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Modern Anesthesia in
Dentistry Newsletter
February 2014
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Oral Sedation part I - Medications
INSIDE THIS ISSUE
1
Benzodiazepines
2
Other medications
3
Commonly used
medications
Benzodiazepines are the
most commonly used
sedative hypnotic
because of their superior
efficacy and large margin
of safety.
Dr Ryan Allred, DMD
Benzodiazepines
Benzodiazepines are the most commonly used medications for oral sedation
mainly because of their wide margin of safety. The main effects of
benzodiazepines are anxiolysis (calming effect), sedation, amnesia and muscle
relaxation. At very high doses, and in combination with other medications,
respiratory depression and cardiac depression are possible.
All benzodiazepines and the so called non-benzodiazepine-GABA agonists
(Lunesta, Ambien) work by binding to the benzodiazepine receptor on the GABA
complex. When the benzodiazepine receptor is activated it modulates GABA
(the main inhibitory neurotransmitter in the brain) to bind more readily to the
GABA receptor, which causes chloride channels to open (the main inhibitory
effect). An important point regarding this mechanism of action is that
benzodiazepines only act indirectly with GABA, they can't independently open
chloride channels without GABA (unlike chloral hydrate, barbiturates, or
propofol). This accounts for why benzodiazepines have somewhat of a ceiling
effect and a large margin of safety.
All benzodiazepines will cause similar effects in a dose dependent manner. One
should chose the agent based on the needed duration of action. Triazolam
(Halcion) and diazepam (Valium) are relatively short acting benzodiazepines,
while lorazepam (Ativan) and alprazolam (Xanax) are longer acting
benzodiazepines. Despite its long elimination half life, Valium is a short acting
medication because it has a short distribution half life (1-3 hours based off its
degree of lipid solubility and how quickly it enters and leaves the brain).
Non-Benzodiazepine-GABA agonists
More recently drug companies have marketed drugs that are non
benzodiazepines in how they are chemically synthesized, but are agonist on the
benzodiazepine receptors. Thus, despite marketing claims, they act clinically
like benzodiazepines and can also be reversed by flumazenil just like other
benzodiazepines. These drugs include zolpidem (Ambien), zaleplon (Sonata) and
eszopiclone (Lunesta). For example, 10mg Ambien would be nearly identical to
0.25mg Halcion except that Ambien is more expensive.
Dentistry Newsletter
Modern Anesthesia in Dentistry Newsletter
Page 2
Antihistamines
Antihistamines main use is in prevention of allergies/allergic reactions due to
histamine release from mast cell degranulation by blocking the H1 histamine
receptor. These medications also have anticholinergic effects which can cause dry
mouth as well being antiemetic and mildly antitussive (inhibit cough).
Each drug has a dose
response curve and
as the dose
increases the level
of sedation and
possible side effects
also increase.
First generation antihistamines all cross the blood-brain barrier and thus cause
drowsiness and sedation. Second generation antihistamines, like loratadine
(Claritin), don’t readily cross the blood-brain barrier and don’t cause nearly as much
drowsiness. Common first generation antihistamines used in oral sedation are
diphenhydramine (benadryl), hydroxyzine (Atarax,Vistaril) and promethazine
(Phenergan). Hydroxyzine has been reported to have anxiolytic properties as well as
sedative properties. As a group, the antihistamines are not as effective of a sedative
hypnotic as the benzodiazepines. They have a very wide margin of safety, because
when used alone, at normal dose ranges, they cause no respiratory/cardiac
depression. These agents are sometimes used in a cocktail approach.
Opioids
Opioids are not generally used for oral sedation as they have little anxiolytic
properties, and can cause more respiratory depression. However, some havel added
meperidine (Demerol) into cocktails for oral sedation (chloral hydrate, Vistaril,
Demerol). As discussed later, drug synergism with oral medications can lead to a
more varied response with specific individuals than with a one drug approach. When
used with other sedative hypnotics the effect of opioids is synergistically increased.
Miscellaneous Agents: Chloral Hydrate and Ketamine
Chloral hydrate (Noctec) was one of the first sedative hypnotic agents available,
being synthesized in 1832. It was used commonly in pediatric sedation with a
cocktail of other medications. It worked as a general CNS depressant and was able
to induce deep sedation within 30 minutes. As other agents, such as oral midazolam
(Versed), have become more standard in pediatric oral sedation, the use of chloral
hydrate has diminished. Recently, manufactures have stopped producing the drug.
