Drugs used to treat

respiratory
disorders
Drugs used to treat
respiratory
disorders
 Drugs used to treat respiratory
disorders
• are available in inhalation and systemic
formulations
 Classifications
• Beta2-adrenergic agonists (selective)
• Anticholinergics
• Corticosteroids
• Leukotriene modifiers
• Mast cell stabilizers
• Methylxanthines
• Alpha receptor stimulants
• Monoclonal antibodies
• Expectorants
• Antitussives
• Mucolytics
• Decongestants
• Antihistamines
 beta2-adrenergic agonists

• Beta2-adrenergic agonists are used to treat

symptoms associated with asthma and chronic
obstructive pulmonary disease (COPD).
• Drugs in this class can be either short-acting
or long-acting.
Short-acting beta2-adrenergic agonists
SABA
• Salbutamol (albuterol) - systemic, inhalation
• Terbutaline – systemic
• Fenoterol – inhalation
• Levalbuterol - inhalation
• Metaproterenol - inhalation
• Pirbuterol – inhalation
**onset of action – 1-5min
**duration of action = 4-6hrs
Long-acting beta2-adrenergic agonists
LABA
• formoterol (inhalation)
• salmeterol (inhalation)

• **onset – 30-45min
• Duration – about 12hrs
 MoA
• Stimulate the beta2-adrenergic receptors in
the smooth muscle, by
• increase levels of cyclic adenosine
monophosphate;
• resulting in bronchodilation
• These drugs may lose their selectivity at
higher doses, which can increase the risk of
toxicity.
• Inhaled forms are preferred because they act
locally in the lungs, resulting in fewer adverse
reactions than systemically absorbed forms.
• Short-acting inhaled beta2-adrenergic agonists
are the drugs of choice. for fast relief of
symptoms in the patient with asthma.
• They’re generally used as needed for asthma
(including exercise-induced asthma) and
COPD.
• A patient with COPD may use them around-
the-clock on a specified schedule
• However, excessive use of a short-acting
beta2-adrenergic agonist may indicate poor
asthma control, requiring reassessment of the
patient’s therapeutic regimen.
• Long-acting beta2-adrenergic agonists tend to be
. agents,i.e. inhaled
used with anti-inflammatory
corticosteroids, to help control asthma

• They’re especially useful for the patient with

nocturnal asthmatic symptoms.
• These drugs must be administered on a schedule.
• They aren’t used to relieve acute symptoms
because their onset of action isn’t fast enough.
• They also don’t affect the chronic inflammation
associated with asthma.
 Drug interactions

• Interactions are uncommon when using the

inhaled forms.
• Beta-adrenergic blockers decrease the
bronchodilating effects of beta2-adrenergic
agonists.
• They should be used together cautiously
Adverse reactions to beta2-adrenergic
agonists
• paradoxical bronchospasm
• tachycardia
• palpitations
• tremors
• dry mouth.
 Anticholinergics-Ipratropium,
Tiotropium
• Ipratropium - most common anticholinergic
used for respiratory disorders
• Ipratropium is a bronchodilator used primarily
in the patient suffering from COPD, but it may
also be used as an adjunct to beta2-adrenergic
agonists
• comes in inhaled form that exerts effects
locally.
 .
• Tiotropium - long-acting antimuscarinic
bronchodilator
• is effective for the management of chronic
obstructive pulmonary disease
• it is not suitable for the relief of acute
bronchospasm
 .
• Ipratropium & tiotropium inhibit muscarinic
receptors, which results in bronchodilation

• The drugs works by blocking the

parasympathetic nervous system, rather than
stimulating the sympathetic nervous system.
 The most common adverse reactions
to anticholinergics include
• nervousness
• tachycardia
• nausea and vomiting
• paradoxical bronchospasm (with excessive use)
• dry mouth.
 Corticosteroids

