Respiratory Pharmacology

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Respiratory Pharmacology

• Tis the Season for Sneezin and
• Wheezin

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(No Transcript)
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Human Nervous System

• Central Nervous System
• Brain
• Spinal Cord
• Peripheral Nervous System
• Arising from the vertebrae
• Autonomic Nervous System
• controlled through hormonal mediator release

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Autonomic Nervous System

• Parasympathetic
• neural transmitter substance
• acetylcholine
• cholinergic response
• responsibility
• maintaining calm operations
• smooth muscle constriction
• bronchoconstriction
• pulmonary vasoconstriction

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Autonomic Nervous System

• Sympathetic
• neural transmitter substance
• nor-epinephrine adrenaline
• adrenergic response
• responsibility
• Fight or Flight
• smooth muscle relaxation
• bronchodilation
• pulmonary vasodilation

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The Role of Cyclic AMP

• Smooth Muscle Relaxation
• Promotes bronchodilation
• Pulmonary Vasodilation
• Beta 2 Effect

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What Does It Look Like?
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A Closer Look
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How Does It Work?
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2nd Messenger SystemsGeneral Function
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2nd Messenger Systems

• For a second messenger to work effectively it
  must have the following characteristics
• Amplification when a few hormone molecules
  signal the cell, it needs to respond with a
  signal that is strong enough to get a job done
  without repeated high levels of stimulation.
• Control --- eventually a response must be shut
  down, and there are instances when its necessary
  to respond a little or a lot so control is
  needed.
• Specificity when a hormone is released, a given
  cell should respond in a specific way. Not all
  cells will respond to this hormone. The hormone
  may not have the same effect in all the cells tat
  do not respond.

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Receptors and Effectors
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Receptor Function

• As you can imagine the challenge of pharmacology
  is to find agonists () and antagonists (-) for
  specific receptors. For instance, beta
  stimulation increases the heart rate and dilates
  the smooth muscle leading to the bronchi. If a
  beta blocker is used to slow the heart rate, it
  could have a very undesirable effect of cutting
  off oxygen. However B1 receptors primarily affect
  the heart and B2 receptors the constriction of
  the airways

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Chronic Obstructive Airway Diseases

• Cystic Fibrosis
• Bronchitis acute - chronic
• Asthma
• Bronchiectasis
• Emphysema

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Manifestations of An Asthma Attack

• Bronchospasm
• Irritable twitchy Airways
• Inflammation
• Increased Mucous Production

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Classes of Respiratory Drugs

• Sympathomimetic Amines
• Parasympatholytics
• Methyl Xanthines
• Mediator Antagonists
• Inhaled Steroids
• Mucolytics
• Anti-Infectives
• Exogenous Surfactants

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Sympathomimetic Amines

• Also Called
• Beta agonists
• Beta adrenergic bronchodilators
• Catecholemines
• Alpha agonists
• decongestant
• vasopressor
• vasoconstrictor
• Examples
• albuterol sulfate (Proventil
• metaproteranol (Alupent
• epinephrine

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Sympathomimetic Amines

• Effects
• Short Term
• acute rescue use
• immediate response
• albuterol (Proventil)
• Long Term
• maintenance
• prophylaxis
• salmeterol (Serevent)

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Sympathomimetic Amines

• Major Action
• Stimulate production of cyclic AMP
• Smooth muscle relaxation
• Bronchodilation
• Pulmonary vasodilation
• Routes
• inhaled via nebulizer or MDI
• PO, GI
• sub-Q ( terbutaline

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Sympathomimetic Amines

• Side Effects
• Cardiovascular (B1)
• tachycardia
• hypertension
• Somatic tremor
• Nausea
• Insomnia

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Parasympatholytics

• Also Called
• Anticholinergics
• Examples
• atropine sulfate
• ipratropium bromide ( Atrovent
• Major Action
• inhibits acetylcholine release
• limits bronchoconstriction

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Parasympatholytics

• Routes
• inhalation via nebulizer and MDI
• Side Effects
• cardiovascular
• tremors
• peripheral pooling
• atropine flush
• nausea
• allergic reactions (Atrovent)
• drying of secretions

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Methyl Xanthines

• Also Called
• Xanthines
• Phosphodiesterase Inhibitors
• PDIs
• Examples
• theophylline
• Aminophylline
• Theodur
• Luflyn

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Methyl Xanthines

• Major Action
• Inhibits the breakdown of cyclic AMP into 5 AMP
• maximizes cyclic AMP
• Routes
• IV
• PO
• Cannot aerosolize

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Methyl Xanthines

• Side Effects
• nausea (titrate)
• tachycardia
• CNS stimulation
• insomnia
• caffeine-like effects
• bad taste in mouth
• Therapeutic Serum Levels
• 10 to 20 mcg/m/L

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Mediator Antagonists

• Also Called
• Prophylactic bronchodilators
• Examples
• cromolyn sodium (Intal)
• nedocromil (Tilade)
• leukotrine inhibitors
• montelukast (Singulaire)
• zafirlukast (Accolate)
• zileuton (Zyflo)

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Mediator Antagonists

• Major Action
• mast cell inhibition
• cromolyn sodium (Intal)
• nedocromil (Tilade)
• leukotrine inhibition
• montelukast (Singulaire)
• zafirlukast (Accolate)
• zileuton (Zyflo)

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Mediator Antagonists

• Routes
• cromolyn sodium (Intal)
• MDI, DPI, SVN (ampoule)
• Intranasal spray
• nedocromil (Tilade)
• MDI
• zafirlukast, montelukast zileuton
• oral tablets

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Mediator Antagonists

• Side Effects
• Inappropriate usage
• Not for use in acute episodes
• May cause bronchospasm via mechanical irritation

