Practical Review of Pharmacology

for Dentistry
Michigan Dental Association Annual Session
May 3, 2014

Joseph A. Best, D.D.S., Ph.D.

Assistant Professor
Division of Oral and Maxillofacial Surgery
Marquette University School of Dentistry

Private Practice
Oral and Maxillofacial Surgery Associates Ltd
Waukesha*Waukesha*Oconomowoc*Mukwonago*Johnson Creek

Practical Review of Pharmacology for Dentistry J.A. Best

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Understanding Pain
The dental team as pain specialists
Developing pain control strategies based on an understanding of the basic science
If you only use one local anesthetic and one analgesic and no adjunctive techniques, you are not
reaching your potential in pain control
Highly variable
Strong emotional component
Complex neurologic pathways involved with both peripheral and central components

Basic pain pathway

Inflammation and pain

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Why does this matter?

Inflammatory mediators
Activate/sensitize nerve terminals
Increase in spontaneous activity
Decrease in threshold

Hyperalgesia
Once tissue injury occurs, a cascade of events occurs that produces a heightened responsiveness of the
injured and surrounding tissue termed hyperalgesia
The hot tooth
The Big picture
Understanding the pathways of pain and where in the pathway your management strategies are
targeting
Can we target at more than one level and is this a more effective pain control strategy
Local Anesthetics
How do local anesthetics work
Prevent the generation and propagation of nerve action potentials
Blocking the sodium channel to prevent sodium influx

Local Anesthetics
How do local anesthetics work
Prevent the generation and propagation of nerve action potentials
Blocking the sodium channel to prevent sodium influx

To be effective, local anesthetics must penetrate the nerve because it is thought that they block
sodium conduction from the inside
pKa helps determine how well an anesthetic can penetrate a nerve

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Why is the pKa of a local anesthetic important?

To be effective, local anesthetics must penetrate the nerve
pKa helps determine how well an anesthetic can penetrate a nerve
Inflamed tissues tend to have decreased pH, therefore there is a tendency for local anesthetics to
be in the charged (hydrophilic) form
pKa determines the % of molecules that are charged
pKa of selective agents
Mepivacaine
Lidocaine
Articaine
Etidocaine
Prilocaine
Bupivacaine
Procaine

7.6
7.7
7.8
7.9
7.9
8.1
9.1

We also must consider nerve anatomy

Onset of Action
Time from when anesthetic is delivered to when pulpal anesthesia is achieved (Induction time)
Effected by:
Concentration of anesthetic
pH of the tissues to be anesthetized
pKa of the anesthetic
Thickness of the tissue and size of the nerve
Blood supply to the area
Potency of the anesthetic
Duration of Action
Time during which the patient has pulpal anesthesia

Blood supply to the area

Degree of protein binding
Vasodilating activity of the agent
Vasoconstrictor activity
Patient to patient variability
Toxicity
Remember that local anesthetics are non-selective
o Can interfere with impulse conduction in any body system
CNS
PNS
Muscle (skeletal, cardiac, smooth)
More likely to occur with topical agents and in pediatric (or small) patients
Toxicity
o Dose dependent
Prevent systemic toxicity by good technique
o Aspiration
o Careful dosing
o Being aware of medical considerations

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o

Being aware of drug interactions

Methemoglobinemia
Local anesthetic metabolites can sometimes oxidate hemoglobin to methemoglobin in susceptible
individuals
Patient presents with cyanosis (blue lips, nail beds) that does not improve with oxygen
Rarely fatal
Seen with prilocaine (Citanest), articane (Septocaine) and the topical agent benzocaine
Treated with intravenous methylene blue
Allergy
Patient reports of local anesthetic allergy are fairly common
TRUE local anesthetic allergies are exceedingly rare
Be VERY careful NOT to tell a patient that they have an allergy to a local anesthetic if they simply
have a bad experience (syncope, palpations, anxiety attack)
Esters
Esters more commonly cause allergy as a result of the formation of p-aminobenzoic acid
If allergic to an ester, the patient is allergic to all esters
Amides
Most investigators consider amides essentially non-allergic Anesthesiol Rev 3:13-16, 1976
If concerned about allergy to one amide, it is ok to try another (no cross-reactivity)
Epinephrine
It is inconsistent with life to be allergic to epinephrine, it is simply impossible
What if someone has a true local anesthetic allergy?
Options?
-Confirm with allergist
-Infiltrate with 50 mg of benadryl (diphenhydramine)
-Oral sedation and nitrous oxide
-I.V. sedation or general anesthetic
Metabisulfites
Used in local anesthetics with vasoconstrictor
Evidence that certain patients (mostly asthmatics) can be hyper-reactive to sulfites that are inhaled
or ingested but usually not injected
Probably not immunologic in nature
If very severe asthmatics or persons with metabisulfite allergy, better to avoid local with
vasoconstrictors
There is NO contraindication to the use of local anesthetics which contain metabisulfite in patients
with a history of allergy to sulfonamide antibiotics (so called sulfa allergy)
Methylparaben
NOT AN ISSUE FOR DENTISTS!
Only used as a preservative in multi-dose vials
No longer used in dental single-use packaging
Malignant Hyperthermia (MH)
Previously thought to be induced by local anesthetics
NO EVIDENCE in the literature to support this view
It is now considered safe to use all commercially available local anesthetics in patients with a
history of MH
J Can Dent Assoc 68:546-51 2002
Metabolism

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Amide

Metabolized in the liver

Esters

Metabolized by plasma pseudocholinesterases

Para-aminobutyric acid is a metabolite (allergen)
Liver disease and local anesthesia
Does not effect duration of local anesthetic (remember what determines duration of action)
Only important with significant liver disease
Best to limit dosing (quadrant dentistry) when dealing with patients with severe liver disease
Also important for esters since plasma pseudocholinesterases are synthesized in the liver
Vasoconstrictors
Why?

