Respiratory Pharmacology
Week 6
Inhaled Steroids

Mode of action at the tissue level
◦ Restoration of epithelium
◦ Reduction of thickening of basement
membrane
◦ Reduction of mucosal edema
◦ Reduction of leukocyte infiltrate
◦ Reduction of mast cell number
Inhaled Steroids

Mode of action at the molecular level:
◦ Blockage of active sites of pro-inflammatory
genes

Mode of action at the cellular level:
◦ Inhibition of release of pro-inflammatory
molecules
Inhaled Corticosteroids

Mode of action
◦ Modify response of the cell in order to inhibit
inflammatory response of the airway
◦ May require hours to days to gain full benefits
◦ Daily compliance is essential to maximizing effects
Inhaled Corticosteroids

Indications
◦ Anti-inflammatory maintenance therapy of
persistent asthma and COPD
◦ Control of seasonal allergic or non-allergic rhinitis
◦ May be administered as orally inhaled aerosol or
intranasal aerosol
◦ http://www.youtube.com/watch?v=LcM7f1iwOGo
Aerobid is
now
Aerospan
Flovent:
DPI/MDI. 3
doses.
Asmanex: twisthaler, grey or
pink depending on dose
Qvar: 40/80 ug dose
Advair: MDI
or DPI, 3
doses,
combo drug
Symbicort: 2
doses,
combo drug
Pulmicort: turbahaler or
respules
Inhaled Corticosteroids

Adverse effects
◦ Decrease type and severity of side effects
compared to systemic administration
◦ Adrenal insufficiency
◦ Acute asthma
Inhaled Corticosteroids

Adverse effects (systemic mostly)
◦ Osteoporosis
◦ Growth suppression
◦ Oropharyngeal infections
Inhaled Corticosteroids

Adverse effects
◦ Dysphonia
◦ Cough
◦ Bronchoconstriction
Corticosteroids Used in Aerosol
Administration
Beclomethasone
dipropionate
QVAR
MDI: 40 and 80 µg/puff.
Adults > 12 years:
40 to 80 µg twice daily, or 40 to 160 µg twice daily
Children > 5 years:
40 to 80 µg twice daily
Triamcinolone
acetonide
(No longer made)
Azmacort
MDI: 100 µg/puff.
Adults > 12 years:
2 puffs three times of four times daily
Children > 6 years:
1 or 2 puffs three or four times daily
Flunisolide
(No longer made)
Aero-Bid
MDI: 250 µg/puff
Adults and children > 6 years:
2 puffs twice daily; adults no more than 4 puffs;
children < 15 years no more than 2 puffs daily
Corticosteroids Used in Aerosol
Administration
Fluticasone
propionate
Flovent
MDI: 44, 110, and 220 µg/puff
Adults > 12 years:
88 µg twice daily; 88 – 220 µg twice daily; or 880 µg twice
daily
Children 4 – 11 years:
88 µg twice daily
DPI: 50, 100, and 250 µg
Adults:
100 µg twice daily; 100 – 250 µg twice daily; or 1000 µg
twice daily
Children 4 – 11 years:
50 µg twice daily
Budesonide
Pulmicort
DPI: 200 µg/actuation
Adults:
200 – 400 µg twice daily; 400 – 800 µg twice daily
Children > 6 years:
200 µg twice daily
SVN: 0.25 mg/2 ml; 0.5 mg/2 ml
Children 1 – 8 years:
0.5 mg total dose once daily or twice daily in divided doses
1 mg given as 0.5 mg twice daily or once daily
Corticosteroids Used in Aerosol
Administration
Fluticasone
propionate/
salmeterol
Advair Diskus
Budesonide /
formoterol
fumarate
Symbicort
Advair HFA
DPI: 100 µg fluticasone / 50 µg salmeterol
250 µg fluticasone / 50 µg salmeterol
500 µg fluticasone / 50 µg salmeterol
Adults and children > 12 years:
100 µg fluticasone / 50 µg salmeterol, one
inhalation twice daily, about 12 hours apart
Children > 4 years:
100 µg fluticasone / 50 µg salmeterol, one
inhalation twice daily, about 12 hours apart
MDI: 45 µg fluticasone / 21 µg salmeterol
115 µg fluticasone / 21 µg salmeterol
230 µg fluticasone / 21 µg salmeterol
Adults and children > 12 years:
2 inhalations twice daily, about 12 hours apart
MDI: 80 µg budesonide / 4.5 µg formoterol
160 µg budesonide / 4.5 µg formoterol
Adults and children > 12 years:
160 µg budesonide / 9 µg formoterol twice daily;
maximum daily: 640 µg budesonide / 18 µg
formoterol
Advair

