lecture of 55 slide

1. Labeled and Unlabeled Uses of
Nebulized Medications
By
Dr . Magdy Shafik Ramadan
Senior Pediatric and Neonatology consultant
M.S, Diploma, Ph.D of Pediatrics

2. Introduction
• The delivery of medications to the lungs via inhalation or
aerosolization has long been recognized as a technique to
ensure high local drug concentration with minimal
systemic side effects.
• This mode of therapy is used successfully to deliver
bronchodilators and steroids to patients with asthma and
COPD.
• The most successful application of this strategy is in the
treatment of infections in patients with cystic fibrosis (CF),
patients with non-CF bronchiectasis (NCFB) and in
ventilator-associated pneumonia (VAP).

3. Pharmacokinetics of Aerosolized Antibiotics
• Antibiotics with concentration-dependent effects (ie,
greater area under the curve/minimum inhibitory
concentration ratio) are typically chosen for
aerosolization, as it is possible to achieve high
concentrations in the airway to maximize bacterial
killing.
• Different from time-dependent antibiotics (time
over minimum inhibitory concentration of 90%),
concentration-dependent antibiotics do not need to
be present in the target tissue for a long period of
time, usually requiring frequent administration

4. • most commonly used aerosolized antimicrobials,
including tobramycin, aztreonam, colistin,
levofloxacin, and ciprofloxacin.
• measurement of sputum concentrations is not an
ideal method for monitoring therapeutic delivery
of these medications, as it is not predictive of
delivery to the distal airway, which is often the
major site of infection.
• These correlations should be interpreted with
caution, and studies showing efficacy with regard
to clinically relevant end points should be used to
guide clinical decision making

5. • Aerosolized Delivery Systems
• factors that affect the respirable dose delivered to
the patient:
• 1-the aerodynamic size of droplets produced
(expressed as mass median aerodynamic diameter
[MMAD]),
• 2-the size distribution of the aerosol particles
(geometric standard deviation),
• 3-the output of the nebulizer.

6. • Ideal droplet size ranges from 1- to 5-m MMAD
for airway deposition and 2-m MMAD for
parenchymal deposition. Larger droplets ( 5-m
MMAD) are less likely to reach distal airways and
can become trapped in the ventilator circuit or
endotracheal tube in mechanically ventilated
patient.

8. • Types of Nebulizers
There are three main types of nebulizers:
• Jet. This uses compressed gas to make an aerosol
(tiny particles of medication in the air).
• Ultrasonic. This makes an aerosol through high-
frequency vibrations. The particles are larger than
with a jet nebulizer.
• Mesh. Liquid passes through a very fine mesh to
form the aerosol. This kind of nebulizer puts out
the smallest particles. It’s also the most expensive.

9. Jet Nebulizers

10. MABISMist II Handheld Ultrasonic
Nebulizer.

11. Mesh Nebulizer

12. List of the Available and Tested Aerosolized Antibiotics Reported in the
Literature for Treatment of Infections Associated With Specific Clinical
Conditions
Antibiotic CF(cystic
fibrosis
NCFB (non-CF
bronchiectasis
VAP (ventilator-
associated
pneumonia
Aminoglycosides
Gentamicin Yes yes yes
Amikacin Yes yes yes
Neomycin Yes
Toberamycin Yes yes yes
Polymixin
Colistin yes yes yes
Glycopeptides
Vancomycin yes
Monobactam
Aztreonam lysine yes
B- Lactam
Ceftazidime
Ticarcillin
Yes
yes
yes

13. Tobramycin
• Tobramycin does not penetrate the lungs and is not
ideal for systemic treatment, unless there are no
other alternatives or there is a high risk of
antimicrobial resistance.
• Nebulization of tobramycin solution for inhalation
results in peak sputum levels 30 min after
administration with minimal, although somewhat
variable, systemic absorption.

15. Aztreonam
• Aztreonam is a synthetic bactericidal monobactam
with activity against Gram-negative bacteria,
including Pseudomonas aeruginosa.
• Aztreonam solution for inhalation (Cayston,
Gilead Sciences, Foster City, California) has an
elimination half-life of 2 h. Approximately 10% of
the delivered dose is ultimately excreted in the
urine, and the remainder is thought to be
expectorated from the airways.

