chapter 32 airway pharmacology. mosby items and derived items © 2009 by mosby, inc., an affiliate...

Chapter 32 Chapter 32

Airway PharmacologyAirway Pharmacology

Mosby items and derived items © 2009 by Mosby, Inc., an affiliate of Elsevier Inc. 2

ObjectivesObjectives

• • Analyze three phases that constitute the course of drug action from Analyze three phases that constitute the course of drug action from dose to effect.dose to effect.

•• Describe classes of drugs that are delivered via the aerosol route.Describe classes of drugs that are delivered via the aerosol route.

•• Compare mode of action, indications, and adverse effects that Compare mode of action, indications, and adverse effects that characterize each major class of aerosolized drug.characterize each major class of aerosolized drug.

•• Compare available aerosol formulations, brand names, and dosages for Compare available aerosol formulations, brand names, and dosages for each specific drug class.each specific drug class.

• • Select the appropriate drug class for a given patient or clinical situation.Select the appropriate drug class for a given patient or clinical situation.

• • Assess the outcomes for each class of aerosol drug therapy.Assess the outcomes for each class of aerosol drug therapy.


Principles of Pharmacology Principles of Pharmacology

The drug administration phaseThe drug administration phase The method by which a drug is made available to the bodyThe method by which a drug is made available to the body

Aerosol therapy is the most common route for drug Aerosol therapy is the most common route for drug administration to the pulmonary patient.administration to the pulmonary patient.

The most common devices used to administer inhaled aerosols The most common devices used to administer inhaled aerosols are the MDI, small-volume nebulizer, and dry-powder inhaler.are the MDI, small-volume nebulizer, and dry-powder inhaler.


Principles of Pharmacology (cont.)Principles of Pharmacology (cont.)

The drug administration phase (cont.)The drug administration phase (cont.) The advantages of inhaled aerosols areThe advantages of inhaled aerosols are

Can use smaller doses as compared to the systemic routeCan use smaller doses as compared to the systemic route Onset of drug is rapidOnset of drug is rapid Delivery is to the specific organ needing treatmentDelivery is to the specific organ needing treatment Less systemic side effectsLess systemic side effects



The pharmacokinetic phaseThe pharmacokinetic phase Describe the time course and disposition of a drug in the body Describe the time course and disposition of a drug in the body

based on its absorption, distribution, metabolism, and based on its absorption, distribution, metabolism, and elimination.elimination.

Aerosols made up of medications that are fully ionized have little Aerosols made up of medications that are fully ionized have little or no systemic side effects (e.g., ipratropium).or no systemic side effects (e.g., ipratropium).



The pharmacodynamic phaseThe pharmacodynamic phase Describe the mechanisms of drug action by which a drug Describe the mechanisms of drug action by which a drug

molecule causes its effects in the bodymolecule causes its effects in the body

Drug effects are caused by combination of a drug with a Drug effects are caused by combination of a drug with a matching receptor.matching receptor.



Airway receptors and neural control of the lungAirway receptors and neural control of the lung Sympathetic (adrenergic) and parasympathetic (cholinergic) Sympathetic (adrenergic) and parasympathetic (cholinergic)

receptors are in the lung.receptors are in the lung.

The neurotransmitter in the sympathetic system is The neurotransmitter in the sympathetic system is norepinephrine (epinephrine).norepinephrine (epinephrine).

The neurotransmitter in the parasympathetic system is The neurotransmitter in the parasympathetic system is acetylcholine.acetylcholine.



