RELIEVERS

DRUG GROUP EFFICACY SAFETY SUITABILITY COST Total

Short Acting Beta 2 ++++ +++ ++++ +++ 14
Agonist (SABA)
Short Acting Muscarinic ++++ ++ +++ ++ 11
Antagonist (SAMA)

SHORT-ACTING-BETA2-AGONIST (SABA) (ALBUTEROL)

EFFICACY Pharmacodynamic
++++  The pharmacologic effects of albuterol sulfate are attributable to activation
of beta2-adrenergic receptors on airway smooth muscle.
 Activation of beta2-adrenergic receptors leads to the activation of
adenylcyclase and to an increase in the intracellular concentration of
cyclic-3', 5’-adenosine monophosphate (cyclic AMP). This increase of
cyclic AMP is associated with the activation of protein kinase A, which in
turn inhibits the phosphorylation of myosin and lowers intracellular
ionic calcium concentrations, resulting in muscle relaxation.
 Albuterol relaxes the smooth muscle of all airways, from the trachea to the
terminal bronchioles.
 Albuterol acts as a functional antagonist to relax the airway irrespective of
the spasmogen involved, thus protecting against all bronchoconstrictor
challenges. Increased cyclic AMP concentrations are also associated with the
inhibition of release of mediators from mast cells in the airway.
 While it is recognized that beta2-adrenergic receptors are the
predominant receptors on bronchial smooth muscle, data indicate that there
are beta-receptors in the human heart, 10% to 50% of which are cardiac
beta2-adrenergic receptors.
 Albuterol has been shown in most controlled clinical trials to have more
effect on the respiratory tract, in the form of bronchial smooth muscle
relaxation, than isoproterenol at comparable doses while producing fewer
cardiovascular effects. However, inhaled albuterol, like other
beta-adrenergic agonist drugs, can produce a significant cardiovascular
effect in some patients, as measured by pulse rate, blood pressure,
symptoms, and/or electrocardiographic changes.
Pharmacokinetic
 Absorption: After oral inhalation, appears to be absorbed gradually, over
 several hours, from the respiratory tract; however, dose is mostly
swallowed and absorbed through the GI tract.
o When administered by inhalation, it produces significant
bronchodilation within 15 minutes, and effects persist for 3-4 hours.
o The systemic levels of albuterol are low after inhalation of
recommended doses.
Route Onset Peak Duration
Per Orem 15-30min 2-3hours 6-12hours
Inhalation 5-15min 1/2-2hours 2-6hours

