Halcion Web

Triazolam
Halcion
Oral Sedation
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Is
Halcion
the
Fred Quarnstrom, DDS
the
ugly FAGD,
Dirty Duck
FADSA,
FICD
Diplomate, American Dental Board of Anesthesionogy
or beautiful
Black
Swan?
Diplomate,
National Dental
Board of Anesthesiology
Certified, American Association of Dental Consultants
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patients - AAOMS - OCS

Where is the ADA?
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Would
you
please
try
to
relax.
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Mortality from Anesthesia 1970-1979 U. K.

Dentists
1:260,000
Physicians
1:248,000
Single Operator / Anesthetist
1:143,000
One Operator One Anesthetist
1:598,000
Conscious sedation
1:1,000,000
(patient died on a motorcycle later the same day)
note - this study was pre pulse oximeter useage

Dionne, Pharmacologic Considerations in Training of Dentists in
Anesthesia and Sedation, Anes Prog 36:113-116 1989
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The Spectrum of Anesthesia

Normal
Anxiolysis
Conscious
Sedation
1. Protective reflexes intact
Patient can independently
and continuously maintain
an airway
Patient can respond
appropriately to verbal
commands 6/6/05
Deep
Sedation
2. Partial loss of
protective reflexes
Inability to
independently maintain
an airway
May not respond to
verbal commands
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General
Anesthesia
3. Loss of protective
reflexes
Inability to independently
maintain an airway
No pain sensation or reflex
withdrawal from stimuli
Total unconsciousness
Risks of Anesthesia
high
Deep
Sedation
Moderate
Sedation
Local
Anesthesia
Anxiolysis
low
N20
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General
Anesthesia
AGE VS ANESTHETIC-INDUCED,
CARDIAC ARREST / DEATH
incidence
rate
0.05
0.04
0.03
0.02
0.01
<1
1-10 11-20 21-30 31-40 41-60
Marx, Anes., 39:54-58, 1973
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> 60
AGE VERSUS SEVERE MORBIDITY/MORTALITY
4
3
2
1
0
<10
11-20
21-30 31-40 41-60
age range = 21 mo. - 59 yr.
Jastak, Anes Prog, 38:39-44 1991
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AGE VERSUS SEVERE MORBIDITY/MORTALITY
4
3
2
1
0
<10
11-20
21-30 31-40 41-60
age range = 21 mo. - 59 yr.
Jastak, Anes Prog, 38:39-44 1991
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Standards for Conscious Sedation

Level 1 minimal sedation - Anxiolysis
Level 2 Moderate Sedation/Analgesia Conscious Sedation
Level 3 Deep Sedation/Analgesia
Level 4 Anesthesia
Resek,
Jayne, MS RN, Anesthesia
Today vol.11 No. 2 Fall 2000 p. 2
6/6/05
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A drug-induced state during which patients respond

normally to verbal commands. Although cognitive function
and coordination may be impaired, ventilatory and
cardiovascular functions are unaffected.

Level 4 Anesthesia
Resek,
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A drug-induced depression of consciousness during which

patients respond purposefully to verbal commands, either
alone or accompanied by light tactile stimulation. No
interventions are required to maintain a patient airway and
spontaneous ventilation is adequate. Cardiovascular
function is usually maintained.

Level 4 Anesthesia
Resek,
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A drug-induced depression of consciousness during which

patients cannot be easily aroused but respond purposefully
following repeated or painful stimulation. The ability to
independently maintain ventilatory function may be
impaired. Patients may require assistance in maintaining a
patent airway, and spontaneous ventilation may be
inadequate. Cardiovascular function is usually maintained.
Level 4 Anesthesia
Resek,
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Joint Commission on Accreditation of Healthcare
Organizations (JCAHO)
Level 1 - None
Level 2 - conscious sedation - pulse oximeter and
Blood Pressure, ability to resuscitate.
Monitoring YES
Patient assessment - ASA status YES - 1 OR 2
Staff - someone is always with the patient YES
Equipment YES
Informed consent YES
Competent at least one level greater than where