Prolong duration
Antagonize vasodilation of local anesthetics
Decrease bleeding
Decrease systemic toxicity
How?

Alpha-1 agonists
Produces vasoconstriction
Agents

Epinephrine
Levonordefrin (Neo-Cobefrin)
Possibly

less cardiac and pressor side effects than epinephrine

Norepinephrine
Sympathomimetics
Activate the sympathetic nervous system
Vasoconstrictors
Contraindications
Untreated pheochromocytoma
Uncontrolled or unstable angina
Uncontrolled hyperthyroidism
MI within last 6 mo.
Use with caution (limit use of epinephrine to 0.04 mg, 2 carpules of 1:100,000)
Moderate to severe cardiovascular disease
CVA history
Moderate to severe hypertension
Adverse reactions to vasoconstrictors
Low dose epinephrine

Can produce syncope-like symptoms

High dose epinephrine

Palpitations
Low Dose Epinephrine

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Increased PP
Decreased DBP
High Dose Epinephrine
Increased PP
Increased DBP, SBP
Specific Local Anesthetics
Selection of anesthetic is based upon

Patient medical history

Duration of action desired
Need for vasoconstrictor
Clinical situation (i.e. active infection)
Availability
Vasoconstrictor drug interactions
Beta-blockers

Nonselective blockers like propranolol, nadolol and timolol can cause an increased alpha response from
systemic epi dose resulting in systemic vasoconstriction with increased BP
Not a problem with selective blockers like atenolol, metoprolol, acebutolol, betaxolol
Adrenergic Receptors
Alpha 1
Constriction arterioles and veins
Beta 1
Heart: increased rate, contractility, conduction and automaticity
Beta 2
Trachea and Bronchiole relaxation
Arteriole and vein dilation (except skin and brain)

Patient on Non-selective Beta-Blocker

Alpha 1
Constriction arterioles and veins
Beta 1
Heart: increased rate, contractility, conduction and automaticity
Beta 2
Trachea and Bronchiole relaxation
Arteriole and vein dilation (except skin and brain)

Patient on Cardio-selective Beta-Blocker

Alpha 1
Constriction arterioles and veins
Beta 1
Heart: increased rate, contractility, conduction and automaticity
Beta 2
Trachea and Bronchiole relaxation
Arteriole and vein dilation (except skin and brain)

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lidocaine
(Xylocaine, Alphacaine, Lignospan, Octocaine)
Class: Amide
Onset: 2-4 min
Duration: 60-120 min (180-240 with epi)
Max dose: 4.4 mg/kg
Available as:
2.0% +/- 1:100,000 or 1:50,000 (36 mg per 1.8 cc)
Also available without epi (not very effective due to very short duration)
Popular for a reason: cheap, effective and safe
bupivacaine
(Marcaine, Sensorcaine)
Class: Amide
Onset: 2-10 min
Duration: 240-540 min
Max dose: 1.3 mg/kg
Available as:
0.5% +/- 1:200,000 epinephrine(9 mg per 1.8 cc)
May not be ideal for pediatric patients
Great for procedures with significant post-operative pain (3rd molars)
mepivacaine
(Carbocaine, Polocaine, Isocaine, Scandonest)
Class: Amide
Onset: rapid 1-2 min
Duration: 120-180 min Max dose: 4.4 mg/kg
Available as:
3.0% without vasoconstrictor
2.0% with1:20,000 neo-cobefrin (120-240 min duration)
Nice drug for cardiovascular compromised (less vasodilating) patients and infected tissues (pKa
7.6)
prilocaine
(Citanest)
Class: Amide
Onset: rapid 2-5 min
Duration: 100-240 min (120-240+epi)
Max dose: 6 mg/kg
Available as:
4.0% without epi
4.0% (Citanest Forte) with 1:200,000 epi
Methemoglobinemia
etidocaine
(Duranest)
Class: Amide
Onset: rapid 2-3 min
Duration: 240-540 min (+epi)
Max dose: 6 mg/kg
Available as:
1.5% without epi
1.5% with 1:200,000 epi
Long duration with relatively quick onset

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No longer available in U.S.

articaine
(Ultracaine, Septocaine)
Class: Amide
Onset: rapid 2-3 min
Duration: 180-300 min (+epi)
Max dose: 7 mg/kg
Available as:
4% with 1:100,000 or 1:200,000 epi
Claims of better soft-tissue and hard-tissue diffusion
Contraindicated in patients with Sulfa allergy???
Methemoglobinemia/ neurotoxicity questions?
Evidence for articaine over lidocaine?
EFFICACY OF ARTICAINE: A NEW AMIDE LOCAL ANESTHETIC Stanley F. Malamed, D.D.S.;
Suzanne Gagnon, M.D.; Dominique LeBlanc, D.Pharm JADA, Vol. 131, May 2000, Pgs. 635-642
ABSTRACT In three identical randomized, double-blind, multicenter studies, the authors compared the
safety and efficacy of articaine 4% with epinephrine 1:100,000 to lidocaine 2% with epinephrine
1:100,000. A total of 1,325 subjects, ages 4 to 80 years old were treated for simple or complex dental
procedures and received either articaine 4% with epinephrine 1:100,000 or lidocaine 2% with epinephrine
1:100,000. The subjects were randomly selected in a 2:1 ratio to receive articaine (882 subjects) or
lidocaine (443 subjects). The authors found that articaine 4% with epinephrine 1:100,000 provided
clinically effective pain control during most dental procedures and was well tolerated by the 882 subjects
receiving it. The onset and duration of anesthesia compared favorably with other available dental
anesthetics.
Cost
2% Lidocaine with 1:100,000 epi
1 can (50 carp)
$23.95
1 case (500 carp)
$229.50
4% Septocaine with 1:100,000 epi
1 can (50 carp)
$39.75
1 case (500 carp)
$377.50
The

onset and duration of anesthesia compared favorably with other available dental anesthetics.

