Introduction to autacoids and classification

Introduction To Autacoids, Their Classification And Pharmacological Response in the Body

1. By: Diksha
M. Pharmacy (Pharmacology)

2. *
*Generally known as Local Hormones
*Having self healing properties

*a physiologically active substance (such as
serotonin, bradykinin, or angiotensin)

*produced by the body and typically has a
localized effect of brief duration

3. *
*Endogenous Compounds

*Plays an important role in the physiological and
pathological processes

*Having short duration of action
*Synthesized locally and produce their effect on
local tissues

4. *Amine Derivatives: Histamine, 5-
Hydroxytryptamine
(5-HT)

*Peptide Derivatives: Bradykinin, Angiotensins

*Lipids Derivatives: Prostaglandins (PGs),
Leukotriens (LTs),Platelet
activating factor (PAF)


*

5. Pharmacology of
Histamine

6. *



Histidine (from hydrolysis
proteins and from dietary
source)

L- Histidine decarboxylase

Histamine






•Histamine is an important
nitrogenous organic
compound
•Mainly involved in the
pathogenesis of allergic
reactions
•Central mediator released
from mast cells through
allergic reactions
*Histamine

7. L- Histidine decarboxylase
Histamine Histidine
N-methyl Transferase
Diamine oxidase
N-methyl Histamine
Imidazoleacetic acid

N- methyl Imidazoleacetic acid

MAO-B
Phosphoribosyl
Transferase

Imidazoleacetic acid riboside

Metabolites

8. •Smooth Muscle:
Contraction

•Blood Vessels: Dilatation

•Afferent nerve endings:
Stimulation

•Ganglionic Cell:
Stimulation

•Adrenal Medulla: Release
of catecholamines




Effect Through H1
Receptors
Effect Through H2
Receptors


•Glands of GIT: stimulation
of gastric acid secretions

•Blood Vessels: Dilatation

•Heart: Increases the force
of contraction

•Uterus: Relaxation of
smooth muscles

9. •Brain: Sedation due to
inhibition of histamine
release

•Blood Vessels: Dilatation

•Skin, Gastric Mucosa:
Decrease in histamine
release

•Lungs, Spleen: Decrease
secretions due to Decrease
in histamine release




Effect Through H3
Receptors
Effect Through H4
Receptors







•Mast Cells: Modulation of
Allergic Reactions

10. Receptors of Histamine and their location
H1: Heart, Brain,
Mast Cells
H2: Heart, Brain,
Neutrophils, Parietal
Cells
H3: Brain, PNS
H4: Blood Cells
(Mast cells,
eosinophils,
monocytes)

11. Drugs for Histaminergic Receptors
Agonists
Antagonists
Receptor Type
H1 H2 H3
2-
methylhistamine,2-
pyridylethylamine,2-
thiazolyl ethylamine
Mepyramine,
chlorpheniramine
G-Protein Coupled
Receptors
4-methy
histamine,
Dimaprit,
impromidine
Cimetidine,
Ranitidine
G-Protein Coupled
Receptors
ἀ-methyl
Histamine
Thioperamide,
Impromidine
G-Protein Coupled
Receptors

12. *Common cold
* Motion sickess
* Duodenal ulcer(Zollinger
- ellison syndrome)
*Parkinsonism
* Allergic disorders
*Sedative and hypnotic
* Anxiolytic



*CNS depression
* fatigue
* gynecomastia in men
* galactorrhea women
ADRs
Therapeutic Indications

13. Pharmacology of
Serotonin

14. *Serotonin (5–HT)
Tryptophan
(from dietary sources)

Tryptophan Hydroxylase

5 – Hydroxytryptophan

Decarboxylase

5 – Hydroxytryptamine (5-HT)







A key hormone that:

•stabilizes our mood

•feelings of well-being

•happiness

•also helps with sleeping,
eating, and digestion

15. Tryptophan
(from dietary sources)


Tryptophan Hydroxylase


5 – Hydroxytryptophan

Decarboxylase

5 – Hydroxytryptamine (5-HT)



MAO
5 – Hydroxyindole acetaldeyde
5- hydroxyindole acetic
acid (5 - HIAA)
Aldehyde Dehydrogenase
Metabolite

