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Respiratory Pharmacology Week 5 Anticholinergics and Mucolytics. Anticholinergic Agents. Only effective if bronchoconstriction exists due to cholinergic activity USED FOR COPD PATIENTS only May also be used for asthmatics during an attack. Anticholinergic Agents. - PowerPoint PPT Presentation
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RESPIRATORY PHARMACOLOGYWEEK 5
ANTICHOLINERGICS AND MUCOLYTICS
ANTICHOLINERGIC AGENTS
Only effective if bronchoconstriction exists due to cholinergic activity
USED FOR COPD PATIENTS only
May also be used for asthmatics during an attack
ANTICHOLINERGIC AGENTS In combination with beta-agonist in
patients with COPD on regular treatment regimen who require additional bronchodilation
If you give Spiriva, you DO NOT also give Atrovent. Spiriva given QD
http://www.youtube.com/watch?v=KYS3-Kp672Y
ANTICHOLINERGIC AGENTSAdverse effects
Dry mouth
Cough
EXTREMENLY RARE SYSTEMIC SIDE EFFECTS AS IT DOES NOT CROSS BLOOD BRAIN BARRIER
Nervousness
Headache, dizziness
ANTICHOLINERGIC AGENTS
Adverse effectsPharyngitis
Dyspnea
ATROVENT “Back door bronchodilator” that is used in conjunction with a
front door bronchodilator such as Albuterol or Xopenex. It works by opening up the air passages in your lungs by
preventing cholinergic responses. It is not to be used alone for treating an acute attack of breathing
problems, as it takes some time to work and is usually given as a maintenance drug that excels the use of Albuterol or Xopenex for people with COPD.
Ipratropium is only for inhalation by mouth through an inhaler device or for inhalation by a nebulizer.
ATROVENT Generic Name: Iprtropium Bromide Trade Name: Atrovent Classification: Anticholinergic agent How it works: It relaxes airway muscles by impacting
neurotransmitters sent to the autonomic nervous system, a process different than how beta-agonist drugs act. Sometimes given in addition to shorter-acting bronchodilator therapy, if the shorter-acting meds are not doing enough. Tends to have longer-lasting effect than beta-agonist drugs.
Delivery Device: As an aerosol used in a nebulizer or as a DPI as SPIRIVA® HandiHaler® (tiotropium bromide inhalation powder)
Doses: Unit dose is 0.5 mg or 0.02%, usually mixed with Albuterol or Xopenex.
Side Effects: Fever, infection, headache, skin rash or hives, swelling of lips, tongue or face, vomiting, cough, blurred vision, dry mouth
Contraindications/Percautions- If the following exist take precaution when initiating treatment:
COMBO DRUGS Albuterol and Atrovent DuoNeb (Nebulizer solution) Combivent (MDI)
ANTICHOLINERGIC AGENTSIpratropium bromide
Atrovent MDI: 17 µg/puff, 2 puffs four times dailySVN: 0.02% solution, 0.5 mg, three to four times dailyNasal Spray: 0.03%, 0.06% solution, 2 sprays per nostril, 2 to 4 times daily
Onset: 15 minutesPeak: 1 – 2 hoursDuration: 4 – 6 hours
Ipratropium bromide and Albuterol
CombiventDuoNeb
MDI: Ipratropium 18µg/puff, Albuterol 90 µg/puff, 2 puffs four times dailySVN: Ipratropium 0.5 mg and Albuterol 2.5 mg.
Onset: 15 minutesPeak: 1 – 2 hoursDuration: 4 – 6 hours
Tiotropium bromide
Given with handi haler
Spiriva DPI: 18 µg/inhalation, 1 inhalation daily
Onset: 30 minutesPeak: 3 hoursDuration: 24 hours
MUCUS CONTROLLING DRUGS The general term for medications that are
meant to affect mucus properties and promote secretion clearance is “mucoactive.” These include expectorants, mucolytics, mucoregulatory, mucospissic, and mucokinetic drugs
Mucoactive medications are intended either to increase the ability to expectorate sputum or to decrease mucus hypersecretion
EXPECTORANTS Expectorants are defined as medications that
improve the ability to expectorate purulent secretions.
