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Pharmacology in DentistryNiagara Peninsula Dental Association
Dr. Peter Nkansahpnkansah@rogers.comwww.sleepfordentistry.com 1
Pharmacology in DentistryDr. Peter Nkansah
Niagara Peninsula Dental Association
January 12, 2018
Pharmacokinetics & pharmacodynamics
Review of local anaesthetics
Review of analgesics
Review of anti-infectives
Anti-thrombotics
Conscious sedation drugs
Bisphosphonates
Herbal supplements
Overview
Pharmacology in DentistryNiagara Peninsula Dental Association
Dr. Peter Nkansahpnkansah@rogers.comwww.sleepfordentistry.com 2
Editorial by Dr. J. Goodman in Oral Health (March 2013)
Notes that adverse drug reactions are the 4th leading cause of death in the US
90% of the drugs are metabolized by the liver
Most by the CYP450 enzymes
Notes several Internet resources to help with familiarization of the drugs, their metabolism and interactions
“Pharmacology Made Easier”
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Accidental deaths rank 5th as a cause of death in the US
This includes drug-induced deaths
More than 40,000 people in the US in 2010
Heart disease and cancer are #1 and #2
Reverse order in Canada
Death By Drugs
Recent issue of Dispatch noted the reprimand of a colleague for:
The prescription of 5800 tablets of Oxycontin (80 mg) to one patient over a 2-year period
The prescription of 560 tablets of Percocet (5 mg) to one patient over a 2-year period
The prescription of 60 Oxycontin tablets to a patient on one date for the treatment of post-op pain from the placement of 2 implants
Prescriptions for Trouble
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Pharmacokinetics & Pharmacodynamics
What the body does to drugs
Absorption
Distribution
Metabolism
Elimination
Pharmacokinetics
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What drugs do to the body
Includes duration and magnitude of responses
Dose-response considerations
Pharmacodynamics
Local Anaesthetics
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History of Local Anaesthetics
Local anaesthetics have been isolated since the 1860s (cocaine)
Sensory nerve blockade was first described by Halsted in 1884
“Novocaine” (procaine) was the first commonly used local anaesthetic in dentistry
Lidocaine is the original amide LA Commercially available in 1948
Articaine is the newest popular LA Released in Canada in 1982 (US in 2000)
Common LA Preparations
Articaine
Bupivacaine
Lidocaine
Mepivacaine
Prilocaine
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To stop the generation and conduction of nerve impulses
To abort impulses from stimuli, like tooth extraction
E.g. To stop the patient from feeling pain
Purpose of LA
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Mechanism of Action
Local anaesthetics bind to site on Na+ channel
Inhibits the permeability to Na+
Block propagation of action potential
Structure
3 common features:
Lipophilic (aromatic) group
Intermediate chain with amide or ester linkage
Hydrophilic (tertiary amine) group
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By themselves, LA solutions are weakly basic, poorly soluble in water and unstable
Used as salt solutions (usually HCl) which are water-soluble and stable
With the addition of vasopressors, the solutions become acidic
LA Solutions
Amide LAs are primarily biotransformed in the liver
Cytochrome P450 CYP3A4
Medical history concerns:
Severe liver dysfunction
Pseudocholinesterase deficiency (for esters)
Biotransformation & Elimination
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Proximity to target site
Concentration
Lipid solubility
Nerve morphology
pH of the tissue
pKa
Onset determinants
pH at which amount of base = amount of cation
All LA’s have pKa > 7.4
pKa = potency
Dissociation Constant (pKa)
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pKa of Local Anaesthetics
pKa % base at pH 7.4
Time to onset (min)
Mepivacaine 7.6 40 2-4
Articaine 7.8 29 2-4
Lidocaine 7.9 25 2-4
Prilocaine 7.9 25 2-4
Bupivacaine 8.1 18 5-8
Procaine 9.1 2 14-18
Henderson-Hasselbalch Equation
pKa – pH = log 10Ionized (BH+)Unionized (B)
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Example: Lidocaine
pKa – pH = log [ionized/un-ionized]
7.9 – 7.4 = log [ionized/un-ionized]
100.5 = ionized / un-ionized
~3 / 1 = ionized / un-ionized
Drug Ionization
Example: Procaine
pKa – pH = log [ionized/un-ionized]
8.9 – 7.4 = log [ionized/un-ionized]
101.5 = ionized / un-ionized
~32 / 1 = ionized / un-ionized
Drug Ionization
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Example: Lidocaine in site of infection
pKa – pH = log [ionized/un-ionized]
7.9 – 4.9 = log [ionized/un-ionized]
103 = ionized / un-ionized
1,000 / 1 = ionized / un-ionized
Drug Ionization
Lipid solubility
Protein binding
Concentration/dose
Redistribution from site
Duration Determinants
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Maxillary Paraperiosteal (min) IAN Block (min)
Preparation Pulp Soft Tissue Pulp Soft Tissue
Lidocaine w epi 60 150 75 180-300
Articaine w epi 60 120-360 75 120-360
Prilocaine w epi 40 120 75 180
Prilocaine plain 15 60-90 60 150
Mepivacaine w levo 50 180-300 75 180-300
Mepivacaine plain 20 120-180 40 120-180
Bupivacaine w epi 60 240-540 180 240-540
Duration of Action
LA maximum doses
Drug Max (mg/kg)
Max (mg) Max
(mg w/o epi)
# cart. (for 70 kg adult)
lidocaine 7 500 300 13
articaine 7 500 300 7
prilocaine 8 600 400 8
bupivacaine 2 200 75 10
mepivacaine 7 450 300 8
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Expressing a % solution
in mg/ml
Example: 2% lidocaine
2% = 20 mg/ml
1 cartridge has 1.8 ml of fluid
= 36 mg of drug/cartridge
LA Dosage
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Local Anaesthetic ToxicitySigns and Symptoms
Mild (excitatory)
Confused
Talkative
Tremors
Muscle twitch
BP, HR and RR
Severe (depressive)
Tonic-clonic seizures
Drowsiness
Loss of consciousness
Respiratory depression
BP, HR
CV collapse
Intralipid® 20% is a 20% intravenous fat emulsion
Its primary indication for use is as a source of calories and essential fatty acids for patients requiring TPN for extended periods of time
LipidRescue™ is indicated for the treatment of local anaesthetic-induced cardiac arrest that is unresponsive to standard therapy
Intralipid Rescue
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Epinephrine or levonordefrin are added to LA solutions to increase duration and depth of anaesthesia
Use their alpha-agonist interaction with adrenoceptors
Short-lasting drugs by themselves
Vasoconstrictors
Vasoconstrictors
Epinephrine
1:50,000
1:100,000
1:200,000
Levonordefrin
1:20,000
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Epinephrine
Rapid onset
Exogenous epinephrine is metabolized by COMT
Short duration of action
5 to 10 minutes if intravenous injection
10 to 20 minutes if intraoral injection
Maximum single appointment dose for a healthy adult = 0.2 mg (200 mcg)
Trade name = Neocobefrin
1:20,000 = 90 μg per cartridge
Similar concerns to those when using epinephrine
Consider the maximum dose of 0.2 mg
Levonordefrin
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Beware of interactions with:
Non-selective β-blockers
Tricyclic antidepressants
Cocaine or amphetamine use
COMT inhibitors (e.g. Comtan™ for Parkinson’s disease)
Not an issue with MAOI
Vasoconstrictors
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A non-selective α-adrenergic antagonist
Blocks the effects of vasoconstrictors in LA preparations
Increases the redistribution of LA away from injection site
Phentolamine Mesylate
Reduces duration of anaesthesia by 50%
Non-toxic and well-tolerated < age 6 years
Only observed adverse effect is a minor increase in postoperative pain shortly after return to normal sensation
Phentolamine Mesylate
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Injectable Bupivacaine Liposome Suspension
Trade name: Exparel® (Pacira Pharmaceuticals Inc.)
