Top Ten Oral Agents and a Few other Thoughts

Transcription

1 Top Ten Oral Agents and a Few other Thoughts J. JAMES THIMONS, O.D.,FAAO MEDICAL DIRECTOR / OPHTHALMIC CONSULTANTS OF CONNECTICUT JIMTHIMONS@GMAIL.COM

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4 Disclosure I am a consultant for or am on the Medical Advisory Board of: Allergan Alcon AMO Advanced Vision Research Inspire TLC Laser Center Carl Zeiss Meditec Synemed

5 ANTI-VIRALS ACYCLOVIR FAMVIR VALTREX

6 ANTI-VIRALS CLINICAL APPLICATIONS ACUTE VS CHRONIC INFECTION PRIMARY LESIONS EPITHELIAL HERPES SIMPLEX STROMAL HERPES SIMPLEX HERPES ZOSTAR HERPETIC IRIDOCYCLITIS

7 ANTI-VIRALS SIDE EFFECTS RENAL FAILURE/ IMPAIRMENT HYPERSENSITIVITY REACTIONS FACIAL EDEMA VISUAL HALLUCINATIONS

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19 VARICELLA ZOSTAR- KERATITIS PRIMARY INFECTION CHICKEN POX VACCINATION RECOMMENDED BY AMERICAN ACAD of PEDIATRICS RECURRENT INFECTION OPHTHALMIC INVOLVEMENT OPHTHLAMIC ZOSTAR > OVER AGE 60 UNDER 40 50% IIMMUNOCOMPRIMISED

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23 The Cyclines Tetracycline, Doxycycline and Minocycline Isolated from Streptomyces Effective against Gram +/ Gram -/Aerobic/ Anerobic/ Spirochetes/Rickettsia/Chlamydia Similar action / different duration

24 Tetracyclines Tetracycline (Sumycin) Doxycycline (Vibramycin) Coated doxycycline (Doryx)

25 Tetracycline (Sumycin) Formulations 250mg, 500mg tablets/capsules: syrup 125mg/tsp Dosages 250mg, 500mg q.i.d

26 Doxycycline (Vibramycin) Formulations 50mg, 100mg capsules: 100mg tablet: suspension 25/tbs: syrup 50mg/tsp Dosages 50mg, 100mg q.i.d Oracia 40 mg sustained release/ regular Periostat 20 mg Most common use in dentistry

27 The Cyclines Clinical Applications Brucellosis Rickettsia ( Rocky Mountain Spotted fever) Lyme Disease Chlamydia/ Trachoma Primary Meibomianitis Gonococcal Prophylaxis Corneal melting Syndrome Non Healing Corneal lesions Rosacea

28 The Cyclines RCE PLD Lyme s Microbial Keratitis Corneal melt syndrome

29 How could I ever get mad at you GS a 33 y/o Caucasian female presented with a complaint of discomfort, watering and light sensitivity following blunt trauma. PEX: VA: 20/20 OD 20/30- OS SLE: 2 mm area of epithelial damage with staining at 12:00 Occasional A/C cell 2+ injection

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32 How could I be mad at you Treatment: BCL 4 th Generation FQ Acular PF Symptoms resolved after 1 week of Tx Patient dismissed with instructions and Systane q4 hours Muro 128 Unguent hs

33 How could I be mad at you Patient returned to office 10 weeks later with c/o AM pain and return of symptoms. D/C gtts after 4 weeks PEX: VA: 20/30 SLE: As shown 2+ injection

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35 Recurrent Erosions Medical Management Nocturnal lubrication Nocturnal hypertonic saline Bandage contact lens Treat underlying conditions

36 Recurrent Erosions Contributing Factors Dry eyes Blepharitis External disease / tear film abnormalities

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39 Lipid Secretion: Meibomian Glands Transillumination of meibomian glands Meibomian gland dysfunction

40 Recurrent Erosions Treatment Doxycycline 50 mg po bid OM3 s Azasite qd hs BCL 30 day wear Restasis

41 Omega 3 Fatty Acids Re-esterized OM3 Ethyl Ester

42 Interim Analysis Tear Osmolarity (mosm/l) Omega Placeb o Wk 0 Wk 6 Wk

43 Interim Analysis Corneal staining (measured on 0-5 scale)

44 Interim Analysis Ocular Symptom Disease Questionnaire Omega Placeb o Wk 0 Wk 6 Wk

45 Interim Analysis Omega Index levels (%) Omega Placeb o Wk Wk 12

46 Re-Esterified OM3 s :

47 A Challenger for the Title Kashkouli, MB BJO 8/ patients with MGD randomly assigned to: Doxy 200mg/ day x 1 month Azithromycin 500mg x1 then250mg x4 Significant improvement in both groups Bulbar hyperemia and ocular surface staining better in Azith group Azith group showed significantly betteroverall clinical response Doxy group showed increased GI symptoms