Medications that increase airway water or the volume of airway secretions, including secretagogues that are meant to increase the hydration of luminal secretions (eg, hypertonic saline or mannitol) and abhesives that decrease the adhesivity of secretions and thus unstick them from the airway (eg, surfactants).
MUCOLYSIS
Mucolysis is the breakdown of mucus.Mucolysis is needed in diseases in
which there is increased mucus production:Cystic FibrosisCOPDBronchiectasisRespiratory Infections
Turberculosis
MUCOLYSIS These diseases result in a marked slowing of
mucus transport Changes in properties of the mucus Decreased ciliary activity Both
http://www.nebraskamed.com/health-library/3d-medical-atlas/237/mucolytics
MUCOLYTICS Acetylcysteine sodium bicarbonate (NaHCO3) Dornase alfa
Pulmozyme
AIRWAY ANATOMY
MUCUS LAYERGel (1 to 2 mm): Gelatinous and sticky
(flypaper)Sol (4 to 8 mm): Watery, Cilia in this layer
Total layer thickness: 5 to 10 mm thickSurface Epithelial Cells
Pseudostratified ciliated columnarSurface goblet cells (6,800/mm2)Serous cells – Sol layerClara cells – Unknown function (enzymes?)
Submucosal GlandBronchial Gland
MUCUS LAYER Bronchial Gland
Found in submucosa Found down to terminal bronchioles Parasympathetic control (Vagus nerve) Provide the majority of mucus secretion Total volume 40 times greater than goblet cells
MUCUS VS. SPUTUM Mucus is the total secretion from mucous
membranes including the surface goblet cell and the bronchial glands.
Sputum is the expectorated secretions that contains mucus, as well as oropharyngeal and nasopharyngeal secretions (saliva).
MUCOCILIARY ESCALATOR Mucosal Blanket
Sol layer Gel layer
Cilia 200 per cell 6 mm in length Beat 1000/min Move mucus 2 cm/min Paralyzed by cigarette smoke
FUNCTION OF MUCOCILIARY ESCALATOR Protective function
Remove trapped or inhaled particles and dead or aging cells.
Antimicrobial (enzymes in sol/gel) Humidification Insulation (prevents heat and moisture loss)
NOTE: No cilia or mucus in lower airways (respiratory bronchioles on down)
Mucus also protects the epithelium from toxic materials.
STRUCTURE AND COMPOSITION OF MUCUS Composition
95% water Need for water intake to replenish Mucus doesn’t easily absorb water once created
3% protein and carbohydrates 1% lipids Less than 0.3% DNA
STRUCTURE AND COMPOSITION OF MUCUS Glycoprotein
Large (macro)molecules Strands of polypeptides (protein) that make up
the backbone of the molecule String of amino acids
Carbohydrate side chains Chemical bonds “hold” mucus together
Intramolecular: Dipeptide links Connect amino acids
Intermolecular: Disulfide and Hydrogen bonds Connect adjacent macromolecules
MUCUS PRODUCTION Normal person produces 100 mL of mucus
per 24 hour period Most is reabsorbed back in the bronchial
mucosa 10 mL reaches the glottis Most of this is swallowed
Mucus production increases with lung disease
INCREASED MUCUS PRODUCTION Smoking Environmental irritants Allergy Infections Genetic predisposition Foreign bodies
INCREASED MUCUS PRODUCTION Viscosity of mucus ¯ Ciliary effectiveness Mucus plugs Airway Resistance Infections Obstructed bronchioles leads to atelectasis
DISEASES THAT INCREASE MUCUS PRODUCTION Chronic Bronchitis Asthma Cystic Fibrosis Acute Bronchitis Pneumonia
Also some drugs (anticholinergics, antimuscarinics)
FACTORS THAT IMPAIR CILIARY ACTIVITY Endotracheal tubes Temperature extremes High FiO2 levels Dust, Fumes, Smoke Dehydration Thick Mucus Infections
FACILITATION OF MUCUS CLEARANCE Provide adequate hydration
Increase fluid intake orally or IV Remove causative factors
Smoking, pollution, allergens Optimize tracheobronchial clearance Use Mucolytics Reduce Inflammation
DAIRY INTAKE No evidence to support the common belief
that drinking milk increases the production of mucus or phlegm and congestion in the respiratory tract
There is a loose cough associated with milk intake
SECRETION MANAGEMENT Increase the depth of the sol layer
Water Saline Expectorants
Alter the consistency of the gel layer Mucolytics
Improve ciliary activity Sympathomimetic bronchodilators Corticosteroids
BLAND AEROSOLS
“Dilutes” mucus molecule Also known as wetting agents
• Function may be more of an irritant than a wetter Types
• Sterile & Distilled Water Humectant Dense aerosols and asthmatics
• Normal (isotonic) Saline• Hypertonic Saline
Increase mucus production• Hypotonic Saline
EXPECTORANTS Iodides
Unclear function SSKI (Saturated Solution of Potassium Iodide)
Guifenesin At high doses, stimulates bronchial gland secretion Robitussin
Not typically given by RTs
COUGH SUPPRESSANTS Vagal stimulation causes a cough. Irritation of pharynx, larynx, and bronchi lead
to a reflex cough impulse. If the cough is dry and non-productive, it may
be desirable to suppress its activity. Cough suppressants depress the cough
center in medulla Narcotic preparations (codeine)Non-Narcotic preparations
(dextromethorphan)Nebulized Xylocain
Caution in patients with thick secretions.