articaine and neural toxicity

Google search Septocaine
First hit: Septocaine Lawyer
Evidence:
In laboratory studies articaine found to be neurotoxic
Clinically has been associated with slight increase in nerve injury
Int J Oral Maxillofac Surg. 2006 May;35(5):437-43. Epub 2005 Dec 15
: J Can Dent Assoc. 1995 Apr;61(4):319-20, 323-6, 329-30.
Incidence very low (1:785,000)
Application of Articaine
- Avoid as primary drug for IAN blocks?
- Great for minor procedures for maxillary infiltration to avoid palatal injection
- Pediatric patients for all maxillary extractions to avoid palatal injections
- Lower anterior central incisors
- Back-up for failed blocks
If using articaine for blocks
- Be sure to document any zingers

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Physical interaction of the needle with the lingual or inferior alveolar nerve
When this happens either remove the needle or move the needle without injection, do not
want to inject anesthetic into the structure of the perineurium
ballooning the nerve leads to bad outcomes including permanent anesthesia or worse
o
o

Topical agents
Benzocaine (Hurricane) topical gel
o 20% benzocaine
o Usually approximately 9 mg per dose
o methemoglobinemia
Benzocaine topical spray
o 50 mg benzocaine per metered spray
o methemoglobinemia
Tetracaine (Cetacaine)
REMEMBER: these are ester anesthetics
Topical Agents
Lidocaine Patch
Lioderm (5%)
Neuropathic pain
TMD applications ( other transdermal medication for TMD) ?
Duration of Pulpal anesthesia
2% Lidocaine without epi
3% Mepivacaine without epi
3% Prilocaine without epi
2% Lidocaine with 1:100,000 epi
4% Articaine with 1:100,000 epi
0.5% Bupivacaine with 1:200,000 epi
0.5% Etidocaine with 1:200,000 epi
Relative vasodilating effects
Prilocaine
Mepivacaine
Articaine
Lidocaine
Bupivacaine
Etidocaine

10 min
40 min
60 min
60 min
75 min
>90 min
>90 min

0.5
0.8
1
1
2.5
2.5

Dealing with Anesthetic Failures

Managing the hot tooth

Understanding pH and local anesthesia

Understanding hyperalgesia
When is it better to localize, give antibiotics and let things cool down?
Consider conscious sedation
Patient variation

Is it wrong to assume that all anesthetics are equipotent in all patients?

There are no drugs that do not have a bell-shaped response to drug therapy
Have a plan

A secondary delivery technique

Gow-Gates

and field blocks

PDL
Intraosseous

techniques

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Abort

procedure in elective situations

Evaluate the anatomy

Panorex,

clinical exam

Is sedation an option?
Patience
We generally do not allow enough time for local to work, especially for profound pulpal anesthesia
Patients with low pain thresholds and anxiety
Remember the central nervous system links to pain perception
Anxiety control measures significantly augment pain management
Local anesthetic adjunct equipment
PDL injections
Liga-jet
Local anesthetic warmers
Computerized injection wands

Counter-pressure devices
Intra-osseous injection devices
Intraosseous Techniques
Different systems
Success
Primary technique
45-93% effective with short duration
Supplemental technique
80-90% effective with longer duration
Vasoconstrictor
40-100% patients with increased HR

Analgesic Strategies
Classes of Analgesics
Non-opioid analgesics
Salicylates
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Acetaminophen
Peripherally acting
Opioid analgesics
Agonists
Mixed agonist-antagonist
Centrally acting
Non-opioid analgesics (NSAIDs)
Excellent oral efficacy
Relatively low incidence of side-effects
Low abuse potential
Low cost
First line drugs for post-operative dental pain

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NSAIDS: Mechanism of action

Cyclo-oxygenase (two isoforms)

COX-1

ubiquitous, formed in normal quiescent

COX-2

inducible form
expressed in cells after trauma
role in inflammation

COX selectivity
Cox-2 selective agents
These agents are likely to have fewer G.I., renal, and platelet related side effects
Expensive
Acute vs. Chronic pain
Excellent dosing schedules
Same contraindications as other NSAIDs
Increased risk for stroke or M.I.
JAMA 2001 Aug 22-29;286(8):954-9
Cox-2 selective agents
Vioxx (rofecoxib) off the market
Celebrex (celecoxib)
Bextra (valdecoxib) off the market
Prexige (lumiracoxib) Not approved in US
Arcoxia (etoricoxib) FDA approval application withdrawn
Mobic (meloxicam)
Parecoxib (injectable prodrug of valdecoxib)
Cox-189

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Cox-3

Splice variant of Cox-1 in mice

Human?
Involved with fever mechanism
Site of acetaminophen activity
Cross reactive with Cox-1 inhibition
Therapeutic role/use unknown
PNAS | October 15, 2002 | vol. 99 | no. 21 | 13926-13931

Salicylates

Aspirin
650

mg q 4 hours
pain

Mild

Diflunisal (Dolubid)