Marketed as an opioid-free way to manage post-surgical pain
Consists of multivesicular liposomes (DepoFoam®) that release doses of bupivacaine as the chambers break down
Injected into the surgical site
Not used for nerve blocks
Ref.: https://www.exparel.com
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Exparel®
A 1.33% bupivacaine suspension
Maximum recommended dose for adults = 266 mg
Not based on patient weight
Can be mixed with non-liposomal bupivacaine for faster onset
Maximum HCl:Exparel ratio of 1:2
Should not be mixed with other local anaesthetics
Placebo vs. Pharmacology?
If pharmacology works, then topicals must be placed on dried mucosa for 1-2 minutes
NB: Most topical anaesthetics are esters
Some new research into gels containing KNO3 and sprays using ethyl chloride
Topical Anaesthetics
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Topical Anaesthetics
Effective only on surface tissues (2 to 3 mm)
Benzocaine and lidocaine base are insoluble in water
However, they are soluble in alcohol, propylene glycol, polyethylene glycol, and other vehicles suitable for surface application
Adverse reactions to LAToxicity of LA or vasoconstrictor
Psychogenic reactions
Allergic reactions to LA or to metabisulfite
Methemoglobinemia
Paraesthesia
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Toxicity of LA or vasoconstrictor
Adverse reactions
Psychogenic reactions
Syncope is the most common medical emergency
Occurs most often at the time of injection
Changes in heart rate +/- blood pressure
Hyperventilation
Nausea and vomiting
Adverse reactions
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Allergic reactions
The component ingredients in a cartridge are:
Local anaesthetic
Vasoconstrictor
Metabisulfite
Adverse reactions
Adverse reactions
Methemoglobinemia
Condition in which cyanosis develops in the absence of cardiac or respiratory abnormalities
May be congenital or acquired through drugs or chemicals
Prilocaine or large doses of benzocaine
MetHb is normally <1%
Cyanosis and respiratory distress may occur with MetHb>10%
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Methemoglobinemia
Delayed in its onset
Unresponsive to O2
Pulse oximeter readings are abnormal (~85%)
Blood is chocolate brown
Treated by 1% methylene blue IV
Avoid prilocaine or benzocaine in patients with congenital methemoglobinemia
Adverse reactions
Paraesthesia
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There are numerous reports regarding the association between 4% solutions and a higher-than-expected incidence of paraesthesias
Note the risk:benefit equation
Overall paraesthesia incidence is 1:800,000 injections
There has been an RCDSO advisory regarding 4% solutions used for blocks
Paraesthesias
Paraesthesia
Broad term for prolonged anaesthesia or altered sensation, beyond expected duration of action of local anaesthetic
Adverse reactions
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Paraesthesia
Most are transient, usually resolving within 8 weeks
If not, prognosis is very poor
Precise cause not known with certainty
Hemorrhage into nerve sheath
Scar formation
Alcohol or sterilizing solution
Neurotoxicity - controversial
Adverse reactions
A 21-YEAR RETROSPECTIVE STUDY OF REPORTS OF PARESTHESIA FOLLOWING LOCAL ANESTHETIC ADMINISTRATION
Haas and Lennon, JCDA, 1995, 61:319-330
Adverse reactions
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The overall incidence of paraesthesia following local anesthetic administration for non-surgical procedures in dentistry is very low 1:785,000
If, however, paresthesia does occur, the results suggest that it is more likely if either articaine or prilocaine is used
Reasons are speculative only
Adverse reactions
Results (1973-1993)
0
10
20
30
40
50
60
Articaine Bupivacaine Lidocaine Mepivacaine Prilocaine
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Nerve injury caused by mandibular block analgesia
Hillerup and Jensen, Int J Oral Maxillofac Surg, 2006, 35: 437-443
Prospective study in Denmark
Results: Neurologic evidence of neurotoxicity, not mechanical injury
Articaine had > 20-fold in paraesthesia compared to all other locals combined
Adverse reactions
Fink and Kish, Anesthesiology, 1976 Barsa et al, Anesthesia Analgesia, 1982 Rigler et al, Anesthesia Analgesia, 1991 Lambert and Hurley, Anesthesia Analgesia, 1991 Kalichman et al, Journal of Neuropathology, 1993 Selander, Regional Anesthesia, 1993 Lambert et al, Anesthesiology, 1994 Kanai et al, Anesthesia and Analgesia, 1998 Cornelius et al, Journal Cranio-maxillofacial Surgery, 2000 Johnson et al, Anesthesiology, 2002
Studies of Dose-Dependent Neurotoxicity
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Practice Alert: Paraesthesia Following Local Anaesthetic Injection
“Until more research is done, it is the College’s view that prudent practitioners may wish to consider the scientific literature before determining whether to use 4% local anaesthetic solutions for mandibular block injections.”