• Corticosteroids are anti-inflammatory drugs

available in inhaled and systemic forms for the
short- and long-term control of asthma
symptoms
 Inhaled corticosteroids include:

– Beclomethasone/beclometasone
– budesonide
– flunisolide
– fluticasone
– triamcinolone
 Oral corticosteroids include:

• prednisolone
• prednisone
 I.V. corticosteroids include:

• hydrocortisone
• methylprednisolone
Corticosteroids work by inhibiting the
production of:
– cytokines
– leukotrienes
– Prostaglandins
– the recruitment of eosinophils; and
– the release of other inflammatory
mediators.
 .
• Corticosteroids are the most effective drugs
available for the long-term treatment and
prevention of acute asthma attacks
 .
• Inhaled corticosteroids are the preferred drugs
for preventing future attacks in the patient
with mild to severe asthma
• Use of inhaled corticosteroids reduces the
need for systemic steroids in many cases, this
reduces the patient’s risk of developing
serious long-term adverse reactions.
 .
• Systemic forms are usually reserved for
moderate to severe attacks, or in a patient
with milder asthma that fails to respond to
other measures.

• Systemic corticosteroids should be used at the

lowest effective dosage and for the shortest
period possible to avoid adverse reactions.
 Special populations who may require
special care when taking corticosteroids
• Children:
• Growth should be monitored, especially when
they’re taking systemic drugs or higher doses
of inhaled drugs.
 Elderly patients:
• May benefit from receiving drugs that prevent
osteoporosis, such as alendronate during
therapy with corticosteroids, especially if
they’re taking higher doses of inhaled or
systemic steroids.
 Patients with diabetes
• May require closer monitoring of their blood
glucose levels while on steroids
 Breast-feeding women:
• Corticosteroid levels are negligible in the
breast milk of mothers who take less than 20
mg/day of oral prednisone
• The amount found in breast milk can be
minimized if the woman waits at least 4 hours
after taking prednisone to breast-feed her
infant.
 Leukotriene modifiers
• Leukotriene modifiers are used for the
prevention and long-term control of mild
asthma

• Leukotriene receptor antagonists include:

– montelukast
– zafirlukast.
 .
• Montelukast is rapidly absorbed

• Zafirlukast’s absorption is decreased by food,

so it should be given 1 hour before or 2 hours
after meals

• the leukotriene modifiers are highly protein-

bound (more than 90%).
• Leukotrienes are substances released from:
–mast cells .
–eosinophils, and
–basophils
• Leukotrienes can cause:
• smooth-muscle contraction of the
airways
• increased permeability of the
vasculature
• increased secretions, and
• activation of other inflammatory
mediators.
• Leukotrienes may be inhibited by two
different mechanisms..
– blocking their action
– preventing the formation of leukotrienes

• zafirlukast and montelukast prevent

leukotrienes from interacting with their
receptors, thereby blocking their action

• zileuton inhibits the production of

leukotrienes
• Leukotriene modifiers are primarily used to:
.
– prevent and
– control asthma attacks
• in the patient with mild to moderate disease

• Montelukast is also indicated for the

treatment of allergic rhinitis.
 Mast cell stabilizers
• Mast cell stabilizers are used to prevent
asthma attacks, especially in a child or a
patient with mild disease

• They’re also used in an adult or child with mild

to moderate persistent asthma
• Drugs in this class include:
• cromolyn
• nedocromil
 .
• Mast cell stabilizers are minimally absorbed
from the GI tract
• they’re available in inhaled forms that exert
their effects locally
 MoA
• These drugs stabilize the mast cell membrane,
• possibly by inhibiting calcium channels
• thus preventing the release of inflammatory
mediators
 .
• Mast cell stabilizers are often used for children
and patients with exercise-induced asthma.
Adverse reactions to mast cell stabilizers

– pharyngeal and tracheal irritation

– cough
– wheezing
– bronchospasm
– headache.
 Methylxanthines/ xanthines,

• Theophylline
• Aminophylline (a derivative of theophylline)

