Update on Medications and Drug Interactions for the

1
Update on Medications and Drug Interactions for
the Pediatric Dentist

• Pamela J. Sims, Pharm.D., Ph. D.
• Professor
• Department of Pharmaceutical, Social and
  Administrative Sciences
• McWhorter School of Pharmacy
• Samford University
• and
• Adjunct Professor
• Department of Pediatric Dentistry
• University of Alabama School of Dentistry

2
Topics

• Pharmacokinetic differences between children and
  adults
• Preventing infection
• Managing behavior
• Interactions with local anesthesia
• Treating pain
• Treating nausea

3
Pediatric Pharmacokinetic Changes

• Absorption
• increased pH
• Variable motility
• Frequent presence of food and/or milk
• Affects rate and extent

4
Distribution

• Body composition
• Primarily lean body mass
• Increased V of water soluble drugs
• increased LD on mg/kg basis
• Decreased V of fat soluble drugs
• decreased LD on mg/kg basis

5
Fluid compartments as a function of age ( of
weight)
6
Distribution

• Altered Protein Binding
• Decreased plasma protein concentrations
• Lower binding capacity
• Decreased affinity

7
Comparative protein binding of certain drugs
8
Metabolism

• Phase I
• Alternative pathways
• Develops slowly
• concentration same, activity reduced
• Affected by diet and drugs
• Inhibitors
• Inducers

• Phase II
• Glucuronidation slowest to develop
• 3-4 years of age

9
Excretion

• Glomerular Filtration
• Neonate
• RBF 5-6 of CO
• 30 of adult
• Tubular Secretion and Reabsorption
• decreased RBF
• Small, undeveloped tubules

• Creatinine not as helpful a predictor of renal
  function as in adults
• still one way of monitoring nephrotoxic drugs

10
Preventing Infection

• Prophylaxis against endocarditis
• Prophylaxis for joint replacement patients
• Prophylaxis for solid organ transplant patients
• Prophylaxis for immunocompromised patients
• Rheumatoid arthritis
• Type I diabetes
• Lupus
• Oncology patients

11
Dental Procedures and Endocarditis Prophylaxis

• Recommended (1997)
• Dental extractions
• Periodontal procedures
• Dental implant placement and reimplantation of
  avulsed teeth
• Endodontic treatment beyond apex
• Subgingival placement of antibiotic fibers and
  strips
• Initial placement of orthodontic bands
• Intraligamentary local anesthetic injections
• Prophylactic cleaning of teeth or implants where
  bleeding is anticipated

• Recommended 2007
• All dental procedures that involve manipulation
  of gingival tissue or the periapical region of
  teeth or perforation of the oral mucosa

12
Dental Procedures and Endocarditis Prophylaxis

• Not Recommended (1997)
• Restorative dentistry
• Nonintraligamentary local anesthetic inj.
• Post placement and buildup intracanal endodontic
  tx.
• Placement of rubber dams
• Postoperative suture removal
• Placement of removable prosthodontic or
  orthodontic appliances
• Taking of oral impressions
• Fluoride treatments
• Taking of oral radiographs
• Orthodontic appliance adjustment
• Shedding of primary teeth

• Not Recommended 2007
• Routine anesthetic injections through noninfected
  tissue
• Taking dental radiographs
• Placement of removable prosthodontic or
  orthodontic appliances
• Adjustment of orthodontic appliances
• Placement of orthodontic brackets
• Shedding of deciduous teeth
• Bleeding from trauma to the lips or oral mucosa

13
Cardiac Conditions Associated with Endocarditis

• High-risk category 1997
• Prosthetic cardiac valves, including
  bioprosthetic and homograft valves
• Previous bacterial endocarditis
• Complex cyanotic congenital heart disease
• Surgically constructed systemic pulmonary shunts
  or conduits
• Moderate-risk category 1997
• Most other congenital cardiac malformations
• Acquired valvar dysfunction (eg, rheumatic heart
  disease)
• Hypertrophic cardiomyopathy
• Mitral valve prolapse with valvar regurgitation
  and/or thickened leaflets

• Highest Risk of Adverse Outcome 2007
• Prosthetic cardiac valve
• Previous infective endocarditis
• Congenital heart disease (CHD)
• Unrepaired cyanotic CHD, including palliative
  shunts and conduits
• Completely repaired congenital heart defect with
  prosthetic material or device, whether placed by
  surgery or by catheter intervention during the
  first six months after the procedure
• Repaired CHD with residual defects at the site
  or adjacent to the site of a prosthetic patch or
  prosthetic device (which inhibit
  endothelialization)
• Cardiac transplantation recipients who develop
  cardiac valvulopathy

14
Cardiac Conditions for which Endocarditis
Prophylaxis Not Recommended

• Negligible-risk category (no greater risk than
  the general population) (1997)
• Isolated secundum atrial septal defect
• Surgical repair of atrial septal defect,
  ventricular septal defect, or patent ductus
  arteriosus (without residua beyond 6 mo)
• Previous coronary artery bypass graft surgery
• Mitral valve prolapse without valvar
  regurgitation
• Physiologic, functional., or innocent heart
  murmurs
• Previous Kawasaki disease without valvar
  dysfunction
• Previous rheumatic fever without valvar
  dysfunction
• Cardiac pacemakers and implanted defibrillators

• 2007
• Except for the conditions listed, antibiotic
  prophylaxis is not longer recommended for any
  other form of CHD
• Prophylaxis is recommended because
  endothelialization of prosthetic material occurs
  within 6 months after the procedure

15
Prophylactic Regimens for Dental, Oral,
Respiratory Tract, or Esophageal Procedures (1997)
16
Prophylactic Regimens for a Dental Procedure 2007
17
Amino-penicillinsBroader Spectrum

• Ampicillin
• Amoxicillin
• 125, 200, 250, 400 mg chewable tablets
• 250, 500 mg capsules
• 500, 875 mg filmcoated tablet
• 125mg/5cc, 200 mg/5cc , 250 mg/5cc, 400 mg /5cc
  suspension
• 50 mg/ml drop
• Bacampicillin (Spectrobid)

