73R. Resp. Pharmacology 4: Drugs used in treatment if Rhinitis and Rhinorrhoea

Question 1

what is rhinitis

Answer 1

a common debilitating disease involving acute or chronic inflammation of the nasal mucosa

Question 2

describe the symptoms of rhinitis

Answer 2

rhinorrhea(runny nose)
sneezing
itching
nasal congestion and obstruction

Question 3

is rhinitis allergic or non allergic

Answer 3

it can be allergic, non allergic or both/mixed

Question 4

can you describe rhinitis/rhinorrhea in relation to blood flow

Answer 4

Both rhinitis and rhinorrhea involve increased mucosal blood flow, increased blood vessel permeability, or both - these increase the volume of the nasal mucosa and cause difficulty breathing in

Question 5

what do the nasal epithelial cells do?

Answer 5

• Physical Barrier
• Regulation of Innate and Adaptive mucosal immunity
• Secretion of Antimicrobial Peptides:
  (Epithelial cells secrete antimicrobial peptides, which are small proteins that can destroy bacteria, viruses, and fungi. This helps to maintain a healthy nasal environment by preventing infections.)
• Mucociliary Clearance
  (The nasal epithelium is lined with cilia (tiny hair-like structures) and mucus-producing cells.
  The mucus traps inhaled particles, such as dust, allergens, and pathogens.
  The cilia then move the mucus, along with the trapped particles, towards the throat, where it can be swallowed or expelled. This process helps to keep the nasal passages clear and free from harmful substances)

Question 6

which cell junctions allow intracellular communication

Answer 6

Gap junctions

Question 7

which cell junctions aid cell adhesion, proliferation and differentiation

Answer 7

adherens

Question 8

which cell junctions regulate homeostasis (regulating the passage of substances through the space between cells)

Answer 8

tight junctions /zonula occudens

Question 9

which cell junctions are strong adhesive structures that provide mechanical strength to tissues. They help maintain intracellular cohesion and ensure the integrity of the epithelial layer, especially under stress or mechanical forces.

Answer 9

desmosomes

Question 10

which cell junctions anchor epithelial cells to the underlying basal membrane. This adhesion is vital for maintaining the stability and structure of the epithelial layer.

Answer 10

hemidesmosomes

Question 11

what is paracellular transport

Answer 11

movement of substances between epithelial cells rather than through them

Question 12

paracellular transport is regulated by which cell junctions

Answer 12

tight junctions

Question 13

name 4 different mechanisms of drug transport across the nasal epithelia

Answer 13

transcellular diffusion
paracellular transport
carrier mediated transport
vesicle mediated transport

Question 14

describe the different structures and functions in the respiratory tract that affects drug absorption

Answer 14

1. epithelium- physical barrier, limiting drug absorption
2. mucociliary clearance - mucus and cilia work together to clear inhaled particles, reducing drug availability
   3.proteases- enzymes in the resp tract can degrade the drugs before they are absorbed
3. macrophages - immune cells can engulf and digest drugs, decreasing their effectiveness

Question 15

explain the steps of allergic rhinitis

Answer 15

1. inhale pathogen
2. increase IgE
3. IgE binds o basophils and mast cells
4. mast and basal cell degranulation
5. histamine, cystic leukotrienes, tryptase, prostaglandins
6. recruits lymphocytes and eosinophils
7. leads to itching, sneezing, rhinorrhea and nasal congestion

Question 16

what makes a type of rhinitis NOT allergic

Answer 16

non allergic rhinitis is any rhinitis, acute or chronic, that does not involve IgE

Question 17

is occupational rhinitis allergic or non allergic or both

Answer 17

both

Question 18

why might someone get non allergic rhinitis

Answer 18

○ 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)

Question 19

what drug can induce rhinitis

Answer 19

aspirin

Question 20

when treating rhinitis, what would you give as an anti inflammatory

Answer 20

glucocorticoids

Question 21

when treating rhinitis, what would you give to mediated receptor blockades

Answer 21

1. H1 receptor antagonist (antihistamine)
2. muscarinic receptor agonists]
3. CysLT2 receptor antagonist

Question 22

when treating rhinitis, what would you give to fix nasal blood flow

Answer 22

vasoconstrictor

Question 23

what anti allergic drug would you prescribe in someone with rhinitis

Answer 23

sodium cromoglicate

Question 24

what do glucocorticoids do

Answer 24

reduce vascular permeability, recruit and activate inflammatory cells and release cytokine and mediators

Question 25

what is the mainstay therapy for SAR, PAR and are good in NARES

Answer 25

glucocorticoids

Question 26

are glucocorticoids effective in monotherapy

Answer 26

yes

Question 27

how long do glucocorticoids take to reduce all symptoms of rhinitis

Answer 27

several weeks

Question 28

in rhinitis what can glucocorticoids be combined with in moderate-severe cases of rhinitis

