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FA R M A KO LO G I

S A L U R A N P E R N A FA S A N
ATA S

M A H A D R I D H R I K , M . FA R M . K L I N . , A P T
PENDAHULUAN

• ISPA termasuk Flu, rinitis akut, tonsilitis akut, dan laringitis akut
• Flu atau pilek yg paling sering, rata-rata 4 x/tahun pd org dewasa dan
12 x/tahun pd anak-anak
• Insiden tergantung musim, 50% dari pdd menderita pada musim dingin
dan 25% pd musim panas
FLU (COMMON COLD)
DAN RHINITIS AKUT
• Flu disebabkan oleh rinovirus, menyerang nasofaring dan
biasanya disertai rinitis akut.
• Flu paling menular 1 – 4 hari sebelum onset dan selama 3 hari
pertama penyakit ini
• Transmisi melalui sentuhan pada permukaan yang
terkontaminasi dan menyentuh hidung atau mulut daripada
droplet virus ketika bersin
• Gejala: rinoroe, hidung tersumbat, batuk,, dan peningkatan
sekresi mukosa. Jika terjadi kontaminsai bakteri  rinitis
infeksi, sekret hidung kental.
PENGOBATAN COMMON
COLD
• Non Farmakologis
– Istirahat
– Nutrisi yang baik
• Obat-obatan
– Antihistamin (AHI)
– Dekongestan (aminsimpatomimetik)
ANTI HISTAMIN
ANTI HISTAMIN

• H1 antagonists are commonly referred to as


antihistamines
• Antihistamines have several effects:
– Antihistaminic
– Anticholinergic
– Sedative
ANTI HISTAMIN
• BLOCK action of histamine at the receptor sites
– Compete with histamine for binding at unoccupied
receptors.
– CANNOT push histamine off the receptor if already
bound.
• The binding of H1 blockers to the histamine receptors prevents the
adverse consequences of histamine stimulation:
– Vasodilation
– Increased gastrointestinal and respiratory secretions
– Increased capillary permeability
ANTI HISTAMIN

Side Effect
• Anticholinergic (drying) effects, most common:
– Dry mouth
– Difficulty urinating
– Constipation
– Changes in visionDrowsiness
– (Mild drowsiness to deep sleep)
ANTI HISTAMIN
ANTI HISTAMIN
DEKONGESTAN

• Excessive nasal secretions


• Inflamed and swollen nasal mucosa

• Primary causes:
– Allergies
– Upper respiratory infections (common cold)
DEKONGESTAN

• Two main types are used:


• Adrenergics (largest group)
• Corticosteroids

• Two dosage forms:


• Oral
• Inhaled/topically applied to the nasal membranes
ORAL DEKONGESTAN

• Prolonged decongestant effects, but delayed onset


• Effect less potent than topical
• No rebound congestion
• Exclusively adrenergics (Simpatomimetik)
• Examples:
– Phenylephrine
– pseudoephedrine (Sudafed)
LOKAL DEKONGESTAN

• Both adrenergics and steroids


• Prompt onset & Potent
• Sustained use over several days causes rebound congestion, making the
condition worse
• Adrenergics:
ephedrine (Vicks) naphazoline (Privine) oxymetazoline (Afrin)
phenylephrine (Neo Synephrine)
• Intranasal Steroids:
beclomethasone dipropionate (Beconase, Vancenase) flunisolide (Nasalide)
MEKANISME KERJA NASAL DEKONGESTAN
• Site of action: blood vessels surrounding
nasal sinuses
– Adrenergics
• Constrict small blood vessels that supply URI structures As a
result, these tissues shrink and nasal secretions in the swollen
mucous membranes are better able to drain Nasal stuffiness is
relieved
– Nasal steroids
• Anti-inflammatory effect
• Work to turn off the immune system cells involved in the
inflammatory response Decreased inflammation results in
decreased congestion  Nasal stuffiness is relieved
Tabel obat dekongestan hidung dan sistemik
(Amin simpatpmimetik)

OBAT DOSIS INDIKASI


Efedrin D:PO: 25-50 mg, t.i.d, q.i.d Obat bebas dpt dipakai tersendiri atau
dalam kombinasi menyebabkan
vasokontriksi selaput lendir hidung.
Fenilefrin (neo- Larutan 0,25-1 % Untuk rinitis. Kurang kuat dibandingkan
Synephrine, sinex) dengan epinefrin. Dapat menyebabkan sakit
kepala dan hipertensi yang sementara.

Fenilpropanolamin D:PO: 25-50 mg, t.i.d, q.i.d


(propadrine, dristan, Untuk rinitis bermacam-macam kombinsi,
diemtapp) efek pada SSP tidak sebanyak efedrin

Pseudoefedrin
(Actifed, Novafed, D: PO: 60 mg setiap 4-6 jam Untuk rinitis. Perangsangan pada SSP dan
Sudafed) hipertensi tidak seberat efedrin

Oksimetazolin Semprot 0,05%, tetes Dekongestan dengan masa kerja panjang.