Longer half-life, slow onset

1000 mg load then 500 mg BID
Equipotent to Tylenol #3
Adverse reactions

G.I. upset
Inhibition of platelet function
Contraindications
History of allergy
Peptic ulcer disease
Severe Asthmatics
Pregnancy (Dolubid)
Children with influenza or chicken pox (Reyes syndrome)
Patients on coumadin
Renal disease
Liver disease

Proprionic acids
Ibuprofen (Motrin, Advil, others)
o 400-800 mg Q 4-6 hours
Ketoprofen (Orudis, Actron)
o 50-75 mg Q 8 hours
Flurbiprofen (Ansaid)
o 50-150 mg Q 8 hours
Fenoprofen (Nalfon)
o 200-600 mg Q 8 hours
Naproxen (Naprosyn)
o 250-500 mg Q 12 hours
Oxaprozin (Daypro)
o 1200 mg Q day
Adverse reactions
G.I. upset
Inhibition of platelet function
Contraindications
History of allergy to aspirin or NSAIDs
Peptic ulcer disease
Severe Asthmatics
Pregnancy
Liver disease
Renal disease

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Indole
Etodolac (Lodine)

More Cox-2 selective?

Has been shown to be an effective analgesic in dental pain models
Heteroaryl acetic acids
Ketorolac (Toradol)

Can be given parenterally

Expensive orally
Role in dentistry?
Para-aminophenol
acetaminophen (Tylenol)
Weak anti-inflammatory
Analgesic/anti-pyretic
Opioids
Agonists
codeine
hydrocodone (Vicodin)
hydromorphone (Dilaudid)
meperidine (Demerol)
methadone (Dolophine)
Morphine (MS Contin)
oxycodone (Percodan, Percocet)
propoxyphene (Darvon, Darvocet)
tramadol (Ultram)*
tramadol (Ultram)
Mechanism of action
Weak opioid agonist
Serotonin/NE reuptake inhibitor
100 mg = two Tylenol #3 in dental pain study
Dosage 50-100 mg Q 4-6 hours
Cannot be used in patients with seizure history
Excellent in patients with long list of drug sensitivities
Also available in combination with acetaminophen (Ultracet)
Opioids
Mixed agonist/antagonist

pentazocine (Talwin) Less mu effects

pentazocine + naloxone (Talwin Nx)
nalbuphine (Nubaine)
Antagonist

naloxone (Narcan)
naltrexone (Trexan)
Analgesic Strategy
Indication

NSAID

Opioid

Mild pain

ibuprofen 400-600 mg Q.I.D.

tramadol 50 mg T..I.D.

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naproxen 200-400 mg T.I.D.
etodolac 200-300 mg T.I.D.
Moderate pain

ibuprofen 600-800 mg Q.I.D.

naproxen 300-400 mg T.I.D.
etodolac 300-400 mg T.I.D

hydrocodone 5 mg,
Tylenol 325 mg Q4h
pentazocine 50 mg

Severe pain

ibuprofen 800 mg Q.I.D.

naproxen 500 mg T.I.D.
etodolac 400 mg T.I.D

hydrocodone 7.5-10 mg,

Tylenol 325 mg Q4h

NSAID Cost

NSAID

Frequency

Naproxen 550 mg
Ibuprofen 600 mg
QID
Etodolac 400 mg
BID
Diclofenac 50 mg
BID
Ketoprofen SR 200 mg
QD
Diclofenac ER 100 mg
QD
Ketoprofen 75 mg
QID
Ketorolac 10 mg
QID
Celecoxib 100 mg
BID
Rofecoxib 50 mg
QD

Cost/day
BID

$0.64
$1.27
$1.36
$1.69
$1.97
$2.91
$3.39
$3.46
$4.56
$4.74

Whats New
New Cox-2 or Cox-3 Selective Agents
NK1 receptor antagonists (block substance P)
CP-99,994
Opiates in anesthetics?
Articaine with epinephrine and morphine (inflammation)
Caffeine as an additive
Synalgos DC (dihydrocodone, aspirin, caffeine combination)
Panlor DC
Nociceptine/Orphan FQ
New opioid peptide and receptor
Ultra-long acting local anesthetics

Preemptive analgesia
Prevent the formation of proinflammatory cytokines before they are established
NSAID premedication
Steroids
Significant evidence in both medical and dental literature supporting the use of presurgical antiinflammatory medications to decrease post-operative pain
Bleeding is not an issue
This strategy should also include the use of long-acting local anesthetics (Marcaine/Duranest)

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Nausea and Vomiting

Good post operative instructions are the best way to prevent this complication
Mechanism
Stimulation of the chemoreceptor trigger zone in the medulla
Vestibular component (ambulatory vs. recumbent patients)
Treatment
Stop taking the opiate analgesic
Change to a less nausea provoking medication
Have the patient lay still
Antiemetics
Antiemetics
Phenothiazines (dopamine antagonists)
Phenergan (promethazine) 12.5-50 mg q 4-6
Compazine (prochlorperazine) 5-10 mg tid
Zofran ODT (ondansetron)
5-HT3 (serotonin) receptor blocker
Oral Dissolvable Tablet (ODT)
Adult dose 16 mg ODT tablets 1 hour prior to anesthesia
expensive

Oral Sedation
Its nothing personal doctor, but I hate dentists.
Between 6% to 14% of the U.S. population are estimated to VOLUNTARILY avoid dental care
because of anxiety (Milgrom P et al. Treating fearful dental patients, Reston VA, 1985, Reston
Publishing)
The difficult patient
In a survey of dentists, 57% reported that the most stressful factor in dental practice is managing the
difficult patient (Kahn RL etal. Dentistry: What causes it to be a stressful profession? Int Rev Appl
Psych 29:307, 1980)
Can we do anything to help the anxious patient and at the same time help ourselves?
Pain and Anxiety
Anxiety is known to decrease a patients pain threshold (Pain: Clinical and Experimental Perspectives,
St. Louis, 1975, Mosby)
Pain perception has a strong emotional component
Controlling anxiety is critical in managing peri-operative pain

