Role of Oxymetazoline in

management of Rhinosinusitis in
daily practice

Azmi Mir’ah Zakiah

Rhinosinusitis

RHINOSINUSITIS  presence of inflammation in the paranasal sinuses

mucosa and the contiguous mucosa of the nasal passages.
• acute rhinosinusitis less than 1 month
• more than 12 weeks  chronic rhinosinusitis is present. If the duration
is between 4 and 12 weeks, the rhinosinusitis should be considered
subacute.
• Recently, chronic rhinosinusitis (CRS) has been further classified as CRS
with nasal polyps and CRS without nasal polyps.
• The causes of RS are diverse, and often it is not possible to precisely
identify a specific cause.

Meltzer EO, et al. Rhinosinusitis Diagnosis and Management for the Clinician:

A Synopsis of Recent Consensus GuidelinesMayo Clin Proc. • May 2011;86(5):427-443

Etiologi Rhinosinusitis
Nasal Congestion(NC)

• Described as fullness, obstruction, Pathophysiology2

reduced airflow, or being “stuffed
up,”1 • Mucosal inflammation is
the central mechanism
• NC has not been extensively studied. that contribute to
1 congestion 1
Stewart M, Ferguson BJ,
• Allergic Rhinitis(AR) is the common • Inflammation induces the Fromer L. Epidemiology
and burden of nasal
cause for NC. vasodilatation, increased congestion. International

• Burden of NC can be indirectly blood flow and vascular Journal of General

Medicine .2010; 3:37–45
estimated based on AR burden permeability Naclerio RM, Bachert C,
2

Baraniuk JN.
Pathophysiology of nasal
• This reduce the physical congestion. International

• Global incidence of AR is estimated size of the nasal passages Journal of General

Medicine . 2010; 3 :47–57

as 10- 20%1
Diseases causing NC and Quality of Life (QOL)

Allergic Rhinitis Rhinosinusitis Nasal polyposis(NP)

• 10-20% globally • 66-70% Rhinosinusitis • NC is one of the
• Study on 111 have NC severe symptom in NP
patients with • Significant decrease • 2-4% of prevalence
moderate-to-severe in QOL globally
perennial AR reported
significantly lower
scores of QOL
• Impairment in
physical limitations,
pain, social
functioning, general
health perception,
energy/fatigue

1
Stewart M, Ferguson BJ, Fromer L. Epidemiology and burden of nasal congestion. International Journal of General Medicine .
2010; 3:37–45
Adrenergic Receptors

• Classified into 2 types based Adrenergi

on affinities of adrenergic
agonists.
c
receptors
• Nasal decongestants acts on α
and β receptors and decrease
nasal congestion
• Selective α 1 and 2 agonists, α β
α-Adrenergic agonist are
common nasal decongestants
drug class

1
Tripathi KD. Essentials of Medical Pharmacology. New Delhi: Jaypee Brothers Medical Publishers;c2013:125-
137
α1, α2 β1, β2, β3
 Classification of Nasal Decongestants

selective α1 Selective α2 α-Adrenergic

agonist agonist Agonist

Phenylephrine Naphazoline Pseudoephedrine

Phenylpropanolamin
Oxymetazoline Xylometazoline
e

OXYMETAZOLINE
1
Tripathi KD. Essentials of Medical Pharmacology. New Delhi:
Jaypee Brothers Medical Publishers;c2013:125-137
Overview of Nasal Decongestants

