FARMAKOLOGI THT

dr.Sufi desrini M.Sc

Nasal Congestion
Nasal congestion is one of the most frequent symptoms in URT
disorders, such as allergic rhinitis, rhinosinusitis, nonallergic rhinitis,
and nasal polyposis
Nasal congestion is also common symptom in otitis media and asthma
Mucosal inflammation is the central pathophysiological mechanism that
contribute congestion,incl increased venous engorgement, increased
nasal secretion and edema

Nasal Congestion (cont)

Inflammation can
reduce the physical sie
of the nasal passages

Inducing vasodilatation,
increasing BF and
increasing vascular
permeability

Engorgement of nasal
venous sinusoids,
swelling of inferior &
anterior turbinates and
obs of nasal airflow

Figure 1. Allergic sensitization

Figure 2. Early Phase of allergi inflammation

Figure 3. Late phase of allergic inflammation

Figure 4. Allergic cascade of symptoms of allergic rhinitis

Pharmacotherapy
H1-antihistamines
Intranasal Glucocorticoids
Decongestans
Chromones (Amnivisnaga)
Anticholinergics
Antileukotrienes
Allergen-Spesific Immunotherapy

H-1 Antihistamines
inverse agonists
Antihistamines stabilise the inactive form and shift the equilibrium in
the opposite direction. Thus, the amount of histamine-induced
stimulation of a cell or tissue depends on the balance between
histamine and H1 antihistamines.

H-1 Antihistamines(Cont1)
Common H1- receptor antagonists
First generation
Second generation*
Hydroxyzine
Cetirizine
Diphenhydramine
Loratadine
Chlorpheniramine
Desloratadine
Promethazine
Fexofenadine
Levocetirizine
*Two earlier developed agents, astemizole and terfenadine, were
withdrawn in 1986 because of cardiac toxicity adverse effects.

H-1 Antihistamines(Cont2)
onset of effect occurs within 1-3 hours;
Duration of action varies from several hours to 24 hours,
First-generation antihistamines and some of the second-generation
agents are oxidatively metabolised by the hepatic cytochrome P450
system, the exceptions being levocetirizine, cetirizine, and fexofenadine.

H-1 Antihistamines(Cont3)
Levocetirizine and cetirizine are excreted largely unchanged in urine and
fexofenadine is excreted mainly in the faeces but also the urine
Concomitant administration of probenicid reduces the total body and
renal clearance of fexofenadine
The bioavailability of fexofenadine may be altered by simultaneous
consumption of grapefruit juice (reduced rate and absorption of the
drug by almost 30%).

Antihistamines (Cont4)
bahan kuliah THT\daftar obat rhinitis alergi.docx

Nasal Decongestant
Nasal decongestants are vasoconstrictive drugs extremely useful as
nonprescription medication. Both oral and topical dosage forms are
often chosen as therapy in the common cold.

Mechanism of action:
Nasal decongestants belong to the pharmacological
class of sympathomimetic amines. Decongestant
stimulates alpha-adrenergic agonist, by constriction
of blood vessels, reducing its supply to the nose,
decrease the amount of blood in sinusoid vessels
and decrease mucosal edema.

Types of nasal decongestant:

Internally or systemic decongestant: (e.g.
pseudoephedrine, phenylpropanolamine (PPA)
and phenylephrine).
Topical decongestant: drops or sprays (e.g.
xylometazoline, phenylephrine,
oxymetazoline, naphazoline).
Inhaler: (1-desoxyephedrine and
propylhexedrine).

Systemic nasal decongestant:

Mechanism of action:
Potent direct acting alpha-adrenergic
stimulator with weak beta-Adrenergic
activity, causes vasoconstriction of the
arterioles of the nasal mucosa and
conjunctive, activates the dilator muscle of
the pupil to causes contraction, and produce
systemic arterial vasoconstriction.

Side effect of systemic

decongestant:
CNS effect: Nervousness, restlessness,
headach and insomnia.
CV effect: increase blood pressure and
increase heart rate.
Urinary sphincter constriction

Examples of systemic
decongestant:
Pseudoephedrine
Phenylpropanolamine (PPA)
phenylephrine

Indication

Side effect

Pseudoephedrine

Phenylephrine HCL

Its symptomatically relief of

nasal congestion due to
common cold, upper
respiratory allergies and it
promotes nasal or sinus
drainage.