16. Location and Distribution of
serotonin

17. *
5HT 1
5HT 2
5HT 7
5HT 3
5HT 6
5HT 5
5HT 4

5HT 1A

5HT 1B

5HT 1D



5HT 2A

5HT 2B

5HT 2C

18. Receptor Location Action Agonist Antagonist
5HT 1A

5HT 1B

5HT 1D



CNS

CNS, SMOOTH
MUSCLES

CNS, BLOOD
VESSELS


Neuronal
Inhibition
Vasoconstriction








8-OH-DPAT
Buspirone

Ergotamine

Sumatriptan









Methiothepin,
Ergotamine

5HT 2A

5HT 2B

5HT 2C



CNS, PNS, SMOOTH
MUSCLES

GASTRIC REGIONS

CNS




Smooth Muscles
Contraction

ἀ-Me-5-HT
LSD(



KETANSERIN,
Cyproheptadine



Methysergide




5-HT3

PNS
CNS

Chlorophenyl
biguanide


Ondansetron,
Tropisetron


Neuronal
excitation,
emesis

19. Receptor Location Action Agonist Antagonist

5-HT7


CNS,
GI TRACT,
Blood Vessels


Unknown

5-CT,LSD



Not Known


5-HT4


5-HT5


5-HT6


CNS

CNS
PNS
CNS

Unknown


Unknown

Enhances GIT
Motility

Unknown
Unknown

5-methoxy-
tryptamine,
metochlopromide



Not Known

Not Known
Not Known

20. Pharmacological Actions of Serotonin
Effect on CVS: Vasoconstrictor and vasodilatory effect as well
Effect on Smooth Muscles: Stimulation of smooth muscles
Effect on Respiratory System: Hyperventilatory effect
Effect on Glands: Decrease the glandular secretion. Have efficacy in
inflammatory disorders
Effect on Platelets: Activate PAF; Having little effect on Platelet
aggregation

21. •Anxiolytics

•Depression

•Migraine
ADRs
•Abdominal Pain


•Muscle Cramps


•Chest Pain

22. Pharmacology of
Prostaglandins (PGs)

23. *
Prostaglandins (PGs)
•Prostaglandins are a group of Lipids Autacoids

•Made at sites of tissue damage or infection

•Involved in dealing with injury and illness

•Control processes such as inflammation, blood flow,
the formation of blood clots and the induction of
labour

24. Membrane Phospholipids
Arachidonic acid
Phospholipase
A2
PGG2
COX
Peroxidase
PGH2
Thromboxane A2
PGE2, PGD2, PGF2
PGI2
Synthase Enzyme
On hydrolysis,
resultant is
Thromboxane B2
On hydrolysis,
resultant is 6 –
keto PG F1alpha

25. Activity of PGs
Thromboxane A2: Thrombotic Tendency
PGE2: Inflammation, Tumor Growth
PGD2: Anti - inflammatory
PGF2: Loss of Parturition
Prostacyclins PGI2: Protection of GIT mucosa, Resistance to
Thromboembolism

26. Pharmacological Actions of PGs
Blood Vessels
PGE2
PGI2
PGF2 - alpha
TXA2
Heart Bronchi GIT Uterus
PGs Types
Vasodilation
Vasodilation
Vasodilation
Vasoconstriction
Weak
Inotropic
Weak
Inotropic
_
_
Dilatation
Constriction
Dilatation
Constriction

Acid
Secretion
Decrease
Acid
Secretion
Decrease
Contraction
Contraction
_
_

27. Analogues of PGs
PG E1: Misoprostol, Gemeprostol, Alprostadil
PG E2: Dinoprostone
PG F2 alpha: Latanoprost, Carboprost
PG I2: Epoprostenol
USES
NSAIDs Induced Peptic Ulcer
Therapeutic Abortion
Induction of Labour
Therapeutic Abortion
Induction of Labour
Open Angle Glaucoma
Pulmonary Hypertension

28. Pharmacology of
Leukotrienes (LTs)

29. Leukotriene's (LTs)
•Leukotrienes are inflammatory chemicals

• Releases after coming in contact with an allergen or allergy trigger

•Leukotrienes cause tightening of airway muscles and the production of
excess mucus and fluid

•These chemicals play a key role in allergy, allergic rhinitis, and
asthma, also causing a tightening of your airways, making it difficult
to breathe.