Naphazoline Xylometazoline Oxymetazoline Pseudoephedrin Phenylpropanolamine

e
Mode of Selective α2 Selective α2 Selective α2 Alpha-Adrenergic Directly stimulate
action agonist) agonist) agonist) Agonist. adrenergic receptors
but probably
indirectly stimulates
both α- and β-
adrenergic receptors
Duration of Longer duration of Longer duration Long duration
action action (12 hours) of action (10 of action (12
hours)2 hours)
Dose 0.1% topical in 0.05–0.1% topical 0.025–0.05% 30- 60 mg three 25–50 mg daily
nose in nose topical in nose times a day
1
Tripathi KD. Essentials of Medical
Pharmacology. New Delhi:Jaypee
Adverse Impairs mucosal Impairs mucosal Impairs Rise in BP can Rise in BP Brothers Medical
effects ciliary function ciliary function mucosal ciliary occur, especially Publishers;c2013:125-137. 2
causing Atrophic causing Atrophic function in hypertensive, SUDAFED 0.1% NASAL SPRAY.
rhinitis and rhinitis and causing CNS effects MHRA.
anosmia, CNS anosmia, CNS Atrophic http://www.mhra.gov.uk/home/gr
depression and rise depression and rhinitis and oups/par/documents/websiteresou
in BP, initial rise in BP anosmia, CNS rces/con152860.pdf. Accessed
stinging sensation depression and September 18.09.2015
rise in BP
Oxymetazoline
Oxymetazoline-Structure and Mechanism of
action
Imidazole derivative with direct acting
sympathomimetic activity1
Chemical Name - 6-tert-butyl-3-(4,5-
dihydro-1H-imidazol-2-ylmethyl)-2,4-
dimethylphenol
Molecular Formula - C16H24N2O
Molecular weight - 260.37456 g/mol
Mechanism of Action 2
• Oxymetazoline is a direct
acting sympathomimetic
amine
• Acts on alpha-adrenergic
receptors in the arterioles
of the conjunctiva and
1
Oxymetazoline. PubChem.
https://pubchem.ncbi.nlm.nih.g
nasal mucosa ov/compound/oxymetazoline#se
• In nasal it produces
ction=Top. Accessed. August
18,2015.
2
Oxymetazoline. DrugBank.
constriction, resulting in http://www.drugbank.ca/drugs
/DB00935. Accessed. August
decreased blood flow and 18,2015.
decreased nasal congestion
Common Dosage in Different Age Groups

Strength Dosage
Adults1 0.025% 4 to 6 drops to each nostril twice daily as needed
solution
0.05% 2 to 3 drops to each nostril twice daily as needed
solution
0.05% spray 2-3 sprays per nostril q12hr2
Pediatric1 0.025% >= 2 years to 5 years - 2 to 3 drops to each nostril
1
Oxymetazoline Nasal Dosage.
solution twice daily as needed. Drugs.com.
6 years to 18 years: 4 to 6 drops to each nostril twice http://www.drugs.com/dosage/
oxymetazoline-
daily as needed. nasal.html#Usual_Adult_Dose_fo
r_Nasal_Congestion. Accessed
0.05% >= 6 years to 18 years: 2 to 3 drops to each nostril September 18.09.2015. 2
solution twice daily as needed oxymetazoline (OTC).
Medscape.
0.05% spray >= 6 years to 18 years: 1 to 2 sprays to each nostril http://reference.medscape.co
m/drug/afrin-duramist-plus-
twice daily as needed oxymetazoline-343408.
Accessed September 22, 205.
Pharmacology
Pharmacokinetics- described as what the body does to a drug, refers
to the movement of drug into, through, and out of the body.1
Pharmacodynamics - study of what a drug does to the body
Pharmacokinetics2 Pharmacodynamics6
• Absorption • Used as a vasoconstrictor to relieve nasal
• Occasional systemic absorption may congestion
occur.2 Bioavailability of drug is 11%. 3 • Constricts the (Sympathomimetic action)
The time taken for (Tmax)peak plasma smaller arterioles of the nasal passages.
concentration is 5-10 minutes.4 • Produces a prolonged (up to 12 hours)
• Distribution decongesting effect.
• 80% protein binding.3
• Metabolism
• Half life of drug is 5-6 hours. 3
• Elimination
• Oxymetazoline is eliminated via kidney.5

Safe dose or dose above which systemic effects occur7

Adults: Not to exceed 2 doses/24 hr and for no longer than 3-5 days. (dose is 2-3 sprays per
nostril q12hr)
Adverse Reactions and Precautions for
Oxymetazoline Use
Transient burning
Adverse
Stinging
effects1
Sneezing
Increased nasal discharge or dryness of nasal mucosa

• Safe use during • No adequate studies in • Allergy to

pregnancy has not been women for use during Oxymetazoline
established. breastfeeding • Dryness in the nose
• Oxymetazoline nasal • Potential benefits must
solutions should be used be weighed against risks
during pregnancy only before taking this
when instructed by a medication
clinician
Other
Pregnancy2 Breastfeeding2
conditions2

1
Oxymetazoline Hydrochloride. Drug.com. http://www.drugs.com/monograph/oxymetazoline-hydrochloride.html. 2015. Accessed. August 18,2015.
2
OXYMETAZOLINE.toxnet. http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@rn+@rel+1491-59-4.2007. Accessed August 18, 2015.
Triple Action of Oxymetazoline

