Respiratory Drugs (It ain't easy being wheezy) Flashcards
How does the sympathetic system control the airways?
- It stimulates the adrenal gland to release adrenaline which circulates in blood
- It activates B2 - adrenoreceptors in bronchial smooth muscle.
- Relaxation and bronchodilation
What is the drug class of B2-adrenoreceptors?
- B2 adrenergic receptor agonists
What does the Parasympathetic system control the airways?
- It stimulates the vagus nerve which releases acetylcholine
- It activates M3 receptors in bronchial smooth muscle
- Contraction and bronchoconstriction
What is the drug class of M3 receptors?
- Muscarinic ach receptor antagonists
What are B2- adrenergic receptor agonists?
- 1st choice agents for acute conditions
- Fast acting for quick relief
- Examples = Salbutamol (Albuterol), Formoterol
- Long-acting B2 AGONISTS (LABA) - Salmeterol, Formoterol
- Cause bronchodilation
- Stabilise mast cells and inhibit inflammatory mediator release
- Enhanced mucociliary clearance (action on cilia)
What are some adverse effects of B2- adrenergic agonists (Sympathetic)?
- Hypoxaemia - ventilation/perfusion mismatch due to pulmonary vasodilation in blood vessels that were previously constricted by hypoxia - shunting of blood to poorly ventilated area and fall in arterial oxygen
- Tachycardia and arrhythmias
- Skeletal muscle tremor
- Hypokalaemia
- Paradoxical bronchospasm
What is B2-adrenergic agonists tolerance?
- Due to the regular use of B2-adrenergic agonists
- Rise in asthma mortality and morbidity
- There is a decrease in the number of receptors due to the prolonged use of agonists
What are muscarinic acetylcholine receptor antagonists?
- Fast acting relievers - Ipratropium
- Long - acting preventer - Tiotropium
- Inhalation/nebuliser
- Bronchodilation by antagonising action of ACh released by the vagus nerve
- May also be a release of ACh from non-neuronal cells in the airways
- Decrease in mucus secretion in asthma
- increase in mucociliary clearance
- No effect on inflammatory phase of asthma
What are the adverse effects of muscarinic receptor antagonists (Parasympathetic effects)
- Dry mouth
- Blurred vision
- Paradoxical bronchoconstriction
- Urinary retention
- Glaucoma
- Prostatic hypertrophy
- Side effects reduced via inhaled administration = little systemic absorption
What are merhylxanthines?
- E.g. theophylline
- Inhibit phosphodiesterases and blocks adenosine receptors
- Possibly anti-inflammatory
- Incrreases the amount of cAMP = more relaxation of smooth muscle
What are adverse effects of methylxanthines?
- Cardiovascular effects
- Hypokaelaemia
- CNS stimulation
- Gastrointestinal disturbances
- Rarely used now
- Given I.V. or orally
- Narrow therapeutic window
– Monitoring
– Toxicity profile - Metabolised via CYP450
- Interactions
What is the mechanism of action of corticosteroids?
- From adrenal cortex (cortisol)
- E.g. Beclomethasone, fluticasone
- Not the same as sex steroids
- Diffuse into the cytoplasm and bind to the receptor then move to the nucleus to modify transcription
- Increase anti-inflammatory
- Decrease pro-inflammatory mediators
- Can affect gene transcription
- Decrease expression of pro-inflammatory mediators
- Decrease Th2 cytokines
What are adverse reactions of corticosteroids?
Prolonged high doses leads to :
- Adrenal suppression
- Osteoporosis
- Metabolic effects (Cushing’s syndrome)
- Suppression of response to infection
- GI upset
- Hypertension
- ADRs limited with inhaled drugs:
- Oropharyngeal candidiasis (thrush)
- Sore throat
- Croaky voice
- Use a spacer device
What is asthma?
- An inflammatory condition:
– inflammation of the airways
– Bronchial hyper-reactivity
– Reversible airways obstruction - Consists of 2 phases - immediate and late
- Maybe allergic or non-allergic
What is inflammation in asthma?
“Eczema” of the airway (breaking down of skin)
- dilated blood vessels
- infiltration of inflammatory cells (mononuclear cells, eosinophils)
- Mononuclear cell
Mucosa
- Hypertrophied smooth muscle
- Thickened basement membrane
- Mast cell
- Mucus plug with eosinophils and desquamated epithelial cells
What are the treatments for asthma?
1.) B2 adrenergic agonists (e.g. salbutamol- SABA) for fast relief
LABA for prevention (salmeterol, formoterol)
- Combine with anti-inflammatory e.g. inhaled corticosteroid
- cys-leukotriene receptor antagonists (E.g. montelukast)
- Muscarinic antagonists - little used in asthma (usually only in combination with LABA/not all patients respond)
What is COPD?
- Small airways fibrosis
- Muscarinic ACh receptor antagonists used as there is significant cholinergic tone
- Long acting bronchodilators used
- Can combine muscarinic antagonists and B2-agonists
- Glucocorticoids generally ineffective
- long-term O2 therapy
What are leukotriene antagonists?
E.g. Montelukast, Zafirlukast
- Act as antagonists in leukotriene receptors
- Decrease bronchoconstriction, vascular permeability and mucous production
- Decrease eosinophil recruitment
- Given orally, preventative for asthma and seasonal allergic rhinitis in patients with asthma
What type of receptor super-family do the receptors for adrenaline belong to?
G protein coupled
What is the drug target for a methylxanthine drug such as theophylline?
Phosphodiesterase
Which of the following drugs is a long-acting preventer treatment for chronic obstructive pulmonary disease?
Tiotropium
Which of the following are likely adverse effects from administration of ipratropium?
- Reduced saliva
- Blurred vision
What receptor super-family do corticosteroid receptors belong to?
Cytoplasmic/nuclear
What class of drugs does beclomethasone belong to?
Corticosteroid
Which of the following is the best description for the mechanism of action of montelukast?
- Antagonist at leukotriene receptors reducing mucus secretion, eosinophil recruitment and bronchoconstriction
Which of the following are adverse effects resulting from inhaled corticosteroid administration?
- Increased likelihood of infection
- Sore throat
- Osteoporosis