RCDSO Dispatch (2005)
Retrospective Review of Voluntary Reports of Non-Surgical Paresthesia in Dentistry Gaffen and Haas, 2009, Journal of the Canadian Dental
Association, 75(8): 579
OBJECTIVES: To analyze cases of paresthesia associated with local
anesthetic injection that were reported to the province of Ontario’s Professional Liability Program (PLP) from 1999 to 2008 inclusive
To update previous study (1995)
Adverse reactions
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Results: Distribution of paresthesias
0
10
20
30
40
50
60
70
articaine bupivacaine lidocaine mepivacaine prilocaine
Percentage
These data suggest that post-injection paresthesia following a mandibular block is more likely if a 4% solution (articaine or prilocaine) has been administered
These data are consistent with and support previously published findings (Haas and Lennon, 1995)
Conclusions
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JADA (July 2010)
JADA (July 2010)
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Incidence is very low
Yet data are strongly suggestive of an association
No proof of cause-effect
It is not the drug per se
Higher concentrations may simply predispose to greater effect
Conclusions
Analgesics
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Eliminate the source of pain
Consider adjusting regimens according to the patient’s needs and response
Maximize NSAID/acetaminophen doses before adding opioids
Patients who do not respond to one NSAID may respond to another
Avoid chronic use
General guidelines
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AA
lipoxygenase
Leukotrienes
Bronchospasm
Inflammation
COX-1
PG’s
GI protection
Uterine cont.
Renal function
TXA’s
Platelets
COX-2
PG’s
Pain
Inflammation
Arachidonic Acid Cascade
Analgesic (mg) NNT
Ibuprofen 600/800 1.7
Ketorolac 20 1.8
Diclofenac 100 1.8
Acetaminophen 1000 + Codeine 60 2.2
Acetaminophen 500 + Oxycodone 5 2.2
Ibuprofen 400 2.5
Diclofenac 25 2.6
Ketorolac 10 2.6
Naproxen 400/440 2.7
Diclofenac 50 2.7
Ibuprofen 200 2.7
Acetaminophen 1000 3.7
Codeine 60 16.7
Oxford League Table
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Non-steroidal anti-inflammatory agents are central to pain control in dentistry
They inhibit COX-2 +/- COX-1 enzymes
Tissue damage activates COX-2
NSAID
Analgesic
Anti-inflammatory
Anti-pyretic
Anti-dysmenorrheal
NSAID Therapeutic Effects
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NSAID Dosages for Post-Operative Pain
Drug Adult Dose (mg) Frequency Daily Max
ASA 325-1000 q 4-6 h 4,000
Ibuprofen 400 q 4-6 h 3,200*
Diflunisal 1000, then 500 q 12 h 1,500
Naproxen 500, then 250 q 6-8 h 1,375
Ketorolac 10 q 4-6 h 40 (5 days)
Diclofenac 50-100, then 50 q 6-8 h 225
Celecoxib 200 q 12 h 400
Acetylsalicylic Acid
Salicylate-based medicines date back to the Egyptian pharoahs in the 2nd century BC
ASA introduced to modern medicine in 1899 by Dreser
Sold by Bayer as Aspirin
Initially popular as a less-irritating salicylate-based medicine
Now back in favour because of its antiplatelet effect
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Ibuprofen
Patented in 1961 by Dr. A. Dunlop, Dr. S. Adams and their team at the Boots Group
Propionic acid derivative
The target was treatment of rheumatoid arthritis
Sold first in the UK in 1969
An effective and very popular NSAID
Sold as Advil, Motrin, and Nuprin in Canada
Ibuprofen
Effective doses are 200-400 mg every 4-6 hours
Maximum daily dose = 3200* mg
Loading doses are effective
Elimination t½ = 2 hours
Solubilized liquigels and ibuprofen lysine have faster onset and better peak analgesia than conventional tablets
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Naproxen
Developed in 1976 by Syntex Corp. (now Roche Bioscience)
First sold as Naprosyn
Propionic acid derivative
Brand names = Naprosyn, Aleve
Indicated for mild-moderate pain, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, tendonitis, ankylosing spondylitis, gout and dysmenorrhea
Naproxen
Effective dose = 500 mg first, then 250 mg every 6-8 hours
Analgesia of 220 mg naproxen ≈ 200 mg ibuprofen
Peak levels in 2-4 hours
Naproxen sodium peaks in 1-2 hours
Elimination t½ = 12-15 hours
More GI irritation than ibuprofen
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Ketorolac
Developed in by Syntex Corp. (now Roche Bioscience) in 1989
A pyrrole derivative
First marketed as Toradol®
The first injectable NSAID
Tablets are most effective after IM administration
Approved for IV use in the US
Available as a nasal spray in the US (Sprix®)
Ketorolac
Indicated for moderate-severe pain
Effective dose is 30-60 mg IM first, then 15-30 mg every 6 hours
Oral dose = 10 mg every 4-6 hours
As effective as 400 mg ibuprofen
Suggested limit of 5 days of administration because of GI bleed concerns
Ref.: Strom et al., JAMA, 1996
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Diclofenac
A phenylacetic acid derivative that has a two- to threefold preference for COX-2
Sold as Voltaren
Indicated for inflammatory conditions and dysmenorrhea
Associated with greater hepatotoxicity than other NSAIDs
A formulation with misoprostol is available
Misoprostol is abortifacient
Diflunisal
Developed in 1971 by Merck Sharp & Dohme
Salicylate derivative
Brand name = Dolobid
Distinct among the NSAIDs because of its long half-life
Elimination t½ = 8-12 hours
Needs a loading dose, then can be taken only twice a day
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Diflunisal
Main indication for use is for treatment of mild-moderate pain and for osteoarthritis and rheumatoid arthritis
Dosage of 1000 mg first, then 500 mg bid
Relatively slow onset of action
2-3 hours for peak blood levels
Provides better analgesia than acetaminophen
Comparable to combinations with opioids
COX-2 Inhibitors
Vioxx® and Celebrex® are the famous examples
The benefits are:
Less GI bleeding
Fewer gastroduodenal ulcers
Is there a predisposition to myocardial infarction?
Vioxx® voluntarily withdrawn from the market in 2004
GI concerns not a big issue in dentistry because of the short-term post-operative use
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Celecoxib
Brand name = Celebrex®
Indicated for:
Osteoarthritis
Rheumatoid arthritis
Dysmenorrhea
Familial adenomatous polyposis (?)
Mental illness (?)
