Asthma: Quick-Relief (Rescue) Drug list
Asthma: Long-term (Control) drug list
COPD: Quick-Relief (Rescue) Drug list
COPD: Long-term (Control) drug list
Allergic Rhinitis Drug List
Cough Drug list
Abnormal Mucus Secretion: Drug List
Overview of the Anatomy of the Respiratory System
Overview of the Histology of the Lower Airways
Asthma currently afflicts between __________ of the residents of the United States.
7-10%
Asthma is clinically characterized by
recurrent episodes of coughing, dyspnea, and wheezing.
In asthmatics, the stimulation of _______________ results in recurrent episodes of cough.
irritant or stretch receptors within the intrapulmonary airways
In asthmatics, dyspnea and wheezing manifest as a result of
widespread, reversible narrowing of the airways
+
increased responsiveness of the airway smooth muscle to a number of non-specific stimuli
Responsiveness" of the airway smooth muscle in asthma is clinically determined by the
FEV1?FVC ratio (FEV1/FVC)
FEV1 is the forced expiratory volume in
one second
while FVC is the forced vital capacity
When administered an allergen, histamine, or methacholine via oral inhalation, an asthmatic will
exhibit a profound decrease in his or her FEV1?FVC ratio
while a healthy individual will exhibit no change in his or her FEV1?FVC ratio when administered the same agent.
Thus, asthmatics are said to exhibit increased "airway reactivity" or "airway respons
The symptoms of cough, dyspnea, and wheezing in asthmatics are a consequence of
chronically inflamed airways.
Chronic airway inflammation eventually leads to
airway remodeling
Airway inflammation in asthma is often characterized by the presence of
eosinophils, neutrophils, T-lymphocytes, and activated mast cells in the respiratory mucosa
release a number of inflammatory moieties, which can stimulate irritant and stretch receptors within the intrapulmonary airways and lead to recurrent episodes of c
What is commonly observed in asthmatic airways?
Edema
mucus hypersecretion
subepithelial fibrosis
thickening
smooth muscle, goblet cell, and mucus gland hyperplasia and hypertrophy
Asthma is broadly defined as either
extrinsic (atopic)
intrinsic (non- atopic)
Asthma attack
characterized by acute bronchoconstriction
can be triggered by a variety of factors, including
-- environmental allergens (e.g., ragweed and animal fur and dander)
-- viruses
-- exercise
-- cold air
-- occupational asthmagens (e.g., isocyanates and dyes)
Classification of Asthma
Therapeutic Strategy for Managing Asthma
Environmental factors that contribute to asthma must be identified, eliminated, and/or avoided as much as possible.
When pharmacological agents are required to alleviate asthma symptoms, medication selection and use is dictated by the severity of symptoms
Asthma Quick-Relief (Rescue) Medications
--- clinical use
used to provide prompt relief for an acute "asthma attack" (acute bronchoconstriction)
---- by initiating airway smooth muscle relaxation (bronchodilation)
some work by antagonizing the effects of endogenous ACh
Asthma Long-Term (Control) Medications
--- clinical use
used to achieve and maintain control of persistent (mild, moderate, or severe) asthma on a daily basis by serving to attenuate the underlying airway inflammation.
These medications are anti-inflammatory agents.