For Symptomatically
relief of nasal and
nasopharyngeal mucosal
congestion and relief of
redness of the eye due

CNS: nervousness,
irritability, restlessness,
headache and insomnia.
CV: blood pressure and
heart rate is irregular and
palpitation.
GIT: nausea, vomiting.
Neuromuscular and skeletal:
weakness, tremor.

CNS: nervousness,
irritability, restlessness,
headache.
CV: blood pressure and
heart rate is irregular and
palpitation.
GIT: nausea, vomiting.
Neuromuscular and
skeletal: weakness,
tremor.

to irritation.

Dosage form

Drug interaction

Solution oral drops, as

HCL: Dimetapp
decongestant infant
drops:
7.5mg/0.8ml(15ml)
Syrup, as HCL:
30mg/5ml (120ml,
480ml).
Tablet, HCL:30mg,
60mg

MAOI may increase

blood pressure.
Sympathomimetic may
increase toxicity it can
decrease effect of
methyldopa, reserpine.

Nasal decongestant
(therapy should not
exceed 3continuous day):
2-6 years: install 3
drops every 2-4 hours of
0.125% solution as
needed.
Children > 12yrs and
adult: install 1-2 sprays
or 1-2 drops every 4 hrs
of 0.25% to 0.5%

___

_____

In elderly.
hyperthyroidism.
bradycardia.
partial heart
blocker.

____

Hypersensitivity
Hypertension
Ventricular
tachycardia

Caution

Contraindication

Topical Nasal Decongestant

-adrenergic agonists
act on -adrenergic receptors in the nasal mucosa, producing
vasoconstriction of the smaller arterioles of the nasal passages that
leads to shrinkage of the swollen mucosa and improved ventilation
E.q. phenylephrine, xylometazoline, oxymetazoline
Topical decongestants rarely result in serious systemic side effects,
since they are minimally absorbed into the circulation.

Topical Nasal Decongestant (Cont1)

Monotherapy both with oral or intranasal formulation reduces nasal
congestion but provides limited relief from other symptoms of
allergic rhinitis.
The combination of an oral decongestant and second generation
antihistamine provide decongestant efficacy superior to that of either
drug alone in patients with seasonal allergic rhinitis
Use of intranasal (-agonist) decongestants for a period beyond
current labeling (4-6 days) commonly causes rebound congestion.

Topical Nasal Decongestant (Cont2):

Include:
sprays,
drops,
inhalers

1- sprays:
Its advantages:
Have fast onset of action.
Cover large surface area.
Simple to use.
Inexpensive.

Its disadvantage:
Imprecise dosage
Tendency for tip the bottle to become
clogged.

2- drops:
It preferred for small children.
Its disadvantage:

High risk of contamination.

Limited coverage into nasal mucosa.
Easy passage into larynx.

3- inhaler:
Easy to be handle and carry.

Disadvantage:

Unobstructed airway and sufficient air

flow needed to
distribute drug to nasal mucosa.

Side effect of topical decongestant:

Local irritation.
Rebound congestion

Ephederdrine HCL

Brand Name

ephedrine
Nasal
Decongestant

Rhinorrhoea
associated with
allergic and non
allergic rhinitis.

Instill 1-2 drops

into each nostril
up to 3 or 4 times
daily.

Apply 42
microgram as 2
spray into each
nostril 2-3 times
daily.

Indication

Dose

Ipratropium
Bromide
(Antimuscarinic)
Atrovent

Avoid excessive or
prolonged used.

Side effect

caution

Nasal dryness.
Irritation.
Nausea.
Headache.
Antimuscarinic
affect:
-GIT disturbance.
-Palpitation.
Urinary retention

In infant under three

Avoid spraying near
months.
eyes.
Used with:
-Myasthenia
Gravis.
-Narrow angle
glaucoma.
Benign prostatic
hyperplasia.

Contraindications

Drug
interaction

Hypersensitivity to
ephedrine.
Cardiac arrhythmias.
Angle-closure
glaucoma.