(Afrin) Dipakai 2 x sehari, pagi dan sore hari. Dapat
menyebabkan kongesti rebound
BATUK (COUGH)
ANTITUSIF

• Bekerja pada pengendali batuk di medulla untuk menekan refleks batuk


• Batuk adalah cara tubuh untuk mengeluarkan sekret atau material lain dari
saluran nafas
• Bila batuk tidak produktif dan mengiritasi dapat diberikan antitusif
Antitussive Drugs
I I. Central Cough Suppressants:
1. With opioid mechanism of action:
Codeine
Ethylmorphine
Dextromethorphan
2. With non-opioid mechanism of action:
Glaucine
Tusuprex
Broncholytin
II. Peripherally Acting Drugs:
Libexin, Falimint
Codeine (Methylmorphine) - an opioid alkaloid
Analgesic properties –
agonist activity at the opiate receptors
Antitussive action – a direct suppressive action on
the cough center and mucosal secretion.
Delay gastric empting,
 Plasma Amylase and Lipase levels,
 Biliary tract pressure resulting from
contraction of the sphincter of Oddi.
May produce dependence (psychiatric and physical).
Adverse effects : euphoria, hypotension, bradycardia,
constipation, urine retention, physical dependence
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Dekstromethorpan
• Farmakokinetik dekstrometrofan
– Tersedia dlm bentuk sirup atau cairan, kapsul yang dapat
dikunyah, dan pelega tenggorok
– Nama dagang: robittusin DM, romilar, pediacare I, Formula
contac-cold, Formula batuk sucrets, dan banyak lainnya
– Dimetabolisme di hati, dan eksresi urine (TD)

• Farmakodinamik
– Depresi SSO meningkat bila ditelan bersama alkohol, narkotik,
sedatif-hipnotik, barbiturat, atau antideprsi
– Mula kerja 15-30 menit, Lama kerja 3-6 jam
– Efek trapeutik  menekan batuk yang tidak produktif
– ESO: mual, pusing, rasa ngantuk
EKSPECTORAN
• Melunakkan sekret bronkus sehingga dpt dihilangkan
dengan batuk
• Tabel obat antitusif dan ekspektoran
OBAT DOSIS INDIKASI

Antitusif Narkotik
Kodein D:PO: 10-20 mg setiap 4-6 jam Biasanya dicampur dg antihistamin,
dekongestan, dan espectoran

Hidrokodon(Hycod D:PO:5-10 mg, setiap 6-8 jam Seperti kodein


on) D:PO:0,6 mg/kg/hari dlm
dosis terbagi 3-4, tdk melebihi
10 mg/dosis tungga
OBAT DOSIS INDIKASI

Antitusif
nonnarkotik

Dekstrometrofan D:PO:10-20 mg setiap 4-6 jam Menekan batuk, tidak menekan


(romilar, sucrets) A: (6-12 th): 5-10 mg setiap 4-6 jam pernafasan, tidak menimbulkan
A: (2-5 th): 2,5-5 mg setiap 4-6 jam toleransi

Espectoran D:PO:200-400 mg setiap 4 jam Untuk batuk produktif, dpt.


Guaifenesin Diminum dg banyak air untuk
A: (6-12 th): 100-200 mg setiap 4 jam mengencerkan lender
(robittusin)
A: (2-5 th):50-100 mg setiap 4 jam

Kalium iodida Merangsang sekresi dan cairan


D:PO:0,3-0,6 ml setiap 4-6 jam bronkus. Hindari jika terdapat
Gliserol iodin (Iophen,
Organidin) D:PO: 60 mg (tablet) q.i.d hiperkalemia. Dapat menimbulkan
rasa mual, dan muntah
Mucolytic Drugs –
convert sticky and viscous sputum to more liquid one and promote
its  easier release.

1. Activating Hydrolytic Enzymes in Sputum:

Acetylcysteine (ACC) - amp. for inhalation 20%-10 ml, amp. for


injection 10%-2 ml , tab 200 MG
2. Activating Hydrolytic Enzymes and
Endogenous Surfactant Production:
Bromhexine - Ambroxole
Acetylcysteine (ACC) -

an mucolytic of direct action


It is administered by Nebulazation,
PO, Direct Application, or
Intratracheal Instillation.

