Amoxycillin + Bromhexine

1. Amoxycillin +Amoxycillin +
BromhexineBromhexine
Role in respiratory InfectionsRole in respiratory Infections

2. Amoxycillin + BromhexineAmoxycillin + Bromhexine
 A combination of:A combination of:
 Antibacterial + MucolyticAntibacterial + Mucolytic
 What is theWhat is the add-vantageadd-vantage of such aof such a
combination?combination?
 What are the indications where its use wouldWhat are the indications where its use would
be superior?be superior?
 Let us peep into the background of theLet us peep into the background of the
pathophysiology of the respiratory tract topathophysiology of the respiratory tract to
understand this …understand this …

3. RTI OrganismsRTI Organisms
 Viruses – influenza, parainfluenza,Viruses – influenza, parainfluenza,
measles, varicella-zoster, respiratorymeasles, varicella-zoster, respiratory
syncytial virus (RSV). Common, often selfsyncytial virus (RSV). Common, often self
limiting but can be complicatedlimiting but can be complicated
 BacteriaBacteria
 Chlamydia, mycoplasmaChlamydia, mycoplasma
 FungiFungi

4. Respiratory tract defencesRespiratory tract defences
 Ventilatory flowVentilatory flow
 CoughCough
 Mucociliary clearance mechanismsMucociliary clearance mechanisms
 Mucosal immune systemMucosal immune system

5. Lung Clearance
What do
the
Lungs
do?
Mucus Clearance
Effect of Disease
Retention
Adverse
Effects
Diagnosis Treatment
The Lungs: FunctionThe Lungs: Function
Exchange of gasesHow do
they do
it?

6. based on Burri & Weibel 1973
Closer understandingCloser understanding

7. Closer understandingCloser understanding
Bronchial
Epithelium
(seen in
cross-section)
This is what
cilia look like
???
Or like
this ???
The cilia on the right side are
damaged as occurs in chronic
bronchitis, giving rise to decreased
clearance of the mucus secretions
and difficulty in expectoration

8. Knowles and Boucher,
J Clin Invest, 2002:
109: 571-7
Interaction of cilia and mucusInteraction of cilia and mucus
Tarran et al. J Gen Physiol 2001: 118: 223-36
Mucus transport - as seen by time-lapse photos in cell
culture experiments

9. Mucus clearance & retentionMucus clearance & retention
 Mucus Clearance is dependent onMucus Clearance is dependent on
Mucociliary function & Cough reflex,Mucociliary function & Cough reflex,
 Clearance from whole Lung andClearance from whole Lung and
Tracheobronchial would be differentTracheobronchial would be different
 Dependence on Deposition DistributionDependence on Deposition Distribution
 Mucus composition with relation to Salt andMucus composition with relation to Salt and
Water or temperature makes a differenceWater or temperature makes a difference
 Medication / Physiotherapy effect outcomesMedication / Physiotherapy effect outcomes

10. Mucus clearance & retentionMucus clearance & retention
Pavia 1985

11. Mucus retention in chronicMucus retention in chronic
bronchitisbronchitis
Pavia 1985

12. MucokineticsMucokinetics
 Drugs that increase and aid clearance ofDrugs that increase and aid clearance of
respiratory tract secretionsrespiratory tract secretions
 Hypoviscosity agents (Wetting agents)Hypoviscosity agents (Wetting agents)
 MucolyticsMucolytics
 Expectorants (Bronchomucotropics)Expectorants (Bronchomucotropics)

13. Muco-ciliary BlanketMuco-ciliary Blanket
 95% water, 2%95% water, 2%
glycoproteinsglycoproteins
 Gel layer-high viscosityGel layer-high viscosity
from goblet cellsfrom goblet cells
 Sol layer – low viscositySol layer – low viscosity
from submucosalfrom submucosal
bronchial glandsbronchial glands