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Anxiety as a medical problem
It helps to think of dental phobia and anxiety as a medical diagnosis
Would you blame a diabetic for not being able to control their blood sugar?
If your perspective toward a patient with anxiety is that the patient has a treatable medical problem, you
may find it easier to deal with the inherent difficulties in managing these patients.
Anxiety and Pain
Pharmacology, in the form of oral sedation, cannot replace good chair-side manner
Anxiety and Pain control in dentistry must be multi faceted and aimed at maximum patient comfort with
behavioral management, sedation, good local anesthesia and adequate post-operative analgesia
The Big picture
If you control anxiety in your practice you will be better able to control pain
Reducing anxiety with oral sedation can clearly improve pain control during dental procedures
Avoid the pain-anxiety paradox: Pain is a source of anxiety, anxiety is a factor that increases pain, and
increased pain incites further anxiety (Schottestraedt W. )
Failing to control anxiety
Increases stress for the practitioner
Increases incidence for medical emergency situations
Syncope
Angina
Hyperventilation
Bronchospasm
Anxiety attacks
Increase appointment failure rates
When patients simply cannot be managed with local anesthetics alone
What are the options

Nitrous oxide
Oral Sedation
Intramuscular Sedation
Intravenous Sedation
General Anesthesia
So you have a patient with significant anxiety, now what?
Deciding on a management strategy
Decision making based on
Level of anxiety
Mild-iatrosedation, nitrous
Moderate-oral sedation, nitrous, intramuscular, intravenous
Severe-intravenous, general anesthesia
Coexisting disease
ASA scale
Age
Be careful with extremes of age (<6,>65)

Your level of training/experience

Residency

v. weekend courses
BCLS, PALS
Staff experience
ACLS,

Procedure to be preformed
Scaling

v. full-bony impaction

The state of your office

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Are

you prepared to deal with complications

Equipment for emergencies

layout/infrastructure
Whats the use of ACLS
If you dont.
Have equipment or know how to start an I.V.?
Have equipment or know how to place an endotracheal tube?
Delivery of ACLS protocols is dependent on both.
Office

Defining terms
From the ADA Guidelines for the use of Conscious Sedation, Deep Sedation, and General Anesthesia for
Dentists
Analgesia- diminution or elimination of pain
Anxiolysis- diminution or elimination of anxiety
Local Anesthesia- elimination of sensation, in particular pain, in a localized area of the body by topical
application or regional injection of local anesthetic
Conscious sedation- minimally depressed level of consciousness that retains the patients ability to
independently and continuously maintain an airway and respond appropriately to physical stimulation and
verbal command and that is produced by a pharmacologic or non-pharmacologic method or combination
thereof.
Deep Sedation- an induced state of depressed consciousness accompanied by partial loss of protective
reflexes, including the inability to continually maintain an airway independently and/or respond
purposefully to physical stimulation or verbal command, and is produced by a pharmacological or nonpharmacological method or a combination thereof.
General Anesthesia- an induced state of unconsciousness accompanied by partial or complete loss of
protective reflexes, including the inability to continually maintain an airway independently and respond
purposefully to physical stimulation or verbal command, and is produced by a pharmacological or nonpharmacological method or a combination thereof.
What can a dentist without advanced training do safely?
Without advanced training in either dental anesthesia, general practice residency or oral and
maxillofacial surgery, dentists should never intentionally take any patient beyond conscious sedation
Skill in this area CANNOT be attained in a weekend or evening course
Why?????
Its all about the airway
Airway management
If you do not have the experience, ability and equipment to manage a patient that loses an airway, you
have no business taking people beyond conscious sedation
Equipment
Laryngoscope
Endotracheal tubes of various sizes
Oxygen
Laryngeal mask airways
Nasal and oral airways
Bag-valve mask
Emergency surgical airway equipment

Airway Management
Technical skills required
Ability and experience maintaining an airway
Ability and experience in laryngoscopy and intubation
Ability and experience in managing the difficulty airway
Ability and experience with providing a surgical airway if necessary
ACLS: what is the use of being ACLS certified if you cannot start an I.V. or intubate someone!?

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Therefore the goal is..
Anxiolysis
A controlled level of conscious sedation with minimal to no risk for patients to lose the ability to maintain
a patent airway
Intentionally taking people to deeper levels of sedation without proper training or equipment is not
only cavalier it puts patients lives in jeopardy
Low risk does not equal no risk!
The long and short.
Dentists can market sleep dentistry
Dentists can imply that patients are asleep or sleep away the hours in comfort while your
dentistry is completed
But in reality, to attempt to genuinely take patients to levels beyond anxiolysis/conscious sedation
without formal training is dangerous
What does this mean???
If you use oral sedation, and a patient genuinely does not respond at all to giving a local anesthetic
injection, they are deeper than conscious sedation and the airway is potentially at risk
Remember: low risk does not equal no risk
Patient Assessment
ASA Classification
American Society of Anesthesiologists

