Inhaled Drugs beyond Inhaled Drugs beyond BronchodilatorsBronchodilators

China 4000 Years AgoChina 4000 Years Ago

Bennet’s inhalerBennet’s inhaler

This may be the earliest This may be the earliest published image of an published image of an  inhalation device. In  inhalation device. In 1654 an English 1654 an English physician, Christopher physician, Christopher Bennet, himself suffering Bennet, himself suffering with consumption, with consumption, Bennet experimented on Bennet experimented on himself with a number of himself with a number of different remedies.different remedies.

First isolation attempts First isolation attempts

The Plague doctor The Plague doctor illustration is from Devils, illustration is from Devils, Drugs & Doctors Drugs & Doctors (Haggard, 1929). It (Haggard, 1929). It depicts the protective depicts the protective clothing used by doctors clothing used by doctors treating the plague in treating the plague in Marseilles c1720. The Marseilles c1720. The beak was filled with beak was filled with spices to purify the spices to purify the inhaled air. At the time it inhaled air. At the time it was believed that plague was believed that plague was contagious by touch, was contagious by touch, hence the leather gloves hence the leather gloves and wand.and wand.

Kirkwood’s inhalerKirkwood’s inhaler

This advertisement This advertisement from 1874 1888 from 1874 1888 shows Kirkwood’s shows Kirkwood’s inhaler, an apparatus inhaler, an apparatus for delivering fuming for delivering fuming ammonium chloride. It ammonium chloride. It was used as an was used as an antiseptic agent, and antiseptic agent, and was recommended at was recommended at times of contagion times of contagion and epidemic. and epidemic.

Page's InhalersPage's Inhalers

Page's Inhalers were smoked Page's Inhalers were smoked "for the temporary relief of the "for the temporary relief of the paroxysms of asthma and to paroxysms of asthma and to aid in the relief of the aid in the relief of the discomforts dust to excessive discomforts dust to excessive secretions in the nasal secretions in the nasal passage associated with hay passage associated with hay fever and simple nasal fever and simple nasal irritations. Page's Inhalers irritations. Page's Inhalers were produced by the were produced by the Consolidated Chemical Consolidated Chemical Company of Grand Rapids, Company of Grand Rapids, Michigan which was Michigan which was established in 1892.established in 1892.

Early inhalersEarly inhalers

Early Home CareEarly Home Care

The ‘Indispensible’ The ‘Indispensible’ inhaler was created by Dr inhaler was created by Dr Arnold, and was Arnold, and was described as permitting described as permitting the sick to follow the the sick to follow the treatment of Dr Arnold at treatment of Dr Arnold at their own homes. their own homes.

Treatments while you sleep Treatments while you sleep

First Listed inhaled MedicationsFirst Listed inhaled Medications

The first official formulae of inhalation The first official formulae of inhalation medicines were listed in the medicines were listed in the British Pharmacopoeia of 1867British Pharmacopoeia of 1867.  .  Hydrocyanic acid - which was used Hydrocyanic acid - which was used for the treatment of dry cough, for the treatment of dry cough, however, in large doses it is lethal as however, in large doses it is lethal as it can paralyze respiration.  it can paralyze respiration.  Vapor of hemlock is also described, it Vapor of hemlock is also described, it was also used as a treatment for was also used as a treatment for cough. cough. Vapor of creosote is also described, Vapor of creosote is also described, this was used as a treatment for this was used as a treatment for tuberculosis and bronchitis.  tuberculosis and bronchitis.  

Getting inhaled drugs to workGetting inhaled drugs to work

I Will Make This WorkI Will Make This Work

CostCost

Lack of KnowledgeLack of Knowledge

Lack of interestLack of interest

A Guide to Aerosol Delivery Devices For Respiratory

Therapists

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 2nd Edition

3 mechanisms usually cited by which an aerosol particle can

depositInertial impaction, - occurs with larger, fast-moving particles > 10 μm that are filtered in the nose and/or oropharynx

Gravitational settling (sedimentation) is a function of particle size and time, with the rate of settling is proportional to particle size generally 5-10 μm reach the proximal generations of the lower respiratory tract.