• Gram and some Gram - coverage
• More stable in GI tract
• Amoxicillin
• May be taken with food, milk or juice
• Food may delay peak concentrations

18
Cephalosporins

• or other first or second generation oral
  cephalosporin in equivalent adult or pediatric
  dosage.
• Cephalosporins should not be used in an
  individual with a history of anaphylaxis,
  angioedema, or urticaria with penicillins or
  ampicillin

19
First Generation CephalosporinsGood Gram,
Moderate Gram -

• Parenteral Cephalothin, Cefazolin, Cephapirin,
  Cephradine
• Oral Cephalexin (Keflex, Keftab), Cephradine
  (Anspor, Velosef, Eskacef), Cefadroxil (Duricef,
  Ultracef)

• Similar spectrum to ampicillin and amoxicillin
• Not affected by food
• More slowly absorbed in children
• Higher bone penetration than penicillins

20
Oral First Generation Cephalosporins

• Cephalexin Monohydrate (Keflex)
• 250, 500 mg capsule
• 250,500 mg tablet
• 125mg/5cc, 250 mg/5cc oral susp
• Cephalexin HCl Monohydrate (Keftab)
• 250, 500 mg tablet

• Cephradine (Anspor, Velosef, Eskacef)
• 250, 500 mg capsule
• 250 mg/5cc oral susp
• Cefadroxil (Duricef)
• 500 mg capsule
• 1 g tablet
• 250 mg/5cc, 500 mg/5cc oral susp

21
Second Generation CephalosporinsIncreased
activity against Gram-

• Parenteral Cefamandole, Cefmetazole, Cefonicid,
  Cefotetan, Cefoxitin, Cefuroxime
• Oral Cefaclor(Ceclor, Ceclor CD),
  Cefprozil(Cefzil), Cefuroxime Axetil(Ceftin),
  Loracarbef(Lorabid)

22
Oral Second Generation Cephalosporins

• Cefaclor (Ceclor)
• 250, 500 mg capsules
• 125/5, 187/5, 250/5 and 375/5 susp and chewables
• 20-40 mg/kg/day
• Cefaclor (Ceclor CD)
• 375, 500 mg extended release tablets
• 375-500 mg q 12 h

• Cefprozil (Cefzil)
• 250,500 mg tablets
• 125,250/5cc susp
• 250-500 mg q 12 h
• Children 7.5 - 10 mg/kg q 12 h
• Cefuroxime axetil (Ceftin)
• 125, 250, 500 mg tablets
• 125/5cc susp
• 125-500 mg bid
• Children 125-250 mg bid

23
Drug-related Concerns of Penicillin and
Cephalosporin Antibiotics

• Allergy
• Cross-sensitivity between penicillins and
  cephalosporins. If a person is truly allergic to
  penicillin, 10-25 patients will be allergic to
  cephalosporins. If a person is allergic to
  cephalosporins, the patient will generally be
  allergic to penicillins.
• Increased bleeding in patients taking warfarin
  (Coumadin)
• Antibiotics can decrease local flora responsible
  for synthesis of Vitamin K (Vitamin K is the
  antagonist to warfarin and warfarin exerts its
  anticoagulant effects by inhibition of Vitamin K
  dependent clotting factors)

24
Drug-related Concerns of Penicillin Antibiotics

• Decreased efficacy of oral contraceptives
• Todays low dose BCPs require endogenous GI
  flora to conjugate hormone to allow absorption.
  If bacteria are absent, hormone which prevent egg
  implantation will be absent. Patients utilizing
  oral contraceptive agents should use another form
  of BC during the entire cycle in which
  antibiotics were administered.

25
Macrolides

• Azithromycin (Zithromax)
• 250 mg, Z-pak (250 mg), 500, Tri-pak (500 mg) 600
  mg tablet
• 100 mg/5cc, 200 mg/5cc susp
• 1 g susp
• Clarithromycin (Biaxin)
• 250, 500 mg tablet
• 125 mg/5cc, 250 mg/5cc susp
• 500 mg XL

• Erythromycin
• Base (E-mycin, Ery-Tab, Ilotycin, PCE)
• Estolate (Ilosone)
• Ethylsuccinate (EES)
• Stearate (Erythrocin)
• Troleandomycin (Tao)
• 250 mg capsules

26
Drug-related Concerns of Macrolides

• Active Metabolite
• Clarithromycin
• GI upset
• Erythromycin
• Hepatic Enzyme Inhibition
• Erythromycin
• Clarithromycin

27
Drug-related Concerns of Macrolides

• Hepatic Enzyme Inhibition
• Increases blood levels
• Increases risk of toxicity
• Decreases clearance

• Cisapride (Propulcid)
• Phenytoin (Dilantin)
• Carbamazepine (Tegretol)
• Cyclosporine
• Warfarin (Coumadin)
• Corticosteroids
• Theophylline
• Benzodiazepines
• Digoxin

28
Lincosamides

• Lincomycin (Lincocin)
• 500 mg capsules
• Clindamycin (Cleocin)
• (HCl) 75, 150, 300 mg capsules
• (Palmitate) 75mg/5cc solution

• ADR
• Pseudomembranous Colitis (Clostridium difficile)

29
Patients at increased risk of hematogenous total
joint infection

• Immunocompromised/Immunosuppressed
• Inflammatory arthropathies, rheumatoid arthritis,
  systemic lupus
• disease, drug or radiation-induced

• Insulin dependent diabetics
• First 2 years post-replacement
• Previous joint infections
• Malnourishment
• Hemophilia

30
Higher Incidence of Bacteremic Dental Procedures

• Dental Extractions
• Periodontal procedures
• Dental implant placement and reimplantation of
  avulsed teeth
• Endodontic beyond the apex

• Initial orthodontic bands/not brackets
• Intraligamentary local anesthetic injections
• Prophylactic cleaning of teeth or implants where
  bleeding is anticipated

31
Suggested Prophylaxis Regimens

• Patients not allergic to penicillin
• Cephalexin, Cephradine or Amoxicillin
• 2 gm orally 1 hour prior to procedure

• Patients allergic to penicillin
• Clindamycin 600 mg orally 1 hour prior to the
  dental procedure.