Patient with
hypersensitivity to
Ipratropium
Soya lecithin or
related food
products.
Atropine

Increase effect with:

- Sympathomimetic
agent.
- Theophylline.
- Cardiac glycoside.
- Anesthetic.
Decrease effect with:
-Alpha and Beta
adrenergic blockers.

Increase toxicity
with anticholinergic
or drug with
anticholinergic
properties

Nasal drops:
ephedrine HCL
0.5%.

Dosage
form

Solution for
nubulization 0.02%.
Solution for oral
inhalation
18mcg/actuation.
Solution for
intranasal spray
0.03% or 0.06%.

Intranasal Glucocorticoid
the most effective class of medications available for the treatment of
allergic and non-allergic rhinitis
The rationale for using intranasal glucocorticosteroids in the treatment
of allergic rhinitis is that high medication concentrations can be
achieved at receptor sites in the nasal mucosa with minimal risk of
systemic adverse effects
Glucocorticosteroids can suppress many stages of the allergic
inflammatory process by interacting with transcription factors

Intranasal Glucocorticoid (Cont1)

Glucocorticosteroids can suppress many stages of the allergic
inflammatory process by interacting with transcription factors
In clinical studies, intranasal glucocorticosteroids are well tolerated,
and adverse effects are few in number, mild in severity, and similar to
placebo

Anticholinergics
Anticholinergic agents can help reduce anterior watery rhinorrhea
but they have no effect on nasal blockage or the other symptoms of
allergic rhinitis

Antileukotrienes
Antileukotrienes are a class of medication for the treatment of
asthma
effective in improving asthma outcomes
Antileukotrienes administered in mono-therapy, does not give a
control of nasal symptoms.
Antileukotrienes seem to have no effect on nasal obstruction

Allergen-Specific Immunotherapy
Allergen-Specific Immunotherapy (ASI) is the only allergen-specific
therapy
ASI induces immunological tolerance and the induction of blocking
IgG4 antibodies through repeated exposure to allergen(s).
ASI decreases the recruitment of mast cells, basophiles and
eosinophils in the skin, nose, eye and bronchial mucosa

Allergen-Specific Immunotherapy
ASI produces an increase in the level of allergen-specific IgA and IgG4
antibodies, and a decrease in the level of allergen-specific IgE
antibodies.
induces CD4+CD25+FOXP3+ TReg cells that produce high levels of
IL-10 and/or TGF, two cytokines that are known to attenuate
allergen-specific TH2-cell responses.
IL-10 suppresses mast-cell, eosinophil and T-cell responses, and the
pleiotropic functions of TGF maintain a diverse and self-tolerant
T-cell repertoire, including T Reg cells.

EARS

Cerumenolytic
Cerumen is part of the external ear defense mechanisms against
foreign bodies and infectious agent
It is a combination of epithelial cells, dust, foreign bodies as well as
the secretions of the sebaceous glands and apocrine glands
Cerumen impaction is a common problem encountered by the
general physician, the family physician and the otolaryngologist
almost every day

Cerumenolytic (cont2)
Cerumen impaction has important clinical implications on the general
well-being of the patient and might cause hearing loss, pain, itching,
tinnitus, vertigo, external otitis and even chronic cough
Removal of cerumen from the external auditory canal can be
accomplished using physical methods, chemical methods
(cerumenolysis) or any combination of them.

Cerumenolytic (cont3)
Cerumenolytic products act by softening the cerumen and lubricating
the canal, thus facilitating cerumen removal from the ear canal or by
disintegrating the cerumen.

Cerumenolytics (cont4)
Advantages:
Easy application
Effectiveness not superior to saline or water
Complications:
Otitis externa
Allergic reactions
Pain or vertigo if TM is not intact
Transient hearing loss

Cerumenolytics (Cont5)
Clinicians may use cerumenolytic agents or instruct patients in home
use.
Cerumenolytic agents include water
Topical therapy is regularly used to manage cerumen impactions
either as a single therapeutic intervention or in combination with
other techniques, including irrigation of the ear canal and manual
removal of cerumen.

Cerumenolytics (Cont6)
Topical preparations exist in three forms:
water-based;
oil-based;
nonwater-, nonoil-based
Water-based agents have a cerumenolytic effect by inducing
hydration and subsequent fragmentation of corneocytes.

