Pharmacology in implant dentistry

CONTEMPORARY IMPLANT DENTISTRY

CHAPTER 21

PRESENTER: MOSTAFA MONTAZERI

IntroductionIncrease in demand and use of dental implant Indications and protocol for the use of pharmacologic agents

There is no consensus on the pharmacologic protocol

Many practitioners use medications empiricallyin all procedures

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AntimicrobialsAn important complication to prevent after implant surgery is Infection Antimicrobial therapy is an essential component of the surgical procedures

Adverse effects Mild and infrequent

Most common antimicrobials in implant dentistry:1. Antibiotics

2. Antimicrobial rinses (0.12% CHX gluconate)

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AntibioticsAntibiotic therapy in dentistry:

1. Prophylactic (Prevent infections)

2. Therapeutic (Treat infections)

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Prophylactic AntibioticsIn oral implantology No consensus on the use and indications for prophylactic antibiotics

Adverse effects:

1. Development of resistant bacteria

2. Adverse reactions

3. Possible lax surgical technique

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Prophylactic AntibioticsEsposito and Hirsch One of the main causes of dental implant failure may be due to bacterial contamination at implant insertion

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Prophylactic AntibioticsSurgical wound infections

1. Presence of inoculum

2. Overcoming the host’s defenses

3. Allowing for the growth of bacteria

This process has many variables; Prophylaxis is only one component

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The efficacy and impact of antimicrobial prophylaxis has been proven to be significant

Prophylactic AntibioticsIn the most comprehensive and controlled study to date:

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Use of preoperative antibiotics significantlyimproved dental implant survival (4.6% vs. 10%

failure), both in early and later stages

Prophylactic AntibioticsMain goal of use Prevent infections during initial healing period A greater aseptic local environment is achieved

Study by Burke Scientific basis for the preoperative use of antibiotics

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Prophylactic AntibioticsPrinciples drafted from Burke’s study:

1. High-risk procedure

2. Selection of appropriate antibiotic

3. Appropriate tissue concentration of antibiotic

4. Use of the shortest effective antibiotic

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Prophylactic Antibiotics

Surgical wound classification with associated infection ratesClass 1: Clean (<2%)Elective non-traumatic surgery, no acute inflammation, respiratory, GI and biliary tracts no entered

Class 2: Clean-Contaminated (10-15%)Elective opening of the respiratory, GI and biliary tracts enteredElective dental implant and bone procedures (<1% by proper surgical technique and prophylactic antibiotics)

Class 3: Contaminated (20-30%)Inflammation, gross spillage from GI and biliary tracts

Class 4: Dirty/Infected (50%)Established clinical infection, perforation of respiratory, GI and biliary tracts

Principle 1:

The procedure shouldhave a significant riskfor and incidence ofpostoperative infection

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Class 2,3 and 4 procedures Use of prophylactic antibiotics


Factors associated with increased risk of infection for dental implant proceduresSystemic factorsDiabetes, Long term corticosteroid use, Smoking, Immunocompromised systemic disorders, Malnutrition, Obesity, Elderly population, ASA 3 or 4

Local factorsUse/type of grafting material, Periodontal disease, Tissue inflammation, Odontogenic infection, Ill fitting provisional prosthesis, Incision line opening, Inadequate hygiene

Surgical factorsPoor aseptic technique, Skill/experience of the surgeon, Increased duration of surgery, Wound contamination during surgery, Foreign body (Implant)

Principle 1:


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One of the most significant surgical factors Poor aseptic technique:

Proper disinfection and draping, Hand scrubbing, sterile gowns


Duration of the surgical procedure Second most critical risk factor affecting postoperative infection rates

◦ Less than 1 hour 1.3%

◦ More than 3 hours >4%

Rate of infection doubles with every hour of the procedure

Principle 1:


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Skill & Experience of the surgeon:

Less experienced surgeon (<50implants placed) 7.3%increase in failure rates

Principle 1:


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Dental implant as a foreign body:

Presence of the implant can compromise the hosts’ defenses

Normal flora with low-virulence potential

Very difficult to treat

Principle 1:


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Probability of wound infection by type of wound, risk index and ASA status

Principle 1:


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Risk IndexOperationclassification 321

5.4%2.3%1.0%Clean

9.5%4.0%2.1%Clean-contaminated


Most postoperative infections are caused by endogenous bacteria like:

Aerobic G+ cocci; Streptococci

Anaerobic G+ cocci; Peptococci

Anaerobic G- rods; Bacteroides

Oral infections; Mixed 𝑨𝒏𝒂𝒆𝒓𝒐𝒃𝒆𝒔

𝑨𝒆𝒓𝒐𝒃𝒆𝒔=

𝟐

𝟏

Anaerobes need aerobes to provide an environment to proliferate

The ideal antibiotic must be effective against these pathogens

Principle 2:

The appropriateantibiotic for thesurgical procedure mustbe selected

1- The antibiotic shouldbe effective against thebacteria that are mostlikely to cause aninfection

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Adverse effects may vary from nausea to the extreme allergic reactions

Principle 2:


2- Use the antibioticwith least amount ofadverse effects

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Advantages of bactericidal antibiotics:

1. Less reliance on host resistance

2. The bacteria may be destroyed by the antibiotic alone

3. Faster results

4. Better flexibility with dosage intervals

Principle 2:


3- The antibiotic shouldbe ideally bactericidal

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Antibiotic should be given in a dose that will reach plasma levels that are ×3 to ×4 the MIC

To achieve this:

×2 therapeutic dose at least 1 hour before surgery

After bacterial contamination No preventive influence

Principle 3:

An appropriate tissueconcentration of theantibiotic must bepresent at the time ofsurgery

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In a healthy patient:1. Continuing antibiotic after

surgery doesn’t decrease the rate of infections

2. A single dose of antibiotic is sufficient

In a high-risk patient:◦A longer dose of antibiotic

Principle 4:

Use of the shortesteffective antibiotic

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Complications of antibiotic prophylaxis6-7% incidence, life-threatening: minimal

Risks: GI complications, Colonization of resistant strains, Cross reactions, Allergic reactions

Allergic reactions: from mild urticarial (1-3%) to true anaphylaxis (0.01-0.04%)

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Complications of antibiotic prophylaxisPseudomembranous colitis: ◦ Unusual yet increasing complication

◦ Caused by C.difficile (Intestinal flora)

◦ Highest risk: Penicillins, Clindamycin

◦ Most common treatment: Vancomycin or Metronidazole

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Risks for Antibiotic-Induced Pseudomembranous Colitis

LowMediumHigh

TetracyclinsMetronidazole

Vancomycin

PenicillinErythromycinQuinolones

AmpicillinAmoxicillin

CephalosporinClindamycin

Diarrhea and Abdominal Cramping

Complications of antibiotic prophylaxisDevelopment of resistant bacteria:

Begins only after the elimination of host’s susceptible bacteria

Takes at least 3 days of antibiotic use

Short term use (1day) Little effect

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Antibiotics Used in Implant Dentistry1. Beta-Lactams: Penicillin V, Amoxicillin, Augmentin,

Cephalexin/Cefadroxil

2. Macrolides: Erythromycin, Clarithromycin, Azithromycin

3. Clindamycin

4. Tetracyclins

5. Fluoroquinolones: Ciprofloxacin

6. Metronidazole

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Beta-Lactams: Penicillin VoGood absorption

oSerum peak levels: 30 min

oDetectable in blood: 4 hours

oEffective against: Most Strep. species, Oral anaerobes

oMain disadvantage: Compliance (qHd), prone to resistant bacteria

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Beta-Lactams: AmoxicillinoSuperior absorption, 70-80% bioavailability, Very low toxicity

oExcellent tissue diffusion in infected areas

oBroad-spectrum: G- cocci and bacilli, Streptococci and oral anaerobes (> Penicillin V)

