Respiratory Drugs
Muscarinic receptors
A type of G protein receptors
Parasympathetic: rest and digest
Parasympathetic nerves start in the brain and travel to the lung via the vagus nerve.
Synapse appears at the parasympathetic ganglia in the trachea.
Ganglia: nerve clusters
The impulse then travels to the airway smooth muscle.
Causing bronchoconstriction by releasing acetylcholine.
This acts on M3 receptors.
M3 receptors activate G protein-coupled pathways.
Causing the release of calcium ions
To cause contraction.
M2 receptors inhibit acetylcholine.
The sympathetic nervous system does not affect airway smooth muscle.
Only glands and blood vessels.
Airway smooth muscle
Contraction:
Ca2+ interacts with calmodulin to form a Ca2+-calmodulin complex.
This activates myosin light chain kinase (MLCK)
The kinase phosphorylates myosin.
This leads to muscle contraction.
Or Dilation:
B2 adrenoceptors are found on airway smooth muscle.
, These stimulate adenyl cyclase leading to Increased cAMP.
cAMP activates protein kinase A.
this phosphorylates several proteins which reduce intracellular Ca2+
reducing MLCK activity causing muscle relaxation.
Asthma
airway inflammation
can improve with age.
hyper-responsiveness to stimuli
causing bronchoconstriction and increased mucus secretion.
caused by:
o allergens
o cold
o exercise
o respiratory infection
o atmospheric pollutants
o NSAIDs
o Stress
o SCAANER -remember
COPD vs Asthma
COPD Asthma
Middle age childhood
Cause: smoking Allergens and exercise
Non-reversible reversible
Gradually progressive Can improve
neutrophils eosiniophils
Lung epithelial cells release factors that activate neutrophils.
In response to cigarette smoke or infection.
Causing these neutrophils and other inflammatory cells to accumulate
o CD8+ cytotoxic T cells
o B cells
o Macrophages
These cells become activated and trigger an inflammatory cascade.
Triggering the release of tumour necrosis factor-a and other interleukins
These mediators sustain the inflammatory process and lead to tissue damage.
This inflammation can lead to structural changes in the lung to block airflow.
Allergens in the body
An allergen encounters a mast cell.
IgE antibodies are found on its surface.
When the allergen binds it causes the release of histamine, LTB4 and PGD2
(prostaglandin).
These are all bronchoconstrictors.
Chemokines are released by surrounding macrophages to attract other immune cells
and leukocytes to the area.
Muscarinic receptors
A type of G protein receptors
Parasympathetic: rest and digest
Parasympathetic nerves start in the brain and travel to the lung via the vagus nerve.
Synapse appears at the parasympathetic ganglia in the trachea.
Ganglia: nerve clusters
The impulse then travels to the airway smooth muscle.
Causing bronchoconstriction by releasing acetylcholine.
This acts on M3 receptors.
M3 receptors activate G protein-coupled pathways.
Causing the release of calcium ions
To cause contraction.
M2 receptors inhibit acetylcholine.
The sympathetic nervous system does not affect airway smooth muscle.
Only glands and blood vessels.
Airway smooth muscle
Contraction:
Ca2+ interacts with calmodulin to form a Ca2+-calmodulin complex.
This activates myosin light chain kinase (MLCK)
The kinase phosphorylates myosin.
This leads to muscle contraction.
Or Dilation:
B2 adrenoceptors are found on airway smooth muscle.
, These stimulate adenyl cyclase leading to Increased cAMP.
cAMP activates protein kinase A.
this phosphorylates several proteins which reduce intracellular Ca2+
reducing MLCK activity causing muscle relaxation.
Asthma
airway inflammation
can improve with age.
hyper-responsiveness to stimuli
causing bronchoconstriction and increased mucus secretion.
caused by:
o allergens
o cold
o exercise
o respiratory infection
o atmospheric pollutants
o NSAIDs
o Stress
o SCAANER -remember
COPD vs Asthma
COPD Asthma
Middle age childhood
Cause: smoking Allergens and exercise
Non-reversible reversible
Gradually progressive Can improve
neutrophils eosiniophils
Lung epithelial cells release factors that activate neutrophils.
In response to cigarette smoke or infection.
Causing these neutrophils and other inflammatory cells to accumulate
o CD8+ cytotoxic T cells
o B cells
o Macrophages
These cells become activated and trigger an inflammatory cascade.
Triggering the release of tumour necrosis factor-a and other interleukins
These mediators sustain the inflammatory process and lead to tissue damage.
This inflammation can lead to structural changes in the lung to block airflow.
Allergens in the body
An allergen encounters a mast cell.
IgE antibodies are found on its surface.
When the allergen binds it causes the release of histamine, LTB4 and PGD2
(prostaglandin).
These are all bronchoconstrictors.
Chemokines are released by surrounding macrophages to attract other immune cells
and leukocytes to the area.
