1. Prostaglandins, Aangiotensin,
Bradykinin
Dr.Jibachha Sah
M.V.Sc( Pharmacology)
College of Veterinary Science,NPI,
Bhojard,Chitwan

2. The name prostaglandin derives from the prostate gland, chosen
when prostaglandin was first isolated from seminal fluid in 1935 by the Swedish
physiologist Ulf von Euler, and independently by M.W. Goldblatt.
History
The first total syntheses of prostaglandin F2α and prostaglandin E2 were reported
by E. J. Corey in 1969

3. Introduction
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.
They are derived enzymatically from the fatty acid arachidonic acid.
Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring.
They are a subclass of eicosanoids and of the prostanoid class of fatty acid
derivatives.
There are four principal bioactive prostaglandins generated in
vivo: prostaglandin(PG) E2 (PGE2), prostacyclin (PGI2), prostaglandin D2 (PGD2)
and prostaglandinF2α (PGF2α).
There are various prostaglandin namely PGA, PGB, PGE, and PGF. They are found
in many mammalian tissues.

4. Biosynthesis
Prostaglandins (PGs) are a family of fatty acid ecosanoids synthesized from
arachidonic acid via cyclooxgenase, an enzyme involved in the synthesis of PGs,
prostacyclin, and thromboxane, and the target of anti-inflammatory agents such as
ibuprofen.
The unsaturated fatty acidarachidonic acid is the precursor for the synthesis of the
major classes of prostaglandins and leukotrienes, collectively known as
eicosanoids.
The four metabolic pathways are
(i)Cyclooxygenase pathway
(ii)Lipoxygenase pathway
(iii)Isoprostane pathway
(iv)P-450 epoxygenase pathway

5. General mechanism of action
Cyclic adenosine monophosphate (cAMP)

6. Receptor Receptor type
IP Gs
vasodilation
inhibit platelet aggregation
bronchodilation
EP1 Gq
•bronchoconstriction
•GI tract smooth muscle contraction
EP2 Gs
•bronchodilation
•GI tract smooth muscle relaxation
•vasodilation
EP3 Gi
•↓ gastric acid secretion
•↑ gastric mucus secretion
•uterus contraction (when pregnant)
•GI tract smooth muscle contraction
•lipolysis inhibition
•↑ autonomic neurotransmitters ↑ platelet response to their
agonists and ↑ atherothrombosis in vivo
Prostaglandin receptor
The following is a comparison of different types of prostaglandin, including prostaglandin
I2 (prostacyclin; PGI2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and prostaglandin F2α (PGF2α

7. Release of prostaglandins from the cell
Cyclooxygenases
Prostaglandins are produced following the sequential oxygenation of arachidonic acid,
DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases.
The classic dogma is as follows:
COX-1 is responsible for the baseline levels of prostaglandins.
COX-2 produces prostaglandins through stimulation.
However, while COX-1 and COX-2 are both located in the blood vessels, stomach and
the kidneys, prostaglandin levels are increased by COX-2 in scenarios
of inflammation and growth.

8. ●cause constriction or dilation in vascular smooth muscle cells
● cause aggregation or disaggregation of platelets
● sensitize spinal neurons to pain
● induce labor
● decrease intraocular pressure
● regulate inflammation
● regulate calcium movement
● regulate hormones
● control cell growth
● acts on thermoregulatory center of hypothalamus to produce fever
Functions of prostaglandin

9. Role in pharmacology
Inhibition
Examples of prostaglandin antagonists are:
NSAIDs (inhibit cyclooxygenase)
Corticosteroids (inhibit phospholipase A2 production)
COX-2 selective inhibitors or coxibs
Cyclopentenone prostaglandins may play a role in inhibiting inflammation

10. Prostaglandins are produced within the body's cells by the enzyme cyclooxygenase (COX).
There are two COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that
promote inflammation, pain, and fever.
However, only COX-1 produces prostaglandins that support platelets and protect the
stomach.
Nonsteroidal anti-inflammatory drugs (NSAIDs) block the COX enzymes and reduce
prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and
fever are reduced.
The following veterinary is an example of NSAIDs available:
Diclofenac ketoprofen
Ibuprofen Nimusulaide
Meloxicam Flunixin
Phenybutazone Carprofen

