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Module – I
CONTINENTAL PHARMACEUTICALS
Prostaglandins – Introduction
• Chemical substances, made in all tissues of the body
• Derived from fatty acid (Arachidonic acid)
• Very short half life (Few minutes only)
• Not usually stored up, but synthesized “On Demand”
• Serve as signaling molecules – local hormones
• COX is the key enzyme in synthesis of Prostaglandins
• Act locally on neighboring cells (Paracrine)
• Also act on own cell (Autocrine)
– Examples: Prostaglandin (PGE2), Prostacyclin (PGI2) and
Thromboxane A2 (TXA2)
CONTINENTAL PHARMACEUTICALS
Prostaglandins - Functions
• Blood vessels: Vasodilation and antiplatelet activity
• Platelets: adhesion and aggregation
• Uterus: Induce labor
• Cells: Control cell growth
• Bone: Bone formation and cartilage maintenance
• Kidneys: Increase glomerular filtration rate, Na/H2O
homeostasis
• Stomach: Inhibition of acid secretion, bicarbonate and
mucus secretion
• Injured cells: Cause inflammation, pain and fever
CONTINENTAL PHARMACEUTICALS
Cyclooxygenase (COX)
• An enzyme responsible for formation of important
biological mediators called “Prostanoids”, including
Prostaglandins, Prostacyclins and Thromboxanes
• Two isoforms; COX-I and COX-II
• Initially believed that:
– COX-I: Constitutive
– COX-II: Inducible
• Now accepted that:
– COX-II: Both constitutive and inducible
COX – 1 & COX – 2 Distribution
Thromboxane A2 PROSTACYCLIN
Types & Role
Phospholipase A2
Expressed during
Arachidonic Acid inflammation only
COX-1 COX-2
Prostaglandins
Module – II
CONTINENTAL PHARMACEUTICALS
Anti-Inflammatory Drugs
• Steroidal Anti-inflammatory Drugs (Corticosteroids)
– Prednisolone
– Dexamethasone
• Non Steroidal Anti-inflammatory Drugs (NSAIDs)
– Indomethacin
– Ibuprofen
– Diclofenac
– Celecoxib
– Nimsulide
– Aceclofenac
NSAID’s - Prostaglandin Synthesis Inhibitors
Stimulus
Cell membrane (Phospholipid)
(Injury/Trauma etc)
Phospholipase A2
Arachidonic acid
Corticosteroids
NSAID’s
Endoperoxides (PGG, PGH) (Leukotrines)
NAPROXEN
REDUCES PROSTACYCLIN
REDUCES THROMBOXANE-A2 NON-
SELECTIVE
NSAIDs
INHIBITORS OF COX-1 & COX-2
NON-SELECTIVE NSAIDs
DICLOFENAC
IBUPROFEN
LORNOXICAM
PREFERENTIAL INHIBITORS
OF COX-2 MELOXICAM
NIMESULIDE ?
NABUMETONE
VALDECOXIB X
SELECTIVE
CELECOXIB ?
ETORICOXIB
PARECOXIB
LUMIRACOXIB
• RISK OF MYOCARDIAL INFARCTION • OEDEMA / HYPERTENSION • CHONDRODESTRUCTION
Product Profile
Module – III
CONTINENTAL PHARMACEUTICALS
Product Profile
CONTINENTAL PHARMACEUTICALS
Aceclofenac - Introduction
• Aceclofenac is the new approach in development of
NSAIDs (Phenyl acetic acid derivative)
• It is similar to Diclofenac but Neutrophils,
more potent and safer
Monocytes
than Diclofenac and Synovial cells
• Aceclofenac is a pro-drug
• Selectively acts only on inflammatory cells
• Gets hydrolyzed to active metabolites by lysosomal
enzymes of inflammatory cells
• Inhibits only inducible COX-2 in inflammatory cells
• Does not alter normal physiological functions of the
body
SPIANO –– Unique
SPIANO Unique Mechanism
Mechanism
Multifactorial Mode of Action
Aceclofenac Diclofenac
PGE2 - 21%
THROMBOXANE-A2 PROSTACYCLIN
SPIANO
Classical inhibition
Well tolerated and
of prostaglandin
better GI safety
E2
Pain control +
More potent effect
2. Repair, and
with selectivity for
3. ↓ in disease
COX-2
progression
SPIANO
CONTINENTAL PHARMACEUTICALS