32
Fen-Phen, Pondimin or Redux PatientsFenfluramine
or dexfenfluramine w or w/o phentermine

• If a patient needs to undergo a dental procedure
  for which the AHA recommends prophylaxis against
  endocarditis, patient needs an echo.

• If no echo must prophylax
• If valvar disease discovered, must prophylax

33
Oral Infections

• Acute endodontic abscess
• Augmentin
• Clindamycin
• Acute periodontal infections
• Augmentin
• Gingival abscess
• Amoxicillin
• ANUG
• Metronidazole

• Localized juvenile periodontitis
• Doxycycline and scale and root planing
• Augmentin
• Can add metronidazole
• Ciprofloxacin
• Abscessed teeth to be extracted
• Augmentin
• Clindamycin
• Ceftin
• Chlorhexidine mouthwash

34
Antibiotics

• Augmentin
• Amoxicillin/clavulanic acid
• 20 40 mg/kg/day amoxicillin in divided doses q
  8 h
• 20 45 mg/kg/day amoxicillin in divided doses q
  12 h
• Use lowest doses of clavulanic acid
• GI ADE

• For oral susp
• For bid 200/28.5, 400/57, 600/42.9
• 125/31.5, 250/62.5
• Chewable
• For bid 200/28.5, 400/57
• 125/31.25, 250/62.5
• Tablet
• 250/125, 500/125
• For bid 875/125

35
Tetracyclines

• Demeclocycline (Declomycin)
• 150 mg capsule
• 150, 300 mg tablet
• Doxycycline (Vibramycin)
• 50,100 mg capsule, tablet
• 25 mg/5cc oral susp
• 50 mg/5cc syrup

• Minocycline (Minocin)
• 50, 100 mg tablet, capsule
• 50 mg/5cc susp
• Oxytetracycline
• 250 mg capsule
• Tetracycline
• 100, 250, 500 mg capsule
• 125 mg/5cc susp
• 250, 500 mg tablet

36
Drug-related Concerns of Tetracyclines

• Bacteriostatic
• Photosensitivity
• Chelation with any di or trivalent cation
• antacids
• mineral supplements (Ca, Fe, Mg)
• Dairy products
• Sucralfate (Carafate)
• Stains teeth

37
Quinolones

• Ciprofloxacin (Cipro)
• 100, 250, 500, 750 mg tablet
• 5, 10 g/100 mg susp
• 20-30 mg/kg/day in two divided doses
• Cinoxacin (Cinobac)
• 250, 500 mg capsules
• Enoxacin (Penetrex)
• 200, 400 mg tablet
• Gatifloxacin
• 20, 400 mg tablets
• Grepafloxacin (Raxar)
• 200 mg tablet
• Levafloxacin (Levaquin)
• 250, 500 mg tablet

• Lomefloxacin (Maxaquin)
• 400 mg tablet
• Moxifloxacin
• 400 mg tablets
• Norfloxacin (Noroxin)
• 400 mg tablet
• Ofloxacin (Floxin)
• 200, 300, 400 mg tablet
• Sparfloxacin (Zagam)
• 200 mg tablet
• Trovafloxacin (Trovan)
• 100, 200 mg tablets

38
Drug-related Concerns of Quinolones

• Primarily Gram - spectrum
• Resistance develops quickly
• All contraindicated in pregnant and nursing women
• All cause photosensitivity

39
Metronidazole

• Enters cells which contain nitroreductase, where
  its nitro group is reduced
• Unstable intermediate compounds bind to DNA and
  inhibit synthesis causing cell death
• Active against anaerobes and protozoa

• Flagyl
• Active against anaerobes and protozoa
• 250, 500 mg tablet
• 750 mg extended release tablet
• 375 mg capsule
• Bacterial vaginosis
• 500 mg bid for 7 days
• 2 g
• Giardiasis
• 250 mg tid for 7 day

40
Drug-related Concerns of Metronidazole

• Increased Metronidazole levels
• Cimetidine
• Disulfiram-like reaction
• Ethanol
• Acute psychosis or confusional state
• Disulfiram

• Hepatic Enzyme Inhibition
• Anticoagulants
• Hydantoins
• Decreased renal excretion
• Lithium

41
Behavior Management

• Antihistamines
• Anxiolytic Antihistamines
• Anxiolytic Benzodiazepines
• Sedative/Hypnotic Benzodiazepines
• Anesthetic Benzodiazepines

42
ADA Old Definitions

• Conscious Sedation
• A controlled, pharmacologically induced,
  minimally depressed level of consciousness that
  retains the patients ability to maintain a
  patent airway independently and continuously and
  respond appropriately to physical stimulation
  and/or verbal command.
• Drugs, dosages and techniques used should carry a
  margin of safety which is unlikely to render the
  child non-interactive and non-arousable.
• Deep Sedation
• A controlled, pharmacologically-induced state of
  depressed consciousness from which the patient is
  not easily aroused which may be accompanied by a
  partial loss of protective reflexes, including
  the ability to maintain a patent airway
  independently and/or respond purposefully to
  physical stimulation or verbal commands.
• General Anesthesia
• A controlled, state of unconsciousness,
  accompanied by a partial or complete loss of
  protective reflexes, including ability to
  independently maintain an airway or respond
  purposefully to physical stimulation or verbal
  command.

43
ADA New Definitions

• Minimal Sedation
• (Previously associated with anxiolysis and
  conscious sedation)
• A minimally depressed level of consciousness that
  retains the patients ability to independently
  and continuously maintain an airway and respond
  appropriately to physical stimulation or verbal
  command and that is produced by a pharmacological
  or non-pharmacological method or a combination
  thereof. Although cognitive function and
  coordination may be modestly impaired,
  ventilatory and cardiovascular functions are
  unaffected.
• Note In accord with this particular definition,
  the drug(s) and/or techniques used should carry a
  margin of safety wide enough to render unintended
  loss of consciousness unlikely. Further,
  patients whose only response is reflex withdrawal
  from repeated painful stimuli would not be
  considered to be in a state of minimal sedation.
• When the intent is minimal sedation for adults,
  the appropriate dosing of enteral drugs is not
  more than the maximum recommended dose of a
  single drug that can be prescribed for
  unmonitored home use.