ASA I : normal healthy patient, no systemic disease

ASA II: mild systemic disease
ASA III: severe systemic disease that limits activity
ASA IV: Incapacitating systemic disease that is constant threat to life
ASA V: patient not expected to survive 24 hours without surgery
Assessment
Generally you want to limit yourself to providing oral sedation to ASA I and ASA II patients
You especially want to be careful with patients that have
COPD
Congestive heart failure
Angina Pectoris
Heavy smokers
Moderate to severe asthmatics
Patients with significant cardiac or pulmonary disease
ASA III
Managing these cases is a balancing act of risks
-Premium on pain and anxiety control
-Want to avoid stress
-Can this be achieved with local only?
-Nitrous oxide and/or valium can be potentially safer than local only or general anesthesia
-Even I.V. sedation with versed is appropriate in some cases
Now what?
Once you have assessed the patient
What level of anxiety control does the patient need?
Local anesthesia
Local anesthesia with oral sedation
Local anesthesia with nitrous oxide

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Local anesthesia with oral sedation and nitrous oxide
Intravenous deep sedation
General anesthesia

Oral Sedation
Advantages
Safe
Almost universally accepted
Convenient
Economical
Low incidence of adverse reactions
Decrease severity of adverse reactions
No needles or syringes or specialized equipment
When done properly, it is well within the scope of a practicing general dentist without need for advanced
residency training
Disadvantage
Requires a knowledge of pharmacology
Patient compliance
Slow onset/recovery
More Unpredictable
Cannot titrate or tightly control (titration by appointment possible, but not without risk)
Loss of some level of control
Titration within an appointment is potentially dangerous and is not recommended (intentional over-dose)
Indications for Oral Sedation
Provide sedation and ensure a restful sleep during the night prior to anxiety provoking appointment
To provide light levels of sedation for preoperative anxiety reduction
To aid in the anxiety control just prior to utilizing other anesthesia techniques (I.V. sedation)
Drugs used in oral sedation
Opiates
Potent analgesic drugs
Rarely used for oral sedation
Sometimes used in combination with benzodiazepines, but should be done so with caution due to the
potential for deeper levels of sedation
Significant respiratory depression possible
Other drugs

Zolipen (Ambien)
Sedative hypnotic used to treat insomnia
Only mildly anxiolytic
Chloral Hydrate
Popular with pediatric dentists
Unpleasant taste
No analgesic properties
Antihistamines
Barbiturates

Benzodiazepines
The most widely used oral agents for anxiolysis in dentistry
Safe, effective, cheap
Tolerated well orally
Minimal hang-over
Extremely effective antianxiety medications

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Wide therapeutic safety margin

Mechanism of Action
GABA receptors
Cerebral cortex
Limbic system
Cerebellar cortex
Glycine receptors
Brainstem
Spinal cord
Metabolism
Plasma protein bound
Metabolized in the liver
Oxidative
Conjugation
Metabolites can be pharmacologically active leading to longer half-lives for some agents
Metabolites excreted in the urine
Diazepam (Valium)
Pharmacology
Insoluble in water (phlebitis)
Large volume of distribution and low hepatic clearance
Organ effects
Decreased anxiety, sedation, hypnosis and amnesia
Potent anticonvulsant
Mild respiratory depression
Minimal cardiovascular effects
Decreases muscle tone
Clinical Indications

Preoperative and intraoperative sedation

Management of anxiety disorders
Acute alcohol withdrawal
Relief of skeletal muscle spasm
Status epileptics
Contraindications

Glaucoma (acute narrow angle)

Previous hypersensitivity
Pregnancy (first trimester)
Administered with extreme care

Elderly
Children
Patients with limited Pulmonary reserve
Adverse Reactions

Phlebitis (when given intravenous)

CNS depression
constipation, nausea, incontinence

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bradycardia, hypotension
blurred vision, diplopia, nystagmus
uticaria
hiccups
paradoxical reactions
Dosage

Oral: 5-10 mg for 70 kg adult (decreased for elderly); 0.2 to 0.5 mg/kg for children
Midazolam (Versed)
96% protein bound
Metabolized in liver to active metabolites, one-tenth the potency
Absorbed orally, 30-50% bioavailability
Elimination half-life of 2-2.5 hours
Midazolam (Versed)
Organ effects
Decreased anxiety, sedation, hypnosis and amnesia
Stable intracranial pressure
Mild respiratory depression
Minimal cardiovascular effects
Decreases muscle tone
% protein bound, less lipid soluble
Metabolized in liver to inactive metabolites
Elimination half-life of 10-20 hours
Clinical Indications
Preoperative and intraoperative sedation
Management of anxiety disorders
Acute alcohol withdrawal
Relief of skeletal muscle spasm
Status epileptics

Triazolam (Halcion)
Excellent oral sedative
Good for the night before the appointment to help with sleep
0.125-0.25 mg one hour prior to appointment (Maximum 0.5mg)
Use with caution in elderly patients
Care when combining with nitrous in pediatric patients
Excellent amnestic qualities
Sonata (zaleplon)
Non-benzodiazepine with benzodiazepine like effects
Acts through GABA receptors
Used to treat insomnia
Some amnesia
Dose 5-10 mg
Not reversed by romazicon
Nitrous oxide and oral sedation

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When combined with oral sedative hypnotics the level of sedation achieved with nitrous oxide can be
significant
Care should be taken when combining oral and inhalational sedation techniques

Length of procedure
1 hour Sonata (zalepon)
2-3 hours Halcion (triazolam)
4 hours or more Ativan (lorazepam)
Problems with long appointments
In the OR, under general anesthesia
Great concern for development of deep venous thrombosis during procedures taking more than 2-3 hours
Pneumatic stockings are used to prevent this
In the dental chair
What precautions need to be taken for long procedures?
Unknown.
Consent
All consent must be obtained prior to patient taking any sedative/hypnotic drug.
Office preparation
Must be prepared for a medical emergency

Oxygen with appropriate delivery devices

Bag-valve

mask
mask
Nasal cannula
Rebreather

Emergency medical kit

Recovery
Patients may need to stay in the office for an extended period of time to become ambulatory prior to
discharge
Additional equipment
Automatic blood pressure cuff
Pulse oximeter
When to monitor

