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Pharmacology Is Anything New Out There


Pharmacology Is Anything New Out There – PowerPoint PPT presentation

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Title: Pharmacology Is Anything New Out There

PharmacologyIs Anything New Out There?
  • Bob Spoula, MBA RRT
  • Chief Science Officer
  • Edward Hospital

What Are We Doing?
  • Examine the historical perspective of Respiratory
  • Look at recent developments concerning drugs and
    delivery systems
  • Provide framework that may help to improve
    clinical practice
  • Attempt to provide sufficient stimulation to
    allow for 50 contiguous wakeful minutes

A Historical PerspectiveOn Inhalation Therapy
Clearly HMO Prescribed
How Far Have We Come?
  • Do you remember

And then came
Do you remember 1982?
  • No, Bob, of course I dont remember 1982 because
    I wasnt even born yet!
  • But for those of us who were around

Michael Jackson released Thriller, ultimately
selling lOO million copies
The Dow closed at an all-time high of 1065up 14
points from January 1973
Time Magazine picked The Computer as their MOTY!
Albuterol is FDA Approved!
  • Prior drugs not as Beta-2 specific
  • Issues with RT related sympathomimetics
  • CNS stimulation
  • Tachycardia
  • Shakiness
  • Agitation
  • Headaches
  • Nausea / Vomiting
  • Issues addressed due to Beta-2 specificity

When you solve problem No. 1., Number 2 gets a
  • Montreal Protocol drafted in 1987
  • Multi-phase elimination of CFCs and other ozone
    depleting chemicals
  • Problem for Healthcare and RTs
  • Issue is not the medication
  • Issue is how to get the medication OUT!
  • All CFC MDIs prohibited in the U.S. starting Jan
    01, 2009

  • CFCs found to cause harm as early as 1974!
  • Published in Nature journal by Molina and
  • Shared Nobel Prize in 1995 for ozone layer
    depletion research
  • CFCs unfortunately extraordinarily stable!
  • Found that adding a hydrogen molecule causes
    quicker breakdown

To date, there have been virtually no inhalers
that have exploded due to propellants
What to Expect
  • Smaller plume when delivering actuation
  • May cause patients to tell you the inhalations
    feel different, but if it does, somethings

What to Expect
  • Warmer puff, softer mist-like spray
  • Again, not an issue with good patient education
    and proper equipment
  • May be a good opportunity to convert your more
    resistant patients
  • HFAs purportedly cause a gummy or sticky feel
    to surfaces
  • Clean inhaler/chamber more often

Is It Effective?
  • Studies from Chest Journal
  • Ramsdell, Klinger, Ekholm, and Colice, l999
  • HFA Albuterol and CFC Albuterol provided
    comparable bronchodilator efficacy
  • Tinkelman, Bleecker, et al.
  • Regular use of either Proventil HFA or Ventolin
    did not cause asthma control to deteriorate
  • Kleeup, Tashkin, Cline, and Ekholm
  • HFA 134a Salbutamol would be a safe and
    effective substitute for CFC Salbutamol

But it doesnt work
  • Strategies
  • Listen (for at least 90 seconds)
  • Many patients are frustrated by lack of time
    spent at bedside
  • Evaluate patient technique
  • Ensure patient has aerochamber
  • Make sure inhaler cleaned on regular basis
  • Also need to be primed new and after 2 weeks
    inactivity by 3 sprays

But it doesnt work
  • Provide benefit of your experience
  • Nebs may be viable alternative until D/C
  • Compare peak flows of nebs vs. HFA MDI
  • Maybe an underlying exacerbation requiring more
    puffs for this visit
  • Talk about their medication plan
  • Are steroids or LABAs included in plan?

Try Something Different
  • Generic HFA Albuterol will not be available
    until patent expires
  • 3 manufacturers offering HFA Albuterol
  • Ventolin HFA from Glaxo Smith Kline
  • Proventil HFA from Schering Corporation
  • ProAir HFA from IVAX (Teva parent corporation)
  • Active ingredient/dosage is identical according
    to each package insert
  • 120 mcg from canister valve, 108 from mouthpiece

Heres the BIGGEST difference for most
  • Research and development cost money
  • New formulations allow new patents
  • Companies CAN and WILL look to recover
  • R D money in the pricing structure
  • Typical Scenario
  • Generic albuterol monthly - 5
  • Brand name albuterol monthly - 40