44
ADA New Definitions

• Moderate sedation
• A drug-induced depression of consciousness during
  which patients respond purposefully to verbal
  commands, either alone or accompanied by light
  tactile stimulation. No interventions are
  required to maintain a patent airway, and
  spontaneous ventilation is adequate.
  Cardiovascular function is usually maintained.
• Note In accord with this particular definition,
  the drugs and/or techniques used should carry a
  margin of safety wide enough to render unintended
  loss of consciousness unlikely. Repeated dosing
  of an agent before the effects of previous dosing
  can be fully appreciated may result in a greater
  alteration of the state of consciousness than is
  the intent of the dentist. Further, a patient
  whose only response is reflex withdrawal from a
  painful stimulus is not considered to be in a
  state of moderate sedation.

45
ADA New Definitions

• Deep sedation
• A drug-induced depression of consciousness during
  which patients cannot be easily aroused but
  respond purposefully following repeated or
  painful stimulation. The ability to
  independently maintain ventilatory function may
  be impaired. Patients may require assistance in
  maintaining a patent airway, and spontaneous
  ventilation may be inadequate. Cardiovascular
  function is usually maintained.
• General anesthesia
• A drug-induced loss of consciousness during which
  patients are not arousable, even by painful
  stimulation. The ability to independently
  maintain ventilatory function is often impaired.
  Patients often require assistance in maintaining
  a patent airway, and positive pressure
  ventilation may be required because of depressed
  spontaneous ventilation or drug-induced
  depression of neuromuscular function.
  Cardiovascular function may be impaired.

46
ADA New Definitions

• Note Because sedation and general anesthesia
  are a continuum, it is not always possible to
  predict how and individual patient will respond.
  Hence, practitioners intending to produce a given
  level of sedation would be able to diagnose and
  manage the physiologic consequences (rescue) for
  patients whose level of sedation becomes deeper
  than initially intended.
• For all levels of sedation, the practitioner must
  have the training, skills and equipment to
  identify and manage such an occurrence until
  either assistance arrive (emergency medical
  service) or the patient returns to the intended
  level of sedation without airway or
  cardiovascular complications.
• All areas in which local anesthesia and sedation
  are being used must be properly equipped with
  suction, physiologic monitoring equipment, a
  positive pressure oxygen delivery system suitable
  for the patient being treated and emergency
  drugs. Protocols for the management of
  emergencies must be developed and training
  programs held at frequent intervals.

47
Levels of Sedation
48
ASA Physical Status Scale

• Class I Normal Healthy individual
• Class II Mild systemic disease
• (eg, controlled diabetes or hypertension)
• Class III Severe systemic disease that is not
  incapacitating
• (eg, COPD, mental retardation, hemophilia)
• Class IV Incapacitating disease that is a
  constant threat to life
• (eg, unstable angina or renal failure)
• Class V Moribund patient not expected to survive
  24 hours
• Class E Emergency

49
Considerations for the Pediatric Patient

• Patients age
• Level of cognitive and coping skills
• ASA Class
• I or II candidate for level 1,2, 3 or 4
• III or IV should be treated in a hospital setting

50
Antihistamines

• Diphenhydramine (Benadryl)
• Dosage forms
• Capsules 25, 50 mg
• Elixir 12.5 mg/tsp
• Dose
• 5 mg/kg/day
• lt5 yo 12.5-25 mg
• gt5 yo 25-50 mg

• Advantages
• drowsiness
• dry mouth
• low respiratory depression
• no dependence
• Disadvantages
• paradoxical excitement

51
Anxiolytic Antihistamines

• Hydroxyzine
• Atarax (HCl)
• tablets 10,25,50,100 mg
• syrup 2 mg/ml (10mg/tsp)
• Vistaril (Pamoate)
• capsules 25,50,100 mg
• susp 5 mg/ml (25mg/tsp)
• Inj 25 mg/ml as HCl

• Anxiety
• 50 - 100 mg qid
• Children 12.5 - 25 mg qid
• Sedation
• 50 - 100 mg
• Children 0.6 mg/kg
• Pre-operative adjunct
• 50 - 100 mg
• Children 1.1 mg/kg

52
Hydroxyzine

• Advantages
• Sedative
• Dry mouth
• H1 antagonist in GI tract
• No dependence
• Antagonizes vasopressor effects of epinephrine
• No respiratory depression
• May protect from respiratory depression of
  meperidine
• No effect on QT interval

• Disadvantages
• No IV dosage form

53
Benzodiazepines

• Controlled substance
• potential for abuse and dependence
• Anterograde amnesia
• Muscle relaxant
• Potentiated by enzyme inhibitors

• Reversal agent available
• Flumazenil (Romazicon)
• Good margin of safety
• Respiratory depression
• Reduce dose with opiates

54
Anxiolytic Benzodiazepines
55
Anxiolytic Benzodiazepines

• Lorazepam
• Ativan
• tablets 0.5,1,2 mg
• Lorazepam Intensol
• conc. oral sol. 2 mg/ml, 30 ml dropper

• Adults
• 2-4 mg
• 0.5 - 1 mg tid
• increase dose as needed
• Pediatric dose
• 0.05 mg/kg
• Doses gt 0.09 mg/kg produce inc. ataxia w/o inc.
  sedation
• Safety of oral lorazepam in children lt 12 yo not
  established

56
Anxiolytic Benzodiazepines

• Lorazepam
• Ativan
• Intermediate onset
• No active metabolites
• Short acting
• 10-20 hour half-life
• sublingual absorption more rapid than oral