Under no circumstances are long-term (contro
Asthma Quick-Relief (Rescue) Medications
--- types
Sympathomimetic drugs
---- ?2?Non-Selective Agonists
---- ?2 Selective Agonists
Antimuscarinics
--- Ipratropium Bromide
Sympathomimetic drugs for Asthma
--- MOA
cause bronchodilation by binding to the ?2?adrenergic receptor
----- a Gs?protein coupled receptor, on airway smooth muscle cells
increase in intracellular cAMP ---> phosphorylates and activates protein kinase A (PKA)
PKA
----
decreases
intracellular calc
?2?Non-Selective Agonists
Epinephrine
Ephedrine
?2?Non-Selective Agonists
--- route of administration
Epinephrine = injection
Ephedrine = oral
?2?Non-Selective Agonists
--- clinical use
relief of acute bronchoconstriction in individuals with intermittent asthma
medications containing ephedrine also contain guaifenesin, which is an expectorant
(Bronkaid�; Primatene�)
?2 Selective Agonist
Albuterol
Levalbuterol
Terbutaline
?2 Selective Agonist
-- route of administration
Oral --> albuterol, terbutaline
Oral inhalation --> albuterol, levalbuterol
IV --> terbutaline
?2 Selective Agonist
-- clinical use
alleviate acute bronchoconstriction in intermittent and persistent (mild, moderate, and severe) asthma
When given by inhalation, bronchodilation manifests within 15-30 minutes and persists for 3-4 hours
?2 Selective Agonist
-- contraindications
use with caution in individuals with
--- cardiovascular disease
--- diabetes mellitus
--- hypokalemia
potentiated with the co-administration of MAO inhibitors and tricyclic antidepressants
When using these agents, one should take notice if paradoxical bro
?2 Selective Agonist
-- side effects
skeletal muscle tremors
tachycardia
nervousness
hyperglycemia
hypokalemia
not as profound with ?2?selective agonists administered via oral inhalation
Antimuscarinics used for Quick-Relief from Asthma
Ipratropium Bromide
Ipratropium Bromide
--- MOA
non-selective, competitive antagonist of muscarinic receptors
competitively inhibits the binding of ACh to muscarinic
M3
receptors
----- found on the surface of airway smooth muscle cells
[ACh mediates reflex bronchoconstriction, which is initiated follow
Ipratropium Bromide
--- route of administration
oral inhalation
Ipratropium Bromide
--- pharmacokinetics
t1/2 = 2 hours
--- short
duration of action = 6 hours
--- long
hydrophilic --> only a small amount of the drug is absorbed into the systemic circulation
---- few systemic side effects
Ipratropium Bromide
--- clinical use
quick- relief medication
not recommended as first- line therapy
used as an adjunctive with short-acting ?2?selective agonists to alleviate moderate or severe asthma exacerbations at home, hospital ER or ICU
been shown to provide additional benefit when gi
DuoNeb�
ipratropium bromide + albuterol
---- sterile aqueous solution given via nebulization
Combivent�
ipratropium bromide + albuterol
microsuspension given via a metered-dose inhaler
Ipratropium Bromide
--- contraindications
narrow-angle glaucoma
pre-existing bladder obstruction
those with sensitivity to atropine
Ipratropium Bromide
--- side effects
irritation at site of oral inhalation
Long-Term (Control) Medication for Asthma
--- types
Corticosteroids
Long-Acting ?2?Selective Agonists
Leukotriene Modifiers
--- Leukotriene synthesis inhibitors
--- Leukotriene receptor antagonists
Methylxanthines
Monoclonal antibodies
Corticosteroids
class of steroid hormones, which are further subdivided into two different classes
---- glucocorticoids
---- mineralcorticoids
Glucocorticoids
#NAME?
Corticosteroids used for Long-Term treatment of Asthma
Beclomethasone
Budesonide
Ciclesonide
Fluticasone
Methylprednisolone
Mometasone
Prednisolone
Predisone
Ciclesonide
pro-drug that is activated by esterases in bronchial epithelial cells
Corticosteroids
--- MOA
broad anti-inflammatory agents
highly lipophilic --> cross the plasma membrane of cells and bind to the glucocorticoid receptor (GR) in the cytosol
Once the glucocorticoid-GR complex is formed, it translocates to the nucleus and up-regulates the expressio
Beneficial effects of corticosteroids in asthma
i) inhibition of leukocyte infiltration into respiratory mucosa
ii) decrease immunoglobulin E (IgE) synthesis
iii) promote the transcription of
lipocortins
---- anti-inflammatory proteins which inhibit phospholipase A2 --> reduction in the synthesis of le
Corticosteroids
--- route of administration
Oral
--- prednisolone
--- prednisone
Oral inhalation
-- beclomethasone
--
budesonide
-- ciclesonide
--
fluticasone
-- mometasone
IV
-- methylprednisolone
Corticosteroids
--- pharmacokinetics
high lipid solubility --> rapidly and completely absorbed into the systemic circulation when taken orally
Oral or intravenously administered corticosteroids have an effect within a few hours
but, it may require weeks of oral inhalation corticosteroid admi
Corticosteroids
--- clinical use
treat persistent (mild, moderate, or severe) asthma
They are often given in conjunction with other long-term (control) medications as well as quick-relief medications.
