Farmakologi Obat

THT
Setiawati

DEPARTEMEN FARMAKOLOGI
FK UNSOED
Capaian Pembelajaran

• Memahami farmakologi obat

yang digunakan di bagian THT
• Memilih tatalaksana farmakologi
penyakit THT (tepat indikasi,
tepat obat, tepat dosis, tepat
frekuensi dan cara pemberian,
serta sesuai kondisi pasien)
• Menulis resep obat dengan
benar untuk permasalahan di
bagian THT
Keluhan Umum: Jenis Obat:

• telinga sakit. 1.Decongestan

• keluar cairan 2.Antihistamin
• bersin-bersin 3.Mast cell stabilizer
• pilek 4.Corticosteroid
• nyeritelan 5.Anti jamur
• serak 6.Antibiotic
7.Antitusif
8.Analgesik
9.Ceruminolitic
 Ear Drugs

• Antibiotics – To reduce the inflammation.

• Local analgesics – To reduce pain in the ear
• Steroids – To treat inflammation of the skin of the ear
canel.
• Wax emulsifiers – Loosen and remove ear wax.
• Combination of Ear drops – To treat multiple aspects
of Otitis media or Otitis externa (Anti inflammatory,
anti-pruritis, anti-allergic)
• Ear drops – Solution or suspension forms are
common. Ointments less.
 Nose Drugs

• Steroid
• obat antiasma (salbutamol, ipratropium)
• dekongestan
• obat anti inflamasi
 Drugs for throat

• Antitusif
• Anti inflamasi
• Analgesik
• Demulcents: menenangkan tenggorokan dan
mengurangi impuls aferen dari mukosa faring yang
meradang dan teriritasi.
• Ekspektoran: obat yang meningkatkan sekresi
bronkus atau mengurangi kekentalannya, sehingga
memudahkan pengeluarannya melalui batuk
 Kortikosteroid
• Kortikosteroid sering digunakan dalam berbagai
kondisi pada telinga-hidung-tenggorokan (THT)
karena sifat anti-inflamasinya.

• Mekanisme aksi:
Steroid bekerja pada protein transkripsi di
dalam sitoplasma  penurunan jumlah sitokin
inflamasi yang disekresikan oleh
selMengurangi respons sel terhadap
peradangan dan edema pada selaput lendir.
 Kortikosteroid
• Kortikosteroid sering digunakan dalam berbagai
kondisi pada telinga-hidung-tenggorokan (THT)
karena sifat anti-inflamasinya.

• Mekanisme aksi:
Steroid bekerja pada protein transkripsi di
dalam sitoplasma penurunan jumlah sitokin
dan kemokin inflamasi yang disekresikan oleh
selMengurangi respons sel terhadap
peradangan dan edema pada selaput lendir.
 Corticosteroid Drug for the Nose
Intranasal (IN): (Spray or Drop) or Inhalation
• Intranasally administered steroid should be
lipophilic; First pass metabolism is avoided.
• Very low dose is enough for local effect –
reduced systemic toxicity.
• Administered intranasally to treat allergic and
nonallergic rhinitis.
 Sediaan Kortikosteroid Intranasal
• Beklometason (Beconase AQ, QNASL)
QNASL tersedia sebagai bubuk kering intranasal.
• Budesonide (Rhinocort Aqua)
• Triamcinolone dihirup (Nasacort AQ)

• Ciclesonide (Omnaris)
• Flunisolide (AeroBid)
• Flutikason propionat (Flonase)
• Flutikason furoate (Veramyst)
• Mometasone (NASONEX)
Efek samping Kortikosteroid Intranasal

• Sediaan intranasal  sedikit yang mencapai

sirkulasi sistemik  efek samping sistemik
minimal.
• Efek samping lokal dapat berupa epistaksis,
iritasi rongga hidung
 Corticosteroid Drug for the Ears
Tetes Telinga:
• eksim pada lapisan kulit telinga luar, Myringitis
granulosa, untuk mengurangi edema mukosa telinga
tengah pada infeksi telinga tengah aktif dengan perforasi
sentral.
• Dioleskan secara topikal sebagai larutan pada saluran
telinga luar untuk mengurangi peradangan yang
berhubungan dengan alergi atau infeksi.