Diffusion occurs with particles smaller than 1-5 μm reach the lung periphery

Medical MarihuanaMedical Marihuana

Perception of Marihuana UsePerception of Marihuana Use

The Real StoryThe Real Story

Responsibility for the Medical Marihuana Program is The Responsibility for the Medical Marihuana Program is The Bureau of Health Professions (BHP) within the Michigan Bureau of Health Professions (BHP) within the Michigan Department of Community Health (MDCH) Department of Community Health (MDCH)

A qualifying patient is a person who has been diagnosed by a A qualifying patient is a person who has been diagnosed by a physician and have obtain a written certification from a that physician and have obtain a written certification from a that physician as having a debilitating medical condition such as physician as having a debilitating medical condition such as cancer, HIV, AIDS. A primary caregiver means a person who is cancer, HIV, AIDS. A primary caregiver means a person who is at least 21 years old and who has agreed to assist with a at least 21 years old and who has agreed to assist with a patient’s medical use of marihuana and who has never been patient’s medical use of marihuana and who has never been convicted of a felony involving illegal drugs. The caregiver can convicted of a felony involving illegal drugs. The caregiver can assist no more than five patients.assist no more than five patients.

ALBUTEROL FOR ALBUTEROL FOR HYPERKALEMIAHYPERKALEMIA

Hyperkalemia is classified as mild (5.5 to 6.0), Hyperkalemia is classified as mild (5.5 to 6.0), moderate (6.1 to 6.9) and severe (moderate (6.1 to 6.9) and severe (>>7.0). 7.0).

Definitive management of severe Definitive management of severe hyperkalemia is hemodialysis. Temporizing hyperkalemia is hemodialysis. Temporizing measures for moderate hyperkalemia,and measures for moderate hyperkalemia,and severe hyperkalemia, includes severe hyperkalemia, includes – calcium gluconate calcium gluconate – insulin with glucoseinsulin with glucose– kayexalatekayexalate

ALBUTEROL FOR ALBUTEROL FOR HYPERKALEMIA GuidelinesHYPERKALEMIA Guidelines

Albuterol can be administered in moderate to severe Albuterol can be administered in moderate to severe hyperkalemia.hyperkalemia.Mechanism of action is an increased cellular uptake of Mechanism of action is an increased cellular uptake of potassium, similar to the actions of insulinpotassium, similar to the actions of insulinOnset of action was within 30 minutes, however the Onset of action was within 30 minutes, however the maximum effect was at 90 minutes after nebulization.maximum effect was at 90 minutes after nebulization.12-40% of the patients were unresponsive to albuterol 12-40% of the patients were unresponsive to albuterol and it was recommended that insulin should always be and it was recommended that insulin should always be given in conjunction with the albuterolgiven in conjunction with the albuterol Nebulized dose of 10 mg was used in most adults Nebulized dose of 10 mg was used in most adults studies but 20 mg was shown to be more effective at 120 studies but 20 mg was shown to be more effective at 120 minutes.minutes.The potassium level should be measured 90-120 The potassium level should be measured 90-120 minutes after the desired dose is given and compared to minutes after the desired dose is given and compared to the pre-albuterol level; the pre-albuterol level;

HelioxHelioxHelium is a colorless tasteless, non-combustible gas that is biologically inert and insoluble in human tissue It is seven times lighter than air. Combining helium and oxygen (Heliox) results in a gas with a similar viscosity to air but with a substantially lower density.Heliox lowers the resistance of gas flow in the airways and allows for an increase in ventilation due to changing turbulent flow into more efficient laminar flow. It also may decreases the pressure gradient needed to achieve a given level of turbulent flow which may decrease work of breathing. Use of Heliox does not treat the underlying disease, but is used to reduce airways resistance and respiratory muscle work until definitive treatments act.

Heliox HistoryHeliox History

In 1930’s BarachIt recommended Heliox In 1930’s BarachIt recommended Heliox as an adjunct therapy for treatment of as an adjunct therapy for treatment of respiratory failure from obstructions of the respiratory failure from obstructions of the larynx, trachea, and airways larynx, trachea, and airways

Use decreased in the 1940s due to the Use decreased in the 1940s due to the World War II and the loss of helium World War II and the loss of helium sources and development of sources and development of bronchodilators that were more effective. bronchodilators that were more effective.

Heliox resurfaced in the early 1980s Heliox resurfaced in the early 1980s when asthma deaths began to rise when asthma deaths began to rise despite advances in medicine despite advances in medicine

Considerations of HelioxConsiderations of HelioxHeliox usually comes in a 80/20 mixture.