Airway receptors and neural control of the lungAirway receptors and neural control of the lung

(cont.)(cont.)Adrenergic: drug that stimulates a receptor responding to Adrenergic: drug that stimulates a receptor responding to

norepinephrine or epinephrinenorepinephrine or epinephrine

Antiadrenergic: drug that blocks a receptor for norepinephrine or Antiadrenergic: drug that blocks a receptor for norepinephrine or epinephrineepinephrine



Airway receptors and neural control of the lung (cont.)Airway receptors and neural control of the lung (cont.)Cholinergic: drug that stimulates a receptor for acetylcholineCholinergic: drug that stimulates a receptor for acetylcholine

Anticholinergic: drug that blocks a receptor for acetylcholineAnticholinergic: drug that blocks a receptor for acetylcholine


Adrenergic BronchodilatorsAdrenergic Bronchodilators

Indications for useIndications for use Indication for short-acting agentsIndication for short-acting agents

For relief of acute reversible airflow obstructionFor relief of acute reversible airflow obstruction Indication for long-acting agentsIndication for long-acting agents

For maintenance bronchodilation in patients with obstructive For maintenance bronchodilation in patients with obstructive lung diseaselung disease

Indication for racemic epinephrineIndication for racemic epinephrine To reduce airway swelling after extubation or with acute To reduce airway swelling after extubation or with acute

upper airway inflammation from croupupper airway inflammation from croup


Adrenergic Bronchodilators (cont.)Adrenergic Bronchodilators (cont.)

Mode of action and effectsMode of action and effects -Receptor stimulation: causes vasoconstriction and a -Receptor stimulation: causes vasoconstriction and a

vasopressor effectvasopressor effect

11-Receptor stimulation: causes increased heart rate and heart -Receptor stimulation: causes increased heart rate and heart

contractilitycontractility

22-Receptor stimulation: relaxes bronchial smooth muscle, -Receptor stimulation: relaxes bronchial smooth muscle,

stimulates mucociliary activitystimulates mucociliary activity



Adverse effectsAdverse effects Older adrenergic agents such as isoproterenol commonly Older adrenergic agents such as isoproterenol commonly

caused tachycardia, palpitations, and nervousness.caused tachycardia, palpitations, and nervousness.

Newer Newer 22-selective agents are safe, with tremor as the primary -selective agents are safe, with tremor as the primary

side effect.side effect.

Tolerance to the drug may occur.Tolerance to the drug may occur.



Assessment of bronchodilator therapyAssessment of bronchodilator therapy Based on the indication(s) for the aerosol agentBased on the indication(s) for the aerosol agent

Vital signs, breath sounds, and breathing pattern should be Vital signs, breath sounds, and breathing pattern should be evaluated before and after treatment.evaluated before and after treatment.

The patient’s subjective response is important to evaluate.The patient’s subjective response is important to evaluate.



Indications for useIndications for use Indication for anticholinergic bronchodilatorIndication for anticholinergic bronchodilator

Indicated for maintenance bronchodilator therapy for COPD Indicated for maintenance bronchodilator therapy for COPD patientspatients

Indication for combined anticholinergic and Indication for combined anticholinergic and -agonist-agonist COPD patientsCOPD patients Asthma patientsAsthma patients



Mode of action Mode of action These agents act as competitive antagonists for acetylcholine These agents act as competitive antagonists for acetylcholine

on airway smooth muscle.on airway smooth muscle.

Adverse effectsAdverse effects Ipratropium bromide and tiotropium bromide have few systemic Ipratropium bromide and tiotropium bromide have few systemic

side effects since they are fully ionized and are not absorbed. side effects since they are fully ionized and are not absorbed.


Mucus-Controlling AgentsMucus-Controlling Agents

NN-Acetyl--Acetyl-LL-cysteine (NAC)-cysteine (NAC) Given by aerosol or direct tracheal instillationGiven by aerosol or direct tracheal instillation Given to reduce accumulation of airway mucusGiven to reduce accumulation of airway mucus May cause bronchospasm due to its irritating side effectsMay cause bronchospasm due to its irritating side effects

Dornase alfaDornase alfa Indicated for the management of cystic fibrosisIndicated for the management of cystic fibrosis May cause voice alteration, pharyngitis, rash, or chest painMay cause voice alteration, pharyngitis, rash, or chest pain


Mucus-Controlling Agents (cont.)Mucus-Controlling Agents (cont.)