Contoh
• betametason
• deksametason
 Corticosteroid Drug for the Ears
Indications
• Acute allergic rhinitis
• Acute sinusitis
• Acute epiglottitis
• Otitis externa – to reduce external canal
inflammatory oedema
• Sinonasal inflammatory polyposis
• Acute sensorineural hearing loss (sudden deafness)
• Nasal sarcoidosis
• Acute stridor before tracheostomy
• Chronic otitis media
 Efek samping Kortikosteroid
Common Side effects
Complications Associated with
• Short-term Use of Steroids
• Long-term Use of Steroids

Short-term Use of Steroids: Long-term Use of Steroids:

• Hypothalamic-pituitary-adrenal
axis suppression • Osteoporosis
• Hyperglycemia • Cushingn Syndrome
• Gastrointestinal Disturbances • Accelerated
• Psychiatric effects atherosclerosis
• Early cataract
• Skin thinning
• Pupura
 Dekongestan
• Sumbatan pada hidung, sinus, dan dada
disebabkan oleh pembengkakan akibat
peradangan, atau dilatasi pembuluh darah
pada selaput hidung dan saluran napas.

Dekongestan

Hidung
PLOONG
tersumbat
 Dekongestan
Mekanisme Aksi:
• agonis alfa-adrenergik (Simpatomimetik)
• Stimulasi reseptor alfa-adrenergik
menyempitkan pembuluh darah di seluruh
tubuh:
 mengurangi suplai darah ke hidung
 menurunkan jumlah darah di pembuluh
sinusoid
 mengurangi edema mukosa
 Dekongestan
Tipe Dekongestan :

1.DECONGESTAN DIRECT ACTION/ α1adrenergik agonist :

 Phenylephrine oxymetazoline, xylometazoline,
naphazoline
 Mekanisme kerja : berikatan secara selektif pada
reseptor adrenergik  vasokonstriksi pembuluh
darah
2. DECONGESTAN INDIRECT ACTION
 Ephedrine, phenylpropanolamine
 Mekanisme kerja : meningkatkan sekresi
norepinefrin  norepinefrin akan berikatan secara
nonselektif pada reseptor adrenergik α1,α2,β1
 Dekongestan
Farmakokinetik
• Oral
• Topikal : nasal spray, drops
• Kelebihan Topikal : onset lebih cepat, efek samping sistemik
lebih minimal
• Efek samping :
• Stimulasi SSP
• Rebound congesti (rhinitis medikamentosa)
• Stimulasi adrenergik
• Topikal : sensasi hidung terbakar/kering
• Kontraindikasi : hipertensi, konsumsi MAOI dapat
meningkatkan level norepinefrin endogen
 Dekongestan
• 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).

 Dekongestan
Indications
• Nasal and eustachian tube
congestion
• Nasal stuffiness
• Acute or chronic rhinitis
• Sinusitis, allergic conditions
• Before nasal diagnostic
examination to improve
visualization.
 Dekongestan
Systemic Side Effect
• Cardiac arrhythmias
• Headache
• Insomnia
• Peningkatan tekanan darah

Contraindications
• Severe hypertension
• Coronary artery disease
• Narrow angle glaucoma
• Use with Nasal steroids
• Pregnancy and lactation
 Dekongestan

Example of topical decongestant:

Ephedrine HCL, Xylometazoline HCL, Oxymetazoline
HCL, Ipratropium bromide (antimuscarinic).