 Distribution: It does not cross the blood brain barrier. Protein binding 10%
 Metabolism: The terminal plasma half-life of albuterol delivered by
inhalation aerosol was approximately 6 hours
o Information available in the published literature suggests that the
primary enzyme responsible for the metabolism of albuterol in humans
is SULTIA3 (sulfotransferase). When racemic albuterol was
administered either intravenously or via inhalation after oral charcoal
administration, there was a 3- to 4-fold difference in the area under the
concentration-time curves between the (R)- and (S)-albuterol
enantiomers, with (S)-albuterol concentrations being consistently
higher. However, without charcoal pretreatment, after either oral or
inhalation administration the differences were 8- to 24-fold, suggesting
that the (R)-albuterol is preferentially metabolized in the
gastrointestinal tract, presumably by SULTIA3.
 Elimination: The primary route of elimination of albuterol is through renal
excretion (80% to 100%) of either the parent compound or the primary
metabolite. Less than 20% of the drug is detected in the feces. Following
intravenous administration of racemic albuterol, between 25% and 46% of
the (R)-albuterol fraction of the dose was excreted as unchanged (R)-
albuterol in the urine.
o The effect of renal impairment on the pharmacokinetics of albuterol
was evaluated in 5 subjects with creatinine clearance of 7 to 53
mL/min, and the results were compared with those from healthy
volunteers. Renal disease had no effect on the half-life, but there was a
67% decline in albuterol clearance. Caution should be used when
administering high doses of PROAIR HFA Inhalation Aerosol to patients
with renal impairment
SAFETY  Contraindications: Hypersensitivity to albuterol and any other
+++ inhalation aerosol Components. Rare cases of hypersensitivity reactions,
 including urticaria, angioedema, and rash have been reported after the
use of albuterol sulfate
 Adverse Reactions
o Most common adverse reactions (≥3.0% and >placebo) are
headache, tachycardia, pain, dizziness, pharyngitis, and rhinitis
 Warnings and Precautions
o Paradoxical Bronchospasm. Life-threatening paradoxical
bronchospasm may occur. Discontinue and Immediately and
treat with alternative therapy. It should be recognized that
paradoxical bronchospasm, when associated with inhaled
formulations, frequently occurs with the first use of a new
canister.
o Deterioration of Asthma. Asthma may deteriorate acutely over
a period of hours or chronically over several days or longer. If
the patient needs more doses of PROAIR HFA Inhalation Aerosol
than usual, this may be a marker of destabilization of asthma
and requires re-evaluation of the patient and treatment
regimen, giving special consideration to the possible need for
antiinflammatory treatment, e.g., corticosteroid
o Use of Anti-inflammatory Agents. Not a substitute for
corticosteroids. The use of beta-adrenergic-agonist
bronchodilators alone may not be adequate to control asthma in
many patients. Early consideration should be given to adding
antiinflammatory agents, e.g., corticosteroids, to the therapeutic
regimen.
o Cardiovascular effects may occur. Use with caution in patients
sensitive to sympathomimetic drugs and patients with
cardiovascular or convulsive disorders. Like other
beta-adrenergic agonists, can produce clinically significant
cardiovascular effects in some patients as measured by pulse
rate, blood pressure, and/or symptoms. Although such effects
are uncommon after administration at recommended doses, if
they occur, the drug may need to be discontinued. In addition,
beta-agonists have been reported to produce ECG changes, such
as flattening of the T wave, prolongation of the QTc interval, and
ST segment depression. The clinical significance of these
findings is unknown. Therefore, like all sympathomimetic
amines, should be used with caution in patients with
cardiovascular disorders, especially coronary insufficiency,
 cardiac arrhythmias, and hypertension.
o Excessive use may be fatal. Do not exceed recommended dose.
Fatalities have been reported in association with excessive use
of inhaled sympathomimetic drugs in patients with asthma. The
exact cause of death is unknown, but cardiac arrest following an
unexpected development of a severe acute asthmatic crisis and
subsequent hypoxia is suspected.
o Immediate hypersensitivity reactions may occur.
Discontinue immediately. As demonstrated by rare cases of
urticaria, angioedema, rash, bronchospasm, anaphylaxis, and
oropharyngeal edema. The potential for hypersensitivity must
be considered in the clinical evaluation of patients who
experience immediate hypersensitivity reactions while
receiving.
o Coexisting conditions. Like all sympathomimetic amines,
should be used with caution in patients with cardiovascular
disorders, especially coronary insufficiency, cardiac
arrhythmias, and hypertension; in patients with convulsive
disorders, hyperthyroidism, or diabetes mellitus; and in
patients who are unusually responsive to sympathomimetic
amines. Clinically significant changes in systolic and diastolic
blood pressure have been seen in individual patients and could
be expected to occur in some patients after use of any
beta-adrenergic bronchodilator. Large doses of intravenous
albuterol have been reported to aggravate preexisting diabetes
mellitus and ketoacidosis.
o Hypokalemia. As with other beta-agonists, Aerosol may
produce significant hypokalemia in some patients, possibly
through intracellular shunting, which has the potential to
produce adverse cardiovascular effects. The decrease is usually
transient, not requiring supplementation
 Drug Interactions
o Other short-acting sympathomimetic aerosol bronchodilators
and adrenergic drugs: May potentiate effect
o Beta-blockers: May decrease effectiveness and produce severe
bronchospasm. Patients with asthma should not normally be
treated with betablockers.
o Diuretics, or non-potassium sparing diuretics: May potentiate
hypokalemia or ECG changes. Consider monitoring potassium
 levels.
o Digoxin: May decrease serum digoxin levels. Consider
monitoring digoxin levels.
o Monoamine oxidase (MAO) inhibitors and tricyclic
antidepressants: May potentiate effect of albuterol on the
cardiovascular system. Consider alternative therapy in patients
taking MAOs or tricyclic antidepressants.
 Use in specific populations
o Pregnancy
o Labor & Delivery
o Nursing Mothers
o Pediatric Use
o Geriatric Use
 AS compared to Ipatropium

SUITABILITY  It has the following preparations:

++++ o Nebulization or Oral Inhalation
o Chlorofluorocarbons (CFC)-propelled albuterol
o Inhalation powder
o Hydrofluoroalkane (HFA) inhalers
o Oral
 As indicated in the GINA guidelines (2018) page 70
COST-EFFECTIVENESS Salbutamol (Asmalin) 1mg/mL 2.5mL Pulmoneb solution for inhalation - Php
+++ 26.52/nebule
Salbutamol (Ventolin Nebules) 1mg/mL 2.5mL Solution for inhalation - Php
38.37/nebule
Sources https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021457s013lbl.p
df
https://www.drugs.com/ppa/albuterol.html
https://ginasthma.org/wp-content/uploads/2018/04/wms-GINA-2018-report-t
racked_v1.3.pdf
https://www.glowm.com/resources/glowm/cd/pages/drugs/a012.html

SHORT-ACTING-MUSCARINIC-ANTAGONIST (SAMA) (Ipatropium Bromide)