There is little evidence of any severe adverse reactions for patients breathing Heliox since it is an inert gas that has no effect on human metabolism.

Helium has a high thermal conductivity and may be associated with a lowering of body temperature when used for prolonged periods.

Administration is best via a closed system as this allows the best concentration to be delivered to the patient without any mixing of room air to occur.

When using an 80/20 mix FIO2’s >0.45 negate the therapeutic effect of He/O2.

With an 80/20 mix when using an oxygen flow meter multiply by 1.8 to calculate the actual system flow.

Understanding the effects of heliox on ventilator performance.

Heliox cylinders cost about four times as much as oxygen .

Use of Use of HelioxHeliox

Decreases air-trapping in thereby reducing Decreases air-trapping in thereby reducing intrinsic positive end-expiratory pressure intrinsic positive end-expiratory pressure (PEEP). (PEEP). Decreases dyspnea and work of breathing, Decreases dyspnea and work of breathing, Improves distal-airway deposition of aerosol Improves distal-airway deposition of aerosol particles.particles.Upper airways obstruction Upper airways obstruction COPDCOPDCroupCroupAsthmaAsthma

Evidence of HelioxEvidence of HelioxA prospective study by Gluck showed heliox reduced peak airway pressure and PaCO2and helped correct respiratory acidosis in 7 intubated patients with status asthmaticus.

Schaeffer reported that 11 mechanically ventilated for status asthmaticus receiving heliox had improved oxygenation in adult and pediatric patients. A retrospective study by Abd-Allah heliox was used in 28 mechanically ventilated children with status asthmaticus. Heliox was associated with significantly lower mean peak pressure and mean PaCO2 , and a improved arterial pH.

Gerbeaux retrospectively studied 81 nonrandomized patients who were admitted for exacerbation of COPD and respiratory acidosis. 39 patients received 70:30 heliox and 42 did not receive heliox. There were no significant differences in age, gender, medicalhistory, Among those who received heliox, the intubation rate was lower (8% vs 50%, p 0.01), mortality was lower (3% vs 24%, p 0.01), and intensive-care-unit (ICU) admissions were lower (46% vs60%, p 0.23). Among the survivors, mean ICU stay was shorter (8 vs 18 d, p 0.01).

Gross et al found that in children mechanically ventilated for bronchiolitis, heliox did not improve oxygenation.

The White Elephant in the RoomThe White Elephant in the Room

Inhaled VasodilatorsInhaled Vasodilators– The short half-life of inhaled vasodilators The short half-life of inhaled vasodilators

minimizes the systemic effects, minimizes the systemic effects, compared to intravenous, compared to intravenous, subcutaneous,or oral administrationsubcutaneous,or oral administration

– Vasodilators that have been Vasodilators that have been administered via inhalation, clinically and administered via inhalation, clinically and experimentally, include oxygen, nitric experimentally, include oxygen, nitric oxide, milrinone, nitroglycerin, oxide, milrinone, nitroglycerin, prostacyclins, nitroprusside, nitric oxide prostacyclins, nitroprusside, nitric oxide donors, phosphodiesterase inhibitors, donors, phosphodiesterase inhibitors, endothelin receptor antagonists, and endothelin receptor antagonists, and agonists of soluble guanylate cyclase.agonists of soluble guanylate cyclase.

Nitric OxideNitric OxideNitric oxide was regarded as a pollutant until 1987.Nitric oxide was regarded as a pollutant until 1987.NO is a free radical, produced by the endothelium, that relaxes Vascular smooth muscle (via, cGMP) producing vasodilation. Atmospheric concentrations of nitric oxide typically range between 10 Atmospheric concentrations of nitric oxide typically range between 10 and 500 parts per billion but may reach 1.5 parts per million (ppm) in and 500 parts per billion but may reach 1.5 parts per million (ppm) in heavy traffic and 1000 ppm in tobacco smoke. heavy traffic and 1000 ppm in tobacco smoke. In 1991, inhaled nitric oxide was shown to be a selective pulmonary In 1991, inhaled nitric oxide was shown to be a selective pulmonary vasodilator in patients with pulmonary hypertension. vasodilator in patients with pulmonary hypertension. 1992 Nitric Oxide was named molecule 1992 Nitric Oxide was named molecule 1993, inhaled nitric oxide emerged as a potential therapy for the 1993, inhaled nitric oxide emerged as a potential therapy for the acute respiratory distress syndrome (ARDS), because it decreased acute respiratory distress syndrome (ARDS), because it decreased pulmonary vascular resistance without affecting systemic blood pulmonary vascular resistance without affecting systemic blood pressure and improved oxygenation by redistributing pulmonary pressure and improved oxygenation by redistributing pulmonary blood flow toward ventilated lung units in patients with this condition.blood flow toward ventilated lung units in patients with this condition. Short half lifeOxidizes to NO2