you normally
practice
if patients
into
level
Resek,
Jayne,
MS RN, Anesthesia
Today vol.11slip
No. 2 Fall
2000next
p. 2
6/6/05
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NORMAL DISTRIBUTION CURVE

mean
freq.
hyper
hypo
response
1 S.D.= 66%
2 S.D. = 95%
3 S.D. = 99.7%
Pallasch, Anes. Prog. 35:87-101,1988
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Chloral Hydrate
Response
100
ED50
50
LD50
Margin
of
Safety
0
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Dose
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Drug Distribution and Elimination

Compartment models
Volume of distribution
First and zero kinetics
Clearance and extraction ratios
First pass effects
Drug half lives
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Principals of Pharmacotherapy:
Pharmacokinetics
Pallasch, T.J. Anes. Progress 35:133-146 1988
Compartment Models
Simple one compartment model
all drugs spread uniformly through the body
Two and three compartment model - better

varying blood flows
changes in pH
plasma protein binding
tissue affinity for certain drugs
Three compartment model is most accurate

But two compartment is OK in most cases.
central compartment- extra cellular fluid and organs

peripheral tissue compartment - muscle and fat
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Pharmacokinetics
Volume of Distribution
Apparent volume of distribution (Vd)
If Vd is small - drug is bound to plasma - little drug
will be in tissues - higher blood
concentrations
If Vd is large it will be widely distributed through the
tissues - but lower blood concentrations
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Pharmacokinetics
First and Zero Order Kinetics

First-order - a constant percentage crosses a membrane or
is metabolized per unit of time - filtration of is
determined by concentration.
Zero-order - a constant amount of drug is metabolized
per unit of time - independent of drug concentration.
Ethanol metabolism is zero-order. There is a limited
number of receptor cites to metabolize that drug
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Pharmacokinetics
Clearance and Extraction Ratios

Clearance is the amount of blood volume from
which the drug is completely removed,
cleared, per unit of time. ml./min.
It is the total of all clearances of all organs.
Extraction ratio is the difference in drug
concentrations from the arterial to the venous
blood of an organ from 0 to 1. If one, all drug
is removed first pass if 0 non is removed by
that organ.
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Pharmacokinetics
First Pass Effects

Some drugs have such high Extraction ratios that
virtually all is removed First pass through the
liver. If the drug is taken orally literally none
of it reaches the tissue.
Romazicon, flumazenil, is such a drug. It cannot
be given orally as it is absorbed through the
intestinal wall into the portal circulation and
goes directly to the liver where it is almost
100% deactivated.
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Pharmacokinetics
Drug Half Lives, T1/2

This is the time it take any drug concentration to fall
50%. It is based on a two-compartment model,
first-order kinetics (constant % of drug
concentration) and an exponential decline have the concentration for each fixed time
increment. It is generally a reliable indicator
of the rate of removal of a drug from the blood
and body - duration of action.
Exception high fat soluble drug - diazepam, valium
Has a half life of 20 - 50 hours but it is very fat
soluble so blood levels fall like a much shorter
half life
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Pharmacokinetics

Oral
I.V.
100
Distribution from
blood to tissue
distribution
(alpha phase)
75
Half Lives, T1/2
50
Elimination via
liver and kidneys
Elimination
(beta phase)
25
0
0
10
10
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Pharmacokinetics
CHLORAL HYDRATE
CL
O H
CL C C H
CL
O H
chloral hydrate
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CL
H
CL C C H
CL
O H
trichloroethanol
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CHLORAL HYDRATE
age
sex
15
O
22
O
weight
dose
procedure
reaction
drugs
115
3 g.
ex 3rd molars
vomit
narcan
dopamine
120
2.5g.
ex 3rd molars
problem
outcome
blood levels
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epinephrine
c.a.
c.a.
revived
died
65 g/ml
71 g/ml
( normal 5 - 15 g/ml after 1 gm dose)
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CHLORAL HYDRATE INDUCED ARRHYTHMIAS

age
dose
arrhythmia
c. a.
2
9
17
19
21
29
32
33
1.5
0.6
14
17.5
20
10
20
40
PVC
SVT
PVC, VT
PVC, Vfib
VT
PVC, VT
PVC, Vfib
PVC
no
no
no
yes
no
no
yes
yes
antiarrhythmia outcome
drug resistance
no
yes
yes
yes
no
yes
survived
survived
survived
survived
survived
survived
survived
died
In large doses, it shortens the cardiac refractory period.

