BAGIAN FARMAKOLOGI

FAKULTAS KEDOKTERAN
UNIVERSITAS TADULAKO

ANTITUSIF & NASAL

DECONGESTANT
Batuk
• proses eksipirasi eksplosif yg memberikan
mekanisme proteksi normal u/ membersihkan
saluran pernafasan dari sekresi a/ benda asing
bukan penyakit  gejala atau tanda adanya
gangguan pada saluran pernafasan
 Patofisiologi Batuk
• Melibatkan kompleks rangkaian refleks yang bermula dari stimulasi
terhadap reseptor iritan
OBAT BATUK
Antitusif
Ekspektoran
Mukolitik
 ANTITUSIF
Codein, Dextromethorphan, Benzonatate, Difenhidramin Hcl

• Menekan frek batuk kering

• sentral (pusat batuk/medula) 
meningkatkan ambang batas menurunkan
respon pusat batuk
• perifer (tr. respiratorius)  frekuensi dan
blokade reseptor sensorik  intensitas
menghambat peregangan paru batuk
 Codein
Pharmacodynamics
• bekerja dgn cara menekan pusat batuk (medula)
 menghambat impuls batuk
Pharmacokinetics
• Absorption
– gastrointestinal tract  oral
• Distribution
– tersebar luas pd jaringan tubuh, melewati placenta &
jg tdpt di ASI. Ikatan dgn prot. plasma 7% - 25%.
 Codein
• Metabolisme
– di hepar, 70% - 80% conjugation with glucuronic
acid  codeine-6-glucuronide (C6G) ; 5% – 10%
by O-demethylation  morphine ; 10% N-
demethylation to norcodeine
• Excretion
– ± 90% of the total dose of codeine is excreted
through the kidneys
– t½ codein dan metabolitnya  ± 3jam.
 Codein
• Side Effects
– Constipation, Drowsiness, Nausea/vomiting, Addictive
potential
– Cough suppression by opioids may allow accumulation
of secretions and lead to airway obstruction
• Dosis
– Adult: 15-30 mg 3-4 times daily.
– Child : 2-5 yr 3 mg; 6-12 yr 7.5-15 mg. Doses to be
taken 3-4 times daily
 Codein
• Contraindication
– Acute or severe bronchial asthma
– Significant respiratory depression
– use of MAOIs within the last 14 days 
– Known or suspected gastrointestinal obstruction,
including paralytic ileus
– Hypersensitivity to codeine
• Interaction
– Drugs interaction : MAO inhibitors
– Food interaction : Alcohol
 Dextromethorphan
Pharmacodynamics
• bekerja dgn cara menekan pusat batuk (medula) 
menghambat impuls batuk
Pharmacokinetics
• Absorption : GI tract.
• Distribution : Terdistribusi luas pd jaringan tubuh
• Metabolism : di hepar  demetilasi mjd dextrorphan
(active)
• Excretion : >>> urine
 Dextromethorphan
• Contraindications:
– penggunaan MAO inhibitor selama 2mgu  dpt me↑kan
serotonergic effect of Dextromethorphan. This may cause
serotonin syndrome.
– ≠ u/ mengobati batuk yg disebabkan o/ merokok, asthma,
or emphysema
• Side Effects:
– severe dizziness, anxiety, restless feeling, or nervousness;
– confusion, hallucinations; or
– slow breathing
 Benzonatate
• Pharmacodynamics
– menganestesi stretch receptors yg terdapat pada tr.
respiratorius,
• Pharmacokinetics:
– Taken orally as a softgel capsule.
– act 15 - 20 min’ and effect lasts for 3 - 8 hours.
 EKSPEKTORAN
• Sebenarnya tidak lebih baik dari plasebo (IONI, 2017)
• Contoh :
– Glyseril Guaiacolate (Guaifenesin)
– Succus liquairitiae
– Ammonium klorida
 Glyseril Guaiacolate
Pharmacodynamics
• increasing sputum volume and reducing the viscosity of
bronchial secretions, guaifenesin facilitates expectoration of
retained secretions
• helps loosen phlegm (mucus) and thin bronchial secretions,
make coughs more productive
 Glyseril Guaiacolate
• Pharmacokinetics
– Absorption: Well absorbed from the GI tract.
– Distribution :
– Metabolism: di hepar (oksidasi & demetilasi)
– Excretion: Via urine. Elimination half-life: ±1 hr.
 Glyseril Guaiacolate
• Contraindication
– Hypersensitivity
• Side effects
– Significant  Abdominal pain, nausea, vomiting, diarrhoea.
– Rare  Nervous: Dizziness, drowsiness, headache.
Genitourinary: Nephrolithiasis. Endocrine: Hypouricaemia. 
Dermatologic: Rash.
• Dosis
– Adult: As conventional preparation 200-400 mg 4 hrly as needed. As
extended-release tab: 600-1,200 mg 12 hrly as needed. Max: 2,400
mg/daily.
– Child: 4-<6 yr 50-100 mg 4 hrly as needed. Max: 600 mg daily; 6-<12 yr 100-
200 mg 4 hrly as needed. Max: 1,200 mg daily; ≥12 yr Same as adult dose
 MUKOLITIK
Bromhexin, Ambroxol, Erdosistein, Karbosistein, Mesistein

