TOPICAL NASAL STEROIDS

7/29/2019 TOPICAL NASAL STEROIDS

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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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TOPICAL NASAL STEROIDS