May sensitize heart to circulating catecholamines.
Jastak, J.A.D.A., vol 116, march 1988
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Response
100
Chloral hydrate vs Halcion
ED50
50
LD50
Margin
of
Safety
Margin
of
Safety
0
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Dose
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LD50
NORMAL DISTRIBUTION CURVE

mean
freq.
hyper
hypo
response
1 S.D.= 66%
2 S.D. = 95%
3 S.D. = 99.7%
Pallasch, Anes. Prog. 35:87-101,1988
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APPREHENSION CONTROL
sedation - mildly sleepy people are less
likely to feel fearful
barbiturates
alcohol - trichloroethanol (chloral hydrate)
anti anxiety medication
mephenesin
meprobamate - 1955
benzodiazepine
librium - 1960
valium - 1965
Snyde, Drugs and the Brain, N.Y.,Scientific American Library, 1986
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TRANQUILIZERS
1945 Frank Berger - While attempting to
discover an antibacterial for penicillin
resistant bacteria, discovered mephenesin
which he noted quieted mice. An effect he
referred to as "tranquilization."
He developed a derivative meprobamate, which
turned out to be a sedative not a tranquilizer.
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BENZODIAZEPINE DRUGS
Roach was attempting to imitate the nonsedating
nonaddicting antianxiety actions attributed to
meprobamate.
( It turned out meprobamate
was a simple sedative.)
The goal was noble. The rational for the search
was flawed as such an agent did not exist.
to relieve anxiety
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BENZODIAZEPINE TRANQUILIZERS
Leo Sternbach 1930 - Cracow, Poland developed quinazolines.
evaluated for Roach in 1955 saw no sedationturned chemicals over to Randall
Lowell Randall found an active agent
Sternbach reexamined chemical properties found it was not a quinazoline - named the
new class benzodiazepines
librium - 1960
valium - 1963
by 1975 15% of population

100,000,000 Rx / yr.
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BENZODIAZEPINE DRUGS
relieve anxiety
produce some drowsiness - patients became
tolerant to this effect in a few days
"vague uneasiness, generalized
fear and associated physical
symptoms of anxiety fade away."
tolerance develops
withdrawal occur
advantage - overdoses are rarely fatal

except with alcohol or barbiturates
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GABA
NH2 - CH2 - CH2- CH2 - CO2

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GABA Receptor
Cl
Cl
Cl
Cl
cell
wall
Cl
B
Cl
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Cl
Diazepam Alcohol Gaba Receptors

Sedativeconvulsant
Benzodiazepine
Cl- ion channel

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Gaba
Diazepam Alcohol Gaba Actions

Cl
Cl
Cl
Cl
Cl
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Cl
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Pharmacology
Compare
Compare to
to valium
valium
Absorption
Absorption
Half
Half life
life
Active
Active metabolites
metabolites
Structure-activity
Structure-activity relationship
relationship
Nitrogen
Nitrogen atom
atom prevents
prevents water
water solublity.
solublity.
Triazo
Triazo ring
ring alows
alows quick
quick metabolism
metabolism
Chlorine
Chlorine atom
atom is
is responsible
responsible for
for
potency.
potency.
Chlorine
Chlorine atom
atom is
is responsible
responsible for
for
benzodiazepine
benzodiazepine action.
action.
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Halcion - Triazolam
N
H C
3
Cl
Cl
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Triazolam Structure-Activity
N
triazo ring is
responsible for
ease of oxidation
N
H C
3
nitrogen is responsible for