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Beta-Lactams: Amoxicillin/Clavulanic Acid (Augmentin)oAffinity for penicillinase-producingbacteria

oAs a suicide molecule; Inactivates the resistant bacteria

oIndication: In case with suspected penicillinase bacteria

oVery practical perioperative antibiotic for sinus augmentation

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Beta-Lactams: Cephalexin/CefadroxiloFirst generationoSimilar spectrum to amoxicillinoAdvantage: Not susceptible to beta-lactamase (S.aureus)oCross-reactivity with penicillin 8-18%oContraindicated only in type 1 hypersensitivity

oSecond and third generations Broader spectrum, Less cross-reactivity, greater resistance to beta-lactamase destruction

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MacrolidesoMost common used in dentistry ErythromycinoBacteriostatic Not ideal first choiceoAgainst Strep., Staph., some anaerobesoAlternative for penicillin-allergic patientsoExcellent absorption but affected by food consumptionoHigh incidence of nauseaoNumerous drug interactions Elevating serum levels of Digoxin, Theophylline, Carbamazepine, Terfenadine predug (Cardiotoxic Torsades de pointes, ventricular tachycardia)

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MacrolidesoThree novel macrolides Clarithromycin (Biaxin), Azithromycin (Zithromax)oThey do not inhibit cytochrome P450 isozymes

oBiaxin Less nausea and better G- activity

oZithromax Effective against H.influenza

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ClindamycinoActive against: Primarily anaerobes, aerobes such as Streptococci and Staphylococci, B.fragilis (superior)oAqueous solution 300mg/2ml Graft materials for sinus augmentation

oBacteriostatic in normal doses

oMain disadvantage: Diarrhea in 20-30% of patients treatedAlso can cause pseudomembranous colitis (PMC)

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ClindamycinoAnti-diarrheal medications should be avoided Hindering of fecal elimination of the pathogen

oIf continuing the drug is necessary Imidazole or Vancomycin, Metronidazole

oIf the condition persist >3 days Internist

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TetracyclinsoWide-spectrum activity: Strep., Staph., oral anaerobes, G-aerobic rodsoHigh degree of bacterial resistance (since 1950s)oPrimary agents for treating implant diseases and infectionsoQuestionable efficacy for managing infrabony defects (Inactivates when chelated with Ca complexes)

oDisadvantages: High incidence of Candidal infections, Photosensitivity reactions

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FluoroquinolonesoBactericidal and broad-spectrum, oral or parental

oCiprofloxacin was of the first generation of this group

oNewer generations Greater activity against resistant bacteria and anaerobes

oProphylactic and therapeutic treatment of sinus lifting procedure

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MetronidazoleoBactericidaloAnaerobic infections (rarely in mixed infections)o+Penicillin Severe infections

oDisulfiram-like reactions; Severe nausea and abdominal cramping

oCounteracts with Warfarin (Coumadin)

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Prophylactic Antibiotics in Oral Implantology1. Amoxicillin: Drug of choice

2. Cephalexin (non-anaphylactic allergy to penicillin)

3. Clindamycin (anaphylactic allergy to penicillin

For sinus involvement procedures:

1. Augmentin

2. Levaquin (History of taking antibiotics within past 4 weeks)

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Therapeutic Use of Antibiotics: Postoperative InfectionsAcute post-op infections: 3rd to 4th day after surgery

Local signs: Pain, inflammation, bleeding, exudate

Systemic signs: Fever, headache, nausea, muscle aches, vomiting, weakness

First-line medication: Broad-spectrum beta-lactam

Duration: 3 days beyond the clinical improvement (usually 7 days)

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Therapeutic Antibiotics in Implant Dentistry

The recommended treatment for intraoral infections:

1. Surgical drainage

2. Systemic antibiotics

3. 0.12% CHX gluconate; Τ1 2 oz BID for 2 weeks

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Therapeutic Antibiotics in Implant DentistryAmoxicillin 500mg; 2 immediately, TID 1 week

In case of allergy:

Clindamycin 300mg; 2 immediately, TID 1 week

No improvement after 4 days Culture and sensitivity test

Until then Levaquin 50mg/day, 1 week

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ChlorhexidineAnother modality for antimicrobial prophylaxis

Potent antibacterial

High substantivity at high concentrations, is bactericidal; by bacterial cytoplasm precipitation

Slow release from tissue surfaces; 12-hours

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ChlorhexidineIn vitro: Inhibitory effect of CHX on cultured epithelium and cell growth

Clinical studies have not shown this

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Chlorhexidine1. Reduce plaque accumulation

2. Enhance mucosal health

3. Improve soft tissue healing

4. Treat periodontal disease

5. Prevent alveolar osteitis

6. Tissue healing after extractions

7. Reverse peri-implantitis

8. No adverse effect on implant surfaces

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ChlorhexidinePreoperative CHX before implant surgery:

Significant reduction of infectious complications (2 to 1)

Six fold difference in implant failures

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Chlorhexidine1. Patient pre-surgical rinse

2. Surface antiseptic

3. Postsurgical rinse: twice a day until incision closure

4. Peri-implant maintaining on daily basis

5. Treatment of postoperative infections

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Management of postoperative inflammation

Cyclooxygenases and Prostaglandins Postoperative pain and inflammation

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Tissue damage

Arachidonic acid release

PGs

Edema

Steroids

NSAIDs Cyclooxygenase

NSAIDsAnalgesic and anti-inflammatory

Do not have a ceiling effect for inflammation

Higher doses to achieve anti-inflammatory effects Serious side effects

Ibuprofen is suggested in implant dentistry

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GlucocorticosteriodsAdrenal cortex Androgens and corticosteroids

Corticosteroids:

1. Glucocorticoids Carbohydrate metabolism, potent anti-inflammatory actions

2. Mineralocorticoids Sodium-retaining

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GlucocorticosteriodsSynthetic glucocorticoids Longer-acting and more potent than natural steroids

Anti-inflammatory effects:

Altering CT response to injury Hyperemia Exudation and cellular migration

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GlucocorticosteriodsDuration (hr)Equivalent dose (mg)PotencyGlucocorticoids

Short-acting

<12201.0Hydrocortisone

<12250.8Cortisone

Intermediate-acting

24-3654.0Prednisone

24-3654.0Prednisolone

Long-acting

>480.7525Dexamethasone

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Glucocorticosteriods: Mechanism of action

Binds to GRs within cells Glucocorticoid-GR complex Alteration of mRNA synthesis Different proteins

Also active lipocortins which inhibitphospholipase A2 (Key enzyme in releasing of arachidonic acid) PGs

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Glucocorticosteriods: Adrenal suppressionAfter 7-10 days after steroid administration

In stressful situations Cardiovascular collapse

Amount of suppression

Short-term use Doesn’t significantly affect HPA axis and restore completely after 7 days

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1. Duration of treatment2. Dose administered

Glucocorticosteriods: TimingShould be based on the production of the natural steroid, Cortisol:

1. from plasma cholesterol 15-30mg/day

2. Stressful situations 300mg

3. Several-fold higher in the morning A dose of Dexamethasone in the morning doesn’t significantly alter the level of cortisol, but in the afternoon Complete suppression of HPA

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Glucocorticosteriods in medicine and dentistryHave been used in 2 ways since 1942:

1. Therapeutic treatment in various inflammatory and autoimmune diseases (Todays still used for this)

2. Prophylactic treatment of inflammation and pain

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Glucocorticosteriods in medicine and dentistry

In the dental literature, they have been shown to:

1. Advantageous in the prevention of post-operative complications after traumatic oral surgery, Intraoral sagittal osteotomy, vestibuloplasty with palatal mucosal grafts

2. Reduction of edema and pain after oral surgery

3. Less need of pain medication after surgery

4. Minimal effect on wound healing, infection and adrenal suppression

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Glucocorticosteriods in implant dentistryIntegral part in the treatment of post-surgical edema after implant procedures

