PRESENTAION ON PHYSIOLOGICAL ROLE OF PROSTAGLANDIN

1. PRESENTED BY :
SREYA. S
M. Pharmacy
Academic year:2019-2021
DEPT OF PHARMACOLOGY

2. INTRODUCTION
Autocoids - Greek Autos :- Self, akos
:- Healing substance or remedy
 CLASSIFICATION
❖ Amine autacoids :- Histamine, 5-
Hydroxytryptamine (Serotonin)
❖ Lipid derived autacoids :- Prostaglandins, Leukotrienes,
Platelet activating factor
❖ Peptide autacoids :- Plasma kinins (Bradykinin,
Kallidin), Angiotensin

3.  .

4. PROSTAGLANDINS
 The prostaglandins (PG) are a group
of physiologically active lipid compounds
called eicosanoids having diverse hormone-like effects in
animals.
 Prostaglandins have been found in almost every tissue in
humans and other animals.
 Prostaglandins were discovered in human semen in 1935
by the Swedish physiologist Ulf von Euler

5. Biosynthesis
 They are synthesized in the
cell from the fatty
acid arachidonic acid.
 Arachidonic acid is created
from diacylglycerol via phos
pholipase-A2, then brought
to either the cyclooxygenase
pathway or the lipoxygenase
pathway. The
cyclooxygenase pathway
produces thromboxane, pros
tacyclin and prostaglandin
D, E and F

6. INHIBITION OF SYNTHESIS
□ Inhibited by NSAIDs
□ Glucocorticosteroids inhibit the release of
arachidonic acid from membrane lipids

7. .

8.  Degradation: Most tissues – rapidly – fastest in Lungs Most PGs,
TXA2 and Prostacyclins (PGI2) – half life of few seconds only
Carrier mediated uptake into cells followed by – side chains are
oxidized and double bonds are reduced and finally yield ionactive
metabolite, and excreted in urine
 Types of Prostaglandins
A) Prostaglandin H2(PGH2):- derived from arachidonic acid and is
a precursor for other biologically significant prostagladins.
B) Prostagladin D2(PGD2):- works by binding to PTGDR receptor.
Actions:-
 Potent bronchoconstrictor
 Promotion of sleep
 Causes vasodilation

9. Prostaglandin E2(PGE2):-
- Works by binding and activating the prostaglandin E2 receptor
Actions:-
 ↓ gastric acid secretion
 ↑ gastric mucus secretion
 uterus contraction (when pregnant)
 GI tract smooth muscle contraction
 Bronchodilator, vasodilator
 Induces pain, heat, fever
D) Prostagladin F2α(PGF2α):- acts by binding to prostaglandin
F2α receptor.
 Uterus contraction
 Bronchoconstriction

10. PGs : Pathophysiological
CVS
 Both PGE2 and PGF2α : Mostly vasodilators - but PGF2α
constricts Pulmonary vein and artery
 PGI2 – uniform vasodilator and potent hypotensive > PGE2
 PGG2 and PGH2 – biphasic response (actually vasoconstrictor)
 TXA – vasoconstrictor
Heart: Stimulates: PGE2 and PGF2α – direct weak and reflex
action
 Role: No role in systemic Vascular regulation – but PGI2
(COX-2 generated) – local vascular tone (dilator)
 PGE₂ keeps ductus arteriosus patent (Aspirin & Indomethacin)
 Exudation: PGs generated by COX-2 with LTs and other
autacoids - inflammation

11. Uterus
 PGE2 and PGF2α – uniformly contracts uterus – pregnant
and non-pregnant … higher as the pregnancy progresses
 Consistent contraction – PGF2α but PGE2 – relaxes not-
pregnant and contracts pregnant uterus
 At term – softens uterus
Role
Initiation and progression of labour by PGF2α (Aspirin
delays)
Semen in high PGs – movement of female genital tract,
transport of sperm and facilitation of fertilization
Dysmenorrhoea – Uncoordinated uterine contraction –
ischemia – pain (Aspirin effective)

12. Bronchial Muscles
 PGF2α, PGD2 ,TXA2 and LTs – Potent
bronchoconstrictor
 PGE2>PGI2 – dilators + inhibit release of Histamine –
but no clinical use (irritation)
 Role:
 Asthma – imbalance between the above
 Aspirin: induces asthma – diverts arachidonic acid to
produce more LTs (LTC4 and LTD4)
 In allergic asthma – Leukotriene

13. GIT
Intestine: PGs (PGE2) – increased propulsive activity –
colic and watery diarrhoea
PGE2 – increases water, electrolyte and mucus secretion
…. PGI2 opposes
Role:
Toxin induced increased fluid movements in secretary
diarrhoea (aspirin reduces fluid volume)
 Colonic polyps and Cancer – reduced colonic cancer and
reduced polyp formation
Stomach: PGE2>PGI2 reduces all gastric acid secretions
(also pepsin) – Gastrin also reduced - even histamine,
gastrin and other induced ones
 Mucus, HCO3 secretion increased with increased blood
flow – Antiulcerogenic