Celecoxib
Dosage is 200 mg bid
Elimination t½ = 10-12 hours
Equal efficacy to 650 mg ASA in dental pain studies
Less effective than ibuprofen or naproxen
No specific advantage in dentistry
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Increased bleeding*
Gastric mucosal damage
Dyspepsia
Renotoxicity
Anaphylactoid reactions
NSAID Adverse Effects
Gastric ulcers
Bleeding dyscrasias or concerns
Significant renal disease
asa (or other NSAID) hypersensitivity
Combination of severe asthma, nasal polyps and multiple allergies
Can lead to ARDS
NSAID Contraindications
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Pregnancy
Especially in the 3rd trimester
Children
asa only
Elderly
Concurrent use of certain other drugs
NSAID Contraindications
Acetaminophen (Paracetamol)
Actual generic name is N-acetyl-p-aminophenol (APAP)
Synthesized in 1878
First used clinically in 1887
Largely discarded in favour of phenacetin, which was believed to be less toxic
Ref.: Bertolini et al., CNS Drug Reviews, 2006
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Acetaminophen (Paracetamol)
Launched in North America and the UK from 1955-57
Phenacetin became “condemned” because of its nephrotoxicity, methemoglobinemia and carcinogenicity
Popularity took off in the 1970s
By 1979, Tylenol was the best-selling health and beauty aid product, passing Crest toothpaste
Ref.: Bertolini et al., CNS Drug Reviews, 2006
Acetaminophen
Analgesic of (popular) choice in dentistry
Effective anti-pyretic and analgesic
Not anti-inflammatory
No NSAID side effects (e.g. anti-platelet, GI)
No respiratory depression
Very safe at normal doses
Category B for use during pregnancy
Hepatotoxic at high doses
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Acetaminophen
Pharmacology
Mechanism of action not entirely understood
Not a COX inhibitor peripherally, but does inhibit the synthesis of prostaglandins peripherally
May inhibit prostaglandin synthesis in the CNS
Potentiates the cannabinoid/vanilloid tone in the brain and in dorsal root ganglia
Marijuana’s THC is a cannabinoid
There are CB1 receptors in the periphery also
Acetaminophen
Use with caution in the following patients:
Liver disease
Fasting
Chronic alcoholism
Poor nutrition
The metabolite, NAPQI, is potentially toxic if not adequately conjugated
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Acetaminophen
Dosages
Adult dose is 500-1,000 mg every 4-6 hours to a maximum of 4 grams per day
Paediatric dose is 10-15 mg/kg every 4-6 hours to a maximum of 80 mg/kg
Toxic at 140 mg/kg
Acetaminophen
Dosages
Now available (here) in an IV formulation
650-1000 mg every 4-6 hours if > 50 kg
12.5-15 mg/kg up to 75 mg/kg/24 h if < 50 kg
Avoids the first-pass hepatic exposure and metabolism
Therefore may be less hepatotoxic
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Two different mechanisms of action for analgesia
Potentially synergistic in the short-term
Potentially renotoxic in the long-term
NSAID & Acetaminophen
Opioids
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Terminology
Opioid
All drugs with opium-like activity
Opiate
Naturally-occurring alkaloids
Narcotics
A “controlled substance”
Most specifically a legal term
Refers to natural, semi-synthetic & synthetic compounds
Opioid History & Context
The first documented descriptions of Papaversomniferum appeared around 1550 BC in ancient Egypt
Morphine was not isolated or named until 1806 by Sertürner
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Opioid History & Context
Mechanism of action
Opioids act at specific CNS and peripheral sites to relieve pain
Act at the descending pain inhibitory system and in the brain (changing signal interpretation)
The significant effects are mediated through the μ and κreceptors
μ receptors may have an unlimited dose response
κ-agonist/μ-antagonist (e.g. nalbuphine) have ceiling effects
Opioid History & Context
Mechanism of action
Possible peripheral analgesic action
Elsharrawy and Elbaghdady (2007) compared supplemental PDL injections with fentanyl vs. mepivacaine with epinephrine for endodontic treatment
Found fentanyl to be more satisfactory than mepivacaine
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Opioids
In dentistry, they are indicated for use in the treatment of moderate to severe pain
Other opioid effects:
Antitussive
Constipation
Sedation
Mood alteration (euphoria)
Respiratory depression
Nausea and vomiting
Opioid History & Context
Current commonly used opioids:
Morphine & codeine
Hydrocodone & oxycodone
Meperidine, fentanyl, & methadone
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Opioids
2 broad categories of patients:
Opioid-naïve
No opioids for the past 7 days
Opioid-tolerant
Ref.: VCU Massey Cancer Centre, July 2010
Mechanism of action
Analgesia site of action is the CNS
Possible peripheral anti-inflammatory action
One study compared supplemental PDL injections with fentanyl vs. mepivacaine with epi
Ref.: Elsharrawy and Elbaghdady, Journal of Pain and Symptom Management, 33(2), 2007
Opioids
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Addiction is a real possibility
The public (and the government) are currently on high alert about the use of opioids in healthcare
Opioids
Equipotent Opioid Doses
Drug Oral dose (mg) IM dose (mg)
Morphine 30 10
Codeine 200 120
Oxycodone 25 10
Meperidine 300 75
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Opioids
Recommended oral doses
Codeine = 60 mg
Oxycodone = 5-10 mg
Meperidine = 100 mg
Opioid Combinations
They have the advantage of convenience
They do not have sensible formulations
Drug Acetaminophen(mg)
Codeine (mg)
Tylenol #1 300 8
Tylenol #2 300 15
Tylenol #3 300 30
Tylenol #4 300 60
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Opioid Combinations
Name Nonopioid Opioid
Percocet 325 mg acetaminophen 5 mg oxycodone
Percocet 325 mg acetaminophen 5 mg oxycodone
Percodan 325 mg ASA 5 mg oxycodone
Opioid Combinations
Name Nonopioid Opioid
OxyContin 5-80 None 5-80 mg oxycodone
OxyNeo 10-80 None 10-80 mg oxycodone
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Codeine for Kids?
As of June 2013, Health Canada no longer recommends codeine for children younger than 12 years
Codeine, as a prodrug, can be metabolized/activated at different rates
Can lead to a morphine overdose
Ref.: Wong, Oral Health, Feb. 2014
Codeine for Kids?
WHO analgesic ladder for paediatric pain:
Mild Pain
•Acetaminophen
•NSAID
Moderate to Severe Pain
•NSAID
•+/- Acetaminophen
•+ Morphine
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Codeine for Kids?Drug Pediatric Dose Maximum Availability
Acetaminophen 15 mg/kg q4-6h PO 90 mg/kg/day
(Not to exceed adult
max: 4 g per 24 hr)
Oral:
32 mg/mL
80 mg/mL
Rectal:
40 mg/kg loading dose,
then 20 mg/kg q6h
Rectal:
120 mg, 325 mg, 650 mg
suppository
Ibuprofen 10 mg/kg q6h PO 40 mg/kg/day
(Not to exceed adult
max: 2.4 g per 24 hr)
Oral:
20 mg/mL
40 mg/mL
100 mg chewable tablet
Morphine
(immediate release)
0.2-0.5 mg/kg q4h PO WHO recommends 5 mg
as a guideline.
Otherwise, there is no
fixed maximum dosage.
Oral:
1 mg/mL
5 mg/mL
10 mg tablet
Morphine for Adults?