1. Drug of choice: Dexamethasone (Decadron)administered before surgery (in the morning)

2. The post-operative regimen should not exceed 3 daysafter surgery (for inflammation peaks between 48-72 hours)

3. The dose should not exceed the equivalence of 300mg of cortisol

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Glucocorticosteriods in implant dentistryAdditional benefit of dexamethasone Antiemeticeffects for the prophylactic treatment of post-operative nausea and vomiting

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Glucocorticosteriods in implant dentistryContraindications:

1. Active infection

2. Tuberculosis

3. Ocular herpes simplex

4. Primary glaucoma

5. Acute psychosis

6. Diabetes mellitus anti-insulin action Glycosuria

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CryotherapyApplication of cold dressing to reduce postoperative inflammation

In the form of ice bags minimize edema by:

1. Vasoconstriction of capillaries

2. Lower temperature Reduce cell metabolism

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Cryotherapy as an anti-inflammatory agentHighly advised in any implant procedure in which excessive inflammation is expected

20min on/ 20min off for the first 24-36 hours

No longer than 2 days

Prolonged use Rebound swelling and cell destruction

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Postsurgical Pain ManagementPain inadequately treated in 50% of all surgeries

Painful experiences Cause hyperalgesia and allodynia

Goal in oral implantology: adequate analgesic levels before cessation of LA and postoperative comfort

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Preemptive analgesiaIntroduction of an analgesic regimen before theonset of noxious stimuli (Advantageous in implant surgery)

Factors affecting duration and intensity of postoperative pain: 1.Extent of reflection 2.Amount of bone preparation 3. Inherent factors 4. Duration of the surgery

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Mechanism of painNoxious stimuli Peripheral nociceptors Transmit signals to the dorsal root ganglion Synapse in the dorsal horn Spinothalamic tract Thalamus Cortex Interpretation of pain

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Mechanism of painRepeated Stimuli Nociceptors becomes more responsive

Sensitivity of nociceptors enhanced and magnified by tissue factors and inflammatory mediators such as:

PGs, kinins, Leukoterines, sP, Histamine

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Mechanism of painThe most important mediator PGs

Also synthesized in brain and spinal cord Enhance pain sensitivity

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Tissue damage

Arachidonic acid

COX-1 COX-2 COX-3 ??

Prostaglandins Prostaglandins

Platelet activity (Hemostasis)GI integrity

Regulation of kidney function

PainInflammation

Fever

NSAIDsAcetaminophen

COX-2 inhibitors

Mechanism of painOpioids Act on CNS by binding to µ-opioid receptors Prevention the release of substance P Prevent transmission on nociceptive pathways and activate inhibitory descending pathway

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Analgesic classifications in dentistry

Non-opioids

NSAIDs

Acetaminophen

Tramadol

COX-2 inhibitors

Opioids

Codeine

Hydrocodone

Oxycodone

Meperidine

Adjuvants

Glucocorticoids

Long-acting anesthetics

Tricyclic antidepressants

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Management of postoperative pain

Non-opioids: AcetaminophenMode of action: Unknown; PG pathways within the CNS with little effect of peripheral PG synthesis

COX-3 enzyme Brain, spinal cord and heart Postulated to be the site of action of Acetaminophen

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Non-opioids: AcetaminophenIndication: Mild to moderate pain

Excellent analgesic and antipyretic properties

Ceiling dose for analgesic effect (4g/day)

Minimal anti-inflammatory qualities

Main side effect: Liver damage (long-term)

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Non-opioids: NSAIDsEffective in all levels of pain

Work very well as analgesics and anti-inflammation

Analgesic doses Ceiling effect

Anti-inflammation doses No ceiling effect

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Non-opioids: NSAIDsSide effects:

1. GI disturbances (Dyspepsia, erosions, ulcerations)

2. Liver effects

3. Cardiac effects

Largest number of serious drug-related complications

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Relative risk of NSAIDs for GI complications