B.O.B.s Quick Quiz
  • Which of these drugs are taken by BOTH Britney
    Spears and racehorses?
  • A. Pergolide
  • B. Xylazine
  • C. Clenbuterol

B.O.B.s Quick Quiz
  • Which of these drugs are taken by BOTH Britney
    Spears and racehorses?
  • A. Pergolide
  • B. Xylazine
  • C. Clenbuterol

Pergolide was withdrawn by the FDA in 2007. It
was previously used as an alternative therapy for
Parkinsons. It is also used for equine Cushings
syndrome (still available in Canada)
B.O.B.s Quick Quiz
  • Which of these drugs are taken by BOTH Britney
    Spears and racehorses?
  • A. Pergolide
  • B. Xylazine
  • C. Clenbuterol

Xylazine is used for sedation and muscle
relaxation in horses and other large mammals. Of
special note, it is used in combination with
Special K (Ketamine), but we know Britney would
NEVER do that..the only Special K in her life is
the and only K-FED!
B.O.B.s Quick Quiz
  • The correct answer is Clenbuterol!

Clenbuterol is used worldwide in the tx of
allergic respiratory disease in horses. Due to
its CNS stimulation, it also seems to accelerate
metabolism, making Clen the hottest dietary
supplement in Hollywood. Although you and I
would have to get it through illicit sources on
the internet, Im sure Britneys vetinarian makes
sure she has plenty of Clen available, just in
case her horses start to wheeze.
C.O.P.D. and Smoking
C.O.P.D. and Smoking
  • New initiative at Edward Hospital
  • New reports printed from nursing admission
  • Therapists go out and talk with patients,
    present literature, answer questions
  • Patient responses
  • Thank you. I have some literature already.
  • I already quit. Its been 3 days now, since my
  • You people are killing me. You know all the
    answers, dont you?! Give me my treatment and
    leave me the hell alone!
  • (Insert your response here)
  • Its not their fault..

Its Bigger Than All Of Us
  • Current population of the U.S?
  • 300 Million
  • 1 birth every 7 seconds, 1 death every 11 seconds
  • Current estimated smokers in U.S.
  • 50 Million (about 20 of total)
  • 1.5 Billion cigarettes roll off the assembly
    line each day!

How did all this start?
Contrary to Popular Belief
Remember Christmas is just around the corner
Did Not Start With These Guys.
How did all this start?
A Long, Long Time Ago
  • Can be traced back to over 5000 years ago
  • Embraced for the longest time

The Science of Addiction
Cigarette Smoking Faster than an injection, more
reinforcing than crack cocaine
It all starts with nicotine!
NEVER MIND the formaldehyde, ammonia, hydrogen
cyanide, arsenic, and DDT or 4000 other
identified chemicals
The Science of Addiction
  • Within six seconds
  • Nicotine stimulates the nicotinic Ach receptors
  • Causes dopamine release
  • Dopamine associated with the reward center
  • Influences molecules that control
  • Mood
  • Energy level
  • Memory

Another illustration of the power of
addiction The head of Regent Seven Seas
announced that smokers cancelled bookings worth
US3 million (3.6 million) when the line
announced it would ban smoking in cabins and
The Science of Addiction
Millions of years of human physiology
R.T. handing out pamphlets
We Need A BIGGER Weapon!
Changing the Game
  • Im not going to do it, and you cant make me..
  • Unless I can change your attitude from the inside

How many psychoanalysts does it take to change a
light bulb?
Only one, but the light bulb has got to WANT to
Enter Chantix! (Varenicline)
  • Mechanism of Action
  • Blocks nicotine Ach receptor
  • Agonist to several types of receptors
  • Blocks pleasure response associated with
  • Shown to be superior to NRT (patch, gum)
  • Patients report a response of yuck to smoking
    after a few weeks on Chantix

  • Usage
  • Start Chantix 1 week before attempting to quit
  • You may smoke during that week and quit by day 8
    of the medication
  • Program length is 12 weeks, with an additional 12
    weeks if desired
  • Pleasure response should have been negated at
    that point
  • Still need motivated patient willing to do what
    is necessary

  • Cautions and Warnings
  • Side effects, as reported by Pfizer
  • Gastrointestinal upset
  • Change in taste
  • Vivid or unusual dreams