Answer 28

anti histamines

Question 29

can glucocorticoids be given orally

Answer 29

yes but only for short term in very severe cases

Question 30

what are some examples of glucocorticoids (at least one oral)

Answer 30

Beclometasone - inhaler/nasal spray Fluticasone - nasal spray Prednisolone - oral

Question 31

what is the mechanism of action of antihistamines

Answer 31

competitive antagonist on the H1 receptor preventing histamine from binding reduces the act of histamine causing vasodilation, mucus secretion, capillary permeability and activation of sensory nerves

Question 32

what is some therapeutic uses of antihistamines (when are they effective and in effective)

Answer 32

effective in SAR, EAR and PAR not so effective in Non Allergic Rhinitis

Question 33

compared to other symptoms, how effective is antihistamines in reducing nasal congestion

Answer 33

less

Question 34

how would you administer antihistamines

Answer 34

orally or intranasal spray

Question 35

can you give me an example of an intranasal spray antihistamine

Answer 35

azelastine

Question 36

how many generations of antihistamines are there

Answer 36

2

Question 37

which generation of antihistamines is preferred

Answer 37

second

Question 38

why are 2nd generation antihistamines preferred

Answer 38

because they have less sedation effects (they do not cross the blood brain barrier) and have a lack of anti cholinergic effects

Question 39

can you give me 3 examples of 2nd generation antihistamines

Answer 39

Fexofenadine, loratadine, cetirizine

Question 40

what is the mechanism of action of muscarinic receptor antagonists in rhinitis and rhinorrhea

Answer 40

block the receptors on the nasal glands that ACh binds to

Question 41

what are the therapeutic uses of muscarinic receptor antagonists

Answer 41

good for SAR and PAR

Question 42

what do muscarinic receptor antagonists not do when treating rhinitis etc

Answer 42

they have no effect on itching sneezing and congestion

Question 43

how are muscarinic receptor antagonists administered

Answer 43

intranasally

Question 44

what can the intranasal muscarinic receptor antagonist cause as a side effect

Answer 44

dry nasal membranes

Question 45

what is an example of a muscarinic receptor antagonist

Answer 45

ipratropium (SAMA)

Question 46

what is the mechanism of Cysteinyl leukotriene receptor antagonists

Answer 46

CysLT1 receptor antagonists reduces the action of cysteinyl leukotrienes which are inflammatory mediators so therefore it would block the receptor and reduce nasal mucosa inflammation

Question 47

how do you administer Cysteinyl leukotriene receptor antagonists

Answer 47

orally

Question 48

what is an example of Cysteinyl leukotriene receptor antagonists

Answer 48

montelukast

Question 49

what are Cysteinyl leukotriene receptor antagonists used alongside

Answer 49

antihistimines

Question 50

what is the biochemical pathway of Cysteinyl Leukotriene

Answer 50

1. Mast Cell Activation: It begins with the activation of mast cells, which are a type of white blood cell involved in allergic reactions and inflammation. 2. Release of Arachidonic Acid: Upon activation, mast cells release arachidonic acid from their cell membranes, facilitated by the enzyme phospholipase A2. 3. Formation of Leukotriene A4 (LTA4): Arachidonic acid is then converted into leukotriene A4 (LTA4) through the action of the enzyme 5-lipoxygenase. 4. Conversion to LTB4 and LTC4: LTA4 can be further converted into leukotriene B4 (LTB4) or leukotriene C4 (LTC4). 5. Transport and Release: LTB4 and LTC4 are transported across the mast cell membrane. LTC4 can also be converted into leukotriene D4 (LTD4) and leukotriene E4 (LTE4). 6. Release of Cysteinyl Leukotrienes (CysLTs): Inflammatory cells release CysLTs, which are involved in the inflammatory response. 7. Binding to CysLT1 Receptors: CysLTs bind to CysLT1 receptors on various target cells, contributing to the symptoms of inflammation. 8. Inhibition by Receptor Antagonists: CysLT1 receptor antagonists can block this pathway, reducing inflammation by preventing CysLTs from binding to the CysLT1 receptors

Question 51

what treatment of rhinitis and rhinorrhoea has the mechanism causing mast cell stabilization and is used as a maintenance treatment

Answer 51

sodium cromoglicate

Question 52

how do you administer sodium cromoglicate

Answer 52

nasal administration

Question 53

what is oxymetazoline

Answer 53

alpha1 adrenoreceptor agonist to mimic the effect of noradrenaline. Produce vasoconstriction

Question 54

what can oxymetazoline cause if you use it for more than a few days and why

Answer 54

a rebound increase in nasal congestion upon discontinuation (rhinitis medicamentosa). because of receptor desensitization and downregulation