Intravenous or oral corticosteroids are administered during severe asthma exacerbations
Corticosteroids
--- contraindications
immunocompromised
diabetics
Corticosteroids
--- side effects
oral inhalation, usually -> well-tolerated
oral candidiasis
dysphonia
sore throat
throat irritation
coughing
long-term use
--- weight gain
--- bone loss
--- slow growth
--- behavioral changes
Long-Acting ?2?Selective Agonists
Formoterol
Salmeterol
Long-Acting ?2?Selective Agonists
--- MOA
cause bronchodilation in the same manner as short-acting ?2?selective agonists.
duration of action is much longer --> up to twelve hours.
Long-Acting ?2?Selective Agonists
--- route of administration
oral inhalation
Long-Acting ?2?Selective Agonists
--- pharmacokinetics
Following oral inhalation, both formoterol and salmeterol have been detected in the plasma within 5 minutes
duration of action ~ 12 hrs
These drugs are excreted in the urine and feces.
Long-Acting ?2?Selective Agonists
--- clinical use
treatment of moderate and severe persistent asthma
They are not to be used as monotherapy for long-term control.
--- use with corticosteroids
can be used for quick- relief from acute bronchoconstriction
Corticosteroid/long-acting ?2-selective agonist combinations
Advair
--- fluticasone + salmeterol
Symbicort
--- budesonide + formeterol
Because of their prolonged effect, they reduce the use of quick- relief (rescue) medications and prevent exacerbations throughout the day
Long-Acting ?2?Selective Agonists
--- contraindications
two placebo-controlled studies have shown an increase in asthma-related deaths in individuals taking either formoterol or salmeterol
the U.S. Food and Drug Administration ordered the manufacturers of products containing long-acting ?2?selective agonists t
Long-Acting ?2?Selective Agonists
--- side effects
similar to short-acting ?2?Selective Agonists
Leukotrienes
eicosanoids
synthesized and released by leukocytes (basophils, eosinophils, lymphocytes, neutrophils, monocytes) and mast cells
Leukotriene synthesis is initiated by the oxidation of arachidonic acid by the enzyme 5-lipoxygenase.
Cysteinyl leukotrienes (CysLTs)
consist of leukotriene C4, D4, and E4
intimately involved in asthma pathogenesis
For example, two CysLTs (LTC4 and LTD4) mediate
---- leukocyte-induced migration, aggregation, and adhesion
---- airway smooth muscle contraction
---- microvascular permeabil
Drugs inhibiting the synthesis of CysLTs or drugs which antagonize the CysLT receptors (CysLT1 and CysLT2)
approved as controller medications for asthma in the late 1990s.
Leukotriene Synthesis Inhibitors
Zileuton
Zileuton
-- MOA
inhibits 5- lipoxygenase
---- oxidizes arachidonic acid, which is the first step in the formation of leukotrienes
reduces leukotriene-induced bronchoconstriction, inflammation, microvascular permeability, and mucus secretion
Zileuton
-- route of administration
oral
Zileuton
-- pharmacokinetics
rapidly absorbed into the systemic circulation after oral administration
peak plasma concentrations occur approximately 2 hours following ingestion
Zileuton and its metabolites are primarily excreted in the feces.
Zileuton
-- clinical use
mild and moderate persistent asthma
Zileuton
-- contraindications
those with previously reported hypersensitivity to the drug
those with history of hepatic disease
those with a history of elevations in hepatic enzymes
Zileuton
-- drug interactions
interferes with the metabolism of
--- theophylline
--- warfarin
--- propranolol
doses of these drugs may need to be adjusted when also taking zileuton
Zileuton
-- side effects
neuropsychiatric events
hepatic injury
---- alanine transaminase (ALT) should be monitored before zileuton treatment begins and then every 2-3 months thereafter
Leukotriene Receptor Antagonists
Montelukast
Zafirlukast
Montelukast
--- MOA
selective antagonist of the CysLT1 receptor
reduces leukotriene-induced bronchoconstriction, microvascular permeability, and mucus hypersecretion
Montelukast
--- route of administration
oral
Montelukast
--- pharmacokinetics
rapidly absorbed after oral administration
peak plasma concentrations occur within 3-4 hrs
extensively metabolized
montelukast and its metabolites are excreted in the feces.
