Asthma Drugs Flashcards
Drugs used in Asthma treatment
Relievers - Act as bronchodilators such as short acting beta2 adrenoceptor agonists (SABA), LABA, CysLt1 receptor antagonists
Controllers - Anti-inflammatory agents that reduce airway inflammation such as Glucocorticoids, cromoglicate and humanised monoclonal IgE antibodies
What is aerosol route preferred over oral in Asthma
Aerosol is preferred as it reduces unwanted side effects
Mechanism of beta2-adrenoceptor agonists
Beta2-adrenoceptor agonists stimulate via Gs which activates adenylyl cyclase. This converts ATP to cAMP causing uptake of protein kinase A. This causes phosphorylation of myosin light chain kinase and myosin phosphatase resulting in relaxation
First line treatment for mild intermittent asthma
Short acting B2-adrenoceptor agonist - Salbutamol, Terbutaline
When is oral and IV SABA delievered
Oral in children, IV in emergency
How long does action of SABA last
3 to 5 hours
Adverse effects of SABA
Fine tremors, tachycardia, arrhythmias, hypokalaemia
Can LABA be used as a monotherapy
No, LABA must always be given together with a glucocorticoid. Ex of LABA are Salmeterol and Formoterol.
What medication is useful for nocturnal asthma
LABA, 8 hour action
What can increase risk of bronchospasms
Use of non-selective beta blockers: Propanolol
What does cysteinyl leukotriene do in the body
LTC4, LTD4 and LTE4 from mast cells and infiltrating inflammatory cells cause smooth muscle contraction, mucus secretion and oedema
What type of asthma drugs CysLT1 receptor antagonists
Bronchodilators, block CysLT receptors
Effective add-on therapy for mild, intermittent asthma
CysLT1 receptor antagonist, Montelukast and Zafirlukast
What are CysLT receptor antagonists effective against
Antigen and exercise induced asthma
Drugs with bronchodilatory and anti-inflammaroy
Methylxanthines such as Theophylline, Aminophylline
Second line drugs for Asthma
Methylxanthines, use wit SABA/LAMA or glucocorticoids
Adverse effects of Methylxanthines
In therapeutic window - Nausea, vomiting, abdominal discomfort and headache
Supra-therapeutic - Disarrhythmias, seizures, hypotension
Effects of Methylxanthines
Increase diaphragmatic contraction, reduce fatigue, increase mucus clearance, activates histone deacetylase which may potentiate anti-inflammatory action of glucocorticoids, bronchodilation (high dose)
Two classes of steroid hormones released by adrenal cortex
Mineralocorticoids (zona glomerulosa) and Glucocorticoids (zona fasciculata)
Processes regulated by glucocorticoids
Decrease inflammatory and immunological response
What do mineralocorticoids do
Aldosterone - Regulate retention of salt and water in kidney
Main prophylaxis treatment of Asthma
Glucocorticoids such as beclometasone, budesonide and fluticasone
What receptors do glucocorticoids use for signalling
Glucocorticoids signal via nuclear receptors, GR alpha
Glucocorticoids increase transcription of genes encoding anti-inflammatory proteins and suppress transcription of genes encoding inflammatory ones
How do glucocorticoids switch off expression of inflammatory genes
They recruit histone deacetylase (HDAC) to activate genes and switch off gene transcription
Effects of glucocorticoids
Prevent production of IgE, reduce number of mast cells, and decrease Fc expression (IgE receptors), decrease formation of Th2 cytokines and cause apoptosis of Th2 and eosinophils
Can glucocorticoids relieve allergen or exercise induced asthma
No as it takes time for it’s mechanism of action, prevent inflammation to function.
Can glucocorticoids be given for mild/intermittent asthma
Yes, efficacy develops over several days
Common glucocorticoid adverse effects
Dysphonia - Hoarse and weak voice Oropharyngeal candidiasis (thrush)
Common ICS
Beclometasone, budesonide or flucticasone
What is given in chronic, severe or rapidly deteriorating asthma
Oral prednisolone + ICS to reduce oral dose required and reduce unwanted systemic effects
Second line prophylactic drugs in allergic asthma
Cromones
Second line anti-inflammatory drugs
Cromones eg. Sodium cromoglicate
What inhaled drug is more effective in children than adults
Inhaled sodium cromoglicate
Recent treatment for asthma associated with severe eosinophilia
Monoclonal antibodies directed against IL-5: Mepolizumab
How does Omalizumab (intravenous) work
Monoclonal antibodes againsts IgE. Binds IgE via Fc receptors to prevent attachment to mast cells, reduces Fc receptor expression on inflammatory cells.