48 Take Your Time: It s Worth it! Fraunfelder, FW et al: Cornea subjects/ failed on initial therapy of lubrication/ NaCl Treated with bandage lens x 3 months 75 % had complete resolution at one year from initial Tx 2 had symptoms but no signs 1 patient had symptoms and signs

49 The Way to a Man s Eyelid is Thru His Stomach! BMJ Aug randomized trial meta-analysis 22 trials/ 5000 patients Sequential therapy ( 2x daily PPI with Amoxicillan) was significantly better than triple therapy ( PPI, Clarithromycin, Metronidizole) 87% vs 72% outcome 14 trials 2750 patients 84% vs 75% Resitent to Tx sub Levofloxacin

50 Oral Antibiotics PCN s Cephalosporin s Macrolides

51 Wow! What Happened While I was Asleep? JR a 23 year old Caucasian female awoke with a pain, swelling and a pulsing ache over her left eye. Pt. denies h/o trauma, prior occurrence or vision loss. PEX: VA 20/20 OD, 20/20 OS EOM: Full without pain VF: CFTFC/ OU

52 Wow: What Happened While I Was Asleep? Ta: 18/19 SLE: 2+3 Tender lid edema. Cornea clear, AC=D&Q. Negative discharge. DFE: 0.2 OU Dx:? Tx:

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54 lar Bacterial Disease Posterior Blepharitis Hordeola Canaliculitis Conjunctivitis Keratitis Dacryocystitis Dacroadenitis Preseptal/orbital cellulitis Endophthalmitis

55 Bacterial Flora of the Normal Eye/Adults Staphylococcus epidermidis 75-90%* Diphteroids (C. xerosis) 20-33% Staphylococcus Aureus 20-25%* Streptococcus (S. viridan) 2-6% Hemophilus influenza 3% or more Streptococcus pneumoniae 1-3%* Gram negative rods 1% or more* Pseudomonas aeruginosa 0-5%* * Dominant organisms in microbial keratitis

56 Body depots of bacterial organisms Skin: Lids/hands: Staph/Gr. (+) Nose/nasopharynx: Staph and GR (+) Kids: Hemophilus Oropharynx: Staph and StrepGr (+) Mouth: Strep/Bacteroides Stomach: Helicobacter pylori and rosaceae Small Intestine: Gr (+) cocci and bacilli Large intestine: Greatest conc of bacteria in body (10 organisms/gm) anerobesenterobacteria, enterococcus feacalis, E. coli 12 Genito-urinary tract: Chlamydia, E. coli, Neisseria gonorrhea (Ophthalmia neonatorum)

57 Bacterial conjunctivitis In adults, 75% of cases caused by Gram positive pathogens Staphylococcus epidermidis, S. aureus, Streptococcus pneumoniae Very common in children under 6 years Causal agents of pediatric cases: 42% Haemophilus influenzae 35% S. pneumoniae Everett et al, 1995 Block et al, 2000

58 Staph epidermidis Common Ocular Pathogens Gram (+) Coagulase negative Opportunistic pathogen Frequent cause of CL keratitis Normal flora Staph aureus Chronic bleparitis Coagulase positive Methacillin resistant strain Exotoxins Strep Species Strep pneumonae Enzymes/virulence Seen in cold climates Perforate in 7 days associated with erysipilus cellulitis Inflammatory disease Abscess formation Severe keratitis

59 Important Penicillins Ampicillin: Broad spectrum oral-qid dosing Amoxicillin: Pro-drug of Ampicillin, improved absorption with lower GI side-effects Cloxacillin/Dicloxacillin: Intrinsic betalactamase resistance Augmentin: Amox + Clavulanate Methicillin: IV prep for penicillinase producers Amp + Sulbactam: Unasyn: IV Ticarcillin + Clavulonic acid: IV better penicillinase protection than methacillin

60 Gram (-) species Pseudomonas Hemophilus Klebsiella Serratia Moraxella Neiserria

61 Augmentin Indications/Dosage forms Indications: Preseptal cellulitis Dacryocystitis Pediatric Hemophilus Amoxicillin + Clavulanate@@@@ Dosