Drugs for Rhinitis and Rhinorrhoea Flashcards
What is rhinitis?
A common and often debilitating disease involving acute or chronic inflammation of the nasal mucosa
What are the characteristic symptoms of rhinitis?
- rhinorrohea (‘runny nose’ - watery mucus accumulation in nasal cavity)
- sneezing
- itching
- nasal congestion and obstruction (swelling of nasal mucosa largely due to dilated blood vessels - particularly in cavernous sinusoids)
What is nasal congestion?
Does NOT refer to mucous - refers to dilated blood vessels in respiratory or nasal mucosa
* These dilated blood vessels contribute to swelling of mucosa and lead to obstruction of airflow through nasal cavity
What are the different types of rhinitis?
- Allergic
- Non-allergic
- Mixed
What are the classifications of allergic rhinitis?
- Seasonal (SAR)
- Perennial (PAR)
- Episodic (EAR)
What condition is allergic rhinitis often linked to?
Asthma
What is the mechanism of allergic rhinitis?
- Inhalation of allergen increases specific IgE levels
- IgE binds to receptors on mast cells and basophils
- Re-exposure to allergen causes mast cell and basophil degranulation
- Release of mediators including histamine, cysLTs, tryptase, prostaglandins
- Causes acute itching, sneezing, rhinorrhoea and nasal congestion
- Delayed response caused by recruitment of lymphocytes and eosinophils to nasal mucosa causes congestion and obstruction
What is non-allergic rhinitis?
Any rhinitis, acute, or chronic, that does not involve IgE-dependent events
What are causes of non-allergic rhinitis?
- Infection – infectious rhinitis (largely viral)
- hormonal imbalance – hormonal rhinitis (e.g. pregnancy)
- vasomotor disturbances – vasomotor rhinitis (cause unknown, i.e. idiopathic)
- Nonallergic rhinitis with eosinophilia syndrome (NARES)
- Medications – drug induced rhinitis (e.g. aspirin)
What is occupational rhinitis?
May involve both allergic and non-allergic components
What do both rhinitis and rhinorrhoea?
- Involve increased mucosal blood flow
- Increased blood vessel permeability
- These effects increase the volume of the nasal mucosa and cause difficulty breathing in
What is used to target inflammation in rhinitis?
Glucocorticoids (anti-inflammatory) - will treat allergic rhinitis
What drugs are used to block mediator receptors in rhinitis and rhinorrhoea?
- H1 (histamine) receptor antagonists
* CysLT1 receptor antagonists
What drugs are used to decrease nasal blood flow?
Vasoconstrictors (act on a1 adrenoceptors)
What drugs are anti-allergic in the treatment of rhinitis?
Sodium cromoglicate (immunosuppressant effect)
What is the purpose of a decongestant?
Does not get rid of mucous in the nose, restricts blood flow to vasal mucosa
What is the mechanism of glucocorticoids?
Reduce vascular permeability, recruitment and activity of inflammatory cells and the release of cytokines and mediators
What are glucocorticoids used to treat?
- Mainstay therapy for SAR and PAR
* Also used in NARES and vasomotor rhinitis
How are glucocorticoids administered in rhinitis?
Applies topically as a spray to the nasal mucosa e.g. intranasal administration once daily
How are glucocorticoids used to treat moderate-to-severe and severe intractable rhinitis?
- Moderate-to-severe - may be combined with anti-histamines
* Severe - may be given orally (short term)
What are examples of glucocorticoids?
- beclometasone
- fluticasone
- prednisolone (oral)
What are anti-histamines?
H1 receptor antagonists
What is the mechanism of H1 receptor antagonists?
- Competitive antagonists that reduce effects of mast cell derived histamine
- Less effect on congestion than other symptoms
What effects does histamine normally have?
- vasodilatation and increased capillary permeability
- activation of sensory nerves
- mucus secretion from submucosal glands
What are H1 receptor antagonists effective in treating?
Effective in SAR, PAR and EAR, less so in non-allergic rhinitis
How are H1 receptor antagonists administered?
Administered orally, or as an intranasal spray (azelastine)
Are H1 receptor antagonists used in combination with other therapies?
Effective as monotherapy
What generation of H1 receptor antagonists are preferred?
Available as first and second generation agents
* Second generation agents preferred due to reduced sedation (do not cross blood brain barrier) and lack of anti-cholinergic effects
What are examples of H1 receptor antagonists (anti-histamines)?
- loratidine
- fexofenadine
- cetirizine (also has mild anti-inflammatory action)
What are anti-cholinergic drugs?
Muscarinic receptor antagonists
What are the mechanisms of anti-cholinergic drugs?
ACh released from post-ganglionic parasympathetic fibres activates muscarinic receptors on nasal glands causing a watery secretion that contributes to rhinorrhoea – blocked by muscarinic antagonists
What are the effects of muscarinic receptor antagonists?
Reduce rhinorrhoea in PAR and SAR but have no influence upon itching, sneezing and congestion (note the anti-cholinergic activity of first generation H1 blockers may contribute to their ability to suppress rhinorrhoea)
How are anti-cholinergic drugs administered?
Administered intranasally
What are side effects of muscarinic receptor antagonists?
May cause dryness of nasal membranes, but no other adverse effects
What is the only muscarinic receptor antagonist used in treatment of rhinitis?
Ipratropium is the sole agent used in this class
What is the mechanism of sodium cromoglicate?
Mast cell stabilisation
What is sodium cromoglicate used for in the treatment of rhinitis?
Used for maintenance treatment of allergic rhinitis with an onset of action of 4 to 7 days, but weeks may be required for full effect
How is sodium cromoglicate administered?
Nasal administration - less effective than nasal corticosteroids
What is the mechanism of Cysteinyl Leukotriene receptor antagonists?
CysLT1 receptor antagonists reduce the effects of CysLTs upon the nasal mucosa
What are the effects of CysLT1 receptor antagonists?
Equi-effective with H1 receptor antagonists in treating PAR and SAR, with which their effect may be addictive
How are CysLT1 receptor antagonists administered?
Via oral route
What are CysLT1 receptor antagonists used to treat?
Allergic rhinitis and asthma
What is an example of a CysLT1 receptor antagonist?
Montelukast is the sole agent used in this class
What are the mechanisms of vasoconstrictors?
Act as directly, or indirectly, to mimic the effect of noradrenaline. Produce vasoconstriction via activation of 1-adrenoceptors to decrease swelling in vascular mucosa
What is an example of a vasoconstrictor?
Oxymetazoline, a selective 1-adrenoceptor agonist (given intranasally), is effective, short term, in reducing congestion in allergic rhinitis
Why is nasal administration of oxymetazoline for more than a few days not recommended?
Due to the development of a rebound increase in nasal congestion upon discontinuation - rhinitis medicamentosa
Why does rhinitis medicamentosa occur with oxymetazoline?
Due to a1 receptor desensitisation and down regulation