17. colistin
• Nebulized colistin is commonly used in long-term
management of Pseudomonas.
• I.V. colistin had been used to treat a variety of
bacteria but became less common because of its
nephrotoxicity and neurotoxicity and the development
of safer antimicrobials.
• Berlana et al. concluded that nebulized colistin was
within safety margins and appeared to be efficacious
for the treatment of multidrug-
resistant Acinetobacter baumannii and P.
aeruginosa infections

18. • Of more importance is the possibility of
bronchoconstriction when using inhaled colistin.
Bronchospasms were successfully treated with
bronchodilators.

19. Ciprofloxacin and Levofloxacin
• fluoroquinolones are characterized by significant
tissue penetration.
• levofloxacin and ciprofloxacin have been
evaluated for delivery via aerosolization in
patients with CF, NCFB, and/or VAP.
• Aerosolized levofloxacin has been shown to have
favorable safety and efficacy profile
• levofloxacin achieved high airway concentrations
with little systemic distribution. Similarly,
aerosolized ciprofloxacin achieved high sputum
concentrations with a prolonged half-life .

20. 3 main indication of arezolied antibiotic
• Cystic Fibrosis
• Non-Cystic Fibrosis Bronchiectasis
• Ventilator-Associated Pneumonia

21. Ventilator-Associated Pneumonia
(VAP)
• VAP is the leading cause of death related to
infection in mechanically ventilated patients. MDR
pathogens such as P. aeruginosa, Acinetobacter
subspecies, and S. aureus represent the most
important group of pathogens causing VAP.
• Aerosolized antibiotics are reserved mainly for
adjunctive therapy in these patients with
multidrug-resistant (MDR) pathogens.

22. • The antibiotics most commonly used in clinical
practice for patients with VAP include
aminoglycosides and colistin/polymyxin B.
• the use of concomitant treatment with systemic and
aerosolized antibiotics is reserved for those patients
infected with MDR pathogens.

23. Adverse Effects
• Cough
• Bronchospasm
• Hoarseness
• Dysphagia
• Dysgeusia
• These tend to be reversible events and there
is evidence that their incidence and severity
can decrease with exposure

24. Adrenaline (epinephrine) nebulised
• Indication :
• Management of post-extubation stridor
[evidence for effectiveness is not clear].
• Initial treatment of outpatients with
moderate to severe bronchiolitis.
• Initial treatment of croup.

25. • Preparation/Dilution
• Draw up 0.5 mL/kg (0.5 mg/kg) of adrenaline 1:1,000 [1
mg/1 mL] ampoule and add sodium chloride 0.9% to make
a final volume of 4 mL.
• Evidence summary Efficacy: Nebulised racemic adrenaline
for extubation of newborn infants: There are no trials
proving the efficacy of nebulised adrenaline compared to
placebo or intravenous dexamethasone for post extubation
stridor.
• Treatment and prevention of bronchiolitis in newborns
and infants: Nebulised adrenaline decreases
hospitalisations in patients presenting to ED. There is no
evidence to support the use of adrenaline for in patients.

26. • Treatment of children with croup:
Nebulised adrenaline is associated with
clinically and statistically significant
transient reduction of symptoms of croup 30
minutes post treatment. [Evidence does not
favour racemic adrenaline or Ladrenaline,
or IPPB ( Intermittent Postive Pressure
Breathing )over simple nebulisation.

27. IPPB ( Intermittent Postive
Pressure Breathing

28. Nebulized salbutamol
• NDICATIONS
• VENTOLIN Inhalation Solution is indicated
for the relief of bronchospasm
Approximate
Weight
Approximate
Weight
Dose Volume of
(kg) (lb) (mg) Inhalation
Solution
10-15 22-33 1.25 0.25 mL
>15 >33 2.5 0.5 mL

30. Nebulized Corticosteroids
• our corticosteroids are currently marketed
or nebulization:
• nebulized budesonide ( pulmicort)(BUD),
beclomethasone dipropionate (BDP),
• flunisolide (FLU),
• and fluticasone propionate (FP).
• They are available as unit-dose vials of 2
mL; BUD, FP, and FLU are available as
multiple strength formulations.

31. • Nebulized dexamethasone was as effective
as oral prednisone in the ED treatment of
moderately ill children with acute asthma
and was associated with more rapid clinical
improvement, more reliable drug delivery,
and fewer relapses

32. • Unlabeled Uses of Nebulized Medications
• Lidocaine
• Lidocaine is a common local anesthetic
frequently nebulized during bronchoscopy
procedures, allowing the bronchoscope to
reach greater depths in the airways.
• Some research and case reports suggest that
nebulized lidocaine can be used to alleviate
bronchoconstriction and cough.

