Post on 04-Apr-2018
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TOPICAL NASAL
STEROIDSDR.N.KUMAR
M.S PG
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Hallmark Signs of Inflammation
Redness
Local dilation of blood vessels
Flare
Reddish color several centimeters around the
original injury site
Wheal
Local swelling, occurring in minutes
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Events at the Cellular Level
Increased vascular permeability
Exudate in surrounding tissues
Leukocytic infiltration
White cells are attracted to area
Phagocytosis
White cells and macrophages ingest foreign material
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Events at the Cellular Level
Mediator Cascade
Histamine & other chemicals are released at injury
site
Inflammatory mediators are produced
leukotrienes
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Early Phase Response
After initial triggering event, there is mast cell
degranulation with release of variety of chemical
mediators (histamine; prostaglandin D2;leukotriene C4)
Early phase response is bronchospasm
There is a resulting decrease in expiratory flows
from the lungs
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Late Phase Culmination
Increased mucus production
Increased permeability of vessels causing mucosal
edema of the airway
Shedding of airway wall cells (desquamation)
Goblet cell hypertrophy
Thickening of epithelial basement membrane
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Other Mediators of the Allergic Reaction
Mast cells also influence AR through release of other
proteins, metabolites, and cytokines
Degranulation releases proteins (e.g., tryptase and chymase)
and proteoglycans (including heparin and chondroitin sulfate)
Arachidonic acid metabolites (including leukotrienes and
prostaglandins) synthesized de novo following cell activation
Variety of preformed cytokines released
Occurs more rapidly than from activated T-cells
Antihistamines inhibit antigen-induced release of histamine and
other mediators from mast cells and basophils in vitro
7
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Effects of Histamine in the Allergic Reaction
Eosinophils: increase maturation and migration, and
promotion of apoptosis
IL-5, GM-CSF, eotaxin, adhesion molecules
Neutrophils: increase migration and adhesion
IL-8, leukotrienes, adhesion molecules
IgE: increase production
IL-4, IL-13
8
.
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Glucocorticoids and Inflammation Subcellular:
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Glucocorticoids and Inflammation
Cellular: Block increased permeability of capillary
endothelium induced by acute inflammationPrevent edema/vascular collapse
Suppress antigen phagocytosis
Stabilize lysozymal membranesInhibit hydrolysis
Reduce quantities of inflammatorycells
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PHARMACODYNAMICS of
STEROIDS
Small, lipophilic molecules
readily diffuse across cell membrane into the
cytoplasm binding to glucocorticoid receptors
CS -glucocorticoid receptors complex with
proteins serve as transcription factors causing
reduced synthesis of inflammatory cytokines
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Primary Actions of Steroids
Inhibits recruitment & migration of inflammatory
cells
Act by inhibiting the production of arachidonic acid
Induces gene expression for anti-inflammatory
proteins and receptors
Suppresses gene expression for pro-inflammatory
proteins
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Other Steroidal Effects
Improve responsiveness to Beta 2 agents
Decreases the white cell response tochemotaxis
This causes eosinophil counts to fall
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Pharmacokinetics
50% aqueous spray is deposited in the nostril and
non ciliated anterior part of nose
50% is either absorbed or removed by muco
ciliary clearance within 30minutes
Active drug is absorbed once it reaches the
inflammatory cells
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Contd..
Highly lipophilic eg. FLUTICASONE PROPIONATE,
MOMETASONE FUROATE
has large tissue distribution long elimination time
Less lipophilic eg.BECLOMETHASONE ,BUDESONIDE
absorbed into circulation
Shorter elimination time So less systemic side effects even with prolonged
usage
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Bioavailability
Mometasone
Fluticasone
Budesonide
Beclomethasone
. Flunisolide0
5
10
15
20
25
Mometa F lutic Budes Beclo F luniso l
% Bioavail
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Intranasal Corticosteroids
BECLOMETHASONE DIPROPIONATE
FLUNISOLIDE
BUDESONIDE
FLUTICASONE PROPIONATE
MOMETASONE FUROATE
TRIAMCINOLONE ACETONIDE
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BECLOMETHASONE
DIPROPIONATE
Glucocorticoid with high topical and low systemic
activity
Used in Nonallergic Rhinitis
Intra nasal 50 micrograms in each nostril BD/TDS
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BUDESONIDE
Non halogenated Glucocorticoid
Better than beclomethasone
dose: 200-400 micrograms /day
Prophylaxis and treatment of allergic
rhinitis,vasomotor rhinitis,seasonal rhinitis
Contra indicated in infections and nasal ulcers
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FLUTICASONE PROPIONATE
Newerhigher potency with longer duration and
negligible oral bio availability
Used in Nonallergic Rhinitis
Dose :100-250 micrograms BD
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FLUNISOLIDE
Prophylaxis and treatment of perennial and
seasonal rhinitis
dose:25micrograms one spray in each nostril
BD/TDS
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MOMETASONE FUROATE
Treat and prevent seasonal and perennial rhinitis
Takes 2-4 weeks for full benefits ,hence started
earlier to the season
Dose :50micrograms OD
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TRIAMCINOLONE ACETONIDE
seasonal and perennial allergic rhinitis in adults
and children 6 years of age and older.
dose is 220 mcg per day as two sprays in each
nostril once daily.