Advair Diskus combines an inhaled corticosteroid and an inhaled
long-acting bronchodilator in one easy-to-use device. Advair Diskus
does not replace fast-acting inhalers for sudden symptoms. Advair
Diskus effectively treats the two main components of asthma at the
same time: constriction, the tightening of the muscles around the
airways, and inflammation, the swelling and irritation of the airways.
Constriction and inflammation cause the airways to narrow and
reduce airflow into the lungs, which may result in symptoms such
as wheezing, coughing, chest tightness, or shortness of breath. The
combination of fluticasone (Flovent-steroid) and salmeterol
(Serevent-bronchodilator) is used to prevent wheezing, shortness
of breath, and breathing difficulties caused by asthma, but also be
prescribed for COPD.
Advair



Generic Name: fluticasone propionate and salmeterol xinafoate
Trade Name: Advair (Advair Diskus)
How should Advair Asthma Medication be Used?
1. OPEN
Hold the DISKUS in one hand and put the thumb of your other
hand on the thumbgrip. Push your thumb away from you as far as it
will go until the mouthpiece appears and snaps into position.
2. CLICK
Hold the DISKUS in a level, horizontal position with the
mouthpiece towards you. Slide the lever away from you as far as it
will go until it clicks. The DISKUS is now ready to use.
Every time the lever is pushed back, a dose is ready to be inhaled.
This is shown by a decrease in numbers on the dose counter.
Advair

To avoid releasing or wasting doses:
• Do not close the DISKUS.
• Do not tilt the DISKUS.
• Do not play with the lever.
• Do not advance the lever more than once.
3. INHALE
Before inhaling your dose of Advair Diskus, breathe out as far as is
comfortable, holding the DISKUS level and away from your mouth.
Remember, never breathe out into the DISKUS mouthpiece.
Put the mouthpiece to your lips. Breathe in quickly and deeply
through the Advair Diskus, not through your nose.
Combos

Symbicort (Contains formoterol, a long-acting beta -adrenergic
2
agonist (LABA) and budesonide (steroid); given BID, two doses 160/4.5
mcg, 80/4.5 mcg; MDI)

Dulera (mometasone furoate/ formoterol fumarate dihydrate, BID,
100/5 or 200/5 mcg dose MDI)
Non-Steroidal Anti-Asthma Drugs

Mast cell stabilizers
◦ Indicated for prophylactic control of mild to
moderate asthma
◦ Inhibits degranulation of mast cells in response to
allergic and non-allergic stimuli
◦ Used typically as alternatives to inhaled
corticosteroids, especially in children
Non-Steroidal Anti-Asthma Drugs

Leukotriene inhibitors
◦ Indicated for prophylactic control of mild to
moderate asthma
◦ Used in combination with inhaled steroids to
reduce the dose of the steroid
Non-Steroidal Anti-Asthma Drugs
Cromolyn sodium Intal
Nasalcrom
MDI: 800 µg / actuation
Adults and children > 5 years:
2 inhalations four times daily
SVN: 20 mg / ampule or 20 mg / 2 ml
Adults and children > 2 years:
20 mg inhaled four times daily
Spray: 40 mg / ml (4%)
Adults and children > 2 years:
1 spray each nostril, 3 to 6 times daily every 4 – 6 hours
Nedocromil
sodium
Tilade
MDI: 1.75 mg / actuation
Adults and children > 6 years:
2 inhalations four times daily
Zafirlukast
Accolate
Tablets: 10 and 20 mg
Adults and children > 12 years:
20 mg twice daily, without food
Children 5 – 11 years:
10 mg twice daily
Non-Steroidal Anti-Asthma Drugs
Montelukast
Singulair
Tablets: 10 mg; 4 and 5 mg chewable; 4 mg
packet of granules:
Adults and children > 15 years:
one 10 mg tablet daily
Children 6 – 14 years:
one 5 mg chewable tablet daily
Children 2 – 5 years:
one 4 mg chewable tablet daily
Children 6 – 23 months:
one 4 mg packet of granules daily
Zileuton
Zyflo
Tablets: 600 mg
Adults and children > 12 years:
one 600 mg tablet four times per day
Aerosolized Anti-Infective Agents

Pentamidine isethionate (Nebupent)
◦ Indicated for the prevention of Pneumocystis
carinii pneumonia (PCP)
◦ Not recommended for use in treatment of PCP
(however typically given)
Pentamidine Isethionate
(Nebupent)



Action: The drug interferes with protozoal nuclear
metabolism inhibitionof DNA, RNA, phospholipid and
protein synthesis. It is known to have activity against
pneumocystis carinii.
Indication: Prevention of Pneumocystis carinii
pneumonia (PCP) in high risk, HIV-infected patients.
Dosage: 300mg once every 4 weeks (nebulized)
Pneumocystis pneumonia (PCP)