Almost all cells can produce NO

How does INO WorkHow does INO Work

Fast actingFast acting

INO produces Selective INO produces Selective Pulmonary Pulmonary Vasodilatation Vasodilatation

Does not Cause Does not Cause Systemic Vasodilatation Systemic Vasodilatation

Increases cGMP which Increases cGMP which causes Vasodilatationcauses Vasodilatation

Decrease Decrease intrapulmonary shunt intrapulmonary shunt

Pulmonary EffectsPulmonary Effects– Increased Increased

OxygenationOxygenation– Decreased PVRDecreased PVR

NO ActionNO Action

Mark J.D. Griffiths, M.R.C.P., Ph.D., and Timothy W. Evans, M.D., Ph.DMark J.D. Griffiths, M.R.C.P., Ph.D., and Timothy W. Evans, M.D., Ph.D

NO EffectsNO Effects

Mark J.D. Griffiths, M.R.C.P., Ph.D., and Timothy W. Evans, M.D., Ph.D

IndicationsIndications

Inhaled Nitric OxideInhaled Nitric Oxide

Pulmonary Hypertension Treatment Options Inhaled Nitric vs. Iloprost and FlolanIloprost and Flolan

Ventavis (iloprost)Ventavis (iloprost)

Synthetic analogue of prostacyclin PGISynthetic analogue of prostacyclin PGI22

Dilates systemic and pulmonary vascular bedsDilates systemic and pulmonary vascular beds– 5 mcg @ mouthpiece (10mcg@ chamber) 6-9 times a day while 5 mcg @ mouthpiece (10mcg@ chamber) 6-9 times a day while

awakeawakeAffects platelet aggregationAffects platelet aggregation10 mcg/ml10 mcg/mlMust use 1 of 2 (AAD) Adaptive Aerosol SystemsMust use 1 of 2 (AAD) Adaptive Aerosol SystemsSide effectsSide effectsCOMMON COMMON Cardiovascular: Vasodilatation (27%) Dermatologic: Flushing Cardiovascular: Vasodilatation (27%) Dermatologic: Flushing Musculoskeletal: Trismus (12%) Neurologic: Headache (30%) Musculoskeletal: Trismus (12%) Neurologic: Headache (30%) Respiratory: Increasing frequency of cough (39%)Respiratory: Increasing frequency of cough (39%)SERIOUS SERIOUS Cardiovascular: Hypotension (11%) Respiratory: Pulmonary edemaCardiovascular: Hypotension (11%) Respiratory: Pulmonary edema

I-neb I-neb

Prodose Prodose

NO vs. ILoprostNO vs. ILoprost  Before

NONO(40

ppm)Baseline

2(Before Iloprost)

Iloprost(14–17mg)

CO (liter/min)

3.4 +1.1

3.7 6 + 1.2

3.5 +1.2 4.2 +1.2

PVR (dyneszszcm25)

1,342 + 518

1,159 + 587

1,367 + 492

920 + 387

SvO2 (%)

58 + 14 60 + 13

59 + 15

66 + 13

Hoeper et al. JACC Vol. 35, No. 1, 2000

Aeroneb Pro-XAeroneb Pro-X

nebulizer

Normal saline

ProstacyclinSolution

(20,000 ng/mL)

12 in.aerosol hose

Expfilter

Ventilator

Infusion pump

24 in. aerosol hose

Stop cocks

Connector

IV extension

ValvedTee

Flow meter

AEROSOLIZED PROSTACYCLIN AEROSOLIZED PROSTACYCLIN

(EPOPROSTENOL, FLOLAN(EPOPROSTENOL, FLOLAN))

Needs Needs experienced experienced CaregiversCaregivers

Possibility of Combined TherapyPossibility of Combined Therapy

The treatment with nitric oxide The treatment with nitric oxide alone or combined with alone or combined with prostacyclin or adrenomedullin prostacyclin or adrenomedullin (ADM) were effective in (ADM) were effective in decreasing mean PAP and decreasing mean PAP and improving oxygenation in a improving oxygenation in a piglet model of PH. piglet model of PH. However, nitric oxide However, nitric oxide plusplus prostacyclin and nitric oxide prostacyclin and nitric oxide plusplus ADM were more effective ADM were more effective than nitric oxide alone.than nitric oxide alone. The combination of The combination of aerosolized prostacyclin and aerosolized prostacyclin and ADM with nitric oxide might ADM with nitric oxide might have a role in the treatment of have a role in the treatment of infants with PH refractory to infants with PH refractory to nitric oxide alone. nitric oxide alone.