Indication is moderate-to-severe pain
1 mg IV = 3 mg po
Dosing:
5-15 mg of immediate release morphine every 3 hours
If inadequate, the dosage can be increased by 50%
Ref.: VCU Massey Cancer Centre, July 2010
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Analgesic Strategies
Analgesic Sites of Action
Central (mostly)
Opioids
Acetaminophen
Peripheral (mostly)
NSAIDs
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Strategies
Maximize NSAID (or acetaminophen) before adding opioid
Optimize dosing regimen before switching
If the patient does not respond to one NSAID, they may respond to another
Strategies
Consider:
Pre-operative dosing
Loading doses
Giving the first dose before local anaesthetic wears off
4-hour interval instead of prn for the first day
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Mild to moderate pain
Acetaminophen
(up to 1000 mg)
NSAID
Add codeine to NSAID or acetaminophen
Add oxycodone w/ acetaminophen
Add codeine or oxycodone
Analgesic Algorithm
Antibiotics
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Use only when there is an indication
Choose the narrowest spectrum drug that will be effective
Consider the risk/benefit equation
Prescribe an adequate dose
Adequate frequency
Adequate duration
Prescribing Principles
Wrong drug or dose
Bacterial resistance
Host defences depressed
Poor compliance
Reasons for Failure
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Antibiotic Actions
Bactericidal
Penicillins
Metronidazole
Cephalosporins
Aminoglycosides*
Vancomycin*
Bacteriostatic
Clindamycin
Erythromycin
Tetracyclines
Oral penicillins are penicillin V and amoxicillin
Pen V is narrow-spectrum against gram-positive Strepand others
Drug of choice for orofacial infections
Dose = 300-500 mg qid
Amoxicillin is broad-spectrum and better absorbed orally
Dose = 250-500 mg q8h
Penicillins
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Adverse reactions
Allergy
Diarrhea (2-10% incidence)
Nausea and vomiting
Pseudomembranous colitis
Candidiasis
Penicillins
Allergy rate is 1-10% of the population
Penicillins responsible for 75% of anaphylaxis deaths
400-800 deaths per year in the US
Mild anaphylaxis occurs 1:200 courses
Severe anaphylaxis occurs 1:2,000 courses
Penicillins
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An alternative for penicillin-allergic or penicillin-resistant patients
Active against gram-positive and gram-negative anaerobes and facultative/aerobic bacteria
Dose = 150-300 mg q6h
Clindamycin
Also known as antibiotic-associated diarrhea (AAD)
Occurs in as many as 30% of patients
Broad-spectrum antibiotic use alters the composition of gut bacteria This allows the overgrowth of other bacteria
Clostridium difficile (C. difficile) is the beneficiary of interest here The presence of C. difficile and its toxins cause
pseudomembranous colitis
Characterized by diarrhea, fever and abdominal pain
Pseudomembranous colitis
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Risk factors
Drugs include:
Penicillins (esp. ampicillin)
Cephalosporins
Clindamycin
Erythromycin
Advanced age
Females with genitourinary disease
Uremic patients (e.g. kidney dialysis patients)
Pseudomembranous colitis
Treatment Stop all antibiotics
Keep the patient hydrated
Refer to a physician
Prescribe:
Vancomycin 500 mg po qid for 2 days (if severe)
Vancomycin 125 mg po qid for 10-14 days
Metronidazole 500 mg po tid for 7-14 days
Metronidazole IV
Probiotic therapy (Saccharomyces boulardii) has been tried adjunctively
Pseudomembranous colitis
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Group includes erythromycin, clarithromycin and azithromycin
Erythromycin was the former drug of choice for penicillin-allergic/penicillin-resistant patients
Numerous GI adverse effects
Active against gram-positive aerobic/facultative staph and strep and gram-negative anaerobes
Not particularly good against dental infections
Macrolides
Trade name is Flagyl™
Active against obligate, gram-negative anaerobes only
Used in combination with penicillin
Avoid concurrent use of alcohol or warfarin
Dose = 250-500 mg tid
Metronidazole
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Group includes tetracycline, doxycycline (Vibramycin, Periostat) and minocycline (Minocin)
Broad-spectrum, bacteriostatic
Useful in treatment of periodontal disease
Widespread resistance
Host of adverse effects including: tooth staining, photosensitivity, blood dyscrasias, GI effects
Tetracyclines
CYP3A4 is a major metabolizing enzyme
Part of the cytochrome P450 enzyme system
Clarithromycin, erythromycin and the azole antifungals (e.g. ketoconazole, fluconazole) are potent inhibitors of CYP3A4
Single-dose regimens, as in antibiotic prophylaxis are not of major concern
Antibiotic Drug Interactions
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Anecdotally reported
Scientific evidence implies rifampin (Rifadin®, Rofact™) only
Virtually untestable
Rationale is that antibiotics reduce enterohepaticrecycling of estrogen → subtherapeutic blood levels that allow ovulation
Antibiotics and Oral Contraceptives
From Resnick and Misch (2008):
Overall incidence is 6-7%
Possible reactions include:
GI tract complications
Colonization of resistant or fungal strains
Cross reactions with other medications
Pseudomembranous colitis
Development of resistant bacteria and superinfection
Little concern about short-term use
Antibiotic Adverse Reactions
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Sometimes recommended to combat antibiotic-associated diarrhea (AAD)
May be useful for frail patients or patients who have had this before
Lactobacillus and bifidobacterium are the preferred probiotics
Fermented foods with “friendly” bacteria may also help
E.g. kefir, yogourt, kimchi, miso, sauerkraut, or kombuchatea
Probiotics
Review by Hempel et al. 2012 reviewed and evaluated 82 RCTs for evidence regarding probiotic use in the prevention of AAD
The principal finding was that probiotics did reduce the risk of AAD
NNT=13
The findings did not clearly indicate which probiotics were best
Lactobacillus genus was the most tested, either alone or with other genera (e.g. Bifidobacterium)
Probiotics
JAMA, vol. 307(18), pp. 1959-1969
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Antibiotic prophylaxis
Indicated for patients with: Prosthetic heart valves
History of infective endocarditis
Cardiac transplant with subsequent heart valve problem
Some congenital heart conditions Unrepaired cyanotic disease (incl. shunts and conduits)
Repaired defect (<6 months) with prosthetic material or device
Repaired defect with residual defect at or adjacent to the site of repair
Antibiotic Prophylaxis
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Coverage is not indicated for patients with:
Surgically constructed systemic pulmonary shunts
Isolated secundum atrial septal defect
Previous coronary artery bypass graft surgery
Physiologic (functional, innocent) heart murmurs
Pacemakers and implanted defibrillators
Antibiotic prophylaxis
Indicated for the following procedures: Implant placement
Extractions
Periodontal procedures