Pneumocystis pneumonia (PCP) form of pneumonia, caused by
the yeast-like fungus (which had previously been erroneously
classified as a protozoan) Pneumocystis jirovecii
Pneumocystis is commonly found in the lungs of healthy people, but
being a source of opportunistic infection it can cause a lung
infection in people with a weak immune system.
Pneumocystis pneumonia is especially seen in people with cancer,
HIV/AIDS and the use of medications that affect the immune
system.
also known as Pneumocystis jiroveci[i] pneumonia
Pentamidine Isethionate

Adverse effects
◦ Cough
◦ Bronchial irritation, bronchospasm
◦ Shortness of breath
◦ Given using a scavenger nebulizer/SPAG
Pentamidine Isethionate

Adverse effects
◦ Fatigue
◦ Pharyngitis
◦ Chest Pain
Aerosolized Anti-Infective Agents

Ribavirin (Virazole)
◦ Indicated as anti-viral agent to treat respiratory
syncytial virus (RSV)
◦ Administered via small particle aerosol generator
(SPAG)
Ribavirin-injection


Ribavirin is also used with an interferon medication to
treat hepatitis C in people who have not been treated
with an interferon before.
Ribavirin is in a class of antiviral medications called
nucleoside analogues. It works by stopping the virus that
causes hepatitis C from spreading inside the body. It is
not known if treatment that includes ribavirin and
another medication cures hepatitis C infection, prevents
liver damage that may be caused by hepatitis C, or
prevents the spread of hepatitis C to other people.
Ribavirin

Adverse effects
◦ Skin rash
◦ Eyelid erythema
◦ Occlusion of endotracheal tube
◦ Deterioration of pulmonary function
Aerosolized Anti-Infective Agents

Tobramycin (Tobi)
◦ Indicated for management of chronic infection
with Pseudomonas aeruginosa; typically seen with CF
and immune suppressed patients
◦ Treat or prevent colonization
Tobi

Action: Aminoglycoside antibiotic disrupts
protein synthesis eventually resulting in
cell death (gram negative organisms).

Dosage: One 5 mL ampule contains
300mg of tobramycin. Given B.I.D. / Q12
with recommended nebulizer (Pari type
neb)
Tobramycin

Adverse effects
◦ Ototoxicity and tinnitus
◦ Bronchospasm
◦ Fetal harm (deafness)
Aerosolized Anti-Infective Agents

Zanamivir (Relenza)
◦ Indicated for treatment of uncomplicated illness
due to influenza virus
Relenza



used in the treatment and prophylaxis of influenza
caused by influenza A virus and influenza B virus.
The bioavailability of zanamivir is 2%. After inhalation,
zanamivir is concentrated in the lungs and oropharynx,
where up to 15% of the dose is absorbed and excreted
in urine.
Dosing is limited to the inhaled route. This restricts its
usage, as treating asthmatics could induce
bronchospasms
Zanamivir

Adverse effects
◦ Bronchospasm
◦ Under treatment of bacterial infection appearing
as viral infection
Aerosolized Anti-Infective Agents

Amphotericin B
◦ Indicated for the treatment of fungal infections,
especially in lung transplants
amphotericin B

amphotericin B binds the main
component of fungal cell membranes,
forming a transmembrane channel that
leads to monovalent ion (K+, Na+, H+ and
Cl−) leakage, which is the primary effect
leading to fungal cell death.
Amphotericin B

Adverse effects
◦ Nausea
◦ Vomiting
◦ Bronchoconstriction
Aerosolized Anti-Infective Agents
Pentamidine
isethionate
Nebupent
300 mg powder in 6 ml sterile water, once every four weeks
Ribavirin
Virazole
6 g powder in 300 ml sterile water (20 mg / ml solution); given
every 12 – 18 hr / day for 3 – 7 days by SPAG
Tobramycin
TOBI
300 mg / 5 ml ampule:
Adults and children > 6 years:
300 mg bid, 28 days on drug, 28 days off drug
Zanamivir
Relenza
DPI: 5 mg / inhalation:
Adults and children > 7 years:
2 inhalations (one 5 mg blister / inhalation) bid,
12 hours apart for 5 days
Amphotericin B
Fungizone
10 mg three times per day for six to 8 weeks
Nitric Oxide

Indicated for the treatment of pulmonary
hypertension in neonates

Causes relaxation of vascular smooth
muscle, producing pulmonary vasodilation
Nitric Oxide

Contraindicated in neonates with right to
left shunts
Nitric Oxide

Adverse effects
◦ Hypotension
◦ Formation of Methemoglobinia
◦ Withdrawal