• Theophylline is the most commonly prescribed

oral methylxanthine
• Aminophylline is preferred when an I.V.
methylxanthine is required
• Caffeine is also a xanthine derivative
 .
• When theophylline is given as an oral solution
or a rapid-release tablet, it’s absorbed rapidly
and completely

• High-fat meals can increase theophylline

concentrations and the risk of toxicity.
 .
• Absorption of some of theophylline’s slow-
release forms depends on the gastric pH.
• Food can alter absorption
• When converting the patient from I.V.
aminophylline to oral theophylline, the dosage
is decreased by 20%.
• Theophylline is approximately 56% protein-
bound in adults and 36% . protein-bound in
neonates
• It readily crosses the placental barrier and is
secreted in breast milk
• Smokers and patients on dialysis may need
higher doses
• Elderly patients and those with liver
dysfunction may require a lower dose
• Theophylline levels must be measured to
. toxicity
evaluate efficacy and avoid

• The therapeutic serum concentration is 10 to

20 mcg/ml (SI, 44 to 111 µmol/L)

• Levels must be assessed when drug therapy is

initiated, when the dosage is changed, and
when drugs are added or removed from the
patient’s regimen.
• Theophyline decreases airway reactivity and
relieves bronchospasm. by relaxing bronchial
smooth muscle
• Theophylline inhibits phosphodiesterase,
resulting in:
– smooth-muscle relaxation
– bronchodilation, and
– decreased inflammatory mediators
• Much of theophylline’s toxicity may be due to
increased catecholamine release.
• In chronic bronchitis, emphysema, and apnea,
theophyline increases the sensitivity of the
.
brain’s respiratory center to carbon dioxide
and stimulates the respiratory drive

• Theophylline reduces fatigue of the

diaphragm

–used to treat neonatal apnea (periods

of not breathing in the neonate) and
–has been effective in reducing severe
bronchospasm in an infant with cystic
fibrosis.
 .
• Theophylline and its salts are used as second-
or third-line therapy for the long-term control
and prevention of symptoms related to:
– asthma
– chronic bronchitis
– emphysema.
Adverse reactions to methylxanthines
• Adverse GI system reactions include:
– nausea and vomiting
– abdominal cramping
– epigastric pain
– anorexia
– diarrhea.
 Adverse central nervous system
reactions include:
– headache
– irritability
– restlessness
– anxiety
– insomnia
– dizziness.
 Adverse cardiovascular reactions
include:
– tachycardia
– palpitations
– arrhythmias.
 Monoclonal antibodies
– Omalizumab
• anti-immunoglobin (Ig) E monoclonal antibody
• used in patients with moderate-to-severe asthma
• Omalizumab inhibits the binding of IgE to its
receptor on the mast cell and basophils
• This in turns inhibits the release of allergic
substances which potentiate asthma symptoms
• Tried in those not responding to high dose
corticosteroid therapy
 Expectorants

• thin mucus so it’s cleared more easily out of the

airways
• They also soothe mucous membranes in the
respiratory tract
• increase production of respiratory tract fluids
• The result is a more productive cough.
– Guaifenesin, ammonium chloride, sodium
chloride, sodium citrate, guaicolate
Guaifenesin, ammonium chloride are the most
commonly used expectorants
 Uses of expectorants
.
• relieve symptoms due to ineffective,
productive coughs from disorders, such as:
–bronchial asthma
–bronchitis
–colds
–emphysema
–influenza
–bronchial irritation
–sinusitis.
Adverse reactions to guaifenesin
– nausea
– vomiting (if taken in large doses)
– diarrhea
– abdominal pain
– drowsiness
– headache
– hives
– rash.
 Antitussives
• Drugs that suppress or inhibit coughing.
• are used to treat serious dry, non-productive
coughs that interfere with a patient’s ability to
rest or carry out activities of daily living.
• The major antitussives include:
– Codeine
– Pholcodine
– dextromethorphan
– hydrocodone
• MoA. Suppress the cough reflex by direct
. in the medulla of
action on the cough center
the brain

• Dextromethorphan is the most widely used

cough suppressant and may provide better
antitussive effects than codeine
• it isn’t associated with sedation, respiratory
depression, or addiction at usual doses.