Anti-viral
Anti- inflammatory
Vasoconstrictive effect
OMZ has Virucidal Activity Against Human
Pathogenic Viruses
An in-vitro to demonstrate the antiviral activity of Oxymetazoline
on Human Rhinovirus

1
Koelsch S, Tschaikin
M, Sacher F. Anti-
Rhinovirus-specific
Activity of the Alpha-
sympathomimetic
Oxymetazoline.
Arzneimittel-
Forschung (Drug
A direct dose-dependent virucidal Virus titer was less after Research) .
2007;57(7):475–482.
activity of OMZ against HRV-14 treatment with OMZ

OMZ exhibits a clear dose-dependent Virucidal activity which is evident from

decrease of subsequent plaque formation after infection with pre-treated virus
particles
Oxymetazoline (OMZ) Terminates Rhinitis-
related Inflammation
• Interferes with neutrophil
membranes by activating
cytoplasmatic phospholipase A2
(cPLA2)
• cPLA2 liberates arachidonic acid from
membrane phospholipids which is a
precursor of inflammatory substrates

• Inhibits 5-lipoxygenase (5-LO), the

initial enzyme of leukotriene
synthesis
• Reduced production of pro-inflammatory
LTB4.
1
Speier IB, Oswald B, Maier
• Inhibits respiratory burst activity KL.et al. Oxymetazoline
(NADPH oxidase) Inhibits and Resolves
Inflammatory Reactions in
• Diminishes the production of tissue- Human Neutrophils. J
damaging reactive oxygen species (ROS) Pharmacol Sci.2009; 110:
276 – 284.
 Vasoconstrictive Effect of OMZ adds to its
Nasal Decongestive Efficacy

• Constricts the dilated blood vessels in the nasal mucosa.

• Results in shrinking of nasal membranes due to which drainage of mucus and circulation
of air is improved.
• Reduces nasal stuffiness.

• Provides immediate symptomatic relief.

1
Whittaker C. Nasal sprays:
a short review. S Afr Pharm
J . 2011;78(7):21–23
• Decongestant effects of oxymetazoline longer lasting (up to 12 hours) than 2
Reinecke S. and
ephedrine M.Tschaikin. 2005.
Investigation of the Effect
of Oxymetazoline on the
Duration of Rhinitis. Results
of a placebo-controlled
• 3-5 days is the usual dosage period. double-blind study in
patients with acute rhinitis.
MMW Fortschr Med 147
Suppl 3: 113-118.
Summary of Triple Action of Oxymetazolin
Pharmacodynamic   Scientific Clinical benefit Effect on Course
Properties of Evidence of disease
Oxymetazoline
Antiviral Inhibitis the activity of Causal In vitro Studies 1,2 Fights the faster and
HRV 14, downregulates Effect viruses that stronger
virus receptor ICAM-1 cause rhinitis improvement of
symptoms like
sneezing,
rhinorrhea, nasal
obstruction,
impaired taste
and smell and
Antioxidative/ Inhibits pro- Pathogenetic In vitro Study 3 Inhibits rhinitis
general well-
Anti-inflammatory inflammatory pathways, Effect symptoms
being +
suppresses oxidative
Shortens the
stress
duration of cold
from 6 to 4 days

Vasoconstrictive de-swelling of nasal Symptomatic Clinical Study 4 Decongestion

mucosa Effect of the nose,
easy breathing
and outflow of Clinical Study 5

1)Sacher et al., 2005 Antiviral Properties of Oxymetazolin, DAZ, No. 5: 111-112 Glatthaar-Saalmueller B et al. 2005. Oxymetazoline exerts antiviral activity against human secretion and (vs. Saline solution)
rhinovirus-14 and downregulates expression of ist receptor ICAM-1 on human umbilical vein endothelial cells. OEGAI Annual Meeting, Graz/Austria, December 01-03: P51.
3)Beck-Speier et al., 2006, Oxymetazoline Inhibits Proinflammatory Reactions: Effects on Arachidonic Acid-Derived Metabolites, JPET 316: 843-851. Westerveld et germs
al,1995, Anti-oxidant actions of oxymethazoline an xylomethazoline, Eur J Clin Pharmacol 291: 27-31 Connell JT., 1969, Effectiveness of topical nasal decongestants.
Annals of Allergy 27: 541-546 Reinecke S. & Tschaikin M., 2005, Investigation of the effect of oxymetazoline on the duration of rhinitis. Results of a placebo-controlled
double-blind study in patients with acute rhinitis. MMW Fortschr Med 147 Suppl 3:113-118
terima kasih