57
Anxiolytic Benzodiazepines

• Diazepam
• Valium
• 2,5,10 mg tablets
• 5 mg/5ml solution
• 5 mg/ml Intensol sol
• 5 mg/ml inj

• Adult
• 5-10 mg
• Pediatric
• 0.2-0.3 mg/kg 90 minutes prior to procedure

58
Anxiolytic Benzodiazepines

• Diazepam
• History of use in children
• Rapid onset
• Active metabolites
• desmethyldiazepam
• temazepam
• oxazepam
• Long Acting
• 20-80 hr half-life

59
Anesthetic Benzodiazepines

• Midazolam
• Versed
• 1 mg/ml inj
• 5 mg/ml inj
• 2 mg/ml syrup
• peds 2-16 yo only
• Adult
• IM 0.07-0.08 mg/kg up to 1 hr before procedure
• IV dilute 1mg/ml with NaCl or D5W and administer
  slowly

• Pediatric
• IM 0.1-0.15 mg/kg, 30-60 min prior
• IV
• lt5 yo0.05-0.1 mg/kg
• 5-12 yo 0.025-0.05 mg/kg
• gt12 yo 1-5 mg, titrate slowly over 10-20 min
• Oral
• 0.2-0.4 mg/kg, 30-45 min prior
• Rectal
• 0.3 mg/kg
• Nasal
• 0.2-0.3 mg/kg

60
Drug-related Effects of Benzodiazepines

• Additive effects with other CNS depressants
• Amnesia
• Paradoxical reactions
• Flumazenil (Romazicon)Benzodiazepine Antagonist
• 0.01 mg/kg (max 0.2 mg) over 15 seconds, may
  repeat after 45 seconds

61
Drug Interactions of Benzodiazepines

• Effect increased by other CNS depressants
• Effect increased by enzyme inhibitors
• Cimetidine (Tagamet), Macrolides (Erythromycin,
  Biaxin), Oral contraceptives, Disulfiram
  (Antabuse), Isoniazid
• Effect decreased by enzyme inducers
• Rifampin, Smoking, Phenytoin
• Effect antagonized by CNS stimulants
• Theophylline

62
Sedative/Hypnotic

• Chloral Hydrate (Noctec)
• 250, 500 mg capsules
• 250, 500 mg/5cc syrup
• Adults
• Sedative 250 mg tid
• Hypnotic 500-1000 mg 15-30 minutes before
  procedure
• Pediatric
• Sedative 25 mg/kg/day up to 500 mg single dose
• Hypnotic 50 mg/kg/day up to 1 g single dose
• Doses of 75 mg/kg uses for dental sedation with
  NO

63
Chloral Hydrate

• Good margin of safety
• Low respiratory depression
• No anxiolytic properties
• Agitation before sedation and after

• Controlled substance
• abuse and dependence
• No reversal agent

64
Interactions with Local Anesthesia

• Patients treated for ADD/ADHD
• Patients treated for narcolepsy
• Patients treated for obesity
• Patients treated for depression
• Patients treated for enuresis

• Stimulants
• Antidepressants
• Antipsychotics
• Beta-Blockers
• Monoamine Oxidase Inhibitors (MAOIs)

65
Dental Issues

• Local anesthesia
• Contents of a Local Anesthetic Cartridge
• Local Anesthetic
• Esters
• Amides
• Vasoconstrictor
• Preservative
• Sodium Metabisulfite
• Sodium Chloride and Sterile Water

66
Systemic side effects

• Local anesthetic
• CNS excitation
• seizures
• depression
• CV excitation
• arrhythmias

• Vasoconstrictor
• Increase heart rate
• Increase blood pressure

67
Distribution and Activity of Receptors
68
ADD/ADHD Treatment in Alabama insured by The Oath
69
Psychostimulants for ADD/ADHD and Narcolepsy

• Methylphenidate
• Standard methylphenidate
• Ritalin SR
• Concerta
• Coated with immediate release
• contains an osmotic pump providing gradual
  release over 10 hours
• produces slightly ascending serum concentrations
• tablet remains intact and leaves GI tract as an
  empty shell
• take qd

• Amphetamines
• Dextroamphetamine
• Adderall
• Dexedrine Spansules
• Pemoline (Cylert)

70
Vasoconstrictor Interactions with CNS Stimulants

• Decongestants
• Diet aids
• Psychostimulants
• Methylphenidate
• Ritalin
• Concerta
• Amphetamines
• d-Amphetamine
• Adderall
• Bronchodilators
• Albuterol
• Theophylline

• Additive CNS stimulation with other
  sympathomimetic agents

71
Antidepressants

• ADD/ADHD
• Atomoxetine (Strattera)
• Anxiety
• Social Phobia
• Panic Disorder
• OCD
• Depression
• Enuresis
• Sleep Disorders
• Premenstrual Dysphoric Disorder

72
Vasoconstrictor Interactions with Antidepressants

• Antidepressants
• Block reuptake of norepinephrine and/or serotonin

• Interaction
• Increased and prolonged effects on receptors
• Increased alpha and beta stimulation
• increased heart rate
• increased cardiac contractility
• increased peripheral resistance

73
Interacting Antidepressants

• Tricyclic Antidepressants
• Tertiary Amines
• Amitriptyline (Elavil)
• Clomipramine (Anafranil)
• Doxepin (Adapin, Sinequan)
• Imipramine (Tofranil)
• Trimipramine (Surmontil)
• Secondary Amines
• Amoxapine (Asendin)
• Desipramine (Norpramin, Pertofrane)
• Maprotiline (Ludiomil)
• Nortriptyline (Aventyl, Pamelor)
• Protriptyline (Vivactil)

• Miscellaneous
• Amoxapine (Asendin)
• Venlaxafine (Effexor)
• Mirtazapine (Remeron)
• Selective norepinephrine reuptake inhibitors
• Atomoxetine (Strattera)

74
Vasoconstrictor Interactionswith Antipsychotics
and Antiemetics

• blockade of alpha adrenergic receptors
• orthostatic hypertension
• reflex tachycardia
• potentiation of antihypertensives

