BLOK RESPIKARVAS II

OBAT
FLU DAN BATUK
dr. Tara Mandiricha, M.Si

Department of Pharmacology
Faculty of Medicine
University of Muhammadiyah Malang
 Y S
D A
O

Topic
T

Decongestant
Antitussive
Mucolytics/Mucokinetic

Antihistamine
Cough Mechanism

Chung KF & Pavord ID, 2008. Prevalence, pathogenesis, and causes of chronic cough. The Lancet: Chronic Cough; Vol: 371 (9621); pg 1364-1374
 DRUGS FOR COUGH

DRUGS FOR COUGH

Antitussive Adjuvant
Mucokinetic Antihistamine

Opioid Non Opioid Bronchial Secretion Mucolytic 1st Generation

Enhancer Bronchodilator

2nd Generation
Codein • Bromhexine
• Noscapine
• Ambroxol • Salbutamol
• Dextromethorphan • Chlorpheniramine
• Acetylcysteine • Terbutaline
• Dexchlorpheniramine
• Carbocysteine
• Promethazine

• Cetirizine
• Loratadine
• Fexofenadine
• Levocetirizine
• Desloratadine
Drug for Cough
• Cough is a protective reflex that serves to clear the airways of excessive secretions and foreign
matter and which sometimes becomes excessive, and troublesome to patients
• Classification: Acute, Sub Acute, Chronic
• Causal therapy should be preferred if feasible. If not, however, in cases such as in acute respiratory
infection due to virus or only effective if postponed (such as TB), symptomatic therapy can be
considered along with therapy to causes underlying the cough

Bakhtiar A & Juwita PM, 2020. Management of Cough. Jurnal Respirasi: Vol. 6 (2); 85-96.
Birring, Surinder; de Blasio, Francesco; Dicpinigaitis, Peter; Fontana, Giovanni; Lanata, Luigi; Page, Clive; Saibene, Federico; Zanasi, Alessandro (2019). Antitussive therapy: A role for levodropropizine. Pulmonary Pharmacology & Therapeutics, (), S1094553918302852–.
doi:10.1016/j.pupt.2019.03.003
Decongestant
Drug
Mechanism of Action
Agonis reseptor-alfa
Systemic Drugs
Vasokonstriksi --> mukosa & sekresi • Pseudoephedrine
turun --> hidung longgar • Phenylpropanolamine
• Phenylephrine

Topical Drugs
• Ephedrine 0.25%
• Naphazoline HCl 0.05%
• Oxymetazoline 0.025%; 0.05%
 Decongestant Topical
Cara Pemberian

Spray

Drops

Adverse Effects

• Long term --> Rebound vasodilatation

• How to minimize the AE:
• Use 3-4 days
• Dont use high dose or often frequent
• Dont use in Allergt Rhinitis --> overuse
Decongestant Oral

Kemampuan vasokonstriksi < dekongestan nasal (effikasi <)

Phenylephrine - poor oral bioavailability (rapidly degraded in gut).
ES rebound congestion (-)
ES sistemik >>> ~ Distribusi Reseptor
potential drug interactions: MAOIs, TCAs, dll
 Antitussive Oral
Central
• Opioid:
• Ex: Hydrocodone and Codeine
• Combinations with other medications (e.g. antihistamines, decongestants, expectorants)
- Prescription
- Over-the-counter (OTC) Monograph* --> codeine as an antitussive
• Indication(s)
- Relief of cough asscociated with allergies or common cold
- Symptomatic relief of cough (Hycodan only)
• Mechanism of action:
- μ (mu) receptor
~ Central
~ Peripheral
 Antitussive Oral
Central

• Opioid:
• Higher risk of addiction
• Codeine is mostly used and often considered as a basic antitussive. It is activated by CYP2D6 into
morphine, which then undergoes glucuronidation
• A fast metabolizer patient changes most codeine into morphine through the liver, causing toxicity
potential.
• Dosage:
 Antitussive Oral
Central
2. Non Opioid
• Preferable for acute cough due to lower potential of misuse and addiction than its opioid counterpart
• Dextromethorphan significantly suppresses acute cough
• Dextromethorphan has a relatively slow onset and reaches its peak after two hours of administration
• Slow penetration through the blood-brain barrier and retention to the nerve system causes the longer working duration of
this antitussive
• It is structurally related to alkaloid opioids such as morphine but does not interact with the mu receptor
• One proposed mechanism is that DM works on the nucleus tractus solitarius, the estimated site where the pulmonary
vagal afferent fibers synapse in the central nervous system. This site in the brainstem functions as a gate for the cough
reflex. DM is known to have many interactions with several different receptor sites.
• DM is known for its main site of action at N-methyl-D-aspartate (NMDA) receptors as a non-competitive antagonist.
• Dosage:

https://www.ncbi.nlm.nih.gov/books/NBK538216/
 Antitussive Oral
Target kerja :
• Perifer : menurunkan sensitivitas reseptor batuk thd substansi kimia seperti bahan irritan, autokoid
• Uap menthol, miny Eucalyptus (permen batuk)
• Anestesi lokal topikal (benzokain, lidokain :utk persiapanbronkoskopi)
• Benzonatate
• Pusat batuk : menurunkan sensitivitas ‘cough center’
• Opioid : codein, pholcodein, morfin, hydrocodone (turunan codein)
• Non Opioid : Dextromethorpan (d-isomer dari metil eter opiate), Chlopehedianol, Diphenhydramin
Antitussive Drugs
2. Non Opioid
• GABA (γ-aminobutyric acid)
• Local anesthesia such as lidocaine, benzonatate, bupivacaine, and mexiletine
• Diphenhydramine, a first-generation antihistamine H1
• Butamirate --> widely used in Europe as an OTC antitussive
 Antitussive Drugs
Peripheral Antitussive

• Levodropropizine
• Good tolerability and safety profile
• Equivalent efficacy and less sedative effects
• Can modulate the response of vagal C-fibers to chemical stimuli [
• Menthol is produced by Mentha arvensis
• Throat lozenges can also reduce cough and flu symptoms through relieving activity on the
mucosal membrane

Birring, Surinder; de Blasio, Francesco; Dicpinigaitis, Peter; Fontana, Giovanni; Lanata, Luigi; Page, Clive; Saibene, Federico; Zanasi, Alessandro (2019). Antitussive therapy: A role for levodropropizine. Pulmonary Pharmacology & Therapeutics, (), S1094553918302852–.
doi:10.1016/j.pupt.2019.03.003
Expectorant Drugs
• Expectorant reduces irritation to cough receptors by increasing mucus accumulation through
“coughing up”
• Recommended to relieve cough due to thick secretion production --> ex. COPD and chronic
bronchiectasis
• Ambroxol, a bromhexine active metabolite, is the most popular medicine in German. It also
shows other antitussive effects other than expectorant.
• Pholcodine and guaifenesin are also used as an expectorant.
• Ammonium chloride is an acid-producing salt that is considered to provide an expectorant effect
in loosening phlegm
 Mucolytic Drugs
• Non-selectively reduce viscosity and elasticity of respiratory tract secretion by reducing
polymer network that is responsible for the gel-like structure of mucus or sputum
• Classic mucolytic disrupts mucin polymer by breaking disulfide bond connecting mucin
monomer covalently into a long and rigid oligomer or by dispersing tangled mucin through
breaking the bond of hydrogen ions or van der Waals
• Ex: Doranse alfa (Pulmozyme) --> given through inhalation with a dose of 2.5 mg/day
• Mechanism of action: reduced viscosity and adhesion of respiratory tract secretions and
longterm use could increase pulmonary function, reduced damage to lung function, and reduced
the need for hospitalization and antibiotic therapy
 Mucolytic Drugs
Komposisi Mukus :
• —95% is water
• —3% is protein
• —< .03% DNA
 Mucolytic Drugs

Berdasarkan mekanisme kerjanya ada 4 golongan :

• Expectorants: mengencerkan mukus shg mudah dikeluarkan
• Mucolytic agents : merusak struk kimia mukus shg viskositas turun &
mdh dikeluarkan
• Wetting agents / hypoviscosity agents
• Adhesives / surfactants : menurunkan adhesivitas sputum &
meningkatkan efisiensi tansfer energi dari silia ke lapisan mukus
 Mucolytic Drugs
N- Acetylcysteine (NAC)
Mechanisms of action of N-acetylcysteine (NAC).
• NAC acts as a mucolytic, antioxidant and antinflammatory agent.
• The free sulfhydryl group confers NAC with the ability to reduce disulphide bonds,
thus decreasing mucus viscosity and facilitating mucociliary clearance.
• The antioxidant activity of NAC may be both direct (the free sulfhydryl group may
serve as a ready source of reducing equivalents) and indirect (through replenishment of
intracellular GSH levels) antioxidant effects.
• Thus, NAC may break the vicious oxidative cycle by reducing oxidative stress and,
subsequently, infl ammation.
• Overall, these effects may result in improvements in symptoms, lung function and
reduced exacerbation rates.
Indication: COPD, Chronic Bronchitis, acetaminopen antidotum
• p.o, aerosol
• ES : Bronchospasm (utk asma, shg perlu dipakai bersama bronkodilator),Stomatitis,
Nausea, Rhinorrhea

Santus P, Corsico A, SOlidoro P, et al. 2014. Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcystein.
Journal of Chronic Obstructive Pulmonary Disease: COPD, 00:1-13