Whats The Latest?
  • FDA Alert Issued 2/1/08
  • Serious neuropsychiatric symptoms
  • Agitation, depression, suicide ideation, and
    attempted suicide
  • May 2008- FAA bans use of Chantix and instructs
    those affected by the ban (pilots, ATC) to stop
    flying for 72 hours after discontinuing use
  • ISMP reported 1001 new cases of adverse effects
    due to Chantix (vs. 17 for NRT and 44 for Zyban)
  • ISMP notes that there has been a high degree of
    publicity about the potential side-effects

  • Like anything else, Chantix is a cost-benefit
  • Average smoker attempts to quit SIX times before
  • Chantix showed 44 success rate when properly
  • Zyban showed 30 success rate
  • Primarily used for anti-depression therapy
  • Placebo showed 18 success rate

Each patient case needs to be decided based on
individual factors after all available
information has been gathered
  • Of course, there are exceptions to every rule!

B.O.B.s Quick Quiz
  • What innovative method of extinguishing a
    cigarette did an angry German man use when his
    girlfriend lit up in their apartment in
    February 2008?
  • A. Smothered it with their dog
  • B. Doused it with lighter fluid
  • C. Dunked her and the smoke in their bathtub
  • D. Used a powder-based fire extinguisher

B.O.B.s Quick Quiz
  • What innovative method of extinguishing a
    cigarette did an angry German man use when his
    girlfriend lit up in their apartment in
    February 2008?
  • A. Smothered it with their dog
  • B. Doused it with lighter fluid
  • C. Dunked her and the smoke in their bathtub
  • D. Used a powder-based fire extinguisher

B.O.B.s Quick Quiz
  • What innovative method of extinguishing a
    cigarette did an angry German man use when his
    girlfriend lit up in their apartment in
    February 2008?
  • A. Smothered it with their dog
  • B. Doused it with lighter fluid
  • C. Dunked her and the smoke in their bathtub
  • D. Used a powder-based fire extinguisher

B.O.B.s Quick Quiz
  • What innovative method of extinguishing a
    cigarette did an angry German man use when his
    girlfriend lit up in their apartment in
    February 2008?
  • A. Smothered it with their dog
  • B. Doused it with lighter fluid
  • C. Dunked her and the smoke in their bathtub
  • D. Used a powder-based fire extinguisher

B.O.B.s Quick Quiz
  • What innovative method of extinguishing a
    cigarette did an angry German man use when his
    girlfriend lit up in their apartment in
    February 2008?
  • D. Used a powder-based fire extinguisher

A virulent anti-smoker in Germany was so angry
when his girlfriend lit up he emptied a fire
extinguisher to put out the cigarette, caking her
and their apartment in powder.
Surfactant Replacement Therapy
  • Surfactant deficiency identified as early as 1959
  • Replacement not well understood
  • Tried to nebulize Colfosceril 1960s
  • Needs proteins and PG to spread, absorb
  • Alveolus lined with Type I and Type II cells
  • Type II Cells secrete surfactant
  • If Type II damaged or immature, may have
    surfactant deficiency
  • Mechanical ventilation can lead to Type II damage
  • (Iatrogenic RDS)

Surfactant Replacement Therapy
  • Indications for SRT
  • Prophylactic use
  • Babies less than 28 32 weeks
  • Weight less than 1300 grams
  • LS Ratio lt 21
  • Absence of PG in amniotic fluid
  • Rescue use
  • Have signs of distress
  • Need ventilatory assistance
  • CXR shows RDS
  • O2 needs increase

Effects of Surfactant Therapy
  • Reduces surface tension
  • Stabilize the alveoli
  • Prevents atelectasis at end-expiration
  • Decrease work of breathing
  • Increases PO2 due to more stable alveoli
  • Increase lung compliance
  • Avoid complications due to air leak

How Do You Choose?
  • Exogenous Surfactant Choices
  • 1. Natural (animal) options
  • Survanta (bovine extract)
  • Curosurf (pig lung extract)
  • Infasurf (calf lung extract)
  • Doctasurf (MD lung extract)
  • 2. Synthetic options
  • Exosurf
  • ALEC (Available in U.K.)
  • Surfaxin

How Do You Choose?
  • Natural Surfactant Choices
  • Comes from natural sources
  • Proteins present for absorption
  • Limited supply
  • Time-consuming, expensive

How Do You Choose?
  • Artificial Surfactant Choices
  • Comes from laboratory
  • No proteins means less infection
  • Unlimited supply
  • May not perform as well
  • Some components not studied in infants

Current Research
  • Roger Soll (University of Vermont) published
    several studies in 1999 trying to answer
  • Which One?
  • How Often?
  • When to Give?