• predominance of beta adrenergic effects
• increased heart rate
• increased cardiac contractility
• peripheral vasodilation

75
Interacting Antipsychotics and Antiemetics

• Phenothiazines
• Acetophenazine (Tindal)
• Chlorpromazine (Thorazine)
• Fluphenazine (Prolixin)
• Mesoridazine (Serentil)
• Perphenazine (Trilafon)
• Prochlorperazine (Compazine)
• Promazine (Sparine)
• Promethazine (Phenergan)
• Thioridazine (Mellaril)
• Trifluoperazine (Stelazine)

• Thiothixene (Navane)
• Haloperidol (Haldol)
• Clozapine (Clozaril)
• Loxapine (Loxitane)
• Molindone (Moban)
• Risperdal (Risperidone)
• Zyprexa (Olanzapine)
• Seroquel (Quetiapine)

76
Beta-adrenergic blockers

• Hypertension
• Arrhythmias
• Mitral Valve Prolapse
• Migraine
• Performance anxiety
• Stage fright

77
Vasoconstrictor Interactions with
Beta-adrenergic Antagonists

• Blockade of beta 1 and beta 2 receptors
• Causes unopposed alpha peripheral vasoconstriction

• Initial hypertensive episode followed by
  bradycardia

78
Interacting Beta-adrenergic Antagonists

• Non-selective beta antagonists
• Carteolol (Cartrol)
• Nadolol (Corgard)
• Penbutolol (Levatol)
• Pindolol (Visken)
• Propranolol (Inderal)
• Sotalol (Betapace)
• Timolol (Blocadren)
• Labetalol (Trandate, Normodyne)

• Selective beta 1 antagonists
• Acebutolol (Sectral)
• Atenolol (Tenormin)
• Betaxolol (Kerlone)
• Bisoprolol (Zebeta)
• Metoprolol (Lopressor)

79
Monoamine Oxidase Inhibitors (MAOIs)

• Social Phobia
• Panic Disorder
• Depression

80
Monoamine Oxidase Inhibitors (MAOIs)

• Social Phobia
• Panic Disorder
• Depression
• Parkinsons

• Antidepressants
• Isocarboxazid (Marplan)
• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Selegiline (Emsam)
• Transdermal 6, 9, 12 mg/24h)
• Antiparkinson
• Selegiline
• Eldepryl 5 mg capsule
• Carbex 5 mg tablet
• Zelapar 1.25 mg orally disintegrating tablet

81
Vasoconstrictors and MAOIs

• MAOIs potentiate indirect or mixed-acting
  sympathomimetic substances
• by inhibiting metabolism of MAO B
• severe headache, hyperpyrexia, hypertension

• Interaction with direct-acting agents is minimal
• EMSAM inhibits MAO A and therefore is
  contraindicated with epinephrine and levonordefrin

82
Sympathomimetic Agents

• Direct acting-directly stimulates receptor
• epinephrine
• norepinephrine
• levonordefrin
• isoproterenol
• dopamine
• methoxamine
• phenylephrine

• Indirect-acting-releases norepi from nerve
  terminal
• tyramine
• amphetamine
• methamphetamine
• Mixed-acting-both direct and indirect actions
• ephedrine

83
Treating Pain

• Mild to moderate
• Acetaminophen
• Aspirin
• NSAIDs
• Moderate
• Acetaminophen/Codeine
• Moderate to severe
• Acetaminophen/Hydrocodone
• Acetaminophen/Oxycodone
• Meperidine

84
Acetaminophen Pediatric Dosing
85
Acetaminophen

• Not NSAID
• not anti-inflammatory
• no cross-hypersensitivity
• Pregnancy
• generally safe
• Lactation
• generally safe

• Central action on prostaglandins
• no renal effects
• safest in pregnancy
• safest in renally compromised
• no GI effects
• no platelet effects
• safest with anticoagulants

86
AcetaminophenAdverse effects

• Hepatotoxicity
• overdose
• 10-15 g
• children less susceptible
• chronic alcoholics more susceptible
• not a contraindication
• Chronic toxicity
• Adults 3 g per day

87
Aspirin Dosages in Children
88
Ibuprofen Pediatric Dosing
89
Nonselective NSAIDs

• Acetic Acids
• Diclofenac (Voltaren)
• Indomethacin
• Nabumetone (Relafen)
• Sulindac (Clinoril)
• Tolmetin (Tolectin)
• Oxicams
• Piroxicam (Feldene)
• Meloxicam (Mobic)
• Pyranocarboxylic acid
• Etodolac (Lodine)
• Pyrrolizine carboxylicacid
• Ketorolac (Toradol)

• Propionic Acids
• Fenoprofen (Nalfon)
• Flurbiprofen (Ansaid)
• Ibuprofen (Motrin)
• Ketoprofen (Orudis)
• Naproxen /Naproxen Na (Anaprox, Naprosyn)
• Oxaprozin (Daypro)
• Fenamates
• Meclofenamate
• Mefenamic acid (Ponstel)

90
Nonselective NSAIDs GI Effects

• Nausea
• Most 3-9
• Ketorolac 12
• Tolmetin 11
• Diarrhea
• Ibuprofen , Piroxicamlt3
• Diclofenac, Etodolac, Flurbiprofen, Ketorolac,
  Oxaprozin, Sulindac, Tolmetin 3-9
• Nabumetone 14

• Dyspepsia
• Most 3-9
• Etodolac 10
• Ketoprofen 11.5
• Ketorolac 12
• Nabumetone 13
• Stomatitis
• Most 1-3
• Additive effects with aspirin
• GI toxicity

91
Nonselective NSAIDs Adverse drug effects and
interactions

• Inhibits platelet aggregation
• reversibly
• normal function when drug eliminated

• Potentiates the effects of anticoagulants
• Warfarin (Coumadin)
• Anisindione (Miradon)
• Dicumarol
• Potentiates the effects of other antiplatelet
  drugs
• Dipyridamole (Persantine)
• Ticlodipine (Ticlid)
• Anagrelide (Agrylin)
• Clopidogrel (Plavix)
• Cilostazol (Pletal)