Cerumenolytics (Cont7)
Oil-based preparations are not true cerumenolytics.
They lubricate and soften cerumen without disintegrating cerumen.

Table 1. Topical preparation (Hand 2004)

Preparation

Active constituents

Water-based

Acetic acid,
Cerumenex,
Hydrogen peroxide,
Sodium bicarbonate
Sterile saline solution

Aqueous acetic acid

Triethanolamine polypeptide
Hydrogen peroxide solution
Sodium bicarbonate
Water

Oil-based

Almond oil
Arachis oil
Earex
Olive oil
Mineral oil/liquid petrolatum

Almond oil
Arachis oil
Arachis oil, Almond oil,rectified camphor oil
Olive oil
Liquid petrolatum

Non-water-, non-oilbased

Audax
Debrox

Choline salicylate, glycerine

Carbamide peroxide (ure-hydrogen peroxide)

Cerumenolytics (Cont8)
One systematic reviewand meta-analysis evaluated 15 preparations,
including saline and plain water, and concluded that without
syringing, there was weak evidence that both water-based and oilbased ear drops were more effective than no treatment
Nonwater-, nonoil-based preparations were more effective than
oil-based preparations.

(Hand C, Harvey I. The effectiveness of topical preparations for the

treatment of earwax: a systematic review. Br J Gen Pract
2004;54:8627)

Cerumenolytics (Cont9)
the evidence indicates that any type of cerumenolytic agent tends to be
superior to no treatment but lacks evidence that any particular agent is
superior to any other.
In vitro studies support using a true cerumenolytic rather than an oilbased lubricant for disintegration of cerumen, with a longer period of
treatment tending to be more efficacious.
Use of a cerumenolytic improves success of irrigation, but no
cerumenolytic has been shown to be superior to another in this respect

Cerumenolytics (Cont10)
Instilling a preparation immediately prior to irrigation has not been shown
to be superior or inferior to using cerumenolytics for several days before
irrigation.
cerumenolytics should be avoided in patients with active infections of
the ear canal

ANTIMICROBIAL THERAPY
one of the most common diagnoses made by pediatricians and family
medicine physicians :
OTITIS MEDIA
a continuum of chronic and acute manifestations that can have long term
sequelae for the child
Long term sequelae of OM include: hearing loss, impaired cognitive
development, tympanic membrane perforation, facial paralysis, meningitis,
and brain abscess

Antimicrobial therapy (Cont1)

Antimicrobial therapy is the mainstay of therapy in various types of
OM
Several goals of antimicrobial pharmacotherapy:
Resolution of symptomatology and middle-ear effusion, prevention
of sensoneuronal hearing loss, and prevention of OM sequelae
The degree of efficacy of individual antimicrobials to treat OM should
be based on the agents ability to attain these goals.

Antimicrobial therapy (Cont2)

Factors in chosing antimicrobials for otitis media :
Antimicrobial bacteria; spectrum Patient type
Type of otitis media (acute, chronic, with effusion)
Recurrent, nonrecurrent, first time infection
Assesment of compliance
Safety

Antimicrobial therapy (Cont3)

Amoxicillin is a drug frequently used in the treatment of AOM and as
first line atimicrobial agent for AOM
Amoxicillin penetrates the middle ear in concentrations high enough
to exceed the minimal inhibitory concentrations of common bacteria
present in AOM(Pichichero et al, 1994)
adverse effects associated with the use of amoxicillin are usually
gastrointestinal in nature (diarrhea and cramping)

Antimicrobial therapy (Cont4)

Amoxicillin is susceptible to -lactamase destruction.
Beta-lactamase is a enzyme produced by many gram negative and gram
positive aerobic and anaerobic organisms. It cleaves -lactam antibiotics
(penicillins and cephalopsorins) rendering them inactive.
90% of M catarrhalis isolates and 40-50% of H influenzae isolates in the
United States produce beta-lactamases

Antimicrobial therapy (Cont5)

If the patient has had recurrent OM or chronic otitis media
(COM)failure therapy with hihg-dose amoxicillin/F -lactamase
resistance the recommendations :
Amoxicillin-clavulanic acid, oral cefuroxime axetil and IM
ceftriaxone
AOM may be caused by viral processes antibiotics will offer no
activity.

Terimakasih