Reimplantation of avulsed teeth
Endodontics beyond the apex of the tooth
Intraligamentary injections
Subgingival placement of fibres or strips
Placement of orthodontic bands
Polishing of teeth or implants where bleeding is expected
Antibiotic Prophylaxis
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Drug Adult Dose Paedo Dose
Amoxicillin 2 g 50 mg/kg
Clindamycin 600 mg po/IV 20 mg/kg po/IV
Azithromycin 500 mg 15 mg/kg
Clarithromycin 500 mg 15 mg/kg
Ampicillin 2 g IM/IV 50 mg/kg IM/IV
Antibiotic Prophylaxis
Patients already taking an antibiotic used for prophylaxis should:
Be prescribed an antibiotic from a different class
Be scheduled at least 9 days after the completion of the current prescription
Antibiotic prophylaxis
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May be indicated for patients at increased risk including:
< 2 years post-surgery
Inflammatory joint disease
Immunosuppression (incl. drug-induced, radiation-induced, HIV)
Previous joint infections
Type I diabetes mellitus
Total Joint Prosthesis
Prophylaxis may be indicated for patients at increased risk including: < 2 years post-surgery
Inflammatory joint disease (e.g. rheumatoid arthritis, lupus)
Immunosuppression (incl. drug-induced, radiation-induced, HIV)
Previous joint infections
Type I diabetes mellitus
Hemophilia
Malignancy
The literature is unclear
Prophylaxis for Total Joint Prostheses
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Regimens:
Amoxicillin or cephalexin 2 g po, 1 hour pre-op
Clindamycin 600 mg po/IV, 1 hour pre-op
Total Joint Prostheses
Literature Review 2003 Total Joint Advisory Statement from the ADA and AAOS
(the American Academy of Orthopedic Surgeons)
Recommended prophylaxis for 2 years for specific dental procedures
AAOS issued a new statement in 2009 that consolidated dental and medical procedures
“Given the potential adverse outcomes and cost of treating an infected joint replacement, the AAOS recommends that clinicians consider antibiotic prophylaxis for all total joint replacement patients prior to any invasive procedure that may cause bacteremia.”
Total Joint Prostheses
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Literature Review
Statement from ADA and AAOS in 2012
1. “The practitioner might consider discontinuing…routinely prescribing prophylactic antibiotics…”
This is a limited recommendation meaning that the quality of the supporting evidence is unconvincing
Total Joint Prostheses
Literature Review
Statement from ADA and AAOS in 2012
2. “We are unable to recommend for or against the use of topical oral antimicrobials in patients…”
This is inconclusive recommendation meaning that there is an unclear balance between benefits and potential harm
Patient preference should be a major guiding factor
Total Joint Prostheses
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Literature Review
Statement from ADA and AAOS in 2012
3. “In the absence of reliable evidence linking poor health to prosthetic joint infection, it is the opinion of the work group that patients with prosthetic joint implants or other orthopaedic implants maintain appropriate oral hygiene.”
A consensus opinion stands because of experts agreeing as opposed to the review of empirical evidence
Practitioners can be flexible about whether or not to follow consensus opinions
Patient preference is important again
Total Joint Prostheses
Clinical Practice Guideline from the ADA, January 2015
Q: For patients with prosthetic joints, is there an association between dental procedures and PJI [prosthetic joint infections]
“…the 2014 Panel judged with moderate certainty that there is no association between dental procedures and the occurrence of PJIs”
The Panel consisted of experts from the ADA only
Total Joint Prosthesis
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The concept of using antibiotics to enhance the outcome of implant surgery is not new
Adel et al. (1981) used Penicillin V for 10 days
Adel (1985) used 2 g Penicillin V for 10 days
Buser et al. (1990) used short-term amoxicillin or erythromycin
Antibiotics & Implant Surgery
Cochrane Review by Esposito et al. (2008) investigated the use of antibiotics to prevent complications in implants
Two randomized controlled studies were subjected to meta-analysis
Showed a statistically significant higher number of implant failures in the group that did not receive antibiotics
“It might be recommendable to suggest the use of one dose of prophylactic antibiotics prior to dental implant placement
2 g of amoxicillin preoperatively?
Antibiotics & Implant Surgery
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Clavulin® = amoxicillin and clavulanic acid
Dose = 875/125 mg bid for 7 days
Chlorhexidine 0.12% rinse
Start both medications 1 day pre-operatively
Sinus Lift Pre-/Perioperative Medication
Possible complications that may require medications are:
Site infection
Chlorhexidine 0.12% mouthrinse bid for 2 weeks
Nasal congestion
Pseudoephedrine (Sudafed®) 120 mg q12h
Phenylephrine (Sudafed PE®) 10 mg q4h
Oxymetazoline 0.05% (Claritin® Nasal Pump, Drixoral®) 2 sprays in each nostril q12h
Afrin® in the US
NB: other formulations of Claritin® are loratidine, an antihistamine
Sinus Lift Postoperative Considerations
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Bisphosphonates
They inhibit bone resorption by inhibiting osteoclasts and impairing angiogenesis
Indicated in the treatment of:
Osteoporosis
Paget’s Disease
Prolonged glucocorticoid therapy
Metastatic cancers (e.g. breast, lung, prostate and renal)
Osseous lesions associated with multiple myeloma
Bisphosphonates
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Associated with osteonecrosis of the jaws
Other bones rarely affected
Oral vs. intravenous
Consider as 2 distinct risk groups
Oral formulations include alendronate (Fosamax™), risedronate (Actonel™), ibandronate (Boniva™) and etidronate (Didrocal™)
Bisphosphonates
Bisphosphonate-associated osteonecrosis (BON) incidence estimates:
~0.8%-20% of patients in cancer therapy
0.01%-0.04% of patients taking oral formulations
0.09%-0.34% in cases of dental extractions
30 million prescriptions in the US in 2006
< 10% of BON cases associated with oral bisphosphonates
Ref.: ADA, JADA 139(12): 1674-1677, 2008
Osteonecrosis Incidence
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General dentistry
Areas of bony infection should be treated immediately
No change in routine care
Periodontal disease
Try to use non-surgical therapies with re-evaluation in 4-6 weeks
Use bone grafting and guided tissue regeneration judiciously
ADA Recommendations
Oral and maxillofacial surgery
Discuss risks (though small) and alternate treatments (e.g. RCT, FPD’s, RPD’s)
Post-operative prophylactic antibiotic use should be for risk of infection vs. use of bisphosphonates
Implants
Placement of implants may pose increased risk
Peri-implantitis should be approached non-surgically first
ADA Recommendations
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A twice-yearly injection that also prevents osteoclast activity by affecting precursor cells
Branded as Prolia™