Conclusions (Not Recommendations)
  • Soll concluded that
  • Both types are effective
  • Quicker response, less barotrauma with natural
  • Response is more sustained with multiple natural
  • Prophylactic usage overwhelmingly effective
  • Decrease mortality by 40-70

Whats the Latest?
  • Soll and Pfister, 2005
  • Surfactant protein analogs..can ameliorate RDS
    and improve clinical outcome
  • Ghodrat, 2006
  • Consistent pharmaceutical quality, unlimited
    supply, and no risk of disease transmission
  • Moya, et al., Pediatrics - 2005
  • Lucinactant (Surfaxin) reduces the incidence of
    BPD compared with colfosceril palmitate
  • Decreases RDS-related mortality rates, compared
    with beractant.
  • Strongly suggest that administration of
    lucinactant to infants at risk for RDS results in
    neonatal survival that is at least comparable
    with, if not superior to, that of infants given
    the animal-derived surfactants beractant and
    poractant alfa.
  • Phase 3 Clinical Trials SELECT and STAR

Whats the Latest?
  • May 2008
  • Discovery Labs received an approvable letter
    from the FDA
  • Set forth remaining conditions that must be
    satisfied in order to gain U.S. marketing
    approval for Surfaxin
  • 0f Note
  • FDA and Discovery Labs agreed on content of the
    package insert
  • Letter contained no requirements for additional
    clinical trials
  • Discovery Labs addressed quality and
    manufacturing issues raised by the FDA, and are
    prepared for commercial Surfaxin production

Nitric Oxide
  • Named the Molecule of the Year in 1992
  • Common substance in various concentrations
  • Present in
  • Auto exhaust
  • Cigarette smoke
  • Room air
  • Fireflies
  • Plant cells

Nitric Oxide
  • Nitric Oxide exerts effects on
  • Kidney function
  • Uterine contraction
  • Endocrine glands
  • Pancreas, adrenalin, hypothalamus
  • Autonomic Nervous System
  • Various areas in the brain
  • Smooth muscle relaxation most significant in use
    of inhaled Nitric Oxide

Nitric Oxide
  • NO is NOT a selective pulmonary vasodilator, but
    becomes one when inhaled
  • Hess, MacIntyre, et al., Respiratory Care 2002
  • Better than systemic agents because
  • Inhaled gases never reach unventilated lung units
  • NO has an affinity for Hb 106 times vs. O2
  • Has a half life of less than 5 seconds

Why Neonatal Usage?
Patent Ductus Arteriosus
Areas of High Pressure
Patent Foramen Ovale
Right-to-Left Shunts of Fetal Circulation
The Ugliness of PPHN
Blood shunts right to left Bypasses lungs, does
not make pulmonary circuit Oxygen content
decreases,increasing pulmonary vascular
resistance Increased PVR caused more shunting,
more blood bypasses pulmonary circuit Constant
cycle also leads to arteriole remodeling
(hypertrophy), which worsens gas exchange
Nitric Oxide to the Rescue!
  • Inhaled Nitric Oxide used to decrease PVR,
    increase oxygenation
  • Since inhaled gas works only in ventilated part
    of lung, avoid V/Q mismatch and worsening hypoxia
  • Not always so easy to give

Early Days of Nitric Oxide
  • Early setups involved H-cylinders, multiple
    blenders, industrial scrubbers, flow
    calculations, MetHb poisoning, and lots of

Nitric oxide delivery setup, Childrens Memorial,
early 1990s
The Only FDA Approved Indication
  • INOmax, in conjunction with ventilatory support
    and other appropriate agents,is indicated for the
    treatment of term and near-term ( gt 34 weeks)
    neonates with hypoxic respiratory failure
    associated with clinical or echocardiographic
    evidence of pulmonary hypertension, where it
    improves oxygenation and reduces the need for
    extracorporeal membrane oxygenation.