Medically compromised patients

Multi-drug oral sedations
Combination of oral sedative with nitrous oxide
Instructions to patients
Patients must be escorted to and from the office by a responsible adult
Escort should stay in the office
Public transportaion?
Patients should generally take the oral premedication on a relatively empty stomach (faster and more

predictable uptake)
Patients need to understand the level of sedation expected
Complications
Nausea and vomiting
Very rare with oral sedation
Sedation level not adequate
Increase dose for next appointment

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Giving a second dose of the sedative on the same
Is the patient a candidate for oral sedation?
Over

day is controversial and not recommended

sedation

When using recommended doses, this is rare

Usually can be managed by simply monitoring
Decrease dose at next visit
Be prepared to provide oxygen if necessary

the patient

Complications
Allergic reactions
Very rare
Should be prepared for this with emergency kit
Idiosyncratic reactions
Removal of inhibition
Crying, semi-uncooperative
Seen much more frequently with I.V. benzodiazepines
Treated with monitoring and avoiding the medication in the future
Reversal if available
Benzodiazepine reversal
Flumazenil (Romazicon)
This is an I.V. drug
Unless you know how to start an I.V., this may not be an option
I.M. use of flumazenil has not been studied in humans (off label use)
What dose?
Where?
How?
1/2 life vs. benzodiazepine given
Pediatric patients
Not small adults
Diminished pulmonary reserve
Small airway
Can desaturate very rapidly
Need to be managed very carefully
Under the age of 13, best managed by practitioners with advanced training
Final thoughts on sedation
Expanded scope of anesthesia requires
Efforts to clearly understand the drugs you are using
Comfort in managing the potential complications
Goal for general dentist or specialist without advanced anesthesia training should by anxiolytic conscious
sedation
Consider referral or hospital affiliation for patients needing anesthesia scope outside of your expertise
Big picture
Avoid the anxiety and Pain Paradox
Managing anxiety can be done safely and effectively in your practice
Avoid ASA III and IV patients
Use great care in treating children and the elderly
Know your patients and the drugs you prescribe them

Antibiotics
General Considerations

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Antibiotics exploit the differences between prokaryotes (bacteria) and eukaryotes (human cells)
Selective toxicity
Cell walls
Ribosomal structures
Unique enzymes
The more selective a drug the wider the therapeutic index
Empiric vs. Organism specific therapy
Generally antibiotics are either bacteriocidal or bacteriostatic
Remember the importance of the patients immune and inflammatory defense mechanisms in
combating infection.
Antibiotics do not replace prompt surgical or endodontic management
Indications for Antibiotic Therapy
Management of head and neck odontogenic infections
Prophylaxis for the prevention of SBE or other medical indications
Infection prevention?
Compromised host
Long procedure or procedure with high infection rate
Little or no evidence for routine use
What are the goals of antibiotic therapy?
To prevent or treat odontogenic infections
Choice of antibiotic is typically empiric, a best guess of the typical bacteria known to cause
odontogenic infections
Odontogenic infection change with time
Gram +

GramAerobic

What Bacteria?

Cocc

Rods

Anaerobic

Gram +

Gram

Staph
Strep
*Peptostreptococcus
*Peptococcus

*Nisseria
*Veillonella

*Lactobacillus
*Actino
*Eubacteria
*Clostridium

Eiknella
H. Influenza
Enterobacteria
*Fusobacterium
*Bacteroides

*Anaerobe
Choosing antibiotics
Consider what bacteria your covering
Early mild odontogenic infection
Mixed with Predominantly aerobic Alpha-hemolytic gm + strep

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Mild to moderate odontogenic infection
Mixed aerobic gm + cocci and anaerobic gm - rods
Severe multi-space occupying odontogenic infection
Mixed with Predominantly anaerobic gm- rods
Consider patient medical situation
Consider expense
Sinus coverage considerations
Sinus flora differs from oral flora
Hemophilus Influenza
Streptococcus pneumonia, viridans strep
Staph aureus
Consider sinus coverage if sinus exposure and infection
Penicillins
Mechanism
inhibit crosslinking of cell wall components
bacteriocidal (gram + cocci)
Penicillin V
Advantages
Bacteriocidal
Pen V is appropriate spectrum for the majority of simple odontogenic infections
Clearly the drug of choice for most dental applications
generally cheap, well tolerated
Disadvantages
resistance, hypersensitivity, rare neurotoxicity
Amoxicillin (Ampicillin)
first line drug in treating infections involving the maxillary sinus
Augmentin
Amoxicillin and clavulinic acid
Broad spectrum- reserved for serious odontogenic infections (all anaerobes, all Strep., methicillinsensitive S. aureus, S. epidermidis, H. influenza and Enterococcus)

Penicillin

PCN-sensitive
streptococci

Penicillinase

Clavulinic acid

PCNstreptococci

The AHA protocol for SBE prevention

Written by cardiologists for surgeries involving the upper respiratory tract and oral cavity

Intention is to cover common bacterial found in both oral and sinus sites

Therefore, Amoxicillin is the drug of choice

o
Do not translate that to mean that Amoxicillin is the drug of choice for all odontogenic
infections

Cephalosporins
Similar mechanism of action to penicillins
10% cross reactivity with true penicillin allergic patients
Susceptible to beta lactamases

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In general:
First Generation
Gram +
Cefadroxil (Duricef)
Cefazolin (Ancef)
Cephalexin (Keflex)

Second Generation
Gram-/+
Cefaclor (Ceclor)
Cefotetan (Cefotan)
Cefuroxime (Ceftin)