Side effect of topical decongestant:

• Local irritation.
• Rebound congestion
 Antihistamin
General Mechanism of Action of Antihistamines

• Blocks action of histamine at receptor

• Competes with histamine for binding
• Displaces histamine from receptor
• Most beneficial when given early
25
 Antihistamin
Mechanisms of Action
• Histamine released from mast cells in the
tissues when an allergic reaction  vasodilation
in the blood vessels, mucous membranes
become swollen and red. Irritates the tissue
directly, causing pain and itching.
• Antihistamines acts by blocking H1 histamine
receptor sites:
 Dry up secretion.
 Shrink edematous mucous membranes
 Decrease itching and redness
 Antihistamin
Example of antihistamin
• First generation • Second generation
– Alkylamines  – Terfenadine
Chlorpheniramine
maleate
– Fexofenadine HCl
– Ethanolamines  – Loratadine
Diphenhydramine HCl – Cetirizine
– Ethylenediamines 
Tripelennamine
– Piperazines  Azatadine
– Phenothiazines 
Promethazine HCl
– Piperadines 
Hydroxyzine HCl
 Antihistamin
First Generation Second Generation
• Dapat menembus blood • Generally do not cause
brain barier  efek sedasi the sedation
(+) (efek histamin pada • Do not cross the blood-
reseptor H1 di SSP : brain barrier as readily as
wakefullness). First Generation
• Aktivitas compounds
ANTIKOLINERGIK (+) : • Lipophobicity
mulut kering, retensi • Large molecular size
urin, efek antiemetik
 Antihistamin
Dosage form
• Oral : Cetirizine, Levocetirizine, Loratadin,
desloratadin, Fexofenadine
• Intranasal : Azelastine (Astelin), Olopatadine
intranasal (Patanase)
• Injeksi
 Antihistamin
Indications
• Allergic Rhinitis
• Sneezing
• Stuffiness
• Itchy nose, and throat
• Runny nose.

Side Effects
• Sedation (by 1st Generation drugs)
• Dry Mouth
• Drowsiness
• Dizziness
• Nausea and Vomiting
 Mast Cell Stabilizers

• Menstabilkan membran sel mast  Mencegah

pelepasan histamin dari sel mast (β2-adrenergic
agonists)
• Penggunaan : sebelum paparan dengan alergen
• Efek perlindungan berlangsung 4-8 jam
• Contoh : Cromoglicic acid, Ketotifen,
Methylxanthines, Olopatadine, Omalizumab,
Pemirolast, Quercetin
 Leukotriene Receptor Antagonists

• Montelukast, zafirlukast.

• Mekanisme kerja : menghambat reseptor leukotrien

• Pemberian oral : absorpsi cepat, menurun dengan

adanya makanan, Ikatan protein 90%, metabolisme
oleh CYP2C9, CYP3A4, CYP1A2
• Sediaan : zafirlukast tablet 20 mg, 2x1 tab 1-2 jam
setelah makan
Leukotriene Receptor Antagonists
 Antitusive

• Decrease coughing by suppressing the cough

center in brain or anesthetizing stretch
receptors in respiratory tract. Main purpose is
to control dry, nonproductive coughs. Not
prescribed to treat a productive cough.
• Example: Dextromethorphan, Codein
 Ceruminolytic