2007;42:1048-1056 Carlo Dani, MD2007;42:1048-1056 Carlo Dani, MD

Inhaled Opioids Inhaled Opioids

Look at me NowLook at me Now

Reason for Inhaled OpioidsReason for Inhaled Opioids

Dyspnea due to Chronic Dyspnea due to Chronic pulmonary disorderspulmonary disorders– ProsPros

Rapid AbsorptionRapid AbsorptionMinimal Systemic effects Minimal Systemic effects

– ConsConsMixed resultsMixed resultsSmall sample sizesSmall sample sizesPossible Respiratory Depression Possible Respiratory Depression Legal issues of administration Legal issues of administration may produce bronchospasm may produce bronchospasm

RecommendationsRecommendationsNot recommended as a standard Not recommended as a standard treatment optiontreatment optionMay be helpful with refractory May be helpful with refractory cases on patient by patient usecases on patient by patient use

Pain managementPain management– ProsPros

Rapid AbsorptionRapid AbsorptionMinimal Systemic effects Minimal Systemic effects

– ConsConsLack of experience in USLack of experience in US

Inhaled InsulinInhaled Insulin

FDA approved 2006FDA approved 2006Rapid ActingRapid ActingNo injections No injections Works best with type 2Works best with type 2Cost more than injectionsCost more than injectionsPossible pulmonary effectsPossible pulmonary effectsDosing can be complicated Dosing can be complicated Dropped by PfizerDropped by PfizerSeveral new drugs in pipelineSeveral new drugs in pipeline

PENTAMIDINE TREATMENT PENTAMIDINE TREATMENT ADMINISTRATIONADMINISTRATION

Brand name Pentam 300Brand name Pentam 300

Indication: prophylaxis of Indication: prophylaxis of Pneumoncystis carinii Pneumoncystis carinii pneumonia in immune- suppressed patients pneumonia in immune- suppressed patients

Dosage Dosage 300 mg every 4 weeks300 mg every 4 weeks

150 mg every 2 weeks150 mg every 2 weeks

30 mg every 2 weeks30 mg every 2 weeks

To prevent possible bronchospasm, patients To prevent possible bronchospasm, patients should be given 2.5 mg of albuterol via MDI should be given 2.5 mg of albuterol via MDI prior to pentamidine NMT.prior to pentamidine NMT.

Filtered Neb, protection of othersFiltered Neb, protection of others

Inhaled CHEMOTHERAPY Inhaled CHEMOTHERAPY (Doxorubicin, Cisplatin )(Doxorubicin, Cisplatin )

chemotherapy so it goes chemotherapy so it goes directly into the lungs. The directly into the lungs. The goal is to maximize the goal is to maximize the delivery to the area needing delivery to the area needing treatment and minimize the treatment and minimize the toxicity to the rest of the body. toxicity to the rest of the body. Furthermore, researchers Furthermore, researchers found there was a 25-fold found there was a 25-fold increase in the amount of increase in the amount of chemotherapy found in the chemotherapy found in the lungs compared with the level lungs compared with the level obtained with traditional obtained with traditional intravenous delivery.intravenous delivery.

Cisplatin Childhood bone Cisplatin Childhood bone cancercancer

Inhaled AlteplaseInhaled Alteplase

Dissolve clotsDissolve clots

Given to stroke patientsGiven to stroke patients

Same safety issues of other Blood Same safety issues of other Blood thinnersthinners

Used as an inhaled drug to treat fibrin cast Used as an inhaled drug to treat fibrin cast in the lungs in the lungs

Nose to Brain

OptiNose has developed innovative nasal drug delivery devices that enable nasal administration of CNS (nose to

brain), systemic and topical nasal formulations. OptiNose’s unique breath actuated devices deliver intranasal drugs to

targeted regions of the nasal cavity, including the sinuses and the olfactory region, without lung deposition, unlike

traditional nasal inhalers, nasal sprays or nebulizers. The Company offers both single and multi-use intranasal delivery devices for liquid and powder formulations. Founded in 2000,

OptiNose has extensively tested the technology in both in-vitro and in-vivo deposition studies and concluded Phase I

studies. The Company has recently completed Phase II clinical studies with rhinosinusitis and migraine therapies.