14. Muco-ciliary BlanketMuco-ciliary Blanket
 Both goblet cells and bronchial sub-mucosalBoth goblet cells and bronchial sub-mucosal
glands increase secretion when irritated.glands increase secretion when irritated.
 Vagal stimulation will also increaseVagal stimulation will also increase
bronchial sub-mucosal gland secretion.bronchial sub-mucosal gland secretion.
 Increased goblet cell secretion = increasedIncreased goblet cell secretion = increased
sputum viscosity.sputum viscosity.
 Increased bronchial sub-mucosal glandIncreased bronchial sub-mucosal gland
secretion = decreased sputum viscositysecretion = decreased sputum viscosity

15. Need forNeed for
MucokineticsMucokinetics
when secretions increase inwhen secretions increase in
amount and/or viscosityamount and/or viscosity

16. MucolyticsMucolytics
 AidAid
mucokinesismucokinesis
by breakingby breaking
up bonds inup bonds in
mucusmucus
 BromhexineBromhexine
is an oralis an oral
mucolyticmucolytic
agent with aagent with a
low level oflow level of
associatedassociated
toxicity.toxicity.

17. Mucolytics: BromhexineMucolytics: Bromhexine
 Causes BronchorrheaCauses Bronchorrhea
 It acts on the mucus atIt acts on the mucus at
the formative stages inthe formative stages in
the glands, within thethe glands, within the
mucus-secreting cells.mucus-secreting cells.
 Bromhexine disrupts theBromhexine disrupts the
structure of acidstructure of acid
mucopolysaccharidemucopolysaccharide
fibres in mucoid sputumfibres in mucoid sputum
and produces lessand produces less
viscous mucus, which isviscous mucus, which is
easier to expectorate.easier to expectorate.

18. ExpectorantsExpectorants
(Bronchomucotropics)(Bronchomucotropics)
 Usually stimulate sol layer production byUsually stimulate sol layer production by
direct irritation or indirect through vagaldirect irritation or indirect through vagal
stimulationstimulation
 Remember, ↑ sol means decreased viscosity!Remember, ↑ sol means decreased viscosity!
 Smoke is a bronchomucotropic!Smoke is a bronchomucotropic!
 Unfortunately, it’s irritation stimulates theUnfortunately, it’s irritation stimulates the
bronchial submcosal glands AND the goblet cellsbronchial submcosal glands AND the goblet cells
so there is in ↑ mucus production & viscosityso there is in ↑ mucus production & viscosity
 Spicy food ↑ sol due to vagal stimulation!Spicy food ↑ sol due to vagal stimulation!
 Expectorants include guaphenesin,Expectorants include guaphenesin,
ammonium chlorideammonium chloride

19. ExpectorantsExpectorants
(Bronchomucotropics)(Bronchomucotropics)
GuaifenesinGuaifenesin
 Vagal stimulation likeVagal stimulation like
without foul taste orwithout foul taste or
severe side effectssevere side effects
 Active ingredient inActive ingredient in
many “cough”many “cough”
medicines.medicines.
 Very effectiveVery effective
expectorant for chronicexpectorant for chronic
bronchitisbronchitis
Ammonium ChlorideAmmonium Chloride
 Vagal stimulation onlyVagal stimulation only
 Found in many children’sFound in many children’s
“cough” syrups because it“cough” syrups because it
is easy to flavoris easy to flavor
 Side effects are like SSKISide effects are like SSKI
and Guaifenesinand Guaifenesin
 Also may cause metabolicAlso may cause metabolic
acidosisacidosis

20. Amoxycillin + BromhexineAmoxycillin + Bromhexine
 Better than most respiratory antibacterialsBetter than most respiratory antibacterials
especially where sensitivity is assured;especially where sensitivity is assured;
 Time tested and trusted antibacterial,Time tested and trusted antibacterial,
 Bonus effects of mucolyticBonus effects of mucolytic
 Eliminates the need for expectorantsEliminates the need for expectorants
 2 benefits at the price of 12 benefits at the price of 1
 Antibacterial + mucokinesisAntibacterial + mucokinesis