Inhaled CorticosteroidsInhaled Corticosteroids

Indications and purposesIndications and purposes Orally inhaled preparations are used for antiinflammatory Orally inhaled preparations are used for antiinflammatory

maintenance therapy of persistent asthma and severe COPD.maintenance therapy of persistent asthma and severe COPD.

The use of nasal steroids is for control of allergic and The use of nasal steroids is for control of allergic and nonallergic rhinitis. nonallergic rhinitis.


Inhaled Corticosteroids (cont.)Inhaled Corticosteroids (cont.)

Mode of actionMode of action Lipid-soluble drugs that act on intracellular receptorsLipid-soluble drugs that act on intracellular receptors

Full antiinflammatory effects require hours to days.Full antiinflammatory effects require hours to days.

Will not provide immediate relief of dyspnea from airways Will not provide immediate relief of dyspnea from airways obstructionobstruction


Inhaled Corticosteroids (cont.)Inhaled Corticosteroids (cont.)Adverse effectsAdverse effects


Inhaled Corticosteroids (cont.)Inhaled Corticosteroids (cont.)

Assessment of drug therapyAssessment of drug therapy Use strategies for assessment similar to those used for Use strategies for assessment similar to those used for

evaluation of bronchodilators.evaluation of bronchodilators.

In additionIn addition Make sure patient understands the importance of consistent Make sure patient understands the importance of consistent

use and not to use it as a rescue drug.use and not to use it as a rescue drug. Instruct patient in the use of a peak flowmeter.Instruct patient in the use of a peak flowmeter. Assess patient for side effects.Assess patient for side effects.


Nonsteroidal Antiasthma DrugsNonsteroidal Antiasthma Drugs

A growing class of drugs for the treatment of asthmaA growing class of drugs for the treatment of asthma

Three types existThree types exist Comolyn-like agents (cromolyn, nedocromil sodium)Comolyn-like agents (cromolyn, nedocromil sodium) Antileukotrienes (zafirlukast, zileuton)Antileukotrienes (zafirlukast, zileuton) Monoclonal antibodies or anti-IgE agents (omalizumab)Monoclonal antibodies or anti-IgE agents (omalizumab)


Nonsteroidal Antiasthma Nonsteroidal Antiasthma Drugs (cont.)Drugs (cont.)

Indications for useIndications for use Used for prophylactic management (control) of mild to moderate Used for prophylactic management (control) of mild to moderate

persistent asthmapersistent asthma

May be used as an alternative to steroids in patients with May be used as an alternative to steroids in patients with persistent asthma symptomspersistent asthma symptoms

Offer no benefit for acute airways obstruction in asthmaOffer no benefit for acute airways obstruction in asthma



Adverse effectsAdverse effectsCromolyn-like agentsCromolyn-like agents

- Considered extremely safe- Considered extremely safe

Antileukotriene agentsAntileukotriene agents

- Headache, dyspepsia, liver enzyme elevation- Headache, dyspepsia, liver enzyme elevation

OmalizumabOmalizumab

- Injection site reaction, viral infections- Injection site reaction, viral infections



Assessment of drug therapyAssessment of drug therapy Strategies similar to those used to assess initial bronchodilator Strategies similar to those used to assess initial bronchodilator

therapy therapy

Clinician should verify that the patient understands that these Clinician should verify that the patient understands that these medications are controller drugs and not rescue agents.medications are controller drugs and not rescue agents.


Aerosolized Antiinfective AgentsAerosolized Antiinfective Agents

Pentamindine isethionatePentamindine isethionateHas been used in the past for the treatment of Has been used in the past for the treatment of Pneumocystis carinii Pneumocystis carinii

pneumonia (PCP)pneumonia (PCP)

Due to limited efficacy, pentamindine is no longer recommended Due to limited efficacy, pentamindine is no longer recommended for PCP treatmentfor PCP treatment

Common side effects include cough, bronchospasm and Common side effects include cough, bronchospasm and wheezing, dyspnea, etc.wheezing, dyspnea, etc.


Aerosolized Antiinfective Aerosolized Antiinfective Agents (cont.)Agents (cont.)