• untuk batuk berdahak, mempercepat ekspektorasi dgn cara

mengurangi viskositas sputum
• >>> pada batuk kronik
• Hati2 penggunaan pd px riw. peptic ulcer  merusak sawar
mukosa lambung
 BROMHEXIN
Pharmacodynamics
• acts on the mucus at the formative stages in the glands,
within the mucus-secreting cells  disrupts the structure of
acid mucopolysaccharide fibres in mucoid sputum and
produces a less viscous mucus, which is easier to expectorate.
• enhances mucus transport by reducing mucus viscosity and by
activating the ciliated epithelium (mucociliary clearance)
Pharmacokinetics
• Absorption: Rapidly absorbed from the GI tract.
Bioavailability: Approx 20%. Time to peak plasma
concentration: Approx 1 hr.
• Distribution: Widely distributed to body tissues. Crosses
blood brain-barrier and placenta (small amounts). Plasma
protein binding: >90%.
• Metabolism: Extensive hepatic first-pass metabolism.
• Excretion: Via urine (approx 85-90%, mainly as metabolites).
t½: 13-40 hr
• Adverse Reactions
– GI side effects; headache, dizziness, sweating, skin rashes.
Inhalation: Cough or bronchospasm.
• Bromhexine and Pregnancy
– Category A: increase the frequency of malformations or
other direct or indirect harmful effects on the foetus
having been observed.
 BROMHEXIN
• Kontraindikasi: 
– Hipersensitivitas.
• Dosis: 
– Adult: 8-16 mg
– Child: 2-5 yr 8 mg daily in 2-3 divided doses; 6-11 yr 4-8
mg; ≥12 yr Same as adult dose.
 AMBROXOL
Pharmacodynamics: 
• active metabolite of bromhexine
• causes an increase in secretion in the respiratory tract
• promotes surfactant production and stimulates ciliary
activity
 assist the flow of mucus and its removal (mucociliary
clearance)
• significant reduction in cytokine release, both in the
blood and in mononuclear and polynuclear cells
Pharmacokinetics:
• Absorption: GI tract. Peak plasma levels are attained after 0.5-
3 hrs.
• Distribution: Plasma protein-binding is around 90%. After oral,
IV and IM administration, ambroxol is distributed rapidly and
extensively from the blood into the tissues. The highest active
ingredient concentrations are measured in the lung.
• Metabolism:  in the liver mainly by conjugation.
• Elimination: Around 30% of an oral dose is eliminated via the
first-pass effect. t½  10 hrs.
 AMBROXOL
• Dosis
– Dewasa: kapsul lepas lambat 1 kali sehari 75 mg, sesudah makan. Dewasa dan
anak di atas 12 tahun:1 tablet (30 mg) 2-3 kali sehari; Anak 6-12 tahun: 1/2 tablet
2-3 kali sehari. Sirup tetes (drops): 15 mg/ml drops (1 mL= 20 tetes): Anak s/d 2
tahun: 0,5 mL (10 tetes) 2 kali sehari; Ambroksol drops dapat dicampur bersama
dengan sari buah, susu atau air.Sirup 15 mg/5 mL (1 sendok takar = 5 mL): Anak
usia 6-12 tahun: 2-3 kali sehari 1 sendok takar; 2-6 tahun: 3 kali sehari 1/2 sendok
takar; di bawah 2 tahun: 2 kali sehari 1/2 sendok takar.
• ADR
– Mild GI effects and allergic reactions.
• Precaution : 1st trimester of pregnancy
• Interaksi : Pemberian bersamaan dengan antibiotik (amoksisilin
sefuroksim, eritromisin, doksisiklin) menyebabkan peningkatan
penerimaan antibiotik kedalam jaringan paru-paru.
 NASAL DECONGESTANT
• Sistemik
– Pseudoefedrin, phenilpropanolamin
• Topikal
– Oxymetazoline, naphazoline, efedrin, sodium chloride
 NASAL DECONGESTANT
Pseudoephedrine
• Pharmacodynamics an α-and β-adrenergic receptor agonist. It
causes vasoconstriction via direct stimulation of α-adrenergic
receptors of the respiratory mucosa. It also directly stimulates
β-adrenergic receptors causing bronchial relaxation, increased
heart rate and contractility.
• Pharmacokinetics: 
– Absorption: cepat diasorbsi dari GI tract.
– Distribusi : terdistribusi luas di jaringan tubuh, bisa ditemukan dlm
ASI.
– Metabolisme : di hepar
– Ekskresi : di urine, >>> dlm btk unchanged drug. Half-life: ±5-8 hr.
• Dosis (as hydrochloride or sulfate)
Dewasa : 60 mg every 4-6 hr. Max: 4 dosis /24jam.
Anak2 : 2-6 yr: 15 mg 3-4 times daily; 6-12 yr: 30 mg 3-4 times
daily.
• Kontraindikasi : Severe hypertension, phaeochromocytoma.
• ADR : Anginal pain; rebound congestion and rhinorrhoea;
fear, anxiety, restlessness, tremor, insomnia, confusion,
irritability and psychotic states; reduced appetite,
nausea, vomiting; gangrene; cerebral haemorrhage and
pulmonary oedema; reflex bradycardia, tachycardia and
cardiac arrhythmias, palpitations and cardiac arrest,
hypotension and dizziness, fainting and flushing. Tissue
necrosis and sloughing; myocardial and arterial necrosis.
• Drugs Interaction
– Increased risk of hypertension and arrhythmias if
given with cardiac glycosides, quinidine.
– Increased risk of vasoconstrictor effects if given with
ergot alkaloids or oxytocin.
– Co-admin with MAOIs may cause hypertensive crisis.
– Anaesthetics e.g. cyclopropane, halothane and other
halogenated anaesthestics
– antihypertensive agents
TERIMAKASIH