L12 - Respiratory Pharmacology Flashcards
How is the airway smooth muscle in the lungs regulated?
by the autonomic nervous system:
- sympathetic = bronchodilaton
- parasympathetic = bronchoconstriction
What happens to the airways in asthma?
- asthma is chronic inflammatory disease of the airways
- contracted smooth muscle
- inflammation and swelling = decreased lumen diameter
- excess mucous
it is hard to breathe out
What are the types of intervention used for asthma treatment/management?
- preventers: anti-inflammatory compounds
- relievers: bronchodilators
What are the types of preventers for asthma?
- corticosteroids
- cromolyns
- leukotriene antagonists
What are the effects of corticosteroids in asthma?
- reduce number of airways inflammatory cells
- reduce damage to airways epithelium
- reduce vascular permeability
must be used regularly for beneficial effects: cannot help with long-term uncontrolled asthma
What are the administration routes for corticosteroids in asthma?
- inhalation
- oral
What is an example of an inhaled corticosteroid?
fluticasone
What is an example of an oral corticosteroid?
prednisolone - liquid or tablet
What are the benefits of an inhaled corticosteroid?
- need lower concentration of drug = very little into systemic circulation
- minimises potential for adverse reactions
What are some of the problems associated with inhaled corticosteroids?
- a lot of the drug is swallowed so difficult to get to the lungs
- problem with disposition around the mouth and upper airways - risk of fungal infection because immuno-suppressant
When is prednisolone given?
orally only for certain circumstances: early during acute asthma exacerbations or for chronic severe asthma
How is prednisolone given?
- given with oxygen (40-60%) and bronchodilators (salbutamol) because the steroid doesn’t take effect immediately while the bronchodilator does
- high dose (40-60 mg daily) for a short course (4-10 days) then stop
What are the adverse effects of oral corticosteroid?
- suppressing pituitary/adrenal function
- euphoria
- buffalo hump
- hypertension
- thinning of skin
- thin arms and legs: muscle wasting
- benign intercranial hypertension
- cataracts
- moon face with red cheeks
- increased abdominal fat
- avascular necrosis of femoral head
- easy bruising
- poor wound healing
- osteoporosis
hyperglycaemia - negative nitrogen balance
- increased appetite
- increased susceptibility to infection
- obesity
Why are leukotriene antagonists effective in asthma treatment?
leukotrienes cause bronchoconstriction so blocking their effect is beneficial:
- anti-inflammatory
- bronchodilation
- reduce vasoconstriction
What is an advantage of leukotriene antagonists over corticosteroids in asthma management?
- leukotrienes less potent because only target leukotriene pathway - less ADR
- steroid receptors are located throughout the body = more systemic side effects
What are the types of leukotriene antagonists?
- leukotriene receptor antagonists
- lipoxygenase antagonsts: inhibit the enzyme involved in the production of all leukotrienes
What drugs are examples of leukotriene receptor antagonists?
- montelukast
- zafirlukast
What drug is an example of lipoxygenase antagonists?
zileuton - inhibits 5-lipoxygenase
What are relievers in asthma treatment? What effect do they have?
- relievers are drugs that are used to manage the symptoms
- they modulate the ANS (B2) to cause bronchodilation
What effect do B agonists have in asthma?
- target B2 receptors
B2 receptors are found in the lungs and their activation causes bronchodilation with minimal effect on the heart
What are the types of B agonists in asthma treatment? Give examples
(reliever) SABA - Short Acting Beta Agonist:
- salbutamol, terbutaline
(controller) LABA - Long Acting Beta Agonist:
- salmeterol, formoterol
What is salbutamol used for?
- acute inhalation treatment of bronchospasm
- prevent exercise-induced asthma `
What is the onset and duration of salbutamol? When is it used?
onset: 10-15 minutes
duration: 2-5 hours
used on an “as required” basis - regular use shows no benefits
- not used for nocturnal asthma because the effects wear off
What are the adverse effects of SABAs?
at high doses:
- sympathetic NS activation = skeletal muscle tremor
- still has effect on heart = increased HR and force of contraction
What are LABAs used for?
they are symptom controllers so used in adjunctive role with inhaled corticosteroids as prophylactic
- used in nocturnal asthma because effect lasts through the night
What is an example of a fixed dose combination inhaler? What are the advantages of combination inhaler over separate drug administration?
- symbicort: LABA + glucocorticoid
- better outcomes than when taken separately and allows steroid dose to be reduced = reduce ADR
What is the first line treatment for asthma?
beta agonists
What are the autonomic NS receptor types that are targeted in asthma treatment and why?
beta receptors:
- B2 receptors are found in the lungs and their activation causes bronchodilation
muscarinic receptors:
- nearly all types are found in the lungs and their activation causes bronchoconstriction so can inhibit (lesser effect than B2 receptor targeting)
What is the muscarinic receptor subtype that when activated causes bronchoconstriction?
M3
What is the mechanism of action of muscarinic receptor blockers?
block effects of parasympathetic stimulation via muscarinic receptor antagonism
What is the onset, and duration of muscarinic receptor blockers?
onset: 30+ minutes
duration: 3-5 hours
What is an example of a muscarinic receptor blocker?
ipratopium
What are the adverse effects associated with muscarinic receptor blockers?
- dry mouth because salivary glands have muscarinic receptors
- GI motility disorders (constipation, diarrhea, vomiting)
- cardiac effects
- urinary retention
- blurred vision
headache
Apart from beta agonists and muscarinic receptor blockers, what is another reliever (?) that can cause bronchodilation?
methylxanthines
What is an example of a methylxanthine?
theophylline
What are the effects of theophylline?
phosphodiesterase inhibitor
- prevents the break down of cAMP = increased cAMP which causes bronchodilation
adenosine receptor antagonism
- may produce toxic effects e.g. tachycardia, psychomotor agitation, GI tract disturbances