RibavirinRibavirin An antiviral agent used in the treatment of severe lower An antiviral agent used in the treatment of severe lower

respiratory tract infections caused by respiratory syncytial virus respiratory tract infections caused by respiratory syncytial virus (RSV)(RSV)

Administration of the aerosol requires the use of a small particle Administration of the aerosol requires the use of a small particle aerosol generator (SPAG).aerosol generator (SPAG).

Cost-effectiveness continues to be debated.Cost-effectiveness continues to be debated.



Ribavirin (cont.)Ribavirin (cont.) Adverse effectsAdverse effects

Skin rashSkin rash Eyelid erythemaEyelid erythema ConjunctivitisConjunctivitis

Patients and practitioners who are pregnant should not be Patients and practitioners who are pregnant should not be exposed to ribavirin.exposed to ribavirin.



Inhaled tobramycinInhaled tobramycinIntended to manage chronic infection with Intended to manage chronic infection with P. aeruginosaP. aeruginosa in in

patients with cystic fibrosispatients with cystic fibrosis

Side effects with the inhaled route are usually minimal and Side effects with the inhaled route are usually minimal and include voice alteration and tinnitus.include voice alteration and tinnitus.



Colistimethate sodiumColistimethate sodium An antibiotic used to treat sensitive strains of gram-negative An antibiotic used to treat sensitive strains of gram-negative

bacilli, particularly bacilli, particularly P. aeruginosaP. aeruginosa

The most common side effect seen with the aerosol route is The most common side effect seen with the aerosol route is bronchospasm.bronchospasm.



Inhaled zanamivirInhaled zanamivir An inhaled powderAn inhaled powder

Indicated for the treatment of uncomplicated acute illness due to Indicated for the treatment of uncomplicated acute illness due to influenza virus in adults and children at least 7 years of ageinfluenza virus in adults and children at least 7 years of age

Can cause bronchospasm and allergic reactionsCan cause bronchospasm and allergic reactions



Use of aerosolized amphotericin BUse of aerosolized amphotericin B May be used in lung transplantation patients to prevent or treat May be used in lung transplantation patients to prevent or treat

atypical infectionatypical infection

The aerosolized route reduces the risk of renal damage.The aerosolized route reduces the risk of renal damage.

Can cause nausea, vomiting, and bronchospasmCan cause nausea, vomiting, and bronchospasm


Inhaled Pulmonary VasodilatorsInhaled Pulmonary Vasodilators

Nitric oxide (INOmax)Nitric oxide (INOmax) Indicated for the treatment of neonates (<34 weeks) with Indicated for the treatment of neonates (<34 weeks) with

hypoxic respiratory failure and pulmonary hypertensionhypoxic respiratory failure and pulmonary hypertension

It relaxes vascular smooth muscle in the pulmonary vasculature. It relaxes vascular smooth muscle in the pulmonary vasculature.

The most common side effect is hypotension.The most common side effect is hypotension.


Inhaled Pulmonary Inhaled Pulmonary Vasodilators (cont.)Vasodilators (cont.)

IloprostIloprost Used in the treatment of pulmonary hypertensionUsed in the treatment of pulmonary hypertension

Administered with the I-neb or Prodose nebulizerAdministered with the I-neb or Prodose nebulizer

Acts by dilating the pulmonary vasculatureActs by dilating the pulmonary vasculature

Side effects include headache and increased coughSide effects include headache and increased cough


Antidiabetic AgentsAntidiabetic Agents

Exubera is an inhaled insulin.Exubera is an inhaled insulin.

Used to control hyperglycemia in diabeticsUsed to control hyperglycemia in diabetics

Should not be used by patients who smokeShould not be used by patients who smoke

Potential side effects include cough, dyspnea, pharyngitis, Potential side effects include cough, dyspnea, pharyngitis, increased sputum, and epistaxis.increased sputum, and epistaxis.

chapter 32 airway pharmacology. mosby items and derived items © 2009 by mosby, inc., an affiliate...

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