14. Role:
 PGI2 – regulation of gastric mucosal blood flow – natural
ulcer protective …. NSAID induced ulcers – due to loss of
protective function
 Gastric mucosal PGs are produced by COX -1 – selective
COX-2 inhibitors are NOT ULCEROGENIC
Kidneys:
PGE2 & PGI2 – Diuretic effect
Renal vasodilatation and inhibit tubular reabsorption
(Furosemide like – inhibits Cl- reabsorption
TXA2 – renal vasoconstriction
Role: PGE2 & PGI2 (produced by COX-2) in kidney –
intrarenal blood flow regulation and tubular reabsorption
(less) …. NSAIDs - retain salt and water Renin release –
PGE2 and PGI2

15. CNS
 Poor penetration; injected directly – PGE2 – sedation,
rigidity and behavioural changes; PGI2 – fever
Role: PGE2-Hypothalamus: pyrogen induced fever and
malaise (COX-2 involved – selective COX-2 inhibitors –
antipyrretic
 Neuromodulator – pain perception, sleep and other
functions
ANS
 Inhibition as well as augmentation of NA release –
depends on PG, species and tissue
Role: modulate sympathetic neurotransmission

16. Peripheral nerves
Sensitize afferent nerve endings to pain inducing chemical
and mechanical stimuli – irritate mucous membrane
Role :algesic during inflammation (aspirin cause analgesia)
Eye
PGF2α – induces ocular inflammation and lowers IOP –
enhances uveoscleral and tubular outflow (latanoprost)
Role: Local PGs facilitate aqueous humor drainage (less
COX-2 in glaucoma)
Endocrine
Facilitate release of Anterior Pituitary hormones – GH,
Prolactin, ACTH, FSH, LH --- also Insulin and steroids
Role: terminate early pregnancy in women (luteolysis)

17. Metabolism
Antilipolytic – Insuline like effect - mobilize Ca++ from Bone
Platelets
TXA2 >PGG2>PGH2 – pro-aggregator…… PGI2 and
PGD2 – anti-aggregator ….. PGE2 – inconsistent
effect
Role: TXA2 and PGI2 – mutual antagonists – prevent
aggregation in circulation, but induces aggregation
during injury
TXA2 – produced by COX-1 – amplify aggregation
Aspirin (low dose): haemostasis interference by
inhibiting platelet aggregation (COX-1 inhibition at
portal circulation) – PGI2 not interfered (endothelium

18. CLINICALAPPLICATION OF PGS
 Abortion
 Induction/augmentation of labour
 Cervical priming(ripening)
 Postpartum haemorrhage (PPH)
 Peptic ulcer
 Glaucoma
 To maintain patency of ductus arteriosus
 To avoid platelet damage

19. .

20. MISOPROSTOL (PROSTAGLANDIN E1)
 sold under the brandname Cytotec
Clinical use:
 NSAID induced peptic ulcer
 Therapeutic abortion
 Induction of labour
 It cause ripening & softening & dilatation of cervix.
 It binds to myometrial cells to cause strong contraction
leading to expulsion of product of conception
Common side effects
 diarrhea
 abdominal pain.

21. ALPROSTADIL (PROSTAGLANDIN E1)
 Prostaglandin E1 (PGE1), also known as alprostadil
 It is a naturally occurring prostaglandin which is used as a
medication
USES
 In babies with congenital heart defects, it is used by slow
injection into a vein to open the ductus arteriosus until surgery
can be carried out.
 By injection into the penis or placement in the urethra, it is
used to treat erectile dysfunction.
Common side effects
 when given to babies include decreased breathing, fever,
and low blood pressure.
 When used for erectile dysfunction side effects may include
penile pain, bleeding at the site of injection, and prolonged
erection (priapism).

22. LATANOPROST ( PROSTAGLANDIN F2α)
It sold under the brand name Xalatan
uses
To treat increased pressure inside the eye. This includes ocular
hypertension and open angle glaucoma.
It is applied as eye drops to the eyes . Onset of effects is
usually within four hours, and they last for up to a day.
Common side effects
 blurry vision,
 redness of the eye,
 darkening of the iris .

23. CARBOPROST: ProstaglandinPGF
2α
Carboprost sold under the trade name Hemabate
Uses
Used in postpartum hemorrhage caused by uterine atony
not controlled by other methods.
 termination of pregnancy in the 2nd trimester.
Common side effect
 diarrhea (most common, may be sudden in onset)
 flushing or hot flashes
 fever
 chills
 nausea/vomiting

24. SIDE EFFECTS
 Nausea
 Vomiting
 Watery diarrhoea
 Uterine cramps
 Vaginal bleeding
 Flushing
 Shivering
 Tachycardia
 Fall in BP

25. CONTRAINDICATIONS
Bronchial Asthma
Epilepsy
Hypersensitivity to the drug
Renal disease
Hypertension

26. REFERENCES
Tripathi K.D. Essentials Of Medical Pharmacology. 7th
ed. Jaypee Brothers Medical Publishers; 2014:[182-191]
Rang H.P ,Dale M.M, Ritter J.M, Flower
R.J.Pharmacology. 6th ed.Elsevire: Churchill
livingstone;2008:[226-237
 http://www.medindia.net/articles/prostaglandin.htm
 http://en.wikipedia.org/wiki/prostaglandin

27. THANK YOU