Surfactant Replacement TherapySurfactant Replacement Therapy

Composed of lipids Composed of lipids (90%) and proteins (90%) and proteins (10%).(10%).Instillation directly Instillation directly into the lung into the lung possibly more possibly more effective at this time effective at this time than aerosolized than aerosolized (Ex-osurf).(Ex-osurf).Cost for responders Cost for responders may be to high.may be to high.

Hypertonic SalineHypertonic Saline CF airways lack enough salt and water, researchers thought a CF airways lack enough salt and water, researchers thought a hypertonic saline mist would help clear the thick mucus from hypertonic saline mist would help clear the thick mucus from the lungs. the lungs. 7% hypertonic saline7% hypertonic salinePresented at the 2004 North American Cystic Fibrosis Presented at the 2004 North American Cystic Fibrosis Conference published in the Conference published in the New England Journal of MedicineNew England Journal of Medicine and University of North Carolina at Chapel Hill. and University of North Carolina at Chapel Hill. 0.9% vs 7% 0.9% vs 7% Both groups had increased lung function However the Both groups had increased lung function However the hypertonic group had even better lung function also, the hypertonic group had even better lung function also, the hypertonic saline group had fewer lung infections.hypertonic saline group had fewer lung infections.Average dose 4 mLAverage dose 4 mLYou should not mix any other medications with hypertonic You should not mix any other medications with hypertonic saline. saline. Side effects that were noted included coughing more, sore Side effects that were noted included coughing more, sore throat and chest tightness. (It is known that hypertonic saline throat and chest tightness. (It is known that hypertonic saline can irritate the airways.) can irritate the airways.)

Pulmozyme (Pulmozyme (DNase)Pulmozyme is a man-made form of naturally occurring DNase. It works by "cutting up" the DNA left by neutrophils. Standard dose 2.5 mg Launched in 1994, Pulmozyme was the first new therapeutic drug for the management of CF in more than 30 years. Take every day, whether they have cystic fibrosis symptoms or not. This may help break the cycle of cystic fibrosis progression. Must be stored in the refrigerator at 2-8°C (36-46°F) and protected from strong light.Pulmozyme should not be diluted or mixed with other drugs,.mixing with other drugs could lead to adverse physiochemical and/or functional changes in Pulmozyme or the combined products. Daily administration of Pulmozyme has also been shown to reduce the risk of respiratory tract infections requiring less antibiotics. Pulmozyme should not be used in patients with known allergies to dornase alfa, Chinese Hamster Ovary cell products, or any component of the product.

Pulmozyme ActionPulmozyme Action

http://www.pulmozyme.comhttp://www.pulmozyme.com

Administering Aerosolized Ribavirin Administering Aerosolized Ribavirin Clinical IndicationsClinical Indications

Documented symptomatic Documented symptomatic RSV infectionRSV infection Recipients of allogeneic stem cell transplant Recipients of allogeneic stem cell transplant

Recipients of autologenous stem cell transplantRecipients of autologenous stem cell transplant

ContraindicationsContraindicationsHypersensitivity to DrugHypersensitivity to DrugPregnant or planning to become pregnant within two weeks of Pregnant or planning to become pregnant within two weeks of exposureexposureRequiring mechanical ventilationRequiring mechanical ventilation

Recommended DosageRecommended Dosage33.3 mL of 60 mg ribavirin/mL aerosolized for 2 hrs every 8 hrs33.3 mL of 60 mg ribavirin/mL aerosolized for 2 hrs every 8 hrsTotal of 6 g/day (100 mL divided into 3 doses)Total of 6 g/day (100 mL divided into 3 doses)Given for 5–10 days Given for 5–10 days

NOTENOTE: Administer a Bronchodilator : Administer a Bronchodilator Pre-treatmentPre-treatment

C. HaasC. Haas

SetupSetup

Use Blender, if supplemental OUse Blender, if supplemental O22 is required is required