When multiple
medications are
combined together
significant drug
synergism can occur.
Ketamine is a NMDA antagonist which causes a dissociative anesthesia, basically by
“disconnecting” the cerebral cortex from the thalmus/limbic system, thus the
patient is dissociated from any pain or fear that they may be feeling. This
medication has many unique properties from the other sedative hypnotics including:
analgesia, hallucinations, hyper-salivation, emetogenic, and a cardiac stimulatory
effect. Ketamine tends to maintain airway reflexes and has very little effect on
respiratory function. Since Ketamine is a general anesthetic, the Oregon dental
board states that only those with a general anesthesia permit can use ketamine.
Multiple Drug Synergism
One key point with oral sedation is the fact that each drug has a dose response curve
and as the dose increases the level of sedation and possible side effects also
increase. There are always those who are hyper and hypo responders. Oral sedation
effects are somewhat unpredictable because the dose cannot be titrated to effect
like with IV medications. This becomes even more important when multiple
medications are given in combination. For example, meperidine, chloral hydrate,
and hydroxyzine have been used in the past for pediatric oral sedation. This cocktail
allowed for drug synergism such that the combination of drugs could produce a
markedly greater effect than the sum of the individual drugs and a patient could
become more sedated than the intended level. This means that the dose needed to
reach unconsciousness became much lower if used in combination with other
medications than if used alone (Vinik 1994), thus making over sedation more likely to
occur, such as in the recent Hawaii oral sedation death which used this combination.
Page 3
Modern Anesthesia in Dentistry Newsletter
Drugs Commonly Used in Sedation
Generic name
(Brand name)
Adult Dose
Range
(mg)
Hydroxyzine (Atarax,
Vistaril)
Diphenhydramine
(Benadryl)
Midazolam (Versed)
50-100
Onset
(minutes)
Peak
effect
(minutes)
Special
Comments
14
15-60
0.5-3
2.4-9.3
15-60
0.5-3
2.2-6.8
10-30
30-45
X
1.5-5
15-30
1.3 hours
Antiemetic,
anticholinergic
Antiemetic,
anticholinergic
Mix with Grape
Tylenol to
improve flavor
Great for short
appointment
Triazolam (Halcion)
0.125-0.5
Diazepam (Valium)
2.5-10
X
20-80
20-40
Alprazolam (Xanax)
0.25-2
X
6-27
30-45
0.5-2
ours
1-2 hours
Lorazepam (Ativan)
0.25-4
8
30-60
2-4 hours
Zaleplon (Sonata)
5-20
0.05
mg/kg
X
0.5-1
20
1 hours
Zolpidem (Ambien)
5-10
X
1.5-4.5
30
1.6 hours
25-50
20mg
Pediatric
Dose
range
Sole agent
1-2mg/kg
Elimination
Half Life
(hours)
0.51mg/kg
0.5 mg/kg
Good for
intermediate
appointments
Good for long
appointments
Short
appointments
Short
appointments
_____________________________________________________________________________________
Dr. Ryan Allred is a dentist anesthesiologist practicing in the Portland, Oregon area. He travels to
dental offices providing all levels of anesthesia, from IV sedation to general anesthesia, for
pediatric, adult and medically complex patients. This allows both dentist and patient to have a
smooth and comfortable experience in some of the most challenging cases. More information
about Dr. Allred’s training and services offered by Portland Dental Anesthesia can be found at
www.portlanddentalanesthesia.com.
If you would like meet with Dr. Allred or if you would like help integrating the new CO2
(capnography) rules in your office, call 503-858-4880.
If you have a patient in your office that might need
deep sedation or general anesthesia,
please call 503-858-4880.
Dentistry Newsletter
Modern Anesthesia in Dentistry Newsletter
Page 4
February 2014
Modern Anesthesia in Dentistry Newsletter
In this issue: Oral Sedation part 1-Medications




Benzodiazepines
Antihistamines
Opioids
Miscellaneous agents:
o chloral hydrate
o ketamine
 Drug synergism
Portland Dental Anesthesia
16004 SW Tualatin Sherwood Rd #419
Sherwood, OR 97140