Bronchodilator and anti-inflammatory drugs in the treatment on asthma Flashcards Preview

Year 1: Respiratory > Bronchodilator and anti-inflammatory drugs in the treatment on asthma > Flashcards

Flashcards in Bronchodilator and anti-inflammatory drugs in the treatment on asthma Deck (22)
Loading flashcards...

outline the mechanism and give a named example

they favour relaxation of ASM
act quickly (within 5 minutes - max effect at 30 minutes)
relaxation persists for 3-5 hours
they are 1st line relievers for mild, intermittent asthma
usually administered by inhalation
increases mucus clearance and decreases mediator release from mast cells and monocytes
tachycardia, cardiac dysrhythmia and hypokalaemia can occur
Examples: salbutamol, terbutaline


outline the mechanism and give a named example

uncertain mechanism - might inhibit isoforms of PDE that inactivate cAMP and cGMP (allowing these second messengers to go on and cause ASM relaxation)
Examples: Methylxanthines (e.g. theophylline, aminophylline)


outline the mechanism and give a named example

not recommended for acute relief
useful for nocturnal asthma
should not be used as monotherapy (LABA alone causes desentisation - decreases no. of B2 receptors in airway over time)
must be co-administered with a glucocorticoid
Examples: salmeterol (slow-acting), and formeterol (fast-acting)


disadvantages of oral therapy for asthma

slow systemic clearance
high systemic dose necessary to get appropriate concentration in the lung
high incidence of adverse effects


Beta 2 Agonists
outline the mechanism

physiological antagonists of all spasmogens (not by preventing things from binding) - they independently bind B2 receptors and favour relaxation
(by phosphorylation of MLCK and myosin phosphatase)


CysLT1 receptor antagonists
outline the mechanism

mast cells are activated and release LTA4 (metabolised to LTB4 and LTC4), which are transported to ECF. LTB4 causes inflammation: inflammatory cells to release CysLTs.
CysLTs bind to their receptors and cause bronchoconstriction (early phase) and inflammation (late phase).
However, CysLT1 antagonists block this from happening


CysLT1 receptor antagonists
give a named example

montelukast, zafirlukast
these are effective as add-on therapies
effective against antigen-induced and exercise-induced bronchospasm
administered by ORAL route
some headaches and GI upsets have been reported



these have anti-inflammatory actions, and are also bronchodilators at high doses
they improve lung ventilation by increased diaphragmatic contractility
theophylline activates HDAC - decreasing transcription of genes for inflammatory proteins
administered by ORAL route
narrow therapeutic window (has adverse effects)
even at therapeutic concentrations can cause abdominal discomfort and nausea
problematic due to interactions involving CYO450s


role of glucocorticoids in the body

this is the main steroid hormone in the body. Regulates numerous responses:
-inflammatory responses to decrease
-immunological responses to increase
- also affects liver glycogen deposition, gluconeogenesis, glucose output from liver... and many others
Release of glucocorticoid is mediated by hormone from the anterior pituitary which tells the adrenal cortex to produce glucocorticoid


why are synthetic derivatives of cortisol used to treat asthma instead of cortisol?

endogenoud steroids have both glucocorticoid and mineralocorticoid actions. The latter are unwanted in treatment of inflammatory conditions.
So, synthetic derivatives of cortisol (e.g. beclometasone, budesonide, fluticasone) with little/ no mineralocorticoid activity are used for anti-inflammatory effects.


why is the inhalational route of glucocorticoid administration favoured in the treatment of mild/ moderate asthma?

to minimise adverse systemic effects


molecular mechanism of action of the glucocorticoids

they are lipophilic and so diffuse through membrane. In cytoplasm, they combine with GRa (glucocorticoid receptor), dissociating it from the heat shock protein. The activated receptor translocates to the nucleus, aided by "importins". The activated receptor monomers assemble into homodimers and bind to GRE (glucocorticoid response elements) in the promotor region of specific genes, either transactivating or transrepressing their transcription.


examples of the cellular effects underlying the anti-inflammatory action of the glucocorticoids?

they decrease the formation of Th2 cytokines and cause Th2 cells to apoptose.
They prevent IgE production.
They prevent allergen-induced influx of eosinophils into the lung and cause eosinophils to apoptose.
They reduce the number of mast cells and decrease FcE expression on mast cells.


brief account of the clinical use of glucocorticoids in asthma

They prevent inflammation, and also resolve established inflammation.
They should not be given alone.
They should be used in management of the underlying condition. It takes more than 24 hours for them to have an effect: ineffective at relieving bronchospasm acutely.
Preferred method is inhalational, however sometimes oral is necessary.


coromones (cromoglicates)

second line drugs
used infrequently now
"mast cell stabilisers": supress histamine release from mast cells
have no direct effect on bronchial smooth muscle
weak inflammatory effect
specific agent: sodium cromoglicate: delivered by inhalation, efficacy may take several weeks, requires frequent dosing, more effective in children



a monoclonal antibody against IgE. It binds IgE via Fc on IgE - to supress mast cell response to allergens.
It reduces the FcE receptor expression on various inflammatory cells. However, it's very expensive and requires IV administration


named examples of glucocorticoids, and common adverse effects?

beclometasone, budesonide, fluticasone
In sever asthma, oral prednisolone is used with an inhaled steroif too to reduce systemic effects
Due to steroid deposition in the oropharynx:
- dysphonia (hoarse, weak voice)
- oropharyngeal candidiasis (thrush)


how can drug delivery to lungs be optimised?

use a spacer: this reduces coordination problems and reduces oropharyngeal and laryngeal side effects


dry powder inhalers

these are easy for children to use. The problem is that particles are still quite large


roles of leukotrienes in asthma

Cysteinyl leukotrienes are secreted by inflammatory cells e.g. mast cells and eosinophils.
- increases mucus secretion
- decreases mucus transport
- oedema
-recruits eosinophils from blood to airway and causes these eosinophils to release cationic proteins which damage the epithelium, exposing sensory fibres to stimulate cough
- causes profound bronchoconstriction


muscarinic antagonists as a bronchodilator

blocks end plate M3 receptors, preventing mucus secretion and bronchoconstriction
Example: short-acting = tiotropium, long-acting = ipratropium
Used mostly in COPD, but also in asthma as triple therapy (add to ICS/ LABA)


PDE4 inhibitors

these are anti-inflammatory
rarely used