FUNCTION OF MUCOLYTICS Weakening of intermolecular forces binding
adjacent glycoprotein chains Disruption of Disulfide Bonds
Alteration of pH to weaken sugar side chains of glycoproteins
Destruction of protein (Proteolysis) contained in the glycoprotein core of proteolytic enzymes Breaking down of DNA in mucus
FUNCTION OF MUCOLYTICSDisruption of Disulfide Bonds
acetylcysteine breaks the bonds by substituting a sulfhydril radical –HS
FUNCTION OF MUCOLYTICS Alteration of pH
Sodium Bicarbonate 2% NaHCO3 solutions are used to increase the pH of mucus by weakening carbohydrate side chains
Can be injected directly into the trachea or aerosolized (2-5 mL)
FUNCTION OF MUCOLYTICS Proteolysis
Dornase alfa (Pulmozyme) Attacks the protein component of the mucus
HAZARD OF MUCOLYTICS The problem with all three mucolytics is that
they destroy the elasticity of mucus while reducing the viscosity.
Elasticity is crucial for mucociliary transport. The patient must be able to cough
adequately to remove the mucus.
ACETYLCYSTEINE Indications
Mucolytic by aerosol or direct instillation into the ET tube.
Given orally to reduce liver injury with acetaminophen (Tylenol) overdose. Mix with cola or given by NG tube.
MUCOMYST Draw up with a syringe and instill into
nebulizer
ACETYLCYSTEINE Indicated for treatment of
accumulated airway secretionsChronic obstructive pulmonary disease
Bronchiectasis
Acute tracheobronchitis
ACETYLCYSTEINEUsed to treat or prevent liver
damage in acetaminophen overdose (patient drinks it)
Reduces viscosity of mucus by substituting sulfhydryl group for disulfide group
ACETYLCYSTEINE
May be directly instilled during bronchoscopy to remove mucus plugs
Normal dosage via SVN: 3 – 5 ml
ACETYLCYSTEINESide effects
Airway obstruction secondary to rapid liquefaction of secretions
Disagreeable odor (rotten eggs)
Nausea
Rhinorrhea
Bronchospasm
ACETYLCYSTEINEDiscard 96 hours after opening,
usually refrigerated
Should not be administered in the presence of thin secretions
ALWAYS GIVE WITH A BRONCHODILATOR
DOSAGE OF ACETYLCYSTEINE Concentration
10% or 20% Dosage
3-5 mL of a 20% solution TID or QID Maximum dose 10 mL
6-10 mL of a 10% solution TID or QID Maximum dose 20 mL
1-2 mL of a 10% or 20% for direct instillation
HAZARDS OF ACETYLCYSTEINE Bronchospasm
Asthma – may be a problem during an acute asthma attack. Anecdotal; lack of evidence
If used with asthma, use 10% and mix with a bronchodilator (preferably a short-acting agent).
Increase mucus production Be prepared to suction a patient who cannot
cough or who is intubated.
HAZARDS OF ACETYLCYSTEINE Do not mix with antibiotics in the same
nebulizer (incompatible). Nausea & Vomiting
Disagreeable odor (smells like rotten eggs) due to the hydrogen sulfide.