Assemble SPAG unitAssemble SPAG unit– Set Drive Pressure to 26 psiSet Drive Pressure to 26 psi– Set Nebulizer Flowmeter to max (6-10 L/min)Set Nebulizer Flowmeter to max (6-10 L/min)– Set Drying Chamber Flow to 8 L/min (range 3-8)Set Drying Chamber Flow to 8 L/min (range 3-8)

Attach aerosol tubing to patient face/trach Attach aerosol tubing to patient face/trach mask mask – Not to be used on vent ptsNot to be used on vent pts

Place a blue pad under the SPAGPlace a blue pad under the SPAG

Employee PrecautionsEmployee Precautions

The treatment should be given in the Demistifier The treatment should be given in the Demistifier 2000B HEPA filtration scavenging hood2000B HEPA filtration scavenging hood

‘‘Droplet Precautions’ should be followed for all Droplet Precautions’ should be followed for all patients with RSV (gloves, gown, isolation mask, patients with RSV (gloves, gown, isolation mask, face shield/goggles when w/i 3 feet of patient)face shield/goggles when w/i 3 feet of patient)– During therapy, wear an N-95 mask or the PAPR unitDuring therapy, wear an N-95 mask or the PAPR unit

Pregnant women should avoid contactPregnant women should avoid contact

Those wearing contact lenses should avoid Those wearing contact lenses should avoid contact (wear goggles or take out)contact (wear goggles or take out)

Patient PreparationPatient Preparation

Explain therapy goals and procedureExplain therapy goals and procedure

Administer bronchodilatorAdminister bronchodilator

Ask if patient needs to use the restroomAsk if patient needs to use the restroom

If wearing contact lens, ask to take out or If wearing contact lens, ask to take out or apply gogglesapply goggles

Place a drape sheet over patientPlace a drape sheet over patient

Spag-2 SetupSpag-2 Setup

Drying ChamberDriving Pressure (26 psi)

Nebulizer

Nebulizer Flow 6 to 10 Lpm

Drying Chamber flow 3 to 8 Lpm

(Output is 12.5-15 mL/hr)

Fightting the FluFightting the Flu

RELENZA (ruh-LENS-uh) is a medicine that can both treat influenza (flu, infection caused by influenza virus) and help to prevent getting the flu. While some antiviral medicines only protect against influenza A, RELENZA is effective against both influenza A and B.

RELENZA belongs to a group of medicines called neuraminidase inhibitors. These medications target the influenza virus and prevent it from spreading inside your body. RELENZA treats the cause of influenza at its source, rather than simply treating the symptoms.

Some patients have had bronchospasm (wheezing) or serious breathing problems when they used RELENZA. Many but not all of these patients had previous asthma or chronic obstructive pulmonary disease.

The green MovementThe green Movement

Others That Benefit form Inhaled Others That Benefit form Inhaled DrugsDrugs

Inhaled Anesthetics In the ICUInhaled Anesthetics In the ICU

ProPro– May provide better May provide better

sedationsedation– CostCost– Ability to avoid Ability to avoid

HypotensionHypotension– Used as last ditch tx.Used as last ditch tx.

ConsCons– Untrained personalUntrained personal– Environment Environment

A Gaze Into The FutureA Gaze Into The Future

Advanced delivery TechnologyAdvanced delivery Technology

SPIONS-SPIONS-Superparamagnetic Superparamagnetic iron oxide iron oxide nanoparticlesnanoparticles

Nanobytes Nanobytes

ORBIT-1 ORBIT-1

Treatment for Treatment for BronchiectasisBronchiectasis

First Patient February First Patient February

Phase 2b studyPhase 2b study

96 Patients 96 Patients randomized 100 – randomized 100 – 150 mg of Liposomal 150 mg of Liposomal CiprofloxacinCiprofloxacin

Carbon MonoxideCarbon Monoxide

Carbon monoxide is lethal at certain doses that kills Carbon monoxide is lethal at certain doses that kills thousands of Americans every yearthousands of Americans every year

"The therapeutic window for carbon monoxide is very "The therapeutic window for carbon monoxide is very small, it's equivalent to the amount you'd receive sitting small, it's equivalent to the amount you'd receive sitting in a traffic jam in Mexico Cityin a traffic jam in Mexico City

May improve transplant out comes-- Hmox expression May improve transplant out comes-- Hmox expression goes up, it reduces iNOS expression and suppresses a goes up, it reduces iNOS expression and suppresses a key signaling pathway involved in the immune responsekey signaling pathway involved in the immune response

Research team focuses on the relationship between Research team focuses on the relationship between carbon monoxide and nitric oxide.carbon monoxide and nitric oxide.