• The opioid antitussives (typically codeine and

hydrocodone) are reserved for treating an
intractable cough.
 Mucolytics

• Mucolytics act directly on mucus, breaking

down sticky, thick secretions so that they’re
more easily eliminated.
–Acetylcysteine
–Carbocisteine
–Bromhexine
–Ambroxol
–Dornase alfa
• Mucolytics are used with other therapies to treat
.
the patient with abnormal or thick mucus
secretions

– atelectasis caused by mucus obstruction - in

pneumonia, bronchiectasis, or chronic
bronchitis
– bronchitis
– pulmonary complications related to cystic
fibrosis.
 .
• Acetylcysteine is the antidote for Paracetamol
overdose
 Decongestants

• Decongestants may be classified as:

– systemic or
– Topical
• depending on how they’re administered
• systemic decongestants stimulate the
.
sympathetic nervous system to reduce
swelling of the respiratory tract’s vascular
network:

–ephedrine
–phenylephrine
–pseudoephedrine.
• Topical decongestants are also powerful
vasoconstrictors. .
• When applied directly to swollen mucous
membranes of the nose, they provide immediate
relief from nasal congestion
– Ephedrine
– epinephrine, and
– phenylephrine (sympathomimetic amine)
• naphazoline and
• tetrahydrozoline (derivatives of
sympathomimetic amines).
 .
• Topical decongestants act locally on the alpha
receptors of the vascular smooth muscle in
the nose, causing the arterioles to constrict.

• As a result of this local action, absorption of

the drug is negligible.
• Systemic decongestants cause
.
vasoconstriction by stimulating alpha-
adrenergic receptors in the blood vessels of
the body

• This reduces the blood supply to the nose,

which decreases swelling of the nasal mucosa.

• They also cause contraction of urinary and GI

sphincters, dilated pupils, and decreased
insulin secretion.
• Systemic and topical decongestants are used
. of swollen nasal
to relieve the symptoms
membranes resulting from:

– acute coryza (profuse discharge from the

nose)
– allergic rhinitis (hay fever)
– the common cold
– sinusitis
– vasomotor rhinitis.
 .
• Systemic decongestants are commonly given
with other drugs, such as:
– Antihistamines
– Antimuscarinics
– antipyretic analgesics, and
– antitussives
 .
• Topical decongestants provide two major
advantages over systemics:
– minimal adverse reactions and
– rapid symptom relief.
 Adverse reactions to decongestants
• Most result from central nervous system
stimulation and include:
–nervousness
–restlessness
–insomnia
–nausea
–palpitations
–tachycardia
–difficulty urinating
–elevated blood pressure.
• Systemic decongestants exacerbate
– Hypertension
.
– Hyperthyroidism
– Diabetes
– benign prostatic hypertrophy
– glaucoma, and
– heart disease
• They’re also secreted in breast milk in a
breast-feeding woman.
• The most common adverse reaction associated with
. 5 days) of topical
prolonged use (more than
decongestants is rebound nasal congestion.