When the maximum benefit has been achieved
and symptoms have been controlled, reducing the
dose to 110 mcg per day (one spray in each nostrilonce a day)
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Generic Name Dose Frequency (Adult)Systemic
Bioavailability (%)
Beclomethasone bid-qid 44
Flunisolide bid 49
Triamcinolone qd-bid NABudesonide qd-bid 34
Fluticasone propionate qd
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Mechanism of action of topical
steroids
Inhibition of Inflammatory mediator release
during both early and late phase
Reduction in number of inflammatory cells and
TH2 type cytokines within nasal mucosa
Decrease in antigen induced hyper responsiveness
of nasal mucosa to subsequent antigen and
histamine provocation
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contd
Inhibits adhesion molecule expression andRANTES (Regulated upon Activation, Normal T-cell
Expressed, and Secreted)secretion Local synthesis of IgE decreased
Decrease in mucosal eosinophils, IL 5 mRnaexpressing cells
Decreased Trans epithelial migration of CD 1 apositive Langerhans cells in seasonal allergicrhinitis
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INDICATIONS
Allergic rhinitis
Perennial rhinitis
Seasonal rhinitis
Nonallergic rhinitis
Nasal polyps
Rhinitis medicomentosa
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Topical nasal steroid sprays for
Allergic Rhinitis
Most potent drugs
Superior efficacy to both antihistaminics and LT
receptor antagonists
Efficacy starts after 7 to 8 hrs of dosage
Re evaluation of patients after 2 weeks
-local irritation
-patient s responsiveness
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Topical nasal steroids for Acute
and Chronic Rhinosinusitis
Improve the symptoms due to reduction of
inflammation
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Rhinitis medicomentosa
Nasal steroids has Faster onset of symptom
reduction
Improvement of mucosal swelling
Recommended when a vaso constrictor is
withdrawn as in OXYMETAZOLINE induced
rebound congestion
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Role of nasal steroids spray in
FESS patients
Minimise post operative edema
Reduce the need for oral steroids
Decrease the potential for recurrence
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Role of nasal steroids spray in sino
nasal polyps
Reduce the size of polyps
Decrease sneezing,rhinorrhea and nasal blockage
Delay recurrence of polyps after surgery
Postpone the need for surgery
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Nasal spray application in frontal
recess
Frontal recess is the most common site for disease
persistence and recurrence after surgery
Patients position
-MOFFAT head down position
-MYGIND head hanging in hyper extension
-Head down and forward (Praying to Mecca)
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Special Considerations
Levels of mometasone are not measurable in breast
milk, thus exposure is expected to be low
Budesonide is currently the only topical nasal steroid
assigned to pregnancy category B
budesonide, fluticasone and mometasone furoate
relieve itching and respiratory symptoms related to
seasonal and perennial allergies in Hypertension pts
renal clearance of beclomethasone dipropionate and
its metabolites is negligible,So used in CKD pts
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Contrindications AmebiasisNasal corticosteroids may make this
condition worse.
AsthmaNasal corticosteroids may make this
condition worse.
GlaucomaLong-term use of nasal corticosteroids
may worsen glaucoma by increasing the pressure
within the eye.
Herpes simplex (virus) infection of the eye Infections
(virus, bacteria, or fungus)Nasal corticosteroids maycover up the signs of these conditions.
Injury to the nose (recent)
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Contraindications
Nose surgery (recent)
Sores in the noseNasal corticosteroids may
prevent proper healing of these conditions.
Liver disease Tuberculosis (active or history of)
Underactive thyroid
Recent heart attack
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Adverse effects-Local
Septal irritation (10%)
Nasal dryness
Crust formation
Epistaxis (4-8%) -common with Fluticasone
Throat dryness
Headache Candida overgrowth
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Systemic Adverse Effects of
Steroids Short term Infection Risk/Wound Healing
Hypertension
Hyperglycemia
Gastrointestinal
Psychiatric
Hypothalamic Pituitary-Adrenal Suppression Steroid induced myopathy
Long term Avascular necrosis of femoral head
Osteoporosis
Cushanoid Changes
Cataracts, glaucoma
Skin thinning, purpura
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