11. Mechanism of Action NSAID
NSAIDs are defined as "agents which inhibit the formation of eicosanoids from arachidonic
acid".
Prostaglandins (PGs), thromboxanes (TXs) and leukotrienes (LTs) are all eicosanoids which
have an inflammatory-mediating action.
Chemical or physical injury to cells causes induction of the enzyme phospholipase-A2
(PLA2), which converts phospholipids to arachidonate.
This newly-formed arachidonic acid is converted by the action of cyclo-oxgygenase (COX)
enzymes to cyclic endoperoxidases, which can form inflammatory mediators including
PGI2, PGD2, PGE2 and TXA2. Arachidonte may also be converted to 5-HPETE to
eventually form leukotrienes, and some newer NSAIDs target this branch of the pathway

12. Bone cells produce PGE2, PGF2α, prostacyclin, and lipoxygenase products (e.g.,
leukotriene B4), which may also stimulate bone resorption.
Among the varied roles of prostaglandins and thromboxanes are the control
of vascular tone, hemostasis, cytoprotection, regulation of fetal sleep/wake states,
kidney function, thermoregulation, inflammation, cell proliferation, and many
others.

13. Indications and clinical uses
Dinoprost is used for estrus synchronization in cattle and horses by
causing luteolysis.
To treat egg binding in small birds
In pigs, dinoprost is used to induce parturition when given within 3 days of
farrowing.
In dogs, dinoprost has been used to treat open pyometra. In cattle, dinoprost has been
used for treatment of chronic endometritis.
In large animals, dinoprost is used to induce abortion in the first 100 days of gestation, but
use for inducing abortion in small animals has been questioned.

14. Prostaglandin F2α (PGF2α) is used to terminate the luteal phase by
causing lysis of the corpus luteum (CL), thereby allowing the return
to estrus.
most common prostaglandins used are dinoprost (Lutalyse, Pfizer, New
York) and cloprostenol (Estrumate, Schering-Plough Animal Health
Corporation, Union, N.J.).
Dinoprost is a naturally occurring PGF2α, and cloprostenol is
a synthetic prostaglandin analogue.
For prostaglandins to effectively terminate the luteal phase a mature CL
must be present that is responsive to prostaglandin.

15. Dose
The standard recommended dose of dinoprost is 9 μg/kg (5 to 10 mg per 1000
lb/454 kg horse).
The recommended dose of cloprostenol is 250 μg per 1000 lb/454 kg horse (0.55
μg/kg).

16. Abnormally Low Blood Pressure
Diarrhea
Fast Heartbeat
Seizures
Slow Heartbeat
Adverse effect
Fever
Low Amount Of Calcium In The Blood
Short Periods Of Not Breathing
Temporary Redness Of Face And Neck

17. Angiotensin,
Angiotensin is a peptide hormone that causes vasoconstriction and an increase
in blood pressure.
It is part of the renin–angiotensin system, which regulates blood pressure.
Angiotensin also stimulates the release of aldosterone from the adrenal cortex to
promote sodium retention by the kidneys.
Angiotensin I is produced by the action of renin (an enzyme produced by the
kidneys) on a protein called angiotensinogen, which is formed by the liver.
Angiotensin I is transformed into angiotensin II in the blood by the action
of angiotensin-converting enzyme (ACE).

18. Clinical significance
An angiotensin-converting-enzyme inhibitor (ACE) is a pharmaceutical drug used
primarily for the treatment of hypertension and congestive heart failure. Captopril is
an example of an ACE inhibitor.
Drug Name: Captopril
Common Name: Capoten®
Drug Type: ACE inhibitor
Used For: Heart failure, High blood pressure
Species: Dogs, Cats
Administered: Tablets
Available Forms: Capoten® 12.5mg, 25mg, 50mg, and 100mg tablets

19. Mechanism of action
Captopril inhibits the angiotensin converting enzyme (ACE), an enzyme that
converts angiotensin I to angiotensin II.
Angiotensin II acts as a potent vasoconstrictor, meaning it narrows the blood
vessels. By inhibiting this enzyme, it prevents the angiotensin II from ever being
created and relaxes the blood vessels.
This lowers the blood pressure and reduces the amount of work the heart has to
do.
In one study 72 dogs the efficacy and safety of quinapril and captopril in the
treatment of canine heart failure were found to be comparable. Differences exist
between the dosage schedules of both ACE inhibitors.
The recommended dosage schedule for the short acting captopril is three times
daily 0.5 mg/kg bodyweight. Quinapril belongs to a newer generation of ACE
inhibitors with a longer half life. Therefore a dosage of 0.5 mg/kg KGW once daily
was in most cases sufficient for a successful therapy. Morisse .B, Kersten .U. Tierarztl Prax. 1995
Oct;23(5):489-96.