• Other reactions include:

– burning and stinging of the nasal mucosa
– sneezing
– mucosal dryness or ulceration.
 .
• Normal saline 0.9% - relieves nasal congestion
by helping to liquefy mucus
 Adrenaline
• Effective, rapid bronchodilator
• Dose – s.c 0.4ml of 1:1000 solution
• Inhalation – 320mcg per puff
• Max bronchodilation in 15min
• Bronchodilation lasts 60-90 min
• Also used in anaphylaxis
• Adverse effects –
tachycardia/arrythmias/worsening of angina
 Isoprenaline(isoproterenol)
• Acts on beta 1 & beta 2 receptors
• Potent bronchodilator when inhaled
• 80-120 mcg produces max bronchodilation in
5min
• Has 60-90min duration of action
• May cause cardiac arrythmias
 Respiratory stimulants
– Doxapram
• use has largely been replaced by ventilatory
support including nasal intermittent positive
pressure ventilation
• Indicated when ventilatory support is contra-
indicated and in patients with hypercapnic
respiratory failure who are becoming drowsy
or comatose, to arouse patients sufficiently to
co-operate and clear their secretions
 Respiratory stimulants
– Doxapram

• Post operative respiratory depression

• Acute respiratory failure
 Pulmonary surfactants
• Pulmonary surfactants are used in the
management of respiratory distress syndrome
(hyaline membrane disease) in neonates and
preterm neonates
• They may also be given prophylactically to
those considered at risk of developing the
syndrome
• Examples: Beractant, Poractant Alfa
 Oxygen
• Oxygen should be regarded as a drug
• It is prescribed for hypoxaemic patients to
increase alveolar oxygen tension and decrease
the work of breathing
• most common drug used in medical
emergencies.
High concentration oxygen therapy(up to 60%)
• is safe in uncomplicated cases of conditions
such as:
– Pneumonia
– pulmonary thromboembolism,
– fibrosing alveolitis
– Shock
– severe trauma
– sepsis, or
– Anaphylaxis
– acute severe asthma
 Low concentration oxygen therapy
(controlled oxygen therapy)
• chronic obstructive pulmonary disease
• cystic fibrosis
• non-cystic fibrosis bronchiectasis
• severe kyphoscoliosis or severe ankylosing
spondylitis;
• severe lung scarring caused by tuberculsosis
• musculoskeletal disorders with respiratory
weakness
• an overdose of opioids, benzodiazepines, or
other drugs causing respiratory depression.
•Antihistamines
 Antihistamines
• H1-BLOCKERS
• not widely used in the treatment of asthma, but
have an adjunctive role in asthmatics with hay
fever
• Cetirizine and loratadine are non-sedating -
plasma t1/2 of 6.5–10 hrs
• Cetirizine and loratadine do not cause the
potentially fatal drug–drug interaction with
macrolide antibiotics, as was the case with
astemizole or terfenadine
 Antihistamines – other uses
• Nasal allergies
• Rhinitis
• **reduce rhinorrhea & sneezing (thought to
be less effective for nasal congestion)
• Urticaria – Rx rashes, pruritus,
• insect bites & stings
• Drug allergies
• anaphylaxis
• Allergic conjuctivitis
– antazoline
– Azelastine
– Lodoxamine
– nedocromil
– sodium cromoglycate
• Nausea & vomiting
– Promethazine
– Buclizine
– Cinnarizine
– Cyclizine
 Sedating antihistamines
• Promethazine
• Chlorpheniramine
• Cyclizine
 Non-sedating antihistamines
• Cetirizine
• Desloratadine
• Loratadine
• Fexofenadine
• Terfenadine
• Levocetirizine
** reduced penetration across the BBB
 Corticosteroids – uses
• Asthma
• Dermatitis
• Pemphigus
• Leukemia,hodgkins disease, non-hodgkins lym
• Transplant rejection
• ulcerative colitis
• Crohn’s disease
• Hemorrhoids
 Corticosteroids – uses
• Postural hypotension – fludrocortisone
• Septic shock – low doses (hydrocortisone,
fludrocortisone)
• Congenital adrenal hyperplasia
(dexamethasone, betamethasone)
• Raised intracranial pressure/cerebral edema
• Acute hypersensitivity reactions
 Corticosteroids – uses
• Autoimmune hepatitis
• Rheumatoid arthritis
• Sarcoidosis
• Systemic lupus erythematosus
• Temporal arteritis
• Polyarteritis nodosa
• Eye inflammation – local treatment
• Inflammation in otitis externa
• Nasal allergy
 Corticosteroids – uses
• Pain due to nerve compression –
dexamethasone
• Dysphagia
• Dysnea
 Corticosteroids – adverse effects
• Hypertension
• Sodium & water retention
• Potassium loss
• Calcium loss, osteoporosis
• Diabetes
• Muscle wasting
• Peptic ulceration & perforation
• cushings syndrome
 Corticosteroids – adverse effects
• Suppression of growth
• Acute pancreatitis
• Esophageal ulceration
• Candidiasis
• Tendon rupture
• Menstrual irregularities
• Amenorrhea
• Hirsutism
 Corticosteroids – adverse effects
• Weight gain
• Hypercholestoremia
• Hyperlipidemia
• Increased appetite
• Increased susceptibility to infections
• Reactivation of dormant TB
• Insomnia
 Corticosteroids – adverse effects
• Aggravation of schizophrenia
• Aggravation of epilepsy
• Glaucoma
• Increased intra-ocular pressure
• Skin atrophy
• CHF
• Thromboembolism
• Nausea, malaise, hiccups, headache, vertigo
 Case Study
• An 18-year-old man, presents with a history of
recurrent episodes of wheeze after walking
200 metres. He has recently started to go to a
gym and his episodes of wheeze have
worsened.
• He goes to see his clinician. He can talk in
sentences but his respiratory rate is increased.
• His peak flow is 420 L/min which is 80% of
predicted result.
• A diagnosis of mild asthma is made.
• State two drugs that you can prescribe in this
case.
• State two types of drugs that are
contraindicated in asthma
• Describe how to use an MDI. (metered dose
inhaler)
• Patient education is vital for the management
of asthma.