92
NSAIDs Adverse Effects

• Cross-hypersensitivity with aspirin allergy
• Contraindication
• urticaria, asthma, nasal polyps

93
NSAIDsAdverse Drug Effects and Drug Interactions

• Caution with reduced renal function
• Do not prescribe for renal transplant patients

• Lithium
• Increased toxicity
• Methotrexate
• Increased toxicity
• Cyclosporine
• Increased nephrotoxicity

94
NSAIDs Drug Interactions

• Antihypertensives
• decrease effect
• ACE Inhibitors
• Benazepril (Lotensin)
• Captopril (Capoten)
• Enalapril (Vasotec)
• Fosinopril (Monopril)
• Lisinopril (Prinivil, Zestril)
• Moexipril (Univasc)
• Quinapril (Accupril)
• Ramipril (Altace)
• Trandolapril (Mavik)

• Angiotensin II Receptor Antagonists
• Candesartan (Atacand)
• Eprosartan (Teveten)
• Irbesartan (Avapro)
• Losartan (Cozaar)
• Telmisartan (Micardis)
• Valsartan (Diovan

95
NSAIDs Drug Interactions

• Beta Blockers
• Acebutolol (Sectral), Atenolol (Tenormin),
  Betaxalol (Kerlone) Bisoprolol (Zebeta),
  Metoprolol (Lopressor, Toprol XL),
• Carteolol (Cartrol), Nadolol (Corgard),
  Penbutolol (Levatol), Pindolol (Visken),
  Propranolol (Inderal) Sotalol (Betapace), Timolol
  (Blocadren), Labetalol (Normodyne, Trandate)

96
NSAIDs Drug Interactions

• Antihypertensives
• decrease effect
• Loop Diuretics
• Furosemide (Lasix), Bumetanide (Bumex),
  Ethacrynic acid (Edecrin), Torsemide (Demadex)

• Thiazide Diuretics
• Bendroflumethiazide (Naturetin), Benzthiazide
  (Exna), Chlorothiazide (Diuril),
  Hydrochlorothiazide (Hydrodiuril, Esidrix,
  Oretic), Hydroflumethiazide (Diucardin, Saluron),
  Indapamide (Lozol), Methyclothiazide (Enduron,
  Aquatensen), Metolazone (Zaroxolyn, Mykrox),
  Polythiazide (Renese), Quinethazone, (Hydromox)
  Trichlormethiazide (Metahydrin, Naqua, Diurese)

97
NSAIDs Drug Interactions

• Cimetidine
• Increased NSAIDs effect/toxicity
• Probenecid
• Increased NSAIDs effect/toxicity

98
Codeine Combinations with Acetaminophen (CIII)

• Tablets (300 mg)
• Tylenol 2,3,4
• Capsules (325 mg)
• Phenaphen 3,4
• Fioricet w codeine
• 50 mg Butalbital
• 40 mg Caffeine

• Codeine Dose
• 2 15 mg
• 3 30 mg
• 4 60 mg
• Acetaminophen Dose
• 300 - 325 mg
• Codeine Sensitivity
• Nausea most prevalent

99
Codeine Combinations with Acetaminophen (CV)

• 12 mg codeine/ tsp (5cc)
• 120 mg acetaminophen/ tsp (5cc)
• Adult dose 15 ml (1 tablespoonful q 4 h)

• Capital w/Cod susp
• Tylenol w/Cod elixir
• Acetaminophen w/cod sol (various manuf)

100
Codeine Combinations with Acetaminophen (CV)

• Analgesic
• 0.5 1 mg codeine/kg/dose every 4-6 hours
• 10-15 mg/kg/dose acetaminophen every 4-6 hours

• 3-6 yr
• 5 ml (1 tsp)
• 7-12 yr
• 10 ml (2 tsp)
• gt12 yr
• 15 ml (3 tsp)

101
Hydrocodone Combinations with Acetaminophen (CIII)

• 2.5/108 Solution
• Hycet
• 2.5/167 Elixir
• Lortab
• 2.5/500 tablets
• Lortab 2.5/500
• 5/325
• Norco
• 5/400
• Zydone
• 5/500 tablets
• Co-Gesic, Duocet, Hy-Phen, Lorcet, Lortab 5/500,
  Anexsia 5/500 Panacet 5/500, Vicodin

• 5/500 capsules
• Bancap HC, Ceta-Plus, Dolacet, Hydrocet,
  Hydrogesic, Margesic H, Lorcet HD, Stagesic,
  T-Gesic, Zydone
• 7.5/500 Tablets
• Lortab 7.5/500
• 7.5/650 Tablets
• Anexsia 7.5/650, Lorcet Plus
• 7.5/750 Tablets
• Vicodin ES
• 10/650 Tablets
• Lorcet 10/650

102
Hydrocodone

• Children lt 50 kg
• 0.2 mg/kg every 4-6 hours
• Children gt 50 kg
• 5-10 mg every 4-6 hours

103
Meperidine (CII)

• Meperidine (Demerol)
• 50, 100 mg tablets
• 50 mg/5cc syrup
• 50 - 150 mg q 3-4 h
• Children
• 1-1.5 mg/kg/dose q 3-4 h

• Meperidine/Promethazine (Mepergan Fortis)
• 50 mg Meperidine
• 25 mg Promethazine
• 1 q 4-6 h

104
Contraindications of Meperidine

• Patients taking MAOIs within 14 days
• Antidepressants
• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Antiparkinson
• Selegiline (Eldepryl)
• Hyperphenylalaninemia

105
Meperidine Drug InteractionsSerotonin Syndrome

• Serotonergic Drugs
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Fluvoxamine (Luvox)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Escitalopram (Lexipro)

• Cognitive-behavioral
• Confusion/ disorientation (51)
• Agitation/irritability (34)
• Autonomic Nervous System
• Hyperthermia (45)
• Diaphoresis (45)
• Sinus Tachycardia (36)
• Hypertension (35)
• Neuromuscular
• Dilated pupils (28)
• Tachypnea (26)
• Nausea (23)