Montelukast
--- clinical use
mild or moderate persistent asthma
Montelukast
--- contraindications
those reporting previous hypersensitivity to the drug
Montelukast
--- side effects
Churg-Strauss syndrome
neuropsychiatric events (i.e., suicidal thoughts, anxiousness).
Zafirlukast
same MOA, route of administration, pharamacokinetics & clinical use as montelukast
Zafirlukast
--- contraindications
those reporting previous hypersensitivity to the drug
hepatic disease
Zafirlukast
--- side effects
Similar side effects associated with montelukast have also been reported for zafirlukast
Hepatic injury
--- even in individuals with no prior history of hepatic disease, liver enzymes should be measured at baseline and at various time intervals during zaf
Methylxanthines
Theophylline
Aminophylline
Aminophylline
theophylline-ethylenediamine complex
more soluble and often the commonly used therapeutic form of theophylline
Theophylline
--- MOA
1) antagonist of adenosine receptors
---- Adenosine promotes the contraction of airway smooth muscle and histamine release from mast cells.
2) non-selective inhibitor of phosphodiesterase 4 (PDE4) --> increases cAMP levels in airway smooth muscle cells an
Theophylline
--- route of administration
oral & IV
Theophylline
--- pharmacokinetics
good oral bioavailability
wide variation in the half- life of the drug among individuals of different ages due to differences in the rate of metabolism
---- longest in premature infants and newborns
---- shortest in children and adults.
very narrow therap
Theophylline
--- clinical use
prophylactic treatment of mild and moderate persistent asthma
Aminophylline
--- clinical use
given intravenously for the treatment of status asthmaticus
Theophylline
--- contraindications
Can cause cardiac arrhythmias & seizures
--- contraindicated in patients with heart disease and with a history of seizures
Because the plasma concentration of theophylline cannot be reliably estimated from the dose administered and because theophylline is
Theophylline
--- drug interactions
Cimetidine, a histamine H2-receptor antagonist
---- increases the plasma levels of theophylline when co-administered
Theophylline
--- side effects
nausea/vomiting
cardiac arrhythmias
hypotension
cardiac arrest
seizures.
Monoclonal Antibodies used to treat Asthma
Omalizumab
Mepolizumab
Reslizumab
Omalizumab
--- MOA
anti-human IgE monoclonal antibody
binds to IgE at the same site that IgE binds to its high affinity receptor (Fc-RI)
prevents circulating IgE from binding to Fc-RI on mast cells and basophils
thereby prevents mast cell degranulation and the release of in
Omalizumab
--- route
subcutaneous injection
Omalizumab
--- pharmacokinetics
After subcutaneous administration, omalizumab reaches peak plasma concentrations between 6-8 days after the initial injection
Omalizumab
--- clinical use
treatment of moderate to severe persistent asthma
in individuals 12+ yrs old with a positive skin prick test for perennial aeroallergens whose asthma is not well- controlled with high-dose inhaled corticosteroids.
given along with a high-dose inhaled cort
Omalizumab
--- contraindications
individuals with a previous hypersensitivity to the drug
Omalizumab
--- side effects
severe anaphylaxis
malignant neoplasms
Churg-Strauss syndrome
fever
rash
arthralgia
Mepolizumab
--- MOA
anti-human IL-5 monoclonal antibody
prevents IL-5 from binding to the alpha chain of the IL-5 receptor
IL-5 is primarily responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils, which are implicated in the pathoge
Mepolizumab
--- route
Subcutaneously every 4 wks
Mepolizumab
--- pharmacokinetics
bioavailability of mepolizumab is approximately 80% after a single subcutaneous injection
Mepolizumab
--- clinical use
severe asthma with an eosinophilic phenotype in individuals 12+
Mepolizumab
--- contraindications
individuals with a previous hypersensitivity to the drug
Mepolizumab
--- side effects
headache
injection site pain
back pain
fatigue
Reslizumab
anti-human IL-5 monoclonal antibody
shares many of the same properties of mepolizumab
Status asthmaticus
acute, life-threatening exacerbation of asthma that requires aggressive treatment.
Status asthmaticus
--- treatment
1. ?2?selective agonist (albuterol) is continuously given via inhalation. Ipratropium bromide is also given initially via inhalation along with albuterol.