Mechanism of Action:
ACC splits the disulfide (-S-S-) bonds of
mucoproteines, responsible for increased
viscosity of mucus secretions in the lungs -
secretions become less viscous and more liquid.
ACC is a Paracetamol antidote.
The mechanism:
 Restores hepatic stores of Glutatione –
important in biological oxidations and
the activation of some enzymes.
Formula: C10H17N3O6S
 Inactivates the Toxic Metabolites
Preventing Liver Damage

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CLINICAL USES OF ACC:

• Acute and chronic broncho-pulmonary


diseases
• Tracheostomy care
• Pulmonary complications of surgery
• Diagnostic bronchial studies

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Bromhexine and Ambroxole –
are Mucolytic and Expectorant Agents:
Mechanism of Action:
Depolymerization of Mucoproteines and
Mucopolysaccharides of expectoration that
induces its liquefaction.
They also stimulate production of Surphactant -
endogenous Superficially Active Substance
produced in alveolar cells.
 Normalize Secretion of Bronchial Glands,
 Improve reological properties of sputum,
 Reduce its viscosity,
 Relieve excretion of sputum from bronchi
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SINUSITIS

• Peradangan membran mukosa dari satu atau lebih sinus maksillaris,


frontal, ethmoidalis, atau sfenoidalis
• Pengobatan
– Dekongestan nasal atau sistemik
– Asetaminofen, cairan dan istirahat
– Antibiotik (sinusitis akut dan berat)
FARINGITIS AKUT
• Peradangan tenggorok, atau sakit leher dapat disebabkan
oleh virus atau oleh streptokokkus beta hemolitik atau
bakteri lain
• Gejala: demam, batuk
• Pengobatan:
– Obat kumur salin
– Tablet hisap
– Banyak minum
– Asetaminofen
– Bila biakan tenggorok positif thd streptokokkus betahemolitikus
 antibiotik selama 10 hari
TONSILITIS AKUT

• Peradangan tonsil yg umumnya disebabkan oleh streptokokkus


• Gejala: sakit leher, nyeri menelan, menggigil, demam, dan sakit otot
• Pengobatan
– Obat kumur salin
– Meningkatkan jumlah cairan yang masuk
– antibiotik
LARINGITIS AKUT

• Radang pd laring
• Penyebab: stres, pemakaian pita suara yg berlebihan, atau infeksi
pernafasan
• Gejala: edema pita suara  suara serak dan kecil
• Pengobatan
– Istirahat berbicara
– Hentikan merokok
– Obat tidak membantu
ASMA
• Asma adalah gangguan inflamasi kronik saluran napas yang melibatkan
banyak sel dan elemennya.

mengi, sesak napas, dada terasa berat dan


batukbatuk terutama malam dan atau dini hari
ASMA

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PATOGENESIS ASMA
PATOGENESIS
ASMA
FAKTOR RESIKO ASMA
TERAPI FARMAKOLOGI
• Untuk mengatasi dan mencegah gejala obstruksi jalan napas 
pengontrol dan pelega.
Pengontrol sering disebut Termasuk pelega adalah :
pencegah, yang termasuk obat
pengontrol : • Agonis beta2 kerja singkat
• Kortikosteroid sistemik. (Steroid
• Kortikosteroid inhalasi sistemik digunakan sebagai obat pelega
• Kortikosteroid sistemik bila penggunaan bronkodilator yang lain
• Sodium kromoglikat sudah optimal tetapi hasil belum
• Nedokromil sodium tercapai, penggunaannya
• Metilsantin dikombinasikan dengan bronkodilator
• Agonis beta-2 kerja lama, lain).
inhalasi • Antikolinergik
• Agonis beta-2 kerja lama, oral • Aminofillin
• Leukotrien modifiers • Adrenalin
• Antihistamin generasi ke dua
(antagonis -H1)
• Lain-lain
BRONCHODILATORS
1. Agents stimulating β2 – adrenoreceptors of
bronchi:
a) Selective β2-adrenomimetics (AMs):
β2 -AMs of Short action (4–6 hours):
Salbutamol
Terbutaline
Fenoterol
β2 -AMs of Long action (> 12 hours):
Salmeterol
Formoterol
b) Non-selective Adrenomimetics:

Ephedrine, Adrenaline hydrochloride,


Isadrin, Orciprenaline sulfate

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Salmeterol and Formoterol –have lipophilic properties
Salbutamol and Fenoterol have minor length (11 Angstrem)
and hydrophilic properties. These comparatively quickly
“wash out” from receptor’s area and their duration lasts 4-6
hours.

Salmeterol is long (25 Angstrem) molecule and exceeds


Salbutamol in lipophility by dozens times.
The long chain is strongly attaching to the cell membrane and
active center of the drug is capable to activate receptor repeatedly
providing bronchodilation for 12 hours.