• Hidrogen peroksida 3 %
• Fenolgliserin
 Antibiotic
Antibiotics for Ear
Framycetin sulfate
• Framycetin is a broad spectrum
aminoglycoside antibiotic
• framycetin appears to inhibit protein
synthesis in susceptible bacteria by
binding to ribosomal subunits.
• Framycetin is not active against most
anaerobic bacteria
 Antibiotic
Gentamicin
• Gentamicin is a protein synthesis inhibitor.
• It binds the 30S bacterial ribosomal subunit and acts to
inhibit the formation of the initiation complex, causes
mRNA misreading leading to non-functional proteins.
• It also induces the dissolution of polyribosomes during
protein synthesis.
• Aminoglycosides require oxygen for uptake into the
bacterial cell. Thus, they are only active against aerobes.
 Antibiotic
Antibiotics for Nose
Chlorhexidine with neomycin
• Chlorhexidine-neomycin is an antibiotic
available in nasal topical form only.
• It is used to treat minor nasal infection with,
and carriage of, Staphylococci bacteria.
• Chlorhexidine gluconate is an antiseptic that
kills a wide range of bacteria and yeasts, and
some fungi and viruses.
• Neomycin sulphate is an antibiotic of the
aminoglycoside type. It rapidly kills bacteria by
interfering with the production of proteins that
the bacteria need to divide and multiply.
 Antibiotic
Mupirocin
• Mupirocin is an antibiotic.
• It is used inside the nose to treat infections
that are caused by certain bacteria.
• This helps prevent the spread of infection to
patients and health care workers during
outbreaks at institutions.
 Antibiotic
Antibiotics for Oropharyngeal
Doxycycline
• Doxycycline is a tetracycline antibiotic that
fights bacteria in the body.
• Doxycysline reversiably bind to 30s subunit at A
site. And Block the binding of aminoacyl t-RNA
to m-RNA.
• Inhibit the addition of new aminoacid to
growing peptide chain. And Stop the translation
process, new protein cannot be made.
 Antibiotic
Aminoglikosida
• Streptomycin, neomycin, kanamycin, amikacin, gentamicin,
tobramycin, sisomicin, netilmicin., spectinomycin
• Mekanisme kerja : Berikatan dengan ribosom sehingga
menghambat sintesis protein bakteri
• Semua aminoglikosida bersifat bakterisidal dan terutama aktif
terhadap kuman bakteri gram negatif. Amikasin, gentamisin
dan tobramisin juga aktif terhadap Pseudomonas aeruginosa.
• Efek samping utamanya ototoksisitas dan nefrotoksisitas
(terutama pada lansia atau pasien dengan gangguan fungsi
ginjal)
 Antibiotic
Quinolon

• Ciprofloxacin, Gatifloxacin, Gemifloxacin,

Levofloxacin,
Lomefloxacin,Moxifloxacin,Norfloxacin,
Ofloxacin
• Mekanisme kerja : DNA gyrase inhibitors
 Antibiotic
Siprofloksasin

• Aktif terhadap bakteri Gram positif dan

Gram negatif (terutama salmonella,
shigella, kampilobakter, neisseria, dan
pseudomonas).
• Aktivitas sedang terhadap bakteri Gram
positif seperti Streptococcus
pneumoniae dan Enterococcus faecalis
 Antibiotic
Perhatian
• Kuinolon sebaiknya digunakan secara hati-hati pada pasien dengan
riwayat epilepsi atau kondisi yang dapat menyebabkan kejang, defisiensi
G6PD, miastenia gravis (risiko eksaserbasi), pasien gangguan ginjal ,
pada wanita hamil dan ibu menyusui,

• Anak-anak dan remaja (hasil penelitian pada hewan menunjukkan

adanya artropati pada sendi penunjang berat badan).

• Sebaiknya dihindari paparan terhadap sinar matahari yang berlebihan

(hentikan bila terjadi fotosensitivitas).

• Kuinolon juga dapat menimbulkan kejang pada pasien dengan atau

tanpa riwayat kejang. Penggunaan AINS pada saat yang bersamaan
dapat memicu terjadinya kejang.
 Antibiotic
Golongan Penicilin
• Penicillin : Penicilin G (IV), Penicilin VK (PO)
• Penicilin broad spectrum : Amoxilin,
amoxiline/calvulanate, Ampicilin,Piperacilin,
Ticarcilin
• Penicillin Antipseudomonas : Piperacillin, azlocillin,
ticarcillin.
• Penicilin antistaphylococcus : Cloxacilin, dicloxacillin,
nafcillin, oxacillin

• Mekanisme kerja : Menghambat sintesis dinding sel

bakteri
 Antibiotic
Cephalosporin

• Cephalosporin generasi I : Cefadroxil,

cephalexin, cephradine, cefazolin
• Generasi II : Cefoxitin, cefotetan,
cefuroxime,
• Generasi III : Cefotaxime, Ceftazidine,
Ceftriaxone, Cefepime

• Mekanisme kerja : Menghambat sintesis

dinding sel bakteri
 Antibiotic
Sefalosporin generasi pertama:

• Terutama aktif terhadap kuman Gram positif.