lack of water solubility
Cl
Cl is responsible
for potency
Cl
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Cl is responsible for
benzodiazapine action
Copyright
Diazepam vs Triazolam
O
H C
3
H C
3
Cl
Cl
Cl
Diazepam
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Triazolam
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Benzodiazepine Elimination
drug
time to peak elimination

plasma conc. half-life
major active
metabolites
alprazolam
1-2 hr.
12-15 hr.
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Diazepam vs Triazolam
drug

triazolam
1 - 2 hr.
1.5 -5.0 hr.?
major active
metabolites

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drug

major active
metabolites
alprazolam
1-2 hr.
12-15 hr.
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drug

major active
metabolites
alprazolam
1-2 hr.
12-15 hr.
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drug

major active
metabolites
alprazolam
1-2 hr.
12-15 hr.
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Xanax -Alprazolam
Dosage 0.25-1.0 mg adults
Onset 1 hour
Durration 1-2 hours
2004 SW Dental Conference Joseph Giovannitti JR, DMD
QuickTime and a
TIFF (LZW) decompressor
are needed to see this picture.
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QuickTime and a
QuickTime and a
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Effects
Interaction with the Gama Amino Butyric Acid
receptor complex.
Potentiates GABA.
Alters the Chloride ion channel to increase
frequency of their opening.
Interacts with the glycine receptors.
Alters opiate peptide concentrations.
5-HT decreases - a precursor of Seratonin.
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Effects
Central nervous system
Antianxiety, sedative-hypnotic,
anticonvulsant and skeletal muscle
relaxant
All depress CNS to some degree. These tend
to be more antianxiety as compared with
barbiturates and other sedative-hypnotics.
Depress the limbic system and areas of brain
associated with emotion and behavior
particularly the hippocampus and the
amygdaloid nucleus.
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Cardiovascular system
Benzodiazepines cause few alterations in
cardiac output or blood pressure when
administered intravenously to healthy
persons.
Slightly greater than normal doses cause slight
decreases in blood pressure, cardiac output,
and stroke volume in normal subjects and
patient with cardiac disease, but are not
usually clinically significant.
Triazolam did not affect cardovascular
dymanics in doses 4 to 8 times normal.
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Absorption
Rapid peak within 2 hours

Faster in elderly and young women
Faster in daytime than at night
due to longer predose fasting period
2 times faster after a 12 hour fast.
85% absorbed 15% passed through.
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Distribution
No difference in obese and normal patients.
Plasma potient binding at 89%. 49% to serum
proteins.
Crosses readily into central nervous system
because of high lipid solubility.
Crosses the placental barrier and milk of rats.
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Metabolism
Halcion is oxidized first pass in liver and lining
of gut by the cytochrome P450 monooxygenase system
The P450 is made up of many enzymes. The
majority of drug metabolism is by seven
enzymes, 1A2, 3A4, 2c8, 2C9/10, 2C19, 2C19,
2D6, 2F1.
Halcion is metabolized by the 3A4 enzyme.
The presence or absence of an enzyme can be
idiosyncratic or associated with certain patient
subsets6/6/05
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Metabolism
The absence of an enzyme can be
subsets
CYP 2D6: 2-10% of the total population
5-10% of Caucasians 6% of AfroAmericans
0-1% of Asians
CYP 2C19: 18-25% of Afro-Americans and
Asians
2-5% of Caucasians
S.E. Asians may have less 3A4

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Elimination
Half life averages 1.2 to 3.3 hours.
Slower at night.
Longer - elderly - lower liver
oxidixing capacity.
No change with kidney dialysis.
Slower with cirrhosis.
91% eliminated in urine
9% in feces within 72 hr.
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CNS. conc.
drug
blood brain
barrier
plasma conc.
plasma binding
liver
portal circulation
(metabolism)
excretion
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fat
fatpartition
stores
time
1hr.
Copyright
6 hr.
1 d.
6 d.
Bioavailability
Fraction of
unchanged
drug reaching
the systemic
circulation after
administration
by any route
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Oral Dose
IV Dose
Target Organ
Portal
Circulation
Systemic
Circulation
Cytochrome
Excretion Copyright
P450metabolism
Inhalation
N2O
Side effects .5 mg.