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2. Methylxanthines – Spasmolytics of direct action:
a) Theophylline preparations with short period of action:
Theophylline
Euphylline (Aminophylline)
Oxtriphylline
b) Theophylline preparations with long period of action : Theobilong,
Theodur, Theotard, Durophyllin

3. M-cholinoblockers:
Ipratropium bromide (Atrovent)
Tiotropium bromide
Oxitropium bromide

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Aminophylline (Euphylline):
Theophylline 79%
Ethylenediamine 21% complex

Theophylline:
inhibits PDE => cAMP
blocks Adenosine receptors

Anti-Inflammatory action:
It inhibits the late response to antigenic challenge,
and withdrawal of theophylline causes worsening
of asthmatic symptoms, a fall in spirometry, and
significant  in CD4+ and CD8+ Lymphocytes
in bronchial biopsies

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Clinical uses of Euphylline:

 Asthma, including IV in
Acute Severe Asthma
 Chronic Obstructive Pulmonary Diseases
 Acute Bronchospasm
 Left-Sided Heart Failure
 Severe Bronchospasm in Infants

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Drugs with Anti-Inflammatory Activity
I. Steroid Anti-Inflammatory Drugs (SAIDs) –
Glucocorticoids:
1. Natural – Hydrocortisone acetate
2. Synthetic with resorptive action –
Prednisolone, Dexamethasone, Triamcinolone
3. Synthetic with local action –
Beclometasone, Budesonide, Flunisolide, Fluticasone
II. Mast cell stabilizers:
Cromolyn sodium ( Intal -caps for inhalation 0.2 g)
Nedocromil (Nedocromil sodium – aerosol dosed: 2 mg/dose)
Ketotifen (tab. 1 mg)
III. Leukotriene Modifiers:
1. Inhibitors of 5-lipooxygenase: Zileuton
2. Leukotriene Receptor Blockers: Zafirlukast, Montelukast
Cromolyn sodium (caps. 20 mg for inhalation) and
Nedocromil (aerosol: 2 mg/dose) stabilize mast cells and
prevent the release of bronchoconstrictive and
inflammatory substances when mast cells are
confronted with allergens and other stimuli.
They are effective prophylactic anti-inflammatory agents,
but are not useful in managing acute asthmatic attack
because they are not direct bronchodilators.

Mechanism of action:
 stabilize the mast cell membrane and inhibits release
of the spasmogenic mediators of Type I allergic reaction,
including Histamine and slow reacting substance of
anaphylaxis (SRS-A) from sensitized must cells.

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Ketotifen (tab. 1 mg), a cromolyn analog,
is an antihistaminic (H1) with some cromolyn like
action.
Mechanism of action:
 It inhibits stimulation of immunogenic and inflammatory
cells (mast cells, macrophages, eosinophils, lymphocytes,
neutrophils) and mediator release.
 It is believed to inhibit airway inflammation induced by
platelet activating factor (PAF).
Clinicla uses: bronchial asthma, rhinitis, atopic dermatitis,
conjunctivitis, urticaria, food allergy, migraine.
Adverse effects:
sedation, dry mouth, dizziness, nausea, weight gain.

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Montelukast & Zafirlukast

competitively inhibit cysteinyl Leukotriene receptors.


Leukotriene B4 is a potent neutrophil chemoattractant,
LTC4 and LTD4 produce bronchoconstriction, mucosal
edema.

All the leukotriens (LTC4, LTD4 and LTE4) act on the


same cysteinyl-leukotriene receptor.

Zafirlucast and Montelucast relax the airways in mild


asthma, the bronchodilator activity being one third that of
Salbutamol. They Sputum Eosinophilia.
Zafirlukast and Montelukast – are not a cure-all
for asthma;
their main use is as add-on therapy for:
 Mild-to-moderate asthma – that is not controlled
by an ‘as required’ short-acting β2-agonist +
Inhaled GC
 Exercise-induced bronchospasm
 Aspirin- induced asthma

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Glucocorticoids
Beclometasone
Butesonide
Fluticasone
- are given by inhalation with metered-dose inhaler, the full effect being
attained only after several days of therapy.

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GLUKOKORTIKOID SISTEMIK
• Beberapa hal yang harus dipertimbangkan saat memberi steroid oral :
– gunakan prednison, prednisolon, atau metilprednisolon karena mempunyai efek
mineralokortikoid minimal, waktu paruh pendek dan efek striae pada otot minimal
– bentuk oral, bukan parenteral
– penggunaan selang sehari atau sekali sehari pagi hari
ADVERSE EFFECT OF GCs:
Local Effects:
Oropharyngeal Candidiasis – Thrush
Systemic Effects:
BP, Edema, CHF,
Thromboembolism,
Thrombophlebitis,
Cushingoid State (moonface,
buffalo hump, central obesity),
Peptic Ulceration,
Increased Appetite,
Muscle Weakness,
Osteoporosis, Hirsutism,
Growth Suppression in Children.

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THANKS FOR
YOUR ATTENTION

S E E YO U N E X T T I M E . .