Association with MRONJ largely untested to date
Important to ask about injections along with “pills or puffers”
Denosumab
Paper expands BRONJ to MRONJ because of denosumab and antiangiogenic therapies
The risk of MRONJ to osteoporosis patients ranges from 0.017%-0.04% which approximates the placebo risks (0%-0.02%)
Risk appears to increase over time, plateauing after 4 years
Staging and treatment strategies outlined
AAOMS MRONJ Position Paper
Web ref.: https://www.aaoms.org/docs/position_papers/mronj_position_paper.pdf?pdf=MRONJ-
Position-Paper
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Antithrombotics
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3 categories:
1. Antiplatelet drugs
Inhibit platelet aggregation
2. Anticoagulants
Inhibit the formation of fibrin strands
3. Fibrinolytics
Dissolve existing clots
Excellent review by Dr. D. Becker in AnesthesiaProgress, vol. 60, pp. 72-80, 2013
Antithrombotic Overview
Thrombus Formation
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Used to prevent the formation of thrombi in the arteries
The most popular antiplatelet drug is asa (aspirin)
Prescribed for the prevention of MI and ischemic stroke
Used in the treatment of AMI
Mechanism of action is the permanent inhibition of TXA2
synthesis
Antiplatelet Drugs
Clopidogrel (Plavix®) and Prasugrel (Effient®) work by permanently blocking ADP receptors on platelet cell membranes
This means that the platelets do not bind fibrinogen
Both are prodrugs
Clopidogrel has 15% activation
Prasugrel has ≈ 100% activation
Both complicate the approach to control bleeding incidents
Antiplatelet Drugs
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Clopidogrel (Plavix®)
Indicated for secondary prevention in cases of stroke, post-MI, or stent placement
Less spontaneous bleeding than with aspirin
Plasma half-life = 20-50 hours
6 days needed for normalization after discontinuation
~ 4 half-lives
Antiplatelet Drugs
Prasugrel (Effient®)
Same indications as clopidogrel
Plasma half-life = 7 hours
1½-2 days needed for normalization
Antiplatelet Drugs
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Patient assessment
INR does not work for patients on antiplatelet therapy
A platelet function test would be necessary
Ref.: D Mylotte, Cardiovascular & Hematological Agents in Medicinal Chemistry, 9: 14-24, 2011
Antiplatelet Drugs
Dental implications
Ibuprofen and naproxen are competitive inhibitors of asa on platelet cyclooxygenase
The clinical relevance of this fact is insignificant
Problem is avoided by having asa at least 1 hour before the other NSAID
Antiplatelet Drugs
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Dental implications
Low-dose asa and regular-dose clopidogrel do not pose a bleeding risk in minor surgeries
For extensive surgeries, bleeding times return to normal after 4-5 days of withholding the antiplatelet drug
Antiplatelet Drugs
Patients with coronary stents
According to the American College of Chest Physicians, delay elective surguries
6 weeks following bare-metal stent placement
6 months following drug-eluting stent placement
Antiplatelet Drugs
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Used primarily to prevent thromboembolic events
E.g. DVT, post-pulmonary embolus, atrial fibrillation, prosthetic mitral or aortic valve
Can be used in combination with antiplatelet drugs in high-risk patients
The common drugs are warfarin (Coumadin), heparin and dabigatran (Pradexa)
Anticoagulant Drugs
Warfarin (Coumadin) competes with vitamin K in the liver to inhibit the production of a number of clotting factors
This mechanism of action is fairly imprecise
Takes several days for full effect (or full offset)
Elimination t½ = 20-60 hours
Effects measured by PT (or INR)
Can do work with INR < 3-3.5
Contraindicated in pregnancy
Anticoagulant Drugs
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Heparin is injectable (SC or IM) only
Mechanism of action is the potentiation of antithrombinin the plasma
Again, the effects are fairly imprecise
Effects measured by aPTT
Elimination t½ = 1-2 hours
Anticoagulant Drugs
Low-molecular-weight-heparins (LMWH) are as effective as heparin but act more selectively and for longer times
E.g. enoxaparin (Lovenox®), dalteparin (Fragmin®)
Elimination t½ = 5 hours
Anticoagulant Drugs
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NEW: Dabigatran (Pradaxa, Pradax) is an orally-administered direct thrombin inhibitor
Blocks conversion of fibrinogen fibrin
Used to prevent stroke in people with atrial fibrillation
Advantages include a broad therapeutic window, short half-life, fixed dosing, no interaction with cytochrome P450
Effects are difficult to assess
Inconsistent effects on aPTT, and PT largely unaffected
No standardized reversal procedure
Post-operative bleeding effects slightly less than with heparin
Anticoagulant Drugs
Dabigatran
Administered as a prodrug
Dose = 75-150 mg bid
Onset of action = 1 hour
Elimination t½ = 12-17 hours
Best effect assessment by ecarin clotting test (ECT; rare)
Anticoagulant Drugs
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Dabigatran
Dental treatment modifications
Avoid aspirin and NSAIDs
If needed, skip 1-2 doses
Anticoagulant Drugs
NEW: Oral Factor Xa Inhibitors
Rivaroxaban (Xarelto®) and apixiban (Eliquis®) inhibit the conversion of prothrombin thrombin
Anticoagulant Drugs
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Rivaroxaban (Xarelto®)
Indicated for VTE after knee or hip replacement, prevention of stroke, DVT or PE, treatment of DVT or PE
10-20 mg given once per day
Elimination t½ = 7-11 hours
Normal Xa activity returns after ~24 hours
Anticoagulant Drugs
Apixiban (Eliquis®)
Indicated for stroke or VTE prevention
Dose = 5 mg bid
Elimination t½ = 12 hours
Status can be monitored via PT (INR)
Discontinue drug for 24-48 hours before elective surgery or invasive procedures
Anticoagulant Drugs
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Dental implications Risk of postoperative bleeding Minor surgery is OK if the INR is less than 3.5
Vitamin K reversal works for warfarin, not dabigatran
Extensive surgical procedures may need bridge therapy where injectable anticoagulants replace warfarin
CYP2C9 interactions between warfarin and metronidazole, macrolide antibiotics and azole antifungals
Watch out for NSAIDs because of GI bleed risks
Anticoagulant Drugs
“Clot busters” work by converting plasminogen to plasmin
Inactivates fibrinogen and lyses fibrin strands
Recombinant tissue plasminogen activator (rTPA) is the most commonly used agent
Not an issue for outpatient dentistry
Fibrinolytic Drugs
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Sedative Agents
Conscious Sedation(minimal and moderate*)
Deep Sedation
General Anaesthesia
Spectrum of Anaesthesia
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Conscious Sedation
Ref.: RCDSO, 2012
“…a minimally to moderately depressed level of consciousness that retains the patient’s ability to independently and continuously maintain an airway and respond appropriately to physical stimulation and verbal command.”