• Patients should be guided in their use of the

asthma inhaler.

• It is important that you then observe the

patient’s use.
 Instructions given to the patient are as
follows:
• Sit in a comfortable, upright position.
• Remove the cap of the inhaler.
• Shake the inhaler.
• Breathe out and then put the mouthpiece into
your mouth and take a deep inhalation,
simultaneously pressing the inhaler.
• Hold your breath, then exhale slowly.
• Wipe the mouthpiece and replace the lid.
• The inhaler should be stored in a cool dry place.
• If you are to take two puffs, wait half a minute
before repeating the steps above.
 Case study
• a 32-year-old woman, 155 cm, 81 kg, presents
to hospital casualty with a history of increased
breathlessness and wheeze, over the last 5
days. She is known to have had asthma for 20
years. Her last hospital admission was one
month ago. She works in a small kiosk, as a
counter assistant. She lives in a tenth-floor
flat in Nyeri town; she is single.
• On medical examination the following is
found: .
– audible wheeze throughout the chest, using
accessory muscles
– not able to speak in sentences – stops for
breath after two words
– tachycardia – pulse 130 beats per minute
– tachypnoeic – respiratory rate 25 breaths
per minute
– peak expiratory flow rate 150 L/min.
• Describe how you would manage this patient
.
pharmacologically, including the methods of
administration of the medicines that you
prescribe

• Critically review the non-pharmacological

therapies that are available for people with
asthma. Would these be of benefit for this
patient?
 Summary-Asthma is managed in a
stepwise approach
• Step 1:
• Occasional bronchodilator relief (inhaled
short acting beta2-agonist as required).

