73R. Resp. Pharmacology 4: Drugs used in treatment if Rhinitis and Rhinorrhoea Flashcards
what is rhinitis
a common debilitating disease involving acute or chronic inflammation of the nasal mucosa
describe the symptoms of rhinitis
rhinorrhea(runny nose)
sneezing
itching
nasal congestion and obstruction
is rhinitis allergic or non allergic
it can be allergic, non allergic or both/mixed
can you describe rhinitis/rhinorrhea in relation to blood flow
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
what do the nasal epithelial cells do?
- 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)
which cell junctions allow intracellular communication
Gap junctions
which cell junctions aid cell adhesion, proliferation and differentiation
adherens
which cell junctions regulate homeostasis (regulating the passage of substances through the space between cells)
tight junctions /zonula occudens
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.
desmosomes
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.
hemidesmosomes
what is paracellular transport
movement of substances between epithelial cells rather than through them
paracellular transport is regulated by which cell junctions
tight junctions
name 4 different mechanisms of drug transport across the nasal epithelia
transcellular diffusion
paracellular transport
carrier mediated transport
vesicle mediated transport
describe the different structures and functions in the respiratory tract that affects drug absorption
- epithelium- physical barrier, limiting drug absorption
- 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 - macrophages - immune cells can engulf and digest drugs, decreasing their effectiveness
explain the steps of allergic rhinitis
- inhale pathogen
- increase IgE
- IgE binds o basophils and mast cells
- mast and basal cell degranulation
- histamine, cystic leukotrienes, tryptase, prostaglandins
- recruits lymphocytes and eosinophils
- leads to itching, sneezing, rhinorrhea and nasal congestion
what makes a type of rhinitis NOT allergic
non allergic rhinitis is any rhinitis, acute or chronic, that does not involve IgE
is occupational rhinitis allergic or non allergic or both
both
why might someone get 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 drug can induce rhinitis
aspirin
when treating rhinitis, what would you give as an anti inflammatory
glucocorticoids
when treating rhinitis, what would you give to mediated receptor blockades
- H1 receptor antagonist (antihistamine)
- muscarinic receptor agonists]
- CysLT2 receptor antagonist
when treating rhinitis, what would you give to fix nasal blood flow
vasoconstrictor
what anti allergic drug would you prescribe in someone with rhinitis
sodium cromoglicate
what do glucocorticoids do
reduce vascular permeability, recruit and activate inflammatory cells and release cytokine and mediators
what is the mainstay therapy for SAR, PAR and are good in NARES
glucocorticoids
are glucocorticoids effective in monotherapy
yes
how long do glucocorticoids take to reduce all symptoms of rhinitis
several weeks
in rhinitis what can glucocorticoids be combined with in moderate-severe cases of rhinitis
anti histamines
can glucocorticoids be given orally
yes but only for short term in very severe cases
what are some examples of glucocorticoids (at least one oral)
Beclometasone - inhaler/nasal spray
Fluticasone - nasal spray
Prednisolone - oral
what is the mechanism of action of antihistamines
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
what is some therapeutic uses of antihistamines (when are they effective and in effective)
effective in SAR, EAR and PAR
not so effective in Non Allergic Rhinitis
compared to other symptoms, how effective is antihistamines in reducing nasal congestion
less
how would you administer antihistamines
orally or intranasal spray
can you give me an example of an intranasal spray antihistamine
azelastine
how many generations of antihistamines are there
2
which generation of antihistamines is preferred
second
why are 2nd generation antihistamines preferred
because they have less sedation effects (they do not cross the blood brain barrier) and have a lack of anti cholinergic effects
can you give me 3 examples of 2nd generation antihistamines
Fexofenadine, loratadine, cetirizine
what is the mechanism of action of muscarinic receptor antagonists in rhinitis and rhinorrhea
block the receptors on the nasal glands that ACh binds to
what are the therapeutic uses of muscarinic receptor antagonists
good for SAR and PAR
what do muscarinic receptor antagonists not do when treating rhinitis etc
they have no effect on itching sneezing and congestion
how are muscarinic receptor antagonists administered
intranasally
what can the intranasal muscarinic receptor antagonist cause as a side effect
dry nasal membranes
what is an example of a muscarinic receptor antagonist
ipratropium (SAMA)
what is the mechanism of Cysteinyl leukotriene receptor antagonists
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
how do you administer Cysteinyl leukotriene receptor antagonists
orally
what is an example of Cysteinyl leukotriene receptor antagonists
montelukast
what are Cysteinyl leukotriene receptor antagonists used alongside
antihistimines
what is the biochemical pathway of Cysteinyl Leukotriene
- 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.
- Release of Arachidonic Acid: Upon activation, mast cells release arachidonic acid from their cell membranes, facilitated by the enzyme phospholipase A2.
- Formation of Leukotriene A4 (LTA4): Arachidonic acid is then converted into leukotriene A4 (LTA4) through the action of the enzyme 5-lipoxygenase.
- Conversion to LTB4 and LTC4: LTA4 can be further converted into leukotriene B4 (LTB4) or leukotriene C4 (LTC4).
- 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).
- Release of Cysteinyl Leukotrienes (CysLTs): Inflammatory cells release CysLTs, which are involved in the inflammatory response.
- Binding to CysLT1 Receptors: CysLTs bind to CysLT1 receptors on various target cells, contributing to the symptoms of inflammation.
- Inhibition by Receptor Antagonists: CysLT1 receptor antagonists can block this pathway, reducing inflammation by preventing CysLTs from binding to the CysLT1 receptors
what treatment of rhinitis and rhinorrhoea has the mechanism causing mast cell stabilization and is used as a maintenance treatment
sodium cromoglicate
how do you administer sodium cromoglicate
nasal administration
what is oxymetazoline
alpha1 adrenoreceptor agonist
to mimic the effect of noradrenaline.
Produce vasoconstriction
what can oxymetazoline cause if you use it for more than a few days and why
a rebound increase in nasal congestion upon discontinuation (rhinitis medicamentosa).
because of receptor desensitization and downregulation