2. A ?2?selective agonist (terbutaline) and a methylxanthine (aminophylline) are initially given via
Magnesium sulfate
causes
-- airway smooth muscle relaxation
-- inhibits acetylcholine release from efferent nerve terminals
-- decreases histamine release from mast cells
Chronic Obstructive Pulmonary Disease (COPD)
obstructive lung disease
can consist of either chronic bronchitis, emphysema, or both
Although most of the airway obstruction in COPD is irreversible, there are some individuals with COPD that do have a partially reversible component of airway obstruction
Most common cause of COPD
smoking
Chronic bronchitis
characterized by hypertrophy and hyperplasia of bronchial mucus glands
This leads to mucus hypersecretion, small airway obstruction, shortness of breath, wheezing, and an expectorating cough.
Emphysema
irreversible destruction of alveolar septa via neutrophil elastase and other proteases.
This leads to enlargement of the alveoli and reduces the surface area available for gas exchange.
Thus, shortness of breath and wheezing are common symptoms of emphyse
COPD: Quick-relief (rescue) meds
Sympathomemtics: ?2?Selective Agonists
----
Albuterol
---- Levalbuterol
Antimuscarinics
---
Ipratropium bromide
COPD: Quick-relief (rescue) meds
--- combination drugs
Ipratropium bromide + albuterol
---- DuoNeb
---- Combivent
1st line therapy for COPD
antimuscarinics (Ipratroprium Bromide)
COPD: Long-term (control) meds
Long-acting ?2?Selective Agonists
---- Arformoterol
----
Formoterol
----
Indacaterol
----
Salmeterol
Antimuscarinics
---- Aclidinium
----
Tiotropium
---- Umecelidinium
Corticosteroids
---- Beclomethasone
----
Budesonie
---- Ciclesonide
----
Fluticasone
--
COPD: Long-term (control) meds
--- combination drugs
Budesonide + Formoterol
--- symbicort
Fluticasone + Salmeterol
--- advair
Fluticasone + Vilanterol
--- breo ellipta
Glycopyrrolate + Formoterol
--- Bevespi Aerosphere
Tiotropium bromide + Olodaterol
--- Sitolto Respimat
Glycopyrrolate + Indacaterol
--- Ut
Indacaterol
ultra-long acting ?2?selective agonist
Its effects can last up to twenty-four hours and is administered once daily.
Tiotropium
ultra-long acting muscarinic antagonist
effect can last for up to twenty- four hours.
Romflumilast
selective PDE4 inhibitor
used for COPD
Glycopyrrolate
long-acting muscarinic antagonist
Allergic rhinitis
(hay fever)
inflammatory disorder of the nasal mucosa, which is a humoral immune response that is triggered by exposure to aeroallergens.
characterized by
-- sneezing
-- rhinorrhea
-- nasal congestion
-- lacrimation,
-- conjunctival, nasal, and pharyngeal itching
sym
Allergic rhinitis
--- pathogenesis
Symptoms of allergic rhinitis occur when an individual, who has been previously sensitized to an aeroallergen, comes in contact with that same aeroallergen on a different occasion.
Upon a second exposure to the aeroallergen, the aeroallergen binds to aero
Pharmacological Agents Used for the Treatment of Allergic Rhinitis
1st generation Antihistamines
---
Diphenhydramine
--- Promethazine
2nd generation Antihistamines
--- Azelastine
---
Cetirizine
---
Fenoxofenadine
---
Loratadine
--- Olopatadine
Decongestants: ?-Adrenergic Sympathomimetics
--- Epinephrine
--- Oxymetazoline
1st generation Antihistamines
Diphenhydramine
Promethazine
1st generation Antihistamines
--- MOA
non-selective inverse agonists of the histamine H1 receptor
inverse agonists because they stabilize the inactive form of the histamine H1 receptor
Because the structure is similar to that of drugs that bind to muscarinic receptors, some of the therapeutic
1st generation Antihistamines
--- route of administration
Oral tout
1st generation Antihistamines
--- pharmacokinetics
rapidly absorbed and easily cross the blood-brain barrier
onset of action between 15-30 minutes following oral administration
primarily metabolized by the liver
excreted in the urine
1st generation Antihistamines
--- clinical use
alleviate the symptoms of allergic rhinitis in both children and adults
1st generation Antihistamines
--- side effects
ue to the ability of these antihistamines to cross the blood-brain barrier and inactive central histamine H1 receptors, sedation is a common side effect
may also lead to sedation due to their antagonism of muscarinic receptors.