• Step 2:
• Regular inhaled preventer therapy (inhaled
short acting beta2-agonist as required and
regular standard dose inhaled corticosteroid).
•
• Step 3
• Inhaled corticosteroid and long-acting
inhaled beta2-agonists
• (inhaled short-acting beta2-agonist as
required and regular standard-dose inhaled
corticosteroid and regular inhaled long-acting
beta2-agonist PLUS at this step either
leukotriene receptor antagonist or modified-
release oral theophylline or modified-release
oral beta2-agonist therapy).
Step 4
• High-dose inhaled corticosteroid and regular
bronchodilators
• (inhaled short-acting beta2-agonist as
required and regular high-dose inhaled
corticosteroid and inhaled long-acting beta2-
agonist PLUS six-week sequential trial of one
or more of leukotriene receptor antagonist or
modified-release oral theophylline or
modified-release oral beta2-agonist).
• Step 5

• Patient would be on step 4 then add in

regular corticosteroid tablets.
 Mild asthma
• s.c Adrenaline 0.5ml of 1:1000
• No response
• Repeat after 20-30 min
• Response
• Discharge on Salbutamol 4mg TDS
• + Inhaled B2 Agonist
 Moderate asthma
• s.c Adrenaline 0.5ml of 1:1000- upto 3x doses
OR
• Nebulize = (Salbutamol + ipratropium) every
20minutes -- response or tremors
• no response
• Iv aminophyline 6mg/kg slowly over 15min
then 0.9mg/kg/hr
• Response
• Discharge on;
• salbutamol 4mg TDS or theophyline 200mg
bd/tds – review after 1 week
• no response – treat as severe asthma
**add corticosteroid (oral/inhaled) /leukotriene
modifiers /inhaled beta agonist
 Severe asthma
• Oxygen 3-5L/min if cyanosed
• I.v aminophylline LD if not already given
• I.v aminophyline 0.9mg/kg/hr in NS drip
• I.v hydrocortisone 200mg stat
• or
• Methyprednisolone 1g i.v
• Or Dexamethasone 2-4mg iv/im stat
• p.o prednisolone 10-15mg TDS taper in 7-10days
• Add an inhaled corticosteroid/LA B-agonist/
leukotriene /antibiotic
 Chronic asthma
• Salbutamol 4mg TDS Oral
or
• Salbutamol inhaler /steroid inhaler

• Poor response – oral theophyline 100-200mg

TDS
 Status asthmaticus
• Treat as severe
• Administer Oxygen by intranasal catheter 1-
2L/min
• Treat as per acute attack of asthma
• Correct dehydration
• Ventilate if necessary using bag & mask
Long Term & Home Care of asthma
• Mild intermittent