33. • A generally accepted safe range of nebulized
lidocaine is between 100 and 200 mg per
dose.

34. • Evidence for Therapeutic Uses of Nebulized
Lidocaine in the Treatment of Intractable
Cough and Asthma
• Rachel M. Slaton, R. H. Thomas, Joseph Wallace
MbathiPublished 2013MedicineAnnals of Pharmacotherapy
• OBJECTIVE To summarize the efficacy and safety data for use
of nebulized lidocaine in intractable cough and asthma. DATA
SOURCES A literature search was conducted using PubMed
(through November 2012), International Pharmaceutical
Abstracts (1970–December 2012), and Cochrane Library (up to
2012) with the search terms nebulization, nebulized or
nebulised; administration, inhalation; cough; asthma; and
lidocaine. Results were limited to human studies published in
the English language. Referenced… CONTINUE READING
•

35. • CONCLUSIONS
• Although nebulized lidocaine is not first-line
therapy in intractable cough and asthma, it may
provide an alternative treatment option in patients
who cannot tolerate or are unresponsive to other
treatments. Appropriate monitoring precautions
should be used to ensure patient safety.

39. Nebulized Lidocaine in COVID-19, An Hypothesis
Author links open overlay panelZiad A.AliRif S.El-Mallakh
• Abstract
• Coronavirus Diseases-2019 (COVID-19) has caused a large global
outbreak and has been declared as a pandemic by the World Health
Organization (WHO). It has been proposed that COVID-19-related
hyperinflammation and dysregulated immune response might play a
critical role in developing a cytokine storm which usually progresses to
a life-threatening acute lung injury or acute respiratory distress
syndrome in infected individuals. Lidocaine, a local analgesic and anti-
arrhythmic, is known for its anti-inflammatory actions and has been
used to reduce cough and improve respiratory symptoms in severe
asthmatic patients. It has a demonstrated safety profile. It is proposed
that nebulized lidocaine might be beneficial in reducing cytokines,
protecting patients’ lungs and improving outcomes in COVID-19
patients when administered via inhalation as an adjunctive treatment
for severe respiratory symptoms in patients fighting the novel
Coronavirus. Additional investigation is warranted

40. • Opioids
• The most common nebulized opioids are
morphine, hydromorphone, and fentanyl.
• Dyspnea resulting from complications due
to an end-stage disease is often treated with
a nebulized opioid.
• Nebulized opioids are used increasingly to
relieve dyspnea in end-stage diseases.
Research into the use of nebulized opioids
for other indications is conflicting and
requires examination of potential benefits.

41. Magnesium
• Magnesium acts as a smooth muscle relaxant by
interfering with calcium uptake.
• Magnesium may have a counteracting effect against
bronchoconstricting agents such as sodium
metabisulfite, methacholine, and histamine.
• Research into nebulized magnesium focuses on
treating asthma and the potential to counteract
bronchoconstricting agents.

42. • nebulized magnesium could be an effective
treatment for acute exacerbations of asthma,
either as a sole agent or in combination with other
medications.
• The relative lack of adverse effects from
magnesium should also encourage its potential
use.
• 1 ml MgSO4 mixed with 9 ml saline, to have
isotonic mixture to avoid hyperosmolar broncho-
constriction .

43. Miscellaneous
• Nebulization of amikacin, carbenicillin,
ceftazidime, and gentamicin has been reported in
the cystic fibrosis population.
• A study supporting the stability of nebulized
caspofungin has initiated further research
investigating it as a therapeutic alternative to
nebulized amphotericin B.
• A dose-ranging study of nebulized interleukin-2
for pulmonary metastases revealed an acceptable
safety profile; efficacy studies are needed.

44. Nebulized naloxone offered an effective alternative
route of administration in a patient without i.v.
access and suffering from a methadone intoxication.
• A human study in the perioperative setting with
inhaled nitroglycerin and an animal study with
nebulized sildenafil offer two promising therapies.

45. Nebulised heparin as a treatment for COVID-19:
scientific rationale and a call for randomised
evidence
• Abstract
• Nebulised unfractionated heparin (UFH) has a strong scientific and
biological rationale and warrants urgent investigation of its therapeutic
potential, for COVID-19-induced acute respiratory distress syndrome
(ARDS). COVID19 ARDS displays the typical features of diffuse alveolar
damage with extensive pulmonary coagulation activation resulting in fibrin
deposition in the microvasculature and formation of hyaline membranes in
the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease
have high levels of inflammatory cytokines in plasma and bronchoalveolar
lavage fluid and significant coagulopathy. There is a strong association
between the extent of the coagulopathy and poor clinical outcomes. The anti-
coagulant actions of nebulised UFH limit fibrin deposition and
microvascular thrombosis. Trials in patients with acute lung injury and
related conditions found inhaled UFH reduced pulmonary dead space,
coagulation activation, microvascular thrombosis and clinical deterioration,
resulting in increased time free of ventilatory support.