2nd generation Antihistamines
Azelastine
Cetirizine
Fexofenadine
Loratadine
Olopatadine
2nd generation Antihistamines
--- MOA
selective inverse agonists of peripheral histamine H1 receptors.
do not exhibit any antagonism of adrenergic or muscarinic receptors.
2nd generation Antihistamines
--- route of administration
Oral
--
ceretirizine
--
fexofenadine
--
loratadine
Topical
-- azelastine
-- olopatadine
2nd generation Antihistamines
--- pharmacokinetics
orally administered agents exhibit great variability in the time required to reach peak plasma concentrations (1?12 hours)
The half-life of the orally administered drugs varies between 8-14 hours
excreted via the feces and urine
2nd generation Antihistamines
--- clinical use
alleviate the symptoms of allergic rhinitis in both children and adults
2nd generation Antihistamines
--- contraindications
individuals with a previous hypersensitivity to these agents
Fexofenadine should not be taken with
grapefruit juice
since this will inhibit the absorption of the drug in the small intestine.
Ketoconazole
and
Erythromycin increase
the plasma levels of Fexo
2nd generation Antihistamines
--- side effects
Because virtually none of the second- generation antihistamines cross the blood-brain barrier, there is no sedation associated with these drugs.
Headache is a common side effect associated with the orally administered second-generation antihistamines.
Decongestants
?-Adrenergic Sympathomimetics
--- Epinephrine
--- Phenylephrine
---
Pseudoephedrine
--- Oxymetazoline
--- Xylometazoline
?-Adrenergic Sympathomimetics
--- MOA
By binding to ??adrenergic receptors on the vascular smooth muscle of blood vessels in the nose, these drugs decrease the size of the inflamed nasal mucosa.
Consequently, there is significant improvement of nasal airway patency
[Decongestants]
?-Adrenergic Sympathomimetics
--- route of administration
Oral
--
pseudoephedrine
Topical
-- epinephrine
-- phenylephrine
-- oxymetazoline
-- xylometazoline
?-Adrenergic Sympathomimetics
--- pharmacokinetics
metabolized by monoamine oxidase and catechol-O-methyltransferase
?-Adrenergic Sympathomimetics
--- clinical use
used to treat the nasal congestion that is often associated with allergic rhinitis
?-Adrenergic Sympathomimetics
--- contraindications
Pseudoephedrine must be used with caution in individuals with pre-existing cardiovascular disease or those taking monoamine oxidase inhibitors
?-Adrenergic Sympathomimetics
--- side effects
few systemic side effects with the topically applied agents
CNS stimulation is the most common side effect of pseudoephedrine
Corticosteroids used for Allergic Rhinitis
Beclomethasone
Budesonide
Ciclesonide
Fluticasone
Mometasone
Triamcinolone
given as nasal sprays
Antimuscarinics used for Allergic Rhinitis
Ipratropium Bromide Nasal Spray
Leukotriene modifiers
Montelukast
Most effective drugs to control symptoms of Allergic Rhinitis
corticosteroids
Cough
defensive reflex that serves to cleanse the upper and lower airways via a sudden, forceful expiration in response to chemical, inflammatory, mechanical, or thermal stimulation.
common symptom of a number of diseases of the upper and lower respiratory trac
The cough reflex is initiated in response to
the stimulation of irritant or stretch receptors in the upper airways, the tracheobronchial tree, and/or the alveoli.
A cough is produced when these receptors are activated and send a signal to the brainstem and higher order brain regions via
vagal
affere
Antitussives
pharmacological agents, which are used to temporarily treat cough that arises from an acute illness (the common cold or influenza)
not used to treat cough that arises from chronic respiratory diseases such as asthma, chronic bronchitis, emphysema, or pulm
Antitussives
-- drug list
*Codeine
Dextromethorphan*
Benzonatate
Codeine
naturally occurring alkaloid, which is found in the opium poppy
Codeine
--- MOA
inhibits the activation of regions in the brainstem and higher order brain regions which generate cough
Ceratussin DAC
syrup
contains:
-- codeine
-- guaifenesin (expectorant)
-- pseudoephedrine (decongestant)
prescription required
Codeine
--- potential for abuse
dose of codeine required to elicit antitussive effects is much less than the dose of codeine required to initiate analgesia.