20. Captopril may result in these side effects:
Low blood pressure
Loss of appetite
Vomiting
Diarrhea
Rash
High blood pressure if medication is halted abruptly
Captopril may react with these drugs:
Antacids
Diuretics
Rimadyl (and other non-steroidal anti-inflammatory drugs)
Potassium sparing diuretics
Vasodilators
Cimetidine
Digoxin
Potassium chloride or gluconate

21. Direct renin inhibitors can also be used for hypertension. The drugs that
inhibit renin are aliskiren and the investigational remikiren.
Remikiren is a renin inhibitor under development for the treatment of
hypertension (high blood pressure). It was first developed by Hoffmann–La Roche
in 1996.
Renin inhibitors are a group of pharmaceutical drugs used primarily in
treatment of essential hypertension (high blood pressure).
These drugs inhibit the first and rate-limiting step of the renin–angiotensin–
aldosterone system (RAAS), namely the conversion
of angiotensinogen to angiotensin I.

22. Angiotensin I is produced by the action of renin (an enzyme produced by the
kidneys) on a protein called angiotensinogen, which is formed by the liver.
Angiotensin I is transformed into angiotensin II in the blood by the action of
angiotensin-converting enzyme (ACE).
An allowance of up to 160 mmHg systolic is often used since many of patients are
quite anxious in the hospital setting (“white coat effect”).

23. Bradykinin
Bradykinin is an inflammatory mediator. It is a peptide that causes blood vessels to
dilate (enlarge) via the release of prostacyclin, nitric oxide, and Endothelium-
Derived Hyperpolarizing Factor.
Bradykinin is a physiologically and pharmacologically active peptide of
the kinin group of proteins, consisting of nine amino acids.
A class of drugs called angiotensin converting enzyme (ACE) inhibitors increase
bradykinin levels by inhibiting its degradation, thereby increasing its blood pressure
lowering effect.
ACE inhibitors are FDA approved for the treatment of hypertension and heart
failure.

24. Bradykinin receptor
The bradykinin receptor family is a group of G-protein coupled receptors whose
principal ligand is the protein bradykinin.
There are two Bradykinin receptors: the B1 receptor and the B2 receptor.
How is bradykinin produced?
Bradykinin is the major functional vasodilator produced by the kallikrein-kinin
system. Bradykinin exerts its effects via B1 and B2 receptors.
The bradykinin-synthesizing enzyme, kininase II, is identical to angiotensin-
converting enzyme, which produces angiotensin II.

25. Function
Bradykinin is a potent endothelium-dependent vasodilator and mild diuretic, which
may cause a lowering of the blood pressure.
Receptors
Effect
The B1 receptor (also called bradykinin receptor B1) is expressed only as a result of
tissue injury, and is presumed to play a role in chronic pain. This receptor has been
also described to play a role in inflammation
The cardinal signs of inflammation include: pain, heat, redness, swelling, and loss of function.

26. Role of bradykinin
ACE, also referred to as kininase II, is the principal enzyme responsible for the
metabolism of bradykinin (a potent endothelium-dependent vasodilator).
Bradykinin induces vasodilation by stimulating production of nitric oxide,
the arachidonic acid metabolites prostacyclin (PGI-2) and PGE-2, and
endothelium-derived hyperpolarizing factor.

27. Clinical use
Icatibant (Firazyr):
Bradykinin B2 receptor antagonist indicated for acute attacks of hereditary angioedema
(HAE).
Recently, numerous BK receptor antagonists have been synthesized with prime aim
to treat diseases caused by excessive kinin production.
These diseases are rheumatoid arthritis (RA), inflammatory diseases of the bowel,
asthma, rhinitis and sore throat, allergic reactions, pain, inflammatory skin
disorders, endotoxic and anaphylactic shock and coronary heart diseases.