Update on Medications and Drug Interactions for the Pediatric Dentist

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 Today�s low dose BCP�s 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 patient�s 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 patient�s 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 Patient�s 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 <5 yo 12.5-25 mg >5 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 > 0.09 mg/kg produce inc. ataxia w/o inc. sedation Safety of oral lorazepam in children < 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 <5 yo:0.05-0.1 mg/kg 5-12 yo 0.025-0.05 mg/kg >12 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 Additive CNS stimulation with other sympathomimetic agents Decongestants Diet aids Psychostimulants Methylphenidate Ritalin� Concerta� Amphetamines d-Amphetamine Adderall� Bronchodilators Albuterol� Theophylline

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 Selective beta 1 antagonists Acebutolol (Sectral) Atenolol (Tenormin) Betaxolol (Kerlone) Bisoprolol (Zebeta) Metoprolol (Lopressor) Non-selective beta antagonists Carteolol (Cartrol) Nadolol (Corgard) Penbutolol (Levatol) Pindolol (Visken) Propranolol (Inderal) Sotalol (Betapace) Timolol (Blocadren) Labetalol (Trandate, Normodyne)

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 , Piroxicam<3% 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) >12 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 < 50 kg 0.2 mg/kg every 4-6 hours Children > 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 < 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 > 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