Love HormoneLove HormoneUniversity of Haifa has found that the hormone oxytocin, the “love hormone", which affects behaviors such as University of Haifa has found that the hormone oxytocin, the “love hormone", which affects behaviors such as trust, empathy and generosity, also affects opposite behaviors, such as jealousy and gloating. "Subsequent to trust, empathy and generosity, also affects opposite behaviors, such as jealousy and gloating. "Subsequent to these findings, we assume that the hormone is an overall trigger for social sentiments: when the person's these findings, we assume that the hormone is an overall trigger for social sentiments: when the person's association is positive, oxytocin bolsters pro-social behaviors; when the association is negative, the hormone association is positive, oxytocin bolsters pro-social behaviors; when the association is negative, the hormone increases negative sentiments. increases negative sentiments.

Previous studies have shown that the oxytocin hormone has a positive effect on positive feelings. The hormone is Previous studies have shown that the oxytocin hormone has a positive effect on positive feelings. The hormone is released in the body naturally during childbirth and when engaging in sexual relations. Participants in an released in the body naturally during childbirth and when engaging in sexual relations. Participants in an experiment who inhaled the synthetic form of the hormone displayed higher levels of altruistic feelings, and it is experiment who inhaled the synthetic form of the hormone displayed higher levels of altruistic feelings, and it is supposed that the hormone plays an important role in the formation of relationships between people. supposed that the hormone plays an important role in the formation of relationships between people.

However, in earlier studies carried out by other investigators with rodents, it was found that the hormone is also However, in earlier studies carried out by other investigators with rodents, it was found that the hormone is also related to higher levels of aggression. Therefore, it was decided to examine whether the hormone also affects related to higher levels of aggression. Therefore, it was decided to examine whether the hormone also affects negative social sentiments. The present study, which was published in the journal negative social sentiments. The present study, which was published in the journal Biological Psychiatry,Biological Psychiatry, included included 56 participants. Half of the participants inhaled the synthetic form of the hormone in the first session and were 56 participants. Half of the participants inhaled the synthetic form of the hormone in the first session and were given a placebo in the second session; the others were given a placebo in the first session and oxytocin in the given a placebo in the second session; the others were given a placebo in the first session and oxytocin in the second session. Following drug administration each participant was asked to play a game of luck along with second session. Following drug administration each participant was asked to play a game of luck along with another competitor, who was in fact - and without their knowledge - a computer. Each of the participants was another competitor, who was in fact - and without their knowledge - a computer. Each of the participants was asked to choose one of three doors and was awarded the sum of money that was hidden behind that door. asked to choose one of three doors and was awarded the sum of money that was hidden behind that door. Sometimes the participant gained less money than the other player, and sometimes more, creating conditions in Sometimes the participant gained less money than the other player, and sometimes more, creating conditions in which a person might well develop feelings of envy and gloating. which a person might well develop feelings of envy and gloating.

The findings show that those participants who inhaled the oxytocin displayed higher levels of envy when the The findings show that those participants who inhaled the oxytocin displayed higher levels of envy when the opponent won more money and of gloating when they were ahead. Another interesting result was that as soon as opponent won more money and of gloating when they were ahead. Another interesting result was that as soon as the game was over, no differences between the participants were evident with regards to these sentiments. This the game was over, no differences between the participants were evident with regards to these sentiments. This indicates that the negative feelings were empowered only in the course of the game itself. indicates that the negative feelings were empowered only in the course of the game itself.

Possible use of the hormone as a medication for various disorders, such as autism but the hormone's Possible use of the hormone as a medication for various disorders, such as autism but the hormone's undesirable effects must be examined.undesirable effects must be examined.

New Inhaled VasodilatorNew Inhaled Vasodilator

inhaled Treprostinil for the treatment of pulmonary arterial inhaled Treprostinil for the treatment of pulmonary arterial hypertension. The NDA will be subject to a standard review period hypertension. The NDA will be subject to a standard review period of 10 months, with a targeted user fee deadline of April 30, 2009.of 10 months, with a targeted user fee deadline of April 30, 2009.

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