The RCDSO is more concerned about the intent of sedation than the endpoint achieved
Warning:
Any method of sedation and any choice of drug can lead to any level of
consciousness
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Nitrous Oxide
Benzodiazepines
Antihistamines
Useful Conscious Sedation Drugs
The Good:
Fast onset, fast offset
Easy to administer
No lasting effects
0.004% metabolized
Very safe
Has some analgesic properties
Nitrous Oxide and Oxygen
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The Bad:
Difficult for claustrophobic patients
May not be strong enough
Requires active dentist participation
Nitrous Oxide and Oxygen
The Good: Familiar, noninvasive route of administration
No special office equipment is needed*
The Bad: Not titratable or recoverable Benzodiazepines are reversible but not orally
Beware of DOCS* protocols
Slow onset
Patients must be accompanied home
Ref.: Donaldson et al., Anesthesia Progress, 54:118, 2007
Oral Medications
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An anxiolytic-specific category of drugs
Act on GABAA receptors in the CNS to hyperpolarize cells
Lowers brain activity
Little effect on the respiratory and central nervous systems
Metabolized by the CYP450 3A4 enzyme system
Watch out for inducers or other system occupiers
Benzodiazepines
Effects are sedation, anterograde amnesia and anxiolysis
Popular choices are midazolam, triazolam, diazepam, lorazepam and temazepam
Peak of action in about 1 hour, except for midazolam
Be careful with multiple doses or alternate routes of administration (e.g. sublingual)
Benzodiazepines
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Agents include:
Zolpidem (Ambien)
Fast onset, short duration, no active metabolites
Zopiclone (Imovane)
Similar pharmacologic profile to zolpidem
Ramelteon (Rozerem)
A melatonin receptor agonist
Non-BZD GABA Agonists
Sedation is a side effect
Agents include hydroxyzine (Atarax), diphenhydramine (Benadryl) and promethazine (Phenergan)
Very safe
Antihistamines
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Warnings:
1. Oversedation = medical emergency
2. Incremental dosing of oral sedatives is now discouraged in Ontario*
Adverse Events During Paediatric Dental Anaesthesia
Article by Chicka et al. in Pediatric Dentistry, 2012; 34: 231-238
Analyzed 17 closed malpractice insurance claims in the US from 1993-2007
1 GA, 3 LA, 13 sedation & LA
9 outcomes of “major” severity (i.e. death or brain damage)
8 outcomes of “minor” severity (i.e no permanent morbidity)
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Adverse Events During Paediatric Dental Anaesthesia
Article by Chicka et al. in Pediatric Dentistry, 2012; 34: 231-238
82% of the claims involved children < 6 years
Most sedated children are < 6 years (78%)
Average age of “major” outcomes = 3.6 years
There is an inverse relationship between patient age and sedation risk
47% of the outcomes were “minor”
Good management vs. self-limiting events
Adverse Events During Paediatric Dental Anaesthesia
Article by Chicka et al. in Pediatric Dentistry, 2012; 34: 231-238 No single sedative agent was most frequently associated with
“major” outcomes
Drug dose more important than drug choice
41% of the claims involved an overdose of LA
LA toxicity may be masked by concomitant BZD use
Most claims involved events at the dental office
The dentist is likely to be the first responder Important for the dentist and the team to be ready
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Drug Therapy in the Elderly
Pharmacokinetic changes
Pharmacodynamic changes
Systemic disease
Polypharmacy
Factors to consider
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Absorption
Increased gastric pH
Decreased gastric emptying
Impaired gastric motility
Overall minor effect
Pharmacokinetics
CNS drugs have magnified effects (e.g. benzodiazepines)
Can result in
Excessive sedation
Mental confusion
Delirium
Respiratory depression
Pharmacodynamics
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Systemic disease
Some examples of diseases that affect pharmacologic effects include:
Disease Effect
Renal disease ↑ serum half-life and concentration
Congestive heart disease ↑ serum half-life and concentration
Benign prostatic hypertrophy ↑ urinary retention with anticholinergics
Dementia ↓ ability to comply with prescriptions
Use of prescription medications, OTC medications, natural medicines and alternative medicines is very widespread in Canada
Concerns for adverse drug reactions and drug interactions
According to a 2009 report from Ramage-Morin (Statistics Canada)
In 2005, pharmacists dispensed an average of 35 prescriptions per person aged 60 to 79 74 prescriptions per person aged 80 or older
Compared with an overall average of 14 prescriptions per Canadian
Math, co-morbidities and physiologic changes put seniors at risk
Polypharmacy
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53.1% of institutionalized seniors and 12.8% of seniors in private households reported polypharmacy (taking 5 medications or more in the past 2 days)
97% of institutionalized seniors reported taking some medication in the past 2 days
76% of seniors living in private households
Ramage-Morin (2009)
Local anaesthetics
No change in administration
Consider reducing maximum dose if the patient has congestive heart disease
Limit vasoconstrictor dose to 40 μg per appointment
Specific Considerations
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Acetaminophen
Analgesic of choice
Dosage of 325-1000 mg q4h to a daily maximum of 4 g
Reduce the daily maximum if there is alcoholism or significant liver disease
Specific Considerations
NSAIDs
Note the possibilities for bleeding, ulceration or perforation
Increased risk of GI toxicity
Increased risk of renal toxicity
Increased risk of hepatic toxicity
Consider celecoxib (Celebrex®) as your NSAID
Specific Considerations
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Opioids
Level of effect increased
Duration of effect prolonged
Increased likelihood of adverse reactions
Consider using a reduced dose or avoid opioids
Specific Considerations
Antibiotics
Increased risk of pseudomembranous colitis
No need to alter regimens solely because of age
Specific Considerations
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Nitrous oxide & oxygen First choice for conscious sedation
Advantages Titratability
Rapid onset and offset
Disadvantages Patient acceptance
Limited effectiveness
Equipment costs
Not useful for Alzheimer’s/dementia patients
Specific Considerations
Oral sedation Advantages
Easy to administer
No equipment costs*
Disadvantages
Dosage is a guess
Onset is delayed and unreliable
Effects are prolonged
Limited efficacy
Many side effects
May not be suitable/effective for dementia patients
Specific Considerations
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Goals
Review the patient’s current drug list
Simplify the treatment regimens
Reduce the number of drugs and the dosing frequency
Monitor the patient after providing a prescription
Pharmacotherapy for the Elderly Patient
Herbal Supplements
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