Nitric Oxide Benefits
Provides immediate benefits, but not without a
Causes pulmonary artery vasodilation, decreased
Less shunting through PDA and PFO
Complications of NO
  • Inhibits aggregation of platelets
  • Promotes formation of Met Hb
  • Not appropriate for everyone
  • Forms NO2
  • Can be fatal if given to wrong lesion

Biggest Complication of All?
As If The Economic Crisis Wasnt Bad Enough
How About An Alternative?
How About This?
  • Aerosolized prostacyclin (Flolan) for adults
  • Potent vasodilator
  • Inhalation route provides quick benefits
  • Half-life of approx. 2 minutes limits systemic
  • Explored several years prior to inhaled nitric

Take the lead from SFGH.
SFGH Protocol
  • Aersolized prostacyclin is indicated for
    treatment of
  • HRF in adult ventilated patients with PO2/FiO2
    ratio of less than 100
  • Severe pulmonary hypertension in adults with a
    mean PAP of at least 50 mm Hg
  • Response to treatment includes
  • 20 or greater increase in PO2
  • 20 reduction in PAP
  • Clinical signs of improvement
  • Response should be apparent within 10 minutes!

ButDoes It Work?
  • All studies demonstrate that the clinical
    response to inhaled PGI(2)is as good, if not
    better, than INO
  • Brian Walsh, University of Virginia Childrens
    Medical Center
  • The results of this study suggest that inhaled
    IPGE is a safe and selective pulmonary
    vasodilator in HRF
  • Good, Black, Aranda, and Shankaran Childrens
    Hospital of Michigan
  • Inhaled prostacyclin induces a selective
    pulmonary vasodilation that is comparable to the
    effect of inhaled nitric oxide
  • Haraldsson et al., Sahlgrenska University
    Hospital, Sweden

Cost Effectiveness
130 To 170 Per Day
137 per hour
And Now For Something Completely Different
What Defines YOUR Department?
  • Blood Gas Responsibilities?
  • Airway Management?
  • Patient Assessment and Protocols?
  • Assistance with Invasive Procedures?
  • Full presence in ED but not in NICU?

Strength Through Diversity and Flexibility!
Does it involve the pulmonary system at SOME
point in the process?
Yes, but I didnt inhale
  • If you inhale a drug, does that make it a
    respiratory drug?
  • Not necessarily, but it does make us the EXPERTS
    in the area!

Could you troubleshoot this piece of equipment?
Inhaled Insulin!
  • Departure from traditional role, but inhalation
    route makes us the instant experts
  • Additional RT factors
  • Baseline and follow-up PFTs required
  • Smokers not eligible must be smoke-free for six
  • Smokers show a 2X 5X greater rate of absorption
  • Technique is KEY to medication delivery!

  • Pfizer touted benefits starting in the 1990s
  • Bought out co-developer for 1B in 2001
  • Sales projected to be 1.5B annually by 2010
  • Started sales in September 2006
  • Stopped sales in Oct 2007 due to poor response

What Happened?
  • Why did Pfizer pull the plug?
  • Not cost effective
  • Not clinically superior to traditional injections
  • May be difficult to dose properly
  • Still needs to be covered with long-acting
    insulin such as Lantus
  • May be difficult for those with unstable lung
  • Lung cancer concern?
  • 1/4292 placebo patients developed lung CA
  • 6/4740 Exubera patients developed lung CA
  • CA patients were smokers

Why did you even bother?
  • Other companies continuing research
  • Eli Lilly and Company
  • Mannkind
  • Aradigm
  • Size of market drives new competitors
  • Problems already identified by Pfizers

B.O.B.s Quick Quiz
  • Inhaling three 1 mg doses of Exubera results in a
    HIGHER dose than inhaling one 3 mg dose
  • True
  • False

B.O.B.s Quick Quiz
  • Inhaling three 1 mg doses of Exubera results in a
    HIGHER dose than inhaling one 3 mg dose
  • True

Oddly enough, its true. While basic math has not
changed, due to retention of blister
contents,three consecutive 1 mg doses gave more
medication than one 3 mg dose!
HFA Inhalers
  • U.S. Law by January 1st
  • Different formulations from different companies
  • Watch patient technique provide and clean

  • Dont be upset when the patients throw you out
  • Provide information and plant the seed
  • Help them make the Chantix decision on an
    individual basis
  • Understand that a 44 quit rate is amazing!

  • First artificial surfactant with good peer
  • Look at the SELECT and STAR studies
  • Surfactant will continue to be a mainstay of
    therapy in any NICU

  • Adult usage for pulmonary hypertension and
    popping oxygen saturations
  • Take the lead from SFGH its their protocol
  • I dont have an extra 145,000 on me to spend,
    and neither does my hospital

  • Non-traditional roles for traditional routes
  • Blood sugar testing is important, not all that
  • RTs act with a sense of urgency
  • If the patient inhales it, we own it!

Thank You!
My assistants will now be glad to answer any
questions you may have!
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