Open vials should be used within 96 hours to prevent contamination.
SODIUM BICARBONATE Weak base. Increasing the pH of mucus weakens the
polysaccharide chains. Available as 1.4%, 5%, and 7.5% solutions. Dosage: 2-5 mL of a 2.5% solution Q4-Q8.
Mix 5% solution with equal volume of sterile water.
Can be irritating (especially the 5 & 7.5% solutions).
DORNASE ALFA Pulmozyme Clone of the natural human pancreatic DNase
enzyme which digests extracellular DNA. Dornase alfa is a solution of recombinant
human deoxyribonuclease (rhDNase) Approved by FDA in 1994
DORNASE ALFA – PULMOZYME Indications
Reduce viscosity of secretions during an infection by breaking down extracellular DNA.
Used in cystic fibrosis, chronic bronchitis or bronchiectasis. Maintenance therapy in CF
Has no effect on non-infected sputum. http://www.pulmozyme.com/hcp/moa.html
INFECTION Increased WBCs – neutrophilsWBCs contain DNAWBCs release DNA when they die
which increases the viscosity of secretions
Decreases the effectiveness of antibiotics
Pancreas produces an enzyme called deoxyribonuclease (DNase) which breaks down the DNA
FUNCTION OF RHDNASE
COMMON SIDE EFFECT OF PULMOZYME Voice Alteration Pharyngitis/Laryngitis Rash Chest pain Conjunctivitis
Contraindicated in patients hypersensitive to Chinese Hamster Ovary cell products.
CONCENTRATION AND DOSAGE Supplied in single dose vials (unit dose). Concentration is 1 mg/mL (0.1% solution). Each vial contains 2.5 mg /2.5 mL. Administer one unit dose vial (2.5 mL) daily.
Some patients may benefit from BID administration.
Do not mix or dilute with other drugs. Nebulizer specific (per manufacturer).
MUCUS-CONTROLLING AGENTS Dornase alfa (Pulmozyne)
Indicated for the treatment of cystic fibrosis (CF) to reduce number of infections and improve pulmonary function
Breaks down DNA material from neutrophils found in purulent secretions
Normal dosage via SVN: 2.5 mg/ampule, 1 ampule daily
DORNASE ALFA
Side effects (does not cause bronchospasm)Pharyngitis
Laryngitis
Chest pain
SODIUM BICARBONATE Not commonly used, but changes the pH of
mucus. Aerosolizeda. Action: Adjusts the pH of mucus, decreasing the surface tension to facilitate mucolytic action. b. Indication: tracheal irrigation c. Dosage:
- irrigation: 2-5 ml of 2-8.4% NaHC03 in 2-5 ml NS
d. Precaution: mucosal irritation
ETHYL ALCOHOLEthyl Alcohol 30-50% (Ethanol) a. Indication: - pulmonary edema (OLD treatment) Defoaminant b. Precautions: - mucosal irritation - intoxication - vasodilation
AQUEOUS AEROSOLS (BLAND AEROSOLS, NON MEDICATED) Indications
Thin secretions
Used as diluent for medications
May be used to induce sputum (hypertonic saline); >0.9% saline. Normal saline is 0.9% and has no effect in the airway, used a diluent to most medications
AQUEOUS AEROSOLSDistilled water
Osmolarity – hypotonic
Will be absorbed into interstitial space
May cause or contribute to edema
Hypotonic rarely given, if it is given, use a ultra sonic nebulizer
AQUEOUS AEROSOLS Isotonic saline (0.9%)
Osmolarity – equal to lung tissue
Also known as normal saline
Used as diluent for medication
AQUEOUS AEROSOLSHypotonic saline (<0.9%,
commonly 0.45% or half normal) Osmolarity – less than that of lung
Used in ultrasonic nebulizers – due to evaporation, solution will become isotonic by the time it reaches the airway
Can increase resistance due to swelling of secretions
AQUEOUS AEROSOLSHypertonic saline (>0.9%)
Osmolarity – greater than that of lung tissue
Used for sputum induction
AQUEOUS AEROSOLSHypertonic saline (>0.9%)
Draws fluid from interstitial space to mucus bed, thinning secretions
May cause bronchospasm, especially in hyperactive airways