30. Synthesis of LTs

31. Pharmacological Actions of LTs
Effect on CVS: Fall in Blood Pressure
Effect on Smooth Muscles: Bronchoconstriction and spastic
contraction of smooth muscles of GIT
Effect on Afferent Nerve: Carrying pain impulses and
tenderness to inflammation

32. Receptors of LTs and their
drugs
BLT
1 receptor
CysLT
2 receptor
CysLT
1 receptor
BLT
2 receptor
OXE receptor
Receptor Agonist Antagonist
LTB
4
LTB
4
LTD4
5-oxo-ETE
CI-198615, LTD4
CGS23131
LY255283
zafirlukast
HAMI3379
S - Y048

33. Treatment of Asthma

Reduce Bronchospasm
GIT upset

Liver Dysfunction

34. Pharmacology of Platelet
Activating Factor (PAF)

35. *Platelet-activating factor, also known
as PAF, PAF-acether or AGEPC (acetyl-
glyceryl-ether-phosphorylcholine)

* Potent Phospholipid

*Activator and mediator of
many leukocyte functions, platelet aggregation
and degranulation, inflammation,
and anaphylaxis
Lipid Derivative
Platelet Activating Factor ( PAF)

38. *Pharmacology Of PAF

39. •PAF is used to transmit signals between neighbouring cells and acts
as a hormone, cytokines, and other signalling molecules
•PAF signalling system can trigger inflammatory
and thrombotic cascades
•PAF initiates an inflammatory response in allergic reactions
•PAF also induces apoptosis in a different way that is independent of
the PAF receptor
•It is an important mediator of bronchoconstriction
•It causes platelets to aggregate and blood vessels to dilate
•Toxins such as fragments of destroyed bacteria induce the synthesis
of PAF

40. Pharmacology of
Bradykinins

41. *Peptide Derivatives
Bradykinins
•Bradykinin is a peptide that promotes inflammation

•Bradykinin is a physiologically and pharmacologically active
peptide of the kinin group of proteins, consisting of nine amino
acids

•It causes arterioles to dilate via the release of prostacyclin, nitric
oxide, and endothelium-derived hyperpolarizing factor

•It causes veins constrict, via prostaglandin F2, thereby leading to
leakage into capillary beds, due to the increased pressure in the
capillaries

43. *

B
1 receptor: expressed only as a result of tissue injury; play a
role in chronic pain and in inflammation

B
2 receptor: constitutively expressed and participates in
bradykinin vasodilatory role.
B
1 and B
2 receptors belong to G protein coupled
receptor

44. *
*potent endothelium-dependent vasodilator

*mild diuretic

*released locally from mast
cells and basophils during tissue damage; having
role in inflammatory processes

45. Pharmacology of
Angiotensins

46. *Angiotensin is a protein hormone that
causes blood vessels to become narrower

*It helps to maintain blood pressure and
fluid balance in the body
Angiotensin

47. *
•The liver creates and releases a protein called angiotensinogen

• This is then broken up by renin, an enzyme produced in
the kidney, to form angiotensin I

• This form of the hormone is not known to have any particular
biological function in itself but, is an important precursor for
angiotensin II
• As it passes in the bloodstream through the lungs and kidneys, it
is further metabolised to produce angiotensin II by the action of
angiotensin-converting enzyme (ACE). The overall effect of
angiotensin II is to increase blood pressure, body water
and sodium content

49. *Pharmacological Actions of
Angiotensins
Blood vessels – it increases blood pressure by causing constriction
(narrowing) of the blood vessels
Nerves: it increases the sensation of thirst, the desire for salt,
encourages the release of other hormones that are involved in fluid
retention
Adrenal glands: it stimulates production of the hormone aldosterone,
resulting in the body retaining sodium and losing potassium from
the kidneys
The kidneys: it increases sodium retention and alters the way the
kidneys filter blood. This increases water reabsorption in the kidney to
increase blood volume and blood pressure

50. AT1

•Vasoconstriction


•Cell Growth in
Heart and Arteries


•Secretion of
Aldosterone
AT2


•Vasodilation


•Anti – Proliferative



•Apoptosis

51. ACE Inhibitors: Captopril, Enalapril, Lisinopril,
Perindopril, Fosinopril, Benazepril,
Ramipril
Angiotensin – II Receptor Blockers (ARBs): Losartan,
Candesartan, Valsartan, Telmsartan,
Irbesartan

52. •Maintenance of Blood Pressure


•Maintenance of fluid balance