8% sleepiness
4% headach, dizzyness, neuritis,
dry mouth
Reproduction
In rats slightly reduced fertility
but did not affect postnatal
development in rats.
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Cardiovascular system
Benzodiazepines cause few alterations in
cardiac output or blood pressure when
administered intravenously to healthy persons
Slightly greater than normal doses cause slight
decreases in blood pressure, cardiac output and
stroke volume in normal subjects and patients
with cardiac disease, but are not usually
clinically significant.
Triazolam did not affect cardovascular dynamics
in doses 4 to 8 times normal.
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Contraindications to Traizolam
absolute
relative
known
known hypersensitivity
hypersensitivity
lack
lack of
of knowledge
knowledge
inability
inability to
to initiate
initiate resuscitation
resuscitation
myasthemia
myasthemia gravis
gravis
glaucoma
glaucoma
first
first trimester
trimester
lactation
lactation
concurrent
concurrent CNS
CNS depressants
depressants
Cimethadine
Cimethadine (tagamet)
(tagamet)
Erythromycin
Erythromycin
Isoniazid
Isoniazid
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pediatric
pediatric patients
patients
geriatric
geriatric patients
patients
psychiatric
psychiatric patients
patients
no
no FDA
FDA approval
approval for
for
dental
dental sedation
sedation
Copyright
Patient Assessment
ASA Classification American Society of Anesthesiologists
ASA I:
ASA II:
ASA III:
ASA IV:
ASA V:
ASA E:
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normal healthy
mild systemic disease does
not effect the way the live
severe systemic disease
effects the way they live
incapacitating systemic
disease
moribund, 24 hours to live
emergency
Copyright
Patient Assessment
Much the same as for doing dentistry
Cardiovascular Disease
Pregnancy benzodiazepines are known
teratogens
Elderly
Patients on Steroids
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Hypertension
Ischemic heart disease
Valvular heart disease
Congestive heart disease
Dysrhythmia
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Hypertension
Systolic
<140
140
160-200
200 &/or
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Diastolic
<90
&/or 90-95
Effect on Treatment
none
none: reassess BP next 2
appt.
&/or 95-115 reassess in 5 min.,
refer to MD
>115
reassess in 5 min., refer to
MD immediately
Copyright
Hypertension Protocol
Vital signs
Stress reduction
Chairside manner
Profound Local Anesthesia
Conscious sedation
Limit epinephrine to 0.04 mg. 2
cartridges - 1:100,000 epi.
Retraction cord with epi. ???
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Hypertension
stable
Treatment?
Yes?
Dysrhythmia
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unstable
No
Hypertension
stable
unstable
Treatment?
Yes?
No
Consider SBE prophylaxis
Medical consultation
Medical Consultation
Dysrhythmia
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Hypertension
stable
unstable
Treatment?
Yes?
No
Dysrhythmia
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Hypertension
stable
unstable
Treatment?
Yes?
No
Dysrhythmia
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Dysrhythmia
Vital signs
Stress reduction
Chairside manner
Profound local anesthesia
Conscious sedation
Limit epi to 0.04 mg. 2 cartridges
1:100,000
No epi. in retraction cord
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Elderly
Physiologic changes with age
Concomitant disease
Polypharmacy review medication list
Drug interactions
Decrease initial dose
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Patients on Steroids
Physiologic release
20-30 mg of cortisol daily
equivalent to:
20-30 mg of hydrocortisone daily
5-7.5 mg. Of prednisone daily
Coverage is required if:
Stressful procedure
On physiologic dose, at least 1 week in
past year
Double daily dose or 100 mg I.M. Hydrocortisone
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Metabolism
The absence of an enzyme can be
subsets
CYP 2D6: 2-10% of the total population
5-10% of Caucasians 6% of AfroAmericans
0-1% of Asians
CYP 2C19: 18-25% of Afro-Americans and
Asians
2-5% of Caucasians
S.E. Asians may have less 3A4