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Inhaled Corticosteroids

• Examples
• Dexamethasone sodium phosphate Decadron,
  Respirahaler
• Beclomethasone dipropionate Beclovent,
  Vanceril,
• Triamcinolone acetonide Azmacort
• Flunisolide Aerobid
• Fluticasone propionate Flovent
• Budesonide Pulmicort

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Inhaled Corticosteroids

• Major Actions
• anti-inflammatory
• modification of cell transcription
• peak action or effectiveness from hours to days
  depending on the cellular metabolism
• not for acute relief
• dosages vary
• initially used to cause bursts for airway
  clearance

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Inhaled Corticosteroids

• Routes
• MDI
• 2 puffs
• 5 to 10 second breath hold
• 1 minute rest between puff
• rinse mouth after treatment
• if Bronchodilator via SVN is given, give steroid
  10 minutes following SVN treatment
• SVN (2000)
• Pulmocort
• 0.5 ml undiluted

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Inhaled Corticosteroids

• Side Effects
• Short-Term
• anaphylaxis beclomethoasone
• yeast infections
• trouble breathing
• wheezing
• a tight feeling in the chest
• a change in behavior
• feeling depressed
• feeling restless or nervous
• dry mouth

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Inhaled Corticosteroids

• Side Effects
• Long-Term
• moon face (Cushingoid)
• fluid retention
• weight gain
• increase in fat pad dowagers hump
• osteoporosis
• pathologic fractures
• glomerulonephritis

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Mucokinetic Agents

• Also Called
• Mucolytics
• Mucoactive agents
• Mucous controlling agents
• Examples
• Mucomyst n-acetylcysteine
• Pulmozyme dornase alfa
• Bland aerosol therapy
• 2 sodium bicarbonate

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Mucokinetic Agents

• Major Actionss
• Mucomyst breaks down di-sulfide bonds
• Pulmozyme is a proteolytic used primarily for the
  treatment of cystic fibrosis patients
• Bland aerosols mechanically hydrate and loosen
  secretions
• 2 sodium bicarbonate may hydrate or affect
  mucous bonding

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Mucokinetic Agents

• Routes of Administration
• primarily via SVN
• bland aerosols may be administered via large
  volume nebulizers
• may be instilled into endotracheal tubes during
  bronchoscopy
• Mucomyst n-acetylcysteine may be administered
  via ingestion for acetominophen Tylenol
  overdose

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Mucokinetic Agents

• Side Effects
• n-acetylcysteine Mucomyst
• may precipitate wheezing a bronchodilator should
  be added to the aerosol
• airway obstruction due to liquefaction of
  secretions
• nausea and rhinorrhea
• odor hydrogen sulfide
• increased drug concentration at the end of
  treatment
• incompatibility with anti-infectives

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Mucokinetics

• dornase alfa Pulmozyme
• pharyngitis, laryngitis
• rash
• chest pain
• conjunctivitis
• respiratory problems such as cough up to
  pneumothorax
• weight loss
• GI syndrome

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Mucokinetics

• Bland Aerosols
• swelling of dried secretions
• fluid overload
• bronchospasm due to mechanical irritation
• mucosal drying
• 2 sodium bicarbonate
• mechanical irritation
• metabolic alkalosis

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Anti Infectives

• Also Called
• Antimicrobials, Antibiotics
• Examples
• Pentamidine isethionate (Pentam, NebuPent
• Ribavirin - virazole

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Anti Infectives

• Aerosolized antibiotics
• gentamicin
• carbenicillin
• colomycin
• ceftazidime
• gentamicin
• tobramycin
• garamycin

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Anti Infectives

• Major Action
• Pentamidine - treatment of pneumocystis carinii
  pneumonia PCP - a protozoan.
• Ribavirin - treatment of respiratory syncytial
  virus RSV
• Aerosolized antibiotics - bacterial organism
  specific

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Anti Infectives

• Routes of Administration
• Pentamidine - oral or aerosolized every two weeks
• Ribavirin - aerosolized via small particle
  aerosol generator SPAG
• Aerosolized antibiotics - SVN

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Anti Infectives

• Side Effects
• Pentamidine
• cough, bronchial irritation, bronchospasm and
  wheezing, shortness of breath, fatigue, bad or
  metallic taste, pharyngitis, conjunctivitis,
  rash and chest pain.
• Decreased appetite, dizziness, rash, nausea,
  night sweats, chills, spontaneous pneumothorax,
  neutropenia, pancreatitis, renal insufficiency
  and hypoglycemia.
• Side effects v. the disease ????

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Anti Infectives

• Side Effects
• Ribavirin
• skin rash, eyelid erythema and conjunctivitis.
• When used in conjunction with mechanical
  ventilators may cause sticking of exhalation
  valve and other sensors.
• Pulmonary function may deteriorate

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Anti Infectives

• Side Effects
• Aerosolized Antibiotics
• bronchospasm
• anaphylaxis
• need for higher flow rates
• right drug - right job

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Exogenous Surfactants

• Examples
• Survanta beractant - natural bovine extract
• Exosurf colfosceril palmitate with cetyl
  alcohol and tyloxapol - -a synthetic mixture

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Exogenous Surfactants

• Major Action
• Replacement therapy for low LS ratios
• Rescue for RDS infants
• Prophylactic in infants less than 1350 grams or
  who larger infants who show signs of respirator
  distress

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Exogenous Surfactants

• Routes of Administration
• Instilled directly into endotracheal tubes
• Side Effects
• Procedural
• Physiological

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Summary

• Indications for Respiratory Drugs
• bronchodilation
• secretion control
• anti-infection
• prophylaxis
• rescue
• maintenance
• anti-inflammatory
• right tool - right job