Third Generation
GramCefixime (Suprax)
Ceftriaxone (Rocephin)

Cephalexin (Keflex)
Tolerated well orally
Inexpensive
Similar coverage to Pen V with addition of Staph coverage
Good alternative in patients with questionable pen allergy
Cefuroxime (Ceftin)
Mechanism
inhibit crosslinking of cell wall components
bacteriocidal (gram + cocci, some gram -)
Advantages
Broader coverage (B. fragilis)
Sinus coverage in PCN allergic
Staph coverage
Disadvantages
10% crossreactivity with PCN allergic
Macrolides
Mechanism of action
prevent translocation of polypeptide chain by binding the 50s ribosomal subunit
Bacteriostatic
Effective in bacteria lacking cell walls (mycoplasma, legionella, chlamydia)
Effective against gram + aerobes and some gram- aerobes
Erythromycin (E-mycin)
Coverage
bacteriostatic (bacteria lacking cell walls, gram + aerobes, except H. Influenza)
Advantages
Used for PCN allergic
Disadvantages
bacteriostatic, GI upset
Hunt et al.*- Erythromycin was ineffective against 50% of Strep and Staph isolates from
odontogenic infections
Azithromycin (Zithromax)
Similar coverage to erythromycin but fewer resistant strains (better gm - coverage, H. flu)
Well tolerated orally, less GI side effects
Q 24 hour dosing, high compliance
Expensive
Equipotent in periapical abscess to Amox- clavulinic acid (J Int Med Res 26:275)
Clarithromycin (Biaxin)
Similar to azithromycin in spectrum of coverage
Can have similar GI upset to erythromycin
BID dosing

Clindamycin (Cleocin)
Mechanism of Action
Binds to 50s ribosome and prevents chain elongation
bacteriostatic (gram+s, most anaerobes)

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Advantages
Similar action to erythromycin, but broader coverage appropriate for odontogenic infections
Excellent bone penetration

Disadvantage
Pseudomembranous Colitis
Metronidazole (Flagyl)
Mechanism
inhibit DNA synthesis
bacteriocidal against anaerobe
Advantages
Adjunct to penicillin V for anaerobe coverage
C. diff colitis treatment
Disadvantages
reaction with alcohol
nausea, urine changes

Flouroquinolones
Mechanism of action
o Inhibit DNA gyrase
o Bactericidal

Levofloxacin (Levaquin)
o Third generation flouroquinolone
o Good bone penetration (?)
o Relatively broad coverage (comparable to Augmentin)
o Tendon rupture issues
o QD dosing
o Expensive

Antibiotic Costs
Antibiotic

Frequency

Cost/day

Penicillin V 500 mg

QID

$0.70

Cephalexin 500 mg

QID

$1.21

Amoxicillin 500 mg

TID

$1.23

Clarithromycin 500 mg

BID

$6.98

Clindamycin 300 mg

QID

$7.95

Amoxicillin-clav,

TID

$10.39

Azithromycin z-pak

QD

$11.98

Antibiotic Strategies
Acute, mild odontogenic infection (PA abscess or local early single space)
Pen V 500 mg QID with 1gm loading dose
Keflex 500 mg QID with 1 gm loading dose for questionable Pen allergic patient
Azithromax, Z pack, 500 mg first day, with 250 mg each day for 5 days

Mild to Moderate Odontogenic Infections

Pen V 500 mg QID with 1 gm load and Metranidazole 500 mg TID
Clindamycin 300 mg QID with 450 mg load for pen allergic
Amoxicillin-clavulonate 500 mg TID with 1 gm load
Severe Odontogenic Infections with multi space involvement

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Patient require IV antibiotics!!
Ampicillin and sulbactam, 3gm load with 1.5 gm Q6h
Clindamycin, 600 mg Q 8h for pen allergic

How long?
No hard and fast rules
Generally 5 days after removal of the source
Removal of the source, drainage, adequate dose and frequency of antibiotic are keys to good
outcomes
Avoid complications by not using long-term broad coverage
REMEMBER
Antibiotics do not replace sound surgical or endodontic treatment of infection source!!
Prompt removal of source of infection and incision and drainage of swellings associated with infections
is more important than antibiotic choice and dosing!!
When you choose to use antibiotics, use adequate dose and frequency
Close follow-up is absolutely neccessary

Antibiotics: Whats new?

Antibiotic resistance
Oxacillin resistant Staph Aureus (ORSA)
Vancomycin resistant enteroccocus (VRE)

Methicillin Resistant Staph aureus (MRSA)

When to refer
Refractory infections
Worsening symptoms
Airway compromise
Multispace involvement
Crepitus
Severe trismus
Dysphagia

Final thoughts
Have good drug references in your office
o Pocket Pharmacopoeia
Cheap, small, very useful resource
ISBN 1-882742-06-0
o Pharmacology and Therapeutics for Dentistry
Dental student text with recent edition
Fairly good reference
ISBN 0-8016-7962
o Mosbys Dental Drug Reference
ISBN 0-8016-7851
Final Thoughts
o Lexi Comp Online
o JADA articles on drug interactions
Series of articles appeared in volume 130 No. 1-6
o Goodman and Gilmans The Pharmacological Basis of Therapeutics
The pharmacologists bible
Very complete, very detailed, very thick!

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o
o

Use the internet

PubMed is a free database for finding current information in the literature

Expand your armamentarium

The right drug for the right situation
Know the drugs you use
Dont marry a technique or drug
Establish strategies for dealing with anesthetic, analgesic or antibiotic failures
Remember: all drug responses are a bell shaped curve, responses can be different for different
patients