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Drug interactions
Cimethedine - for ulcer treatment
Erythromycin - an antibiotic
Isoniazid - an antitubercular agent
Reduce the first pass liver clearance by
decreased metabolism and reduction in
hapatic blood flow. Due to decrease in
cytochrome P450-mediated oxidatative
system.
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Halcion Study
Patients
173
Treatments
269
Age
average 31.2 +/- 19.7

range
1.5 - 71
Sex
male
female
Weight
average 135 +/range

23-286
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54
119
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75
Drug Record Forms
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Patient information and consent forms
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Medical History and Sedation Record
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AGE
count
30
20
10
10
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20
30
40
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50
60
70
AGE
count
30
20
10
10
20
30
40
50
60
70
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CopyrightGuidelines
With
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Apprehension Level
terrified
panicked
very afraid
afraid
tense
nervous
calm
start
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30 min.
60 min
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finish
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Amnesia
100%
% of patients
remembering
symbol
80%
60%
40%
20%
pre
med
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30
min
60
min
Copyright
mid
end
procedure
Blood pressure
systolic
160
140
120
100
80
60
diastolic
mmHg.
pre opt. 15 min. 30 min 45 min 60 min

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Pulse Rate - Hemaglobin O2 Saturation

100
90
90
pulse
rate
SaO2
sd +
-2
80
pre
opt.
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15
min
30
min
45
min
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60
min
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Weight vs. Dose of Halcion

.75
.625
.5
.375
n = 100
.25
suggested dose
minimum dose
.125
0
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50
100
150
tended to sleep
good sedation
200
250
300
difficult but possible
uncontrolable
Copyright
ADA Guidelines
Except for unusual circumstances, the maximum
recommended dose (mrd) shall not be exceded.
Only one dose can be given. You may not titrate for effect.
Inaccordwiththisparticulardefinition,titrationoforalmedication
forthepurposesofsedationisunpredictable.Repeateddosingof
orallyadministeredsedativeagentsmayresultinanalterationofthe
stateofconsciousnessbeyondtheintentofthepractitioner.Exceptin
unusualcircumstancestheMaximumRecommendedDose(MRD)of
anoralmediationshouldnotbeexceeded
The FDA stated there is no mrd for halcion used as an oral
sedative.
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.75
no sedation
.625
.5
.375
n = 100
.25
suggested dose
minimum dose
.125
0
50
100
150
tended to sleep
good sedation
200
250
300
uncontrolable
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With
newCopyright
ADA Guideline
no sedation
.75
.625
.5
.375
.25
suggested dose
.125
minimum dose
0
50
100
150
tended to sleep
good sedation
200
250
300
uncontrolable
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With
newCopyright
ADA Guideline
Dose
Dose
of = 0.25mg + 0.125mg
Halcion
weight - 40
70
(weight in pounds)
If at 30 minutes the patient notices NO
sedation and the dentist observes NO Weight vs. Dose of Halcion
sedation, half the original dose is
administered sublingually.
.75
.625
.5
.375
n = 100
.25
suggested dose
minimum dose
.125
0
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50
100
150
tended to sleep
good sedation
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200
250
300
uncontrolable

Oral
I.V.
100
Distribution from
blood to tissue
distribution
(alpha phase)
75
Half Lives, T1/2
50
Elimination via
liver and kidneys
Elimination
(beta phase)
25
0
0
10
10
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Pharmacokinetics
Titration of Halcion half first dose?

