2- pharmacology cough/rhinitis

Question 1

what is rhinitis?

Answer 1

rhinitis is common and often debilitating disease involving acute or chronic, inflammation of nasal mucosa

Question 2

what is rhinitis characterised by?

Answer 2

• rhinorrhea (runny nose - watery mucus accumulating in nasal cavity)
• sneezing
• itching
• nasal congestion & obstruction (swelling of nasal mucosa largely due to dilated blood vessels - particularly in cavernous sinusoids)

= can be allergic, non-allergic or mixed

Question 3

what are the different classifications of allergic rhinitis?

Answer 3

• seasonal allergic rhinitis (SAR)
• perennial allergic rhinitis (PAR) = all year round
• episodic allergic rhinitis (EAR) = intermittent or sporadic

Question 4

what is process from inhalation from allergen to allergic rhinitis symptoms? (not too extensive)

Answer 4

inhalation of allergen increases specific IgE →IgE binds to receptors on mast cells & basophils →re-exposure to allergen causes mast cell & basophil degranulation →released of mediators including histamine, cysLTs (cysteine leukotrienes), tryptase, prostaglandins, causing acute itching, sneezing, rhinorrhea & nasal congestion → delayed response caused by recruitment of lymphocytes and eosinophils to nasal mucosa contributes to congestion & obstruction

Question 5

what drives non-allergic or occupational rhinitis?

Answer 5

• infection (infectious rhinitis)
• hormonal imbalance e.g. pregnancy
• vasomotor disturbances e.g. iodiopathic
• non-allergic rhinitis with eosinophilia syndrome (NARES)
• medications e.g. aspirin

Question 6

what is non-allergic rhinitis?

Answer 6

non allergic could be like in exercise etc, any rhinitis acute or chronic, not involving IgE dependant events

Question 7

what is occupational rhinitis?

Answer 7

working in environments that could be exposed to allergens, may involve both allergic & non-allergic components

Question 8

what about rhinitis & rhinorrhoea means difficulty breathing in?

Answer 8

both involve increased mucosal blood flow, increased blood vessel permeability = both increase the volume of nasal mucosa and cause difficulty breathing in (you breathe through mouth with blocked nose)

Question 9

what are anti-inflammatory treatment for rhinitis?

Answer 9

glucocorticoids

Question 10

what drugs are given for vasoconstrictors?

Answer 10

nasal blood flow

Question 11

what are anti-allergic drugs?

Answer 11

sodium cromoglicate

Question 12

what is mechanism of glucocorticoids?

Answer 12

reduce vascular permeability, recruitment & activity of inflammatory cells & release of cytokines & mediators

Question 13

what is administration of glucocorticoids?

Answer 13

applied topically as a spray to the nasal mucosa (i.e. intranasal administration, usually once daily). can be given orally (short term) in severe cases

Question 14

what types of rhinitis are treated with glucocorticoids?

Answer 14

seasonal or perennial allergic rhinitis
or non-allergic rhinitis with eosinophilia syndrome (NARES)

Question 15

what can glucocorticoids be given in combination with for moderate to severe rhinitis?

Answer 15

combined with antihistamines:
- beclometasone
- fluticasone
- prednisolone (oral)

Question 16

what is mechanism of anti-histamines?

Answer 16

competitive antagonists that reduce effects of mast cell derived histamine including:

• vasodilation & increased capillary permeability (reduce blood flow to nose and increase permeability so dry nose in hayfever)
• activation of sensory nerves
• mucus secretion from submucosal glands

Question 17

what types of rhinitis are treated with anti-histamines?

Answer 17

as monotherapy in SAR, PAR, EAR

= less effective in non allergic rhinitis and less effect on congestion that other symptoms

Question 18

how are anti-histamines administered?

Answer 18

orally or as intranasal spray (azelastine)

Question 19

what are first and second generation agents of antihistamines?

Answer 19

2nd generation preferred as reduced sedation/drowsiness (since do not cross the blood brain barrier) and lack of anticholinergic effects

Question 20

what are examples of antihistamines?

Answer 20

• loratadine
• fexofenadine
• cetirizine (also has mild anti-inflammatory)

Question 21

what is mechanism of anticholinergic drugs?

Answer 21

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

Question 22

what types of rhinitis should be treated with muscarinic antagonists?

Answer 22

= reduce rhinorrhoea in PAR and SAR but no influence on itching, sneezing & congestion

(note the anticholinergic activity of first generation H1 blockers may contribute to their ability to suppress rhinorrhoea)

Question 23

how is muscarinic antagonists administered?

Answer 23

intranasally

Question 24

what are side effects of muscarinic antagonists?

Answer 24

may cause dryness of nasal membranes, but no other adverse effects

Question 25

what is preferred muscarinic antagonist for rhinitis?

Answer 25

ipotropium (non selective & sole agent in this class) which may be surprising as remember from last lecture that inhibiting M2 actually increases Ach release but it’s short lived so preferred

Question 26

what is mechanism of sodium cromoglicate? and what is administration?

Answer 26

mast cell stabilization = used for maintenance treatment for allergic rhinitis (but less common) = nasal administration (less effective than nasal corticoids)

Question 27

what is mechanism of cysteine leukotriene receptor antagonists?

Answer 27

reduce effects of cysteinyl leukotriene on nasal mucosa

Question 28

how effective is cysteinyl leukotriene receptor antagonists?

Answer 28

= equal effect with H1 receptor antagonists (anti-histamine) in treating PAR and SAR

Question 29

what is example of cysteinyl leukotriene receptor antagonist?

Answer 29

montelukast (administered orally)

Question 30

what is an example of a vasoconstrictor given for rhinitis treatment?

Answer 30

oxymetazoline = a selective alpha 1 adrenoceptor agonist (given intranasally) = reduced congestion in rhinitis

Question 31

what is the mechanism of vasoconstrictors to treat rhinitis?

Answer 31

act directly or indirectly as noradrenaline (mimicing effect) and producing vasoconstriction via activation of alpha 1 adrenoceptors to decrease swelling in vascular mucosa