Lecture 12 - Respiratory Pharmacology Flashcards
What is a cough
symotom of a respiratory disease
Protective reflect: prevents lungs from aspiration
What is a useless cough
persistent and unproductive: dry
eg. ashtma, oesophageal reflux, sinusitis and psychogenic
Should a useless cough be suprressed?
yes it should
cough supressants are called - antitussives
always treat underlying cause as cough is a symptom
What is a useful cough?
expels secretions i.e sputum - productive
eg. chest infection
Should a useful cough be suppressed?
No
yes if it is exhausting and dangerous
Mechanism of a cough
Cough receptors in nose or upper airways (lung irritant receptors detected. goes to the
cough centre in the medulla which leads to stimulation leading to cough
How do dry cough - cough suprressants act? and what drugs act to reduce that afferent side
On the afferent side: reduce stimuli
- above larynx - linctuses
Below larynx - steam inhalation, nebulised local anaesthetics
Treat cause: stop smoking
What happens on the efferent side: in dry cough suppressants?
Medullary cough centre - antitussives
- opiods (codeine, methadone, pholcodeine)
- non opiods (dextromethorphan, noscapine)
- sedatives: diphenhydramine, chlorpheniramine
Efferemt side antitussives
Opiods (codeine, methadone, pholcodeine) Non opiods (dextromethorphan, noscapine) Sedatives: diphenhydramine, chlorpheniramine
Productive cough
Expectorants which increase volume of secretion and mucolytics which decrease the viscosity
Examples of expectorants
Guaiphenesin, ipecacuanha
Examples of mucolytics
Acetyl cysteine, recombinaant humane DNase
used for cystic fibrosis
What is the best treatment for a productive cough that shouldn’t be suppressed?
antibiotics
3 common causes of a chronic caugh
upper airways cough syndrome - post nasal drip
bronchial asthma/COPD
Gastrooesophageal reflux disease
Treatment for upper airways cough syndrome - post nasal drip?
anti- allergics, and nasal decongestants
Gastroesophageal reflux disease
anti-reflux therapy with PPi’s
What are the causes of chronic obstructive lung diseases
inflammation, bronchoconstriction and secretions (mucus plugs)
What are the types of bronchial asthma
associated with allergic reactions - Type 1 hypersensitivity
not associated with specific allergen
exercise induced asthma
asthma associated with COPD
Describe the pathology of allergen mediated asthma
Antigen is presented through TH 2 cell to a B cell which induces IgE production and Mast cell activation. This mediates the release of mediators (histamine) and causes the pharmacological effects - bronchoconstriction
Treatment of asthma
non-specific reduction of bronchial hypersensitity -
non - pharmacological : stop smoking, weight reduction
pharmacological: corticosteroids
Dilation of narrowed bronchi
mimicking dilators: sympathomimetics
direct acting bronchodilators: methylaxines
Blockade of constrictor transmitter: Anti-cholinergics
Prevention of release of transmitter
- mast cell stabilisers
Antagonism of released transmitter
- leukotriene receptor antagonists
How to prevent an antigen:antibody reaction
avoidance of allergen
- difficult to find
- insufficient evidence
- avoidance of tobacco and weight reduction
What do corticosteroids do
anti-inflammatory - inhibit influx of inflamm cells, reduce microvascular leakage - decreased oedema
reduce bronchial reactivity - reduce asthma exacerbations and do not relax bronchial smooth muscle
What are the different types of corticosteroids?
inhaled and oral
Inhaled corticosteroids - first line for asthma
beclomethasone, budesonide
fluticasone, flunisolide, triamcinolone
first line regular therapy - mild to mod asthma
oral corticosteroids - for sever asthma
Prednisolone, methylprednisolone
Betamethasone and triamcinolone
for severe asthma
What are the adverse effects of corticosteroids
Iatrogenic Cushings syndrome
- diabetes, hypertension, peptic ulcer, psychosis, delayed puberty
Inhibition of hypothalamic pituitary axis
Other side effects
-oropharyngeal candidiasis
-hoarseness: direct effect vocal cords
Which corticosteroid produces less side effects
cyclesonide - prodrug
How do mast cell stabilisers work and examples?