Relative riskNSAID

1None

2.1Ibuprofen

3.2Ketoprofen

4.3Naproxen

5.5Indomethacin

8 to 11Aspirin

24.7Ketrolac

Non-opioids: NSAIDsVery little effect on platelet aggregation; BTs are not prolonged

Prolonged use Interference with anti-hypertensive drugs (>5 days Monitor blood pressure)

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Non-opioids: IbuprofenMost popular prescribed NSAID

Mild to moderate pain

Analgesic ceiling dose 400mg/dose and 1200mg/day

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Non-opioids: AspirinAt analgesic doses, its relative risk for GI complications is high

Aspirin is NOT a drug of choice in implant surgery; for its antiplatelet effects

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Non-opioids: TramadolCentrally acting analgesic with 2 complementary characteristics:

1. opioid

2. anti-depressant

Mechanism: Inhibition of norepinephrine and serotonin reuptake

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Non-opioids: TramadolFewer opioid-like side effects

Analgesic efficacy similar to codeine (60mg)

Indication: Moderate to moderately severe pain

Alternative in patients with NSAID-related GI complications and opioid intolerance

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Non-opioids: TramadolUltracet(tramadol/acetaminophen) Excellent efficacy in pain studies; 3.75mg tramadol and 325mg acetaminophen

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Non-opioids: COX-2 inhibitorsMain advantage: Lack of GI side effect

Several cardiovascular complications

Not better than Ibuprofen in terms of pain and inflammation management

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Opioids (Narcotics)Primary medications for moderate to severe pain from dental origin

Centrally acting on µ and κ receptors

Morphine: Naturally occurring opioid

Do not have a ceiling effect; As the dose increases, analgesia increases

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Opioids: CodeineNaturally occurring alkaloid

Mild analgesic

Excellent antitussive but with nausea and constipation

Orally: 60% bioavailable; 10% methylated to morphine (analgesic; 90% not analgesic)

Because of the side effects and low potency Not the first choice in oral implantology

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Opioids: HydrocodoneSemi-synthetic narcotic analgesic and antitussive

Actions qualitatively similar to codeine

Usually used as a combination analgesic (+Ibuprofen or acetaminophen)

It is habit forming

Adverse reactions: Dizziness, sedation, nausea, vomiting

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Opioids: OxycodoneSemi-synthetic opioid

Analgesic action similar to morphine

Moderate to severe pain

Excellent oral bioavailability (retains 50% of its analgesic activity)

Combination (+acetaminophen or aspirin)

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Opioids: MeperidineMostly in hospital settings (IM)

Very strong CNS stimulant

Poor oral bioavailability (25%) Poor choice for an orally administered opioid

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Combination Analgesic Therapy for Postoperative PainGoal: Increase the analgesic effect while decreasing possible side effects

Acetaminophen or NSAIDs + An opioid

Because of the ceiling effect of the formers, no additional analgesia with dosage increase

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Mild painSelf-limited

Normal recommended doses of NSAIDs

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Moderate painWill not be resolved totally by NSAIDs

Interfere with function

Disrupt the activities of daily living

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Severe painInterferes with some or all of the activities of daily living

Strong opioid treatment for days

Adjuvant drug therapies

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Control of Postoperative Surgical PainWHO: Analgesic “ladder”; three steps:

1. Maximize the use of NSAIDs for mild to moderate pain, Adjuvants such as glucocorticoids and cryotherapy suggested

2. Non-opioid + adjuvant + opioid (moderate)

3. Non-opioid + adjuvant + opioid (severe)

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Recommend Pain Control Protocol (PCP)

DoseDrug

PCP1: Mild pain expected

400mg, 1 hr before surgeryIbuprofen

PCP2: Mild to moderate pain expected

400mg 1hr before surgery + continue QID for 2 days5mg/500mg as needed

Ibuprofen + Hydrocodone

PCP3: Moderate pain expected

400mg 1hr before surgery + continue QID for 2 days7.5mg/750mg QID for 2 days, then as needed

