Pharmacology. 19/03/20
Inflammation and Anti-inflammatories
1. Learning outcomes
To describe and explain the process and effects of inflammation
To identify and evaluate the role of cyclooxygenase, prostaglandins, leukotrienes, histamine and
steroids in combatting inflammation
To describe and explain the receptor systems for
- Prostaglandins
- Leukotrienes
- Histamine
- Steroids
To discuss the causes and effects of gout and its treatment
To discuss the uses of DMARDS to treat rheumatoid arthritis
To describe and explain the physiology of asthma and the drugs which can relieve the symptom
2. Acute inflammation
Histamine,
prostaglandins and
bradykinin act as
chemotactic factors,
recruiting immune cells
from blood to tissue
3. Inflammatory mediators
On the top we have examples of tissue damage (microbial
infection, etc). Formyl peptide is a bacterial chemotactic factor that
acts as a paracrine (very localised) signalling agent and binds to a
specific receptor we own to detect bacterial molecules (toll
receptors). Surgical trauma results in endogenous chemical
mediators (particularly prostaglandins and leukotrienes), same with
hypoxia reperfusion which is linked with stroke. Innate immune
system is the first to arrive (granulocytes). Necrosis causes
apoptosis in neighbouring cells due to the mediators released due
to necrosis, macrophages “clean the mess”. B and T cells arrive
(long term protection), T cells kill cells that should die and B cells
look for antigens which will be presented to them by macrophages
on their surface (usually, exogenous antigens are presented on
MHC class 2 molecules, and endogenous in MHC class 1). This
causes acute inflammation that should resolve itself, fibroblasts are
recruited by chemotactic factors that form the scab. This process
can be interrupted by repeated inflammation it leads to chronic
inflammation which can lead to dysfunction of immune system (key
ones are allergy and cancer)
, Pharmacology. 19/03/20
Inflammation and Anti-inflammatories
4. Prostaglandins
The arachidonic acid pathway:
Arachidonic acid is a fatty acid derived
from phospholipids found in cell
membrane and revolves around
phospholipase A2 that’s activated to
break it down. Phospholipase A2 has
many different functions and is not
really a target, unlike cyclooxygenase
(COX) which it is. COX metabolises the
other two key steps. COX has a
cyclooxygenase function and a
peroxidase function (bifunctional
enzyme). PGH2 makes the rest of the
family. All the different prostaglandins
have different receptors that are
found in all tissues in the body
(homeostatic role). Prostaglandins
cause vasodilation, pain and fever.
Receptor update: Prostaglandins all have a different family of receptors and this reflects that
have different functions in different tissues. They are all metabotropic and the majority are G s or
Gi some are Gq, receptors are named after the prostaglandin they bind
Leukotrienes are another member of the arachidonic acid pathway, but they don’t require COX.
Arachidonic acid is released y phospholipase A2 that is converted by 5 lipoxygenase and FLAP and then
by 5 lipoxygenase again to create leukotriene A4 which will make either leukotriene B4 or one of the
cysteinyl leukotrienes (attached to a cysteine molecule during their synthesis and it will control which
receptors they can respond to. Leukotrienes cause bronchoconstriction increase in vascular permeability
and chemotaxis.
4. Prostaglandins 2
Inflammation and Anti-inflammatories
1. Learning outcomes
To describe and explain the process and effects of inflammation
To identify and evaluate the role of cyclooxygenase, prostaglandins, leukotrienes, histamine and
steroids in combatting inflammation
To describe and explain the receptor systems for
- Prostaglandins
- Leukotrienes
- Histamine
- Steroids
To discuss the causes and effects of gout and its treatment
To discuss the uses of DMARDS to treat rheumatoid arthritis
To describe and explain the physiology of asthma and the drugs which can relieve the symptom
2. Acute inflammation
Histamine,
prostaglandins and
bradykinin act as
chemotactic factors,
recruiting immune cells
from blood to tissue
3. Inflammatory mediators
On the top we have examples of tissue damage (microbial
infection, etc). Formyl peptide is a bacterial chemotactic factor that
acts as a paracrine (very localised) signalling agent and binds to a
specific receptor we own to detect bacterial molecules (toll
receptors). Surgical trauma results in endogenous chemical
mediators (particularly prostaglandins and leukotrienes), same with
hypoxia reperfusion which is linked with stroke. Innate immune
system is the first to arrive (granulocytes). Necrosis causes
apoptosis in neighbouring cells due to the mediators released due
to necrosis, macrophages “clean the mess”. B and T cells arrive
(long term protection), T cells kill cells that should die and B cells
look for antigens which will be presented to them by macrophages
on their surface (usually, exogenous antigens are presented on
MHC class 2 molecules, and endogenous in MHC class 1). This
causes acute inflammation that should resolve itself, fibroblasts are
recruited by chemotactic factors that form the scab. This process
can be interrupted by repeated inflammation it leads to chronic
inflammation which can lead to dysfunction of immune system (key
ones are allergy and cancer)
, Pharmacology. 19/03/20
Inflammation and Anti-inflammatories
4. Prostaglandins
The arachidonic acid pathway:
Arachidonic acid is a fatty acid derived
from phospholipids found in cell
membrane and revolves around
phospholipase A2 that’s activated to
break it down. Phospholipase A2 has
many different functions and is not
really a target, unlike cyclooxygenase
(COX) which it is. COX metabolises the
other two key steps. COX has a
cyclooxygenase function and a
peroxidase function (bifunctional
enzyme). PGH2 makes the rest of the
family. All the different prostaglandins
have different receptors that are
found in all tissues in the body
(homeostatic role). Prostaglandins
cause vasodilation, pain and fever.
Receptor update: Prostaglandins all have a different family of receptors and this reflects that
have different functions in different tissues. They are all metabotropic and the majority are G s or
Gi some are Gq, receptors are named after the prostaglandin they bind
Leukotrienes are another member of the arachidonic acid pathway, but they don’t require COX.
Arachidonic acid is released y phospholipase A2 that is converted by 5 lipoxygenase and FLAP and then
by 5 lipoxygenase again to create leukotriene A4 which will make either leukotriene B4 or one of the
cysteinyl leukotrienes (attached to a cysteine molecule during their synthesis and it will control which
receptors they can respond to. Leukotrienes cause bronchoconstriction increase in vascular permeability
and chemotaxis.
4. Prostaglandins 2