cromolyn sodium, nedocromil sodium
- inhibit release of mediators - histamine
How are mast cell stabilisers administered
by inhalation and very poorly absorbed
no effect on bronchial smooth muscle
no use in acute bronchospasms
When are mast cell stabilisers useful
when taken prophylactically (as a preventative defensive measure)
main uses: allergy rhinitis, allergic conjunctivitis
side effects: throat irritation, cough, dermatitis, myositis and gastroenteritis
What do Leukotriene pathway inhibitors do?
prevents bronchospasms.
arachidonic acid produces leukotrienes and prostaglandins. 5 They inhibit Lipoxygenase which cause leukotriene synthesis and leukotriene receptor antagonists block receptors from causing bronchospasms.
Inhibition of leukotriene synthesis occurs by
inhibition of 5-lipoxygenase
zileuton - discontinued liver toxicity
Inhibition of leukotriene receptors done by
inhibit binding of leukotriene to receptor
leukotriene receptor inhibitors
montelukast, zafirlukast
When are leukotriene receptor antagonists used?
allergen induced asthma, exercise induced asthma
reduce frequency of exacerbations
given orally: good for children.
Are leukotriene receptor anatagonists useful in acute asthma
nope
side effects of leukotriene receptor anatagonists
headache, gastritis, flu-like symptoms
commonly used leukotriene receptor anatagonists
montelukast - receptor blocker
How is bronchial tone controlled
Theophylline and muscarinic antagonists cause bronchodilation. bronchial dilator drugs sympathomimetics parasymptholytic agents - anticholinergic drugs Methylxanthines
Sympathomimetic
- Act via B2 adrenoceptors
selective B2 agonist agents
-short acting
albuterol, salbutamol - most common terbutaline, fenoterol, metaproterenol
Long acting - salmetrol, formetrol
Non-selective - adrenaline - use in emergency as subcutaneous injection
Selective B2 agonists
dose inhalers or nebulisation onset - immediate peak 15-30 mins duration 3-4 hours first line therapy albuterol-salbutamol
Side effects of selective B 2 agonists
due to b2 receptors in heart muscle and other tissues
- palpitations, tachycardia, cardiac arrhythmias tremor, restlessness, nervousness, hypokalaemia
What role do Phosphodiesterase inhibitors play in bronchodilation
decrease in breakdown of cAMP and hence cause dilation
Methylxanthines
oral or IV
adjuvant therapy in asthma
Adverse effects of methylxanthines
palpitations, cardiac arrhythmia, hypotension GI irritation diuresis, hypokalaemia anxiety, headache, seizures therapeutic window - 55-110 mmol/l
Theophylline
methylxanthine
oral: rapid and complete absorption
90% metabolised
adjuvant therapy
Aminophylline is used for?
and how is it administered?
intravenous
sever asthma
What do anti-cholinergic agents do
act via inhibiting musarinic receptors
selective type: ipratropium, tiotropium, oxitropium
inhibits effects of vagus nerve stimulation
How are anti-cholinergics administered and what are the adverse effects?
inhalation adjuvant therapy in acute sever asthma, COPD Adverse effects: - airway irritation -anticholinergic effects -GI upset, urinary retention
long acting anti-cholinergics
tiotropium
anti cholinergic - colour
green inhalers
corticosteroids - colour
brown inhalers
Selective short acting B2 agonists colour
blue inhalers
Anti IgE monoclonal antibody
Omalizumab inhibits binding of IgE to mast cells Repeat administration - lessens asthma severity -reduces magnitude of response -reduced requirement of steroids -very expensive
Anti IgE monoclonal antibody example
Omalizumab
Ketotifen
Histamine receptor antagonist
some anti-asthma effect
side effects: drowsiness
no proven benefit
Magnesium
patients who fail to respond to inhaled bronchodilators
IV infusion
Ketamine/ volatile anaesthetic agents
anaesthetic agents
bronchodilator properties
no role in routine management
used in life threatening or near fatal asthma
is asthma reversible?
yes it is
COPD reversibility
incompletely reversible airway obstruction
COPD characteristics
occurs in older patients
progressive worsening over age
COPD treatment
approach same as for asthma
Anti-muscarinics - more effective than b2 agonists in COPD
Smoking cessation - major role in COPD