Ibuprofen+Hydrocodone

PCP4: Severe pain expected

400mg 1hr before surgery + continue QID for 4 days10mg/660mg QID for 2 days, then as needed

Hydrocodone

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Local AnestheticsMost commonly used: Amides

1. Low toxicity

2. Relative lack of allergenicity

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Local Anesthetics: LidocaineMost used: 2% lidocaine 1/100’000 epinephrine

Medium-duration anesthetic

Two other forms:

1. 1/50’000 epinephrine

2. With no vasoconstrictor (plain)

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Local Anesthetics: MepivacaineVery similar to lidocaine

Usual dosage: 2% 1/20’000 levonordefrin

Also: 3% plain Short procedures

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Local Anesthetics: ArticaineDiffers structurally from other amides;

1. Better lipid solubility Permeability of the lipid barriers

2. Very short half-life (20min); hydrolyzed 90% by plasma esterases (not by liver)

3. Safer for re-injections in long procedures

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Local Anesthetics: Long-acting anestheticsMaximum postoperative pain: First 12 hours

Most common: Bupivacaine (Marcaine)

Amide; Structurally similar to lidocaine and mepivacaine, More potent and less toxic

High pKa (8.1) Lasts 2-3 times longer

1/200’000 epinephrine Limits ability to affect hemostasis

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Local Anesthetics OverdosageMaximum recommended number of anesthetic capsules:

Lidocaine > Mepivacaine > Bupivacaine > Articaine

Amides Special attention to patients with decreased liver function (chronic alcoholism, hepatitis)

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Local Anesthetics OverdosageHalf-life of lidocaine >2.5 times in hepatic patient

Attention to patients with renal and cardiovascular impairment

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Sedative agentsConscious sedation: Minimally depressed level of consciousness that retains the patient ability to independently and continuously maintain an airway and respond appropriately to physical stimulation or verbal command

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BenzodiazepinesMost effective drugs for dental-related anxiety

Depressant effects on the subcortical levels of the CNS

Anxiolysis and anterograde amnesia

Mechanism: unknown; May have an effect on limbic system and thalamus

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Benzodiazepines: Diazepam (valium)Extremely effective if given orally the night before the surgery (5-10mg)

Advantage for dentistry: Reduces salivary flow, Relaxes skeletal muscles

Main disadvantages: 24 hr half-life for adults, 85 hr for elderly

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Benzodiazepines: Midazolam (Versed)Fast-acting, twice potent as diazepam

Formulated as syrup and inject

Anticonvulsant properties

Excellent muscle relaxant, sedative, amnesic

Should not be combined with other depressants

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Benzodiazepines: Triazolam (Halcion)Short-term hypnotic drug

Orally administered

Fast-acting

Safe and effective for dental procedures (0.25-0.5mg)

Decrease blood pressure by 5 points

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Additional Sedative Anxiolytics: FentanylSynthetic opioid agonist narcotic

Produces analgesia, drowsiness, sedation and euphoria but no amnesia

dose-dependent respiratory depression

Vomiting and nausea (Direct stimulation of dopamine receptors)

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Additional Sedative Anxiolytics: Propofol (Diprivan)IV sedative-hypnotic agent (Alkylphenol)

Ideal for dentistry; Fast-acting and short half-life (2-24 hours)

Rapidly distributed into peripheral tissues (Short clinical effects)

Respiratory depressant trained individuals

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Reversal AgentsFlumazenil Benzodiazepine antagonist

Rapid onset (1-2min), peak 6-10 min

Recommended dose: 200µg every 1-2 min (Max 3mg/hour)

Repeated dose may be required (short half-life)

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Reversal AgentsNaloxone (Narcan) Reversal of Narcotic toxicity

IV, acts after 2 minutes, Last about 45 minutes

Many opioids have longer half-life than naloxone Monitor for re-sedation/ respiratory depression of the patient

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THE END107

Presentations & Public Speaking

Pharmacology in implant dentistry