Halcion
Second
1/2 dose
active
conc.
halcion
Population study of triaazolam
pharmacokinetics B.J.Clin.Pharmc (1986)
22, 639-642
Triazolam pharmacodynamics in obesity, J. Clin
Psychopharmacol Vol 15/no3, June 1995
time
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3
Aggressive Titration of Halcion - guess

3rd dose
2nd dose
active
conc.
First dose
time
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3
Nitrous Oxide Supplementation

second dose at 30 min - 1/2 original dose
apprehension level
nitrous oxide effect
sedation
level
halcion effect
sedation
level
1
time in hours
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Flumazenol
COOCH CH
3
N
H C
3
C H3
N
H C
3
Cl
Cl
Cl
F lumazenol
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Triazolam
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Flumazenil
ethyl 6 - fluoro - 6, 6 - dihydro - 5 methyl - 6 - oxo - 4h - imidazo
(l,5-a) (1,4) benzodiazepine - 3 carboxylate
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Dose
.007 and .014 mg/kg.
Lethal dose in mice and rats is 62.5 and 125 mg
/ kg.
One study suggested lethal dose is 3000 times
theraputic dose.
It has been tested up to 200 mg. IV and oral. In
the case of oral dosages only 18% is active
as it is oxidized in first pass through the liver
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Elimination and Side Effects
Eliminated completely in first pass

through liver by P-450 system. Not
effective orally for this reason.
Side effects are infrequent. These include
mild headache, loss of pupil reactivity
to light, mild hypotension.
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Half life
At 54 minutes (.7 to 1.3 hr. 50 min. average) is
less than midazolam and valium so you may
see some rebound.
Worked within 2 to 5 minutes.
One author saw no improvment after 15
minutes.
Another showed improvment at 15, 30 but not 60
minutes.
1 mg. will last for about 2 hours.
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Flumazenol Reversal of Halcion

flumazenol
active
conc.
halcion
without
reversal
time
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3
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Reversal of
Triazolam by
Romazicon,
IV reversal
SL reversal
Flumazenil,
Much effect
An unpublished
from the
needle stick
study
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Min.
5 10
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15
20
Successful Nitrous Oxide / Oxygen

Sedation
apprehension level
sedation
level
time in minutes
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Inadequate Nitrous Oxide / Oxygen

Sedation
apprehension level
sedation
level
15
time in minutes
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30
45
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60
Inadequate Halcion Sedation

apprehension level
sedation
level
halcion effect
1
time in hours
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Nitrous Oxide Supplementation

apprehension level
sedation
level
halcion effect
sedation
level
1
time in hours
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Deaths from Halcion

Impaired driving
Sexual Assault
Death due to drugs
Death Drug related
Death drug involved
17
4
45
20
8
Cases from 1979-1990 in Canada
Joynt,
Brian, Journal of Analytical
Toxicology, vol.17 May/June 1993 p171-177
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Deaths from Halcion

Impaired driving
17
9 combination with other drugs
Sexual Assault
4
Death due to drugs
45
Death Drug related
20
Death drug involved
8
Joynt,
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Deaths from Halcion

Impaired driving
17
Sexual Assault
4
male and female - love drug
Death due to drugs
45
Death Drug related
20
Death drug involved
8
Joynt,
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Deaths from Halcion

Impaired driving
Sexual Assault
Death due to drugs
4 were halcion alone
1 10 ng/ml
3 40 ng/ml
Death Drug related
Death Drug involved
17
4
45
20
8

Joynt,
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Deaths from Halcion

Death due to drugs
45
4 were halcion alone
1 10 ng/ml
3 40 ng/ml
Peak conc.
0.125 = 1.08 +-0.08 ng/ml
1.67+-0.16 ng/ml elderly
0.25 = 2.02 +-0.15 ng/ml
1.0 = 7.47 +-1.51ng/ml
at .83 hr +-0.32 hr
Joynt,
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Deaths from Halcion

Death due to drugs
45
41 were halcion + other drugs
9 - 190 ng/ml
Peak conc.
0.125 = 1.08 +-0.08 ng/ml
0.25 = 2.02 +-0.15 ng/ml
1.0 = 7.47 +-1.51ng/ml
at .83 hr +-0.32 hr
Joynt,
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Deaths from Halcion

Impaired driving
Sexual Assault
Death due to drugs
Death Drug related
Death drug involved
17
4
45
20
8
Most appear to be self inflicted suicide, an error in patient

compliance or the result of foul play
Joynt,
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Qs Recommendations
This refers only to the use of halcion
MRD is for use as a sleep aid - elderly with no monitoring
ED60 equals about the LD5 of chloral hydrate.
No use on patients under 40 lbs. (5 years of age).