- Daytime symptoms – less than 2 per week

- Night – less than 2 per month
= short acting bronchodilator
 Mild persistent
• Daytime - greater than 2 per week
• Night – greater than 2 per month
= low dose corticosteroid daily
Attack = short acting bronchodilator
 Severe persistent
• Symptoms persistent during the day and
frequent at night
= high dose inhaled corticosteroid + long acting
bronchodilator + systemic steroids when
needed
Attack = short acting bronchodilators
 COPD
• Management In Acute Exacerbations
Bronchodilators - salbutamol 4mg TDS
- Salbutamol inhaler 2puffs every 6-8 hrs
Or – Theophylline 250mg BD or TDS
- Aminophylline 0.9mg/Kg /hr i.v
- Terbutaline nebulizer 0.1-0.4mg QDS
- Ipratropium inhaler
- Prednisolone 30-60mg daily x5-10 days
- Chest physiotherapy/antibiotics
 Summary Notes
• Inhaled short acting beta-2 agonists
(SABAs) are drugs of choice for producing
a rapid relief from bronchoconstriction.
• Note: nebulized medications are frequently
given along with oxygen.
• If pO2 is less than 90%, oxygen should
actually be given first to prevent a beta-2-
induced ventilation/perfusion mismatch.
• If a short-acting beta-2 agonist had been
given, and it only partially relieves
symptoms of bronchoconstriction,
• what other drug could be given next that
might produce additional short-term (vs
long term) relief?
• Ipratropium - MDI
• Clinical experience indicates that adding this
quaternary antimuscarinic can improve the
bronchodilatory response in many patients if the
SABA isn't totally effective, especially in patients
with more severe forms of asthma exacerbations.
• While treatment with an anti-inflammatory
steroid is also warranted (and acutely could be
given by any route of administration in this
clinical setting), it would not be expected to
produce a therapeutic effect until many hours to
days later, because a majority of its effect
involves changes in gene expression.
• However, not everyone responds to anticholinergics,
because there is patient-to-patient variability in the
contribution of parasympathetic tone in asthmatic
bronchoconstriction.
• On average, patients with more severe asthma seem
to benefit the most.
• If clinical status does not improve despite
aggressive conventional therapy with a
short acting beta-2 agonist and systemic
corticosteroids.
• Try - theophylline, which has a narrow
therapeutic window
• What toxic side effects should you be
looking for if theophylline levels become
too high?
1. hyperkalemia
2. bradycardia
3. sedation
4. seizures & arrhythmias
• The px condition may improve after
several days of treatment, and he is
eventually discharged.
• His asthma severity is classified as
moderate & persistent.
• What daily long term therapy should be
prescribed?
 Budesonide – inhaled
• Any degree of persistent asthma requires
the addition of a daily "control" medication.
• The drug of first choice for a control
medication is an inhaled corticosteroid
(ICS).
• A patient with a history of intermediate
asthma who has been using inhaled
salbutamol as needed for the past year.
• However, over the past month he has
needed to use his salbutamol rescue
inhaler more and more often (sometimes
several times a week)
• which change to his asthma treatment
regimen would most likely reduce the
likelihood of worsening of his asthma?
1. switch to formoterol MDI
2. add prednisolone, oral
3. add omalizumab every 2 weeks
4. low dose budesonide + formoterol as
needed
• Recent clinical trials indicate that the
combination of low dose ICS + the fast-
acting LABA (formoterol), taken as
needed, reduces the risk of severe
exacerbations of asthma compared to use
of a SABA alone.
• The ICS reduces inflammation, and
formoterol produces bronchodilation with
an onset of action essentially identical to a
SABA, but with a duration of action that is
3-4 times longer than a SABA.
• A patient develops an anaphylactic-like
reaction including severe urticaria and
bronchoconstriction.
• What is the drug of choice for treating this
condition:
 Adrenaline/Epinephrine
• Adrenaline is a treatment of choice for
anaphylactic reactions.
• It can be given rapidly, and it produces rapid
responses to cause beta-2 mediated
bronchodilation,
• alpha-mediated pressor effects to support blood
pressure (which can be lowered by histamine
release),
• reduced mucosal edema in the upper airway, and
reduced release of inflammatory mediators by
mast cells & basophils.
 Omalizumab
• indicated for patients exposed to perennial
allergens.
• It requires once or twice a month s.c.
injections.
• It is relatively expensive if not covered by
insurance.
• A px is suffering from an asthmatic attack.
Which of the following would be LEAST
likely to reverse bronchoconstriction in this
situation (or in other words....which
treatment option makes no logical sense
to you)?
1. Cromolyn sodium by nebulizer
2. Epinephrine s.c.
3. Ipratropium aerosol
4. Terbutaline, s.c.
5. Theophylline i.v.
• Cromolyn- in that this would be a great
"bad choice". Degranulation inhibitors are
not effective once the inflammatory
mediators have been released from mast
cells and basophils.
• The other drugs listed have documented
bronchodilator effects.
• An inhaled short acting beta-2 agonist
(such as levosalbutamol) would be the
best treatment choice.
• A px suffers an asthma attack and requires
a rapidly acting bronchodilator.
• Unfortunately the pharmacy has run out of
all salbutamol/levosalbutamol inhalers.
• In this situation, what other option if
available, might be most effective to treat
bronchospasm with a relatively rapid onset
of action (but needs to be co-administered
along with a corticosteroid)?
1.Budesonide
2.Fluticasone
3.Formoterol
4.Omalizumab
5.Salmeterol
• Formoterol is a long-acting beta-2 agonist
with a fast onset of action, similar to
SABAs.