106
Opioids

• Phenanthrenes
• Codeine
• Hydrocodone
• Oxycodone
• Morphine
• Hydromorphone
• Levorphanol

• Phenylpiperidines
• Meperidine
• (Fentanyl)
• Diphenylheptanes
• Propoxyphene
• (Methadone)

107
Opioid Pharmacologic Effects

• CNS Effects
• Analgesia
• Euphoria
• Sedation
• Respiratory Depression
• Cough Suppression
• Miosis
• Truncal Rigidity
• Nausea and Vomiting

• CV System
• Hypotension
• GI Tract
• Constipation
• Biliary Tract
• Colic
• Genitourinary Tract
• Urinary Retention
• Decreased Renal Function

108
Warnings for Opioids

• Asthma and Other Respiratory Conditions
• Use with extreme caution with acute asthma,
  bronchial asthma, COPD or cor pulmonale
• Hypotensive Effect
• Increased with coadministration of phenothiazines
  or general anesthesia

109
Opioid Drug InteractionsDental Implications

• Phenothiazines
• Acetophenazine (Tindal)
• Chlorpromazine (Thorazine)
• Fluphenazine (Prolixin)
• Mesoridazine (Serentil)
• Perphenazine (Trilafon)
• Prochlorperazine (Compazine)
• Promazine (Sparine)
• Promethazine (Phenergan)
• Thioridazine (Mellaril)
• Trifluoperazine (Stelazine)

• Additive Pharmacologic Effects
• CNS Depression
• Respiratory Depression
• Orthostasis

110
Inhibitors of CYP3A4 increase opioid effects

• Antifungals
• Fluconazole
• Itraconazole
• Ketoconazole
• Miconazole
• Metronidazole
• Macrolides
• Erythromycin
• Clarithromycin

111
Narcotic Antagonist

• Naloxone (Narcan)
• 0.4 mg/ml, 1 mg/ml
• For OD
• 0.4 - 2 mg IV q 2-3 minutes
• Partial reversal
• 0.1-0.2 mg IV q 2-3 minutes repeat every 1-2 hrs
• Children
• 0.01 mg/kg IV, may repeat q 2-3 min

112
Treating Nausea
113
Anti-emetics

• Hydroxyzine
• Atarax, Vistaril
• Phenothiazines
• Chlorpromazine
• Perphenazine
• Trilafon
• Prochlorperazine
• Compazine
• Promethazine
• Phenergan
• Triflupromazine
• Vesprin
• Triethylperazine
• Torecan

• Metoclopramide
• Reglan
• Anticholinergics
• Cyclizine
• Marezine
• Meclizine
• Antivert, Bonine
• Dimenhydrinate
• Dramamine
• Trimethobenzamide
• Tigan

114
Anti-emetics

• 5-HT3 Receptor Antagonists
• Dolasetron
• Anzemet
• Gransetron
• Kytril
• Ondansetron
• Zofran

• Droperidol
• Inapsine
• Dronabinol
• Marinol

115
Anti-emetics

• Hydroxyzine
• 25-100 mg
• Children 1.1 mg/kg
• Promethazine
• 12.5 - 25 mg q 4-6 h
• Children 0.25 - 0.5 mg/kg q 4-6 h
• do not adm lt 2 yo

116
Phenothiazines

• Prochlorperazine
• Compazine
• 5, 10, 25 mg tablets
• 10, 15, 30 mg capsules sustained release
• 5 mg/5 ml syrup
• 5 mg/ml inj
• 2.5, 5, 25 mg supp
• Oral
• 5-10 mg 3-4 times daily
• Rectal
• 25 mg bid
• IV
• 5-10 mg 1-2 minutes before induction

• Perphenazine
• Trilafon
• 2, 4, 8, 26 mg tablets
• 16 mg/5 ml conc.
• 5 mg/ml inj
• Triethylperazine
• Torecan
• 10 mg tablets
• 5 mg/ml inj
• IM 2 ml, tid
• Oral 10 30 mg daily in divided doses
• Triflupromazine
• Vesprin
• 10, 20 mg/ml inj
• IM 5- 15 mg q 4 h
• IV 1 mg, up to 3 mg daily

117
5-HT3 Receptor Antagonists

• Ondansetron
• Zofran
• 4, 8, 24 mg tablets
• 4 mg/5ml solution
• 2 mg/ml inj
• 32 mg/50ml premixed
• IV (prevention)
• 4 mg undiluted over gt 30 seconds
• Oral
• 16 mg 1 hr before procedure
• Zofran ODT
• 4, 8 mg

• Dolasetron
• Anzemet
• 50, 100 mg tablets
• 20 mg/ml inj
• IV
• 12.5 mg
• Children 0.35 mg/kg
• Oral (prevention)
• 100 mg 2 h before surgery
• Children 1.2 mg/kg within 2 hr of surgery
• Caution in patients with QTc abnormalities

118
Anti-emetics

• Trimethobenzamide
• Tigan
• 100, 250 capsule
• 100 mg supp (ped)
• 200 mg supp
• 100 mg/ml inj
• Adult
• Oral 250 mg tid-qid
• Rectal, IM 200 mg tid-qid
• Pediatric
• 30 90 lbs 100-200 mg tid-qid
• New indication Post-op N V associated with
  gastroenteritis
• 300 mg opaque purple capsule
• 300 mg po tid qid
• Can be opened and sprinkled on food or in liquids

• Metaclopramide
• Reglan
• 5 mg/5 ml syrup
• 5, 10 mg tablets
• 5 mg/ml inj

119
Antiemetic Dental Implications

• Increased CNS Depression
• Sedation
• Respiratory depression
• Extrapyramidal effects
• Vasodilation
• Orthostatic hypotension
• Lower seizure threshold
• Increase cardiac arrhythmias
• Interaction with vasoconstrictors
• Anticholinergic effects
• dry mouth