EFFICACY Pharmacodynamic
++++  Ipratropium bromide is an anticholinergic (parasympatholytic) agent which,
based on animal studies, appears to inhibit vagally mediated reflexes by
antagonizing the action of acetylcholine, the transmitter agent released at
neuromuscular junctions in the lung. Anticholinergics prevent the increases
in intracellular concentration of cyclic guanosine monophosphate (cyclic
GMP) which are caused by interaction of acetylcholine with the muscarinic
receptor on bronchial smooth muscle
 Controlled clinical studies have demonstrated that Atrovent® (ipratropium
bromide ) Inhalation Aerosol CFC does not alter either mucociliary clearance
or the volume or viscosity of respiratory secretions
Pharmacokinetic
 Absorption: Most of an administered dose is swallowed as shown by fecal
excretion studies. Ipratropium bromide is a quaternary amine. It is not
readily absorbed into the systemic circulation either from the surface of the
lung or from the gastrointestinal tract as confirmed by blood level and renal
excretion studies
 Distribution: Autoradiographic studies in rats have shown that
ipratropium bromide does not penetrate the blood-brain barrier.
Ipratropium bromide is minimally bound (0 to 9% in vitro) to plasma
albumin and a1-acid glycoprotein.
 Metabolism: The half-life of elimination is about 2 hours after inhalation
or intravenous administration. It is partially metabolized to inactive ester
hydrolysis products.
 Elimination: Following intravenous administration, approximately one-half
of the dose is excreted unchanged in the urine. Most of an administered dose
is excreted unchanged in feces. Absorbed drug is excreted in urine and bile.
SAFETY  Contraindications: ATROVENT HFA Inhalation Aerosol is
++ contraindicated in patients with a history of hypersensitivity to
ipratropium bromide or other ATROVENT HFA Inhalation Aerosol
components. ATROVENT HFA Inhalation Aerosol is also contraindicated
in patients who are hypersensitive to atropine or its derivatives
 Adverse Reactions:
o As an anticholinergic drug, cases of precipitation or worsening
of narrow-angle glaucoma, mydriasis, acute eye pain,
hypotension, palpitations, urinary retention, tachycardia,
constipation, bronchospasm, including paradoxical
bronchospasm have been reported.
o Allergic-type reactions such as skin rash, pruritis, angioedema
of tongue, lips and face, urticaria (including giant urticaria),
laryngospasm and anaphylactic reactions have been reported
o CNS: dizziness, headache, nervousness, pain.
o CV: palpitations, chest pain.
o EENT: cough, blurred vision, rhinitis, pharyngitis, sinusitis.
o GI: nausea, GI distress, dry mouth.
o Musculoskeletal: back pain.
o Respiratory: upper respiratory tract infection, bronchitis, cough,
dyspnea, bronchospasm, increased sputum.
o Skin: rash.
o Other: flulike symptoms.
 Warnings and Precautions
o ATROVENT HFA Inhalation Aerosol is a bronchodilator for the
maintenance treatment of bronchospasm associated with COPD
and is not indicated for the initial treatment of acute episodes of
bronchospasm where rescue therapy is required for rapid
response.
o Immediate hypersensitivity reactions may occur after
administration of ipratropium bromide, as demonstrated by
rare cases of urticaria, angioedema, rash, bronchospasm,
anaphylaxis and oropharyngeal edema.
o Inhaled medicines, including ATROVENT HFA Inhalation
Aerosol, may cause paradoxical bronchospasm. If this occurs,
treatment with ATROVENT HFA Inhalation Aerosol should be
stopped and other treatments considered.
 Drug Interactions
o ATROVENT HFA Inhalation Aerosol has been used
 concomitantly with other drugs, including sympathomimetic
bronchodilators, methylxanthines, oral and inhaled steroids,
that may be used in the treatment of chronic obstructive
pulmonary disease. With the exception of albuterol, there are no
formal studies fully evaluating the interaction effects of
ATROVENT and these drugs with respect to effectiveness.
o Anticholinergic agents: Although ipratropium bromide is
minimally absorbed into the systemic circulation, there is some
potential for an additive interaction with concomitantly used
anticholinergic medications. Caution is therefore advised in the
co-administration of ATROVENT HFA Inhalation Aerosol with
other anticholinergic-containing drugs.
 Use in specific populations
o Pregnancy Category B
o Nursing Mothers
o Pediatric Use
o Geriatric Use
SUITABILITY  It has the following preparations:
+++ o Inhalation solution
o Inhaler
o Nasal spray
 GINA guidelines recommendation

COST-EFFECTIVENESS Ipatropium bromide (Atrovent) inhalation solution 0.5mg/2mL - Php 1,758/box

++ of 20s = Php 87.90/nebule
Sources https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021527s005lbl.p
df
https://www.glowm.com/resources/glowm/cd/pages/drugs/ij022.html
https://www.mims.com/philippines/drug/info/atrovent