  and 1
receptors.

38.  Pharmacological Effects
C.V.S.
 Heart:
i. Increased cardiac properties (1)
ii. Reflex vagal effect due to its hypertensive effect
leads to bradycardia (this bradycardia could be
blocked by atropine)
 Blood vessels: generalized V.C. (1)
 Blood pressure: rise of both systolic and diastolic
blood pressure.

39.  Therapeutic Uses
1. Acute hypotensive states e.g. spinal anesthesia
and after ganglion blockers.
2. Shock states when tissue perfusion is good

40.  Adverse Effects
1. Bradycardia and palpitation
2. Headache and anxiety.
3. Severe hypertension leads to cerebral
hemorrhage
4. Cardiac arrhythmias.
5. When used with local anesthesia in fingers, its
extravasation may lead to necrosis and
sloughing.

50. THANK YOU