Thus, if used properly, codeine-containing cough formulations have little potential for abuse.
Codeine
--- pharmacokinetics
excellent oral bioavailability
Dextromethorphan
--- MOA
derivative of the synthetic opioid levorphanol
initiates an antitussive effect in a manner similar to codeine
2x less potent than codeine as an antitussive
Dextromethorphan
--- potential for abuse
devoid of the analgesic, respiratory depressant, and abuse potential of ? opioid agonists such as codeine.
Thus, often found in over-the- counter formulations, including Delsym�, NyQuil�, and Theraflu�
Dextromethorphan
--- side effects
few side effects
can potentiate the activity of monoamine oxidase inhibitors
Benzonatate
non-opioid antitussive
structure is closely related to that of the local anesthetic tetracaine
Benzonatate
--- MOA
anesthetizes the stretch receptors of the lung and thereby diminishing the activity of vagal afferent nerves
Benzonatate
--- route of administration
sold as capsules for oral administration
Benzonatate
--- side effects
hypersensitivity
sedation
dizziness
nausea
Formation of Mucus
Goblet cells and mucous acini within submucosal glands secrete mucins
---- mucins = glycosylated proteins
Mucus is formed when mucins dissolve in
---- water on the surface of the airway epithelium
---- watery secretions released by the serous acini within
Airway surface liquid
Mucus + liquid present on surface of the airway epithelium
2 layers
-- gel layer
-- sol layer
Airway surface liquid: Sol layer
5?7 ?m thick
watery layer that blankets the surface of the underlying airway epithelium
The thickness of the sol layer approximates the length of the cilia extending from the luminal surface of the epithelium
Airway surface liquid: Gel layer
rests upon the sol layer and is a discontinuous mucous blanket.
Since mucus is both elastic and viscous, it can easily trap and hold inhaled foreign matter
Cilia of airway epithelium
As the cilia beats, both the sol and gel layers move in tandem in a cephalad direction
allows for the effective clearance of inhaled foreign particles from the respiratory tract via the "mucociliary escalator"
In normal healthy humans, this process does n
Abnormal mucus secretion
In many diseases involving the respiratory tract
--- goblet cells
--- submucosal glands
--- vagal nerve endings
within the upper and/or lower airways become irritated and leads to excessive mucus production.
Dehydration of airway mucus, which is observed
Mucokinetics
Expectorants
--- Guaifenesin
Mucolytics
--- Acetylcysteine
--- Domase Alpha
Hypoviscosity/Wetting Agents
Guaifenesin
--- MOA
irritates gastric vagal receptor
--> efferent parasympathetic reflexes that ultimately stimulate the release of a less viscous mucus mixture from submucosal glands in the airways.
This reduces mucus viscosity and allows it to be more easily removed from t
Guaifenesin
--- clinical uses
used to remove mucus from the airways in response to the common cold or influenza
not indicated for the removal of mucus from the airways of individuals with chronic lung diseases such as asthma or COPD.
Guaifenesin
--- side effects
nausea/vomiting
diarrhea
Acetylcysteine
--- MOA
disrupts disulfide bonds in mucus, which reduces mucus viscosity.
--> more easily cleared from the airways
Acetylcysteine
--- route of administration
inhalation aerosol
Acetylcysteine
--- clinical uses
Asthma
COPD
Cystic fibrosis
Acetylcysteine
--- side effects
bronchoconstriction
chest tightness
nausea/vomiting
Domase Alpha
highly purified recombinant deoxyribonuclease I (DNase I) from humans
Domase Alpha
--- MOA
cleave extracellular DNA in the mucus
--> reduces mucus viscosity and subsequently enhances its clearance from the airways.
Domase Alpha
--- clinical use
Cystic fibrosis
Domase Alpha
--- route of administration
inhalation aerosol
Domase Alpha
--- side effects
change in or a loss of voice
chest pain
watery eyes
rash
runny nose
These side effects are often short-lived.
Hypoviscosity/Wetting Agents
These agents decrease the viscosity of mucus by diluting the gel layer of the air-surface liquid
Water
Half-Normal Saline (0.5% NaCl)
Normal Saline (0.9% NaCl)
Hypertonic Saline (10% NaCl)
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