Titration is possible
It is very slow.
Can be used to adjust initial dose.
Secondary doses should be no more than the
predicted amount that has been
metabolized
(1/2 original dose at 2 hr. intervals)
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Qs Recommendations
Administered in the office
assistant in the room
Dr. in the office
Monitoring
Pulse oximeter monitoring - constant
BP monitoring (q. 15 min.)
No multiple drugs Single drug plus nitrous oxide OK.
Staff and Dentist must have BLS every year.
The Dentist should be trained and current in
the use of nitrous oxide.
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Solution
Research
Education
Education
Good courses will drive out
Or cause bad courses to be altered.
It is the responsibility of the ADA to educate
and publish when so many are using a drug in
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potentially
dangerous techniques.
Halcion Oral Sedation

Drugs make the world go round.
To get really high
Free online Halcion manual

http://faculty.washington.edu/quarn
select oral halcion

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takes a telescope.
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Triazolam

patients - AAOMS - OCS

Mortality from Anesthesia 1970-1979 U. K.

Single Operator / Anesthetist

One Operator One Anesthetist

(patient died on a motorcycle later the same day)

note - this study was pre pulse oximeter useage

The Spectrum of Anesthesia

1-10 11-20 21-30 31-40 41-60

Marx, Anes., 39:54-58, 1973

AGE VERSUS SEVERE MORBIDITY/MORTALITY

21-30 31-40 41-60

age range = 21 mo. - 59 yr.

Jastak, Anes Prog, 38:39-44 1991

AGE VERSUS SEVERE MORBIDITY/MORTALITY

21-30 31-40 41-60

age range = 21 mo. - 59 yr.

Jastak, Anes Prog, 38:39-44 1991

Standards for Conscious Sedation

Standards for Conscious Sedation

A drug-induced state during which patients respond

Level 2 Moderate Sedation/Analgesia Conscious Sedation

Standards for Conscious Sedation

A drug-induced depression of consciousness during which

Level 3 Deep Sedation/Analgesia

Standards for Conscious Sedation

A drug-induced depression of consciousness during which

Standards for Conscious Sedation

Competent at least one level greater than where

NORMAL DISTRIBUTION CURVE

Pallasch, Anes. Prog. 35:87-101,1988

Drug Distribution and Elimination

Two and three compartment model - better

Three compartment model is most accurate

central compartment- extra cellular fluid and organs

First and Zero Order Kinetics

Clearance and Extraction Ratios

First Pass Effects

Drug Half Lives, T1/2

Drug Half Lives, T1/2

Half Lives, T1/2

CHLORAL HYDRATE INDUCED ARRHYTHMIAS

In large doses, it shortens the cardiac refractory period.

Chloral hydrate vs Halcion

NORMAL DISTRIBUTION CURVE

Pallasch, Anes. Prog. 35:87-101,1988

Snyde, Drugs and the Brain, N.Y.,Scientific American Library, 1986

Snyde, Drugs and the Brain, N.Y.,Scientific American Library, 1986

by 1975 15% of population

Snyde, Drugs and the Brain, N.Y.,Scientific American Library, 1986

advantage - overdoses are rarely fatal

Snyde, Drugs and the Brain, N.Y.,Scientific American Library, 1986

NH2 - CH2 - CH2- CH2 - CO2

Diazepam Alcohol Gaba Receptors

Cl- ion channel

Diazepam Alcohol Gaba Actions

nitrogen is responsible for

time to peak elimination

time to peak elimination

1.5 -5.0 hr.?