46. • In addition, UFH has anti-inflammatory, mucolytic and
anti-viral properties and, specifically, has been shown to
inactivate the SARS-CoV-2 virus and prevent its entry into
mammalian cells, thereby inhibiting pulmonary infection
by SARS-CoV-2.
• Furthermore, clinical studies have shown that inhaled
UFH safely improves outcomes in other inflammatory
respiratory diseases and also acts as an effective mucolytic
in sputum-producing respiratory patients.
• UFH is widely available and inexpensive, which may make
this treatment also accessible for low- and middle-income
countries.
• These potentially important therapeutic properties of
nebulised UFH underline the need for expedited larg

47. Nebulized acetylcysteine

48. Uses
• When inhaled by mouth, acetylcysteine is used to
help thin and loosen mucus in the airways due to
certain lung diseases (such
as emphysema, bronchitis, cystic
fibrosis, pneumonia). This effect helps you to clear
the mucus from your lungs so that you can
breathe easier.
• When taken by mouth, acetylcysteine is used to
prevent liver damage
from acetaminophen overdose.

49. Dosage Forms & Strengths
nebulizer solution
• 10%
• 20%
• Pulmonary Disease
• Facilitation of expectoration via mucolysis
• 1-11 months: 1-2 mL of 20% solution or 2-4 mL of 10%
solution by nebulization q6-8hr PRN
• >11 years: Solution (10 and 20%) may be used undiluted; 3-5
mL of 20% solution or 6-10 mL of 10% solution; administer 1
to 10 mL of 20% solution every 3 to 4 times/day or 2 to 20
mL of 10% every 2 to 6 hours

50. Nebulized Furosemide for the Management of
Dyspnea: Does the Evidence Support Its Use?
• J Pain Symptom Manage 2008;36:424e441. 2008 U.S. Cancer Pain Relief
Committee. Published by Elsevier Inc. All rights reserved.
• Abstract Dyspnea is a common and distressing symptom associated with
multiple chronic illnesses and high levels of burden for individuals, their
families and health care systems. The subjective nature dyspnea and a
poor understanding of pathophysiological mechanisms challenge the
clinician in developing management plans. Nebulized furosemide has
been identified as a novel approach to dyspnea management. This review
summarizes published studies, both clinical and experimental, reporting
the use of nebulized furosemide. The search criteria yielded 42 articles
published in the period 1988 to 2004. Although nebulized furosemide
appeared to have a positive influence on dyspnea and physiological
measurements, caution must be taken with the results primarily coming
from small-scale clinical trials or observation trials. Despite the
limitations of the studies reported, given the range of conditions
reporting effectiveness of nebulized furosemide, further investigation of
this potential novel treatment of dyspnea is warranted.

51. • Nebulized furosemide has been identified as a
novel approach to dyspnea management.
• The search criteria yielded 42 articles published in
the period 1988 to 2004.
• Although nebulized furosemide appeared to have
a positive influence on dyspnea and physiological
measurements, caution must be taken with
the results primarily coming from small-
scale clinical trials.

52. Ambroxol
• Ambroxol in the form of inhalation is an effective
drug for the treatment of cough.
• Indications
• acute or chronic bronchitis;
bronchiectatic disease;
Asthma with frequent episodes of bronchial
obstruction.
respiratory distress syndrome and surfactant
deficiency in infants

53. • Contraindication:
• hypersensitivity
• peptic ulcer of the stomach or duodenum;
• convulsive syndrome (epilepsy);
• dysfunction of myocytes in the muscles of the
bronchi.
• Ambroxol is available as syrup, tablets, pastilles,
dry powder sachets, inhalation solution, drops
and ampules as well as effervescent tablets.

54. Conclusion
• Unlabeled nebulization of opioids, lidocaine,
magnesium, amphotericin B, and colistin is an
alternative method of treatment for patients with
pulmonary problems or infections, or for those
undergoing bronchoscopy.
• More research is needed to develop guidelines for
their use since nebulization may provide benefits to
many patients who otherwise cannot be treated or
would be at a risk of systemic adverse effects of the
drugs.

55. THANK YOU