• Golongan ini efektif terhadap sebagian besarStaphylococcus
aureus dan streptokokus termasuk Streptococcus pyogenes,
Streptococcus viridans dan Streptococcus pneumoniae,
Streptococcus anaerob, Clostridium perfringens, Listeria
monocytogenes dan Corynebacterium diphteria.
• Kuman yang resisten antara lain MRSA, Staphylococcus
epidermidis dan Streptococcus faecalis
 Antibiotic
Sefalosporin generasi kedua:

• Dibandingkan dengan generasi pertama,

sefalosporin generasi kedua kurang aktif
terhadap bakteri gram positif, tapi lebih aktif
terhadap bakteri gram negatif,
misalnya Hemophilus influenzae, Pr. mirabilis,
Escherichia coli dan Klebsiella.
• Golongan ini tidak efektif
terhadapPseudomonas
aeruginosa dan enterokokus.
 Antibiotic
Sefalosporin generasi ketiga:

• Golongan ini umumnya kurang aktif terhadap

kokus gram positif dibandingkan dengan
generasi pertama,
• Tapi jauh lebih aktif
terhadap Enterobacteriaceae, termasuk
strain penghasil penisilinase.
 Antifungal
• Fungal infections of the mouth are usually caused
by Candida spp. (candidiasis or candidosis).
• Different types of oropharyngeal candidiasis are
managed as follows:
• Thrush
• Acute erythematous candidiasis
• Denture stomatitis
• Chronic hyperplastic candidiasis
• Angular cheilitis
 Antifungal
Drugs used in oropharyngeal candidiasis
Miconazole
– Miconazole inhibits the fungal enzyme 14α-sterol
demethylase, resulting in a reduced production of
ergosterol.
– In addition to its antifungal actions, miconazole, similarly
to ketoconazole, is known to act as an antagonist of
the glucocorticoid receptor
 Antifungal
Nystatin
– nystatin binds to ergosterol, a major component of the
fungal cell membrane.
– When present in sufficient concentrations, it forms
pores in the membrane that lead to K+ leakage,
acidification, and death of the fungus.
– Nystatin when taken by mouth is used to treat yeast
infections in the mouth or stomach.
– Oral nystatin is not absorbed into your bloodstream
and will not treat fungal infections in other parts of the
body or on the skin.
– Too toxic for synthetic use, Used only topically
 Epistkasis
• Penekanan

• Topikal Vasokonstriktor : dekongestan (oxymetazoline

0.025% nose drops, phenylephrine solution) dan lokal
anestesi (4 percent cocaine solution, tetracaine,
lidocaine/Xylocaine solution)

• Chemical cautery  silver nitrate

• Hemostatic packing with absorbable gelatin foam

(Gelfoam) or oxidized cellulose (Surgicel).
• Use of desmopressin spray (DDAVP) may be considered in a
patient with a known bleeding disorder
 Epistkasis
Sediaan

Silver nitrate stick

Phenylephrine 1%
CO-PHENYLCAINE FORTE® spray
(lignocaine hydrochloride 50mg/ml &
phenylephrine hydrochloride 5mg/ml ,
spray )

Gelfoam

Cocaine 45 solution

DDAVP
 Otitis Eksterna

• Penyebab: biasanya bakteri, kadang

jamur, non infeksius
• Pencetus : trauma & kelembaban tinggi
pada liang telinga
 Tatalaksana Acute Otitis Eksterna ec Bakteri

• Analgetik oral untuk atasi nyeri  NSAIDs

• Terapi antbiotik sistemik jika ada kondisi
premorbid seperti DM, imunodefisiensi.
• Tanpa kondisi premorbid : antibiotik topikal non
ototoksik
• Jika ada obstruksi telinga (ex. Serumen) 
aural toilet terlebih dahulu
• Antibiotik yang sensitif terhadap Pseudomonas
aeruginosa dan Staphylococcus aureus.
 Otitis Eksterna
Sediaan Antiseptik Topikal

• Acetic acid 2% in alcohol, 4 x 3-4 tetes per

hari
• aluminum acetate solution
 Otitis Eksterna
Sediaan Antibiotik Topikal Telinga

• Antibiotik
– Aminoglycoside : Neomycin
– Polymyxin B
– Quinolone (Ofloxacin 0.3% solution )
– Kombinasi antibiotik tersebut

• Antibiotik kombinasi kortikosteroid ( hydrocortisone

atau dexamethasone)
– Ciprofloxacin 0.3% and hydrocortisone suspension
– Polymyxin B–hydrocortisone
 Advantages and Disadvantages of Common Anti-infective
Topical Agents
Class Advantages Disadvantages
2 % acetic acid Generic product is inexpensive Can be irritating to inflamed external
solution and effective against most auditory canal; possibly ototoxic
infections without causing
sensitization

Neomycin otic Effective, and generic product is Can be a potent sensitizer, causing
preparations inexpensive contact dermatitis in 15% of patients;
ototoxic

Polymyxin B alone Avoids potential neomycin No activity against Staphylococcus and

sensitization other gram-positive microorganisms
Aminoglycoside Less locally irritating than 2% Potential ototoxicity; moderately
solutions acetic acid solution, neomycin expensive
otic preparations or polymyxin B
alone

Quinolone otic Highly effective without causing Expensive; increased community

solutions local irritation or sensitization; exposure of an important class of
no risk of ototoxicity; twice-daily antibiotics, with potential for causing
dosing resistance
 Otitis Media
• Acute : Amoxicillin oral, 30 mg/kg/dosis setiap 8 jam selam 5–10
hari  co-amoxiclav  golongan cephalosporin (ex. ceftriaxone
(50 mg/kg/hari untuk 3 hari)
• Alergi golongan penisilin : azithromycin (10 mg/kg/hari utk hari
1, dilanjutkan 5 mg/kg/hari single dose, selama 4 hari) atau
Clarithromycin (15 mg/kg/hari, 2 x sehari) atau clindamycin (30—
40 mg/kg/hari dibagi dlm 3 dosis)
• chronic, suppurative : fluoroquinolone eardrop (ex ofloxacin
drops, 2 drops setiap 8 jam selama 4 minggu) setelah dilakukan
aural toilet.
• Analgetik untuk mengurangi nyeri
Pemilihan antibiotik dipengaruhi
pola resistensi kuman yang ada
pada populasi tersebut.
 Ototoksik

Ototoksik  obat yang dapat

menyebabkan hilangnya
pendengaran dan/ tinitus
 Ototoksik
• Antibiotics : aminoglycosides, amphotericin B, chloramphenicol,
minocycline, polymyxine B, sulfonamides, vancomycin
• Painkillers : acetylsalicylic acid, ibuprofen, naproxen,
indomethacin, peroxicam
• Antimalarial: quinine
• anti-cancer drugs : bleomycin, cis-platinum,carboplatinum,
methotrexate, vinblastin
• Blood pressure controlling medications: acebutolol
• Diuretic bendroflumethazide, bumetadine, chlor-thalidone,
ethacrynic acid, furosemide (only in IV)
• Glucocorticosteroids :prednisolone
• anti-anxiety
• anti-depression drugs
 Ototoksik
Is Drug-Induced Tinnitus
Temporary or Permanent?

• Temporary : acetylsalicylic acid, ibuprofen

and naproxen
• Often permanent : aminoglycoside
antibiotic
 Ototoksik
How Soon Will the Tinnitus Occur After
Taking a Drug?

• Very quickly  loop diuretics IV

• Take several days  aminoglycoside
antibiotic
• After stopped taking the drug 
benzodiazepines
 Ototoksik
Aminoglikosida

• Neomycin do not appear to be ototoxic in humans unless

the tympanic membrane is perforated.
• When a solution of an aminoglycoside antibiotic
combine with an aminoglycoside antibiotic used
intravenously  increasing risk of ototoxic effect (on
open or raw wound, have kidney damage)
• Neomycin is the drug that is most toxic to the structure
involved in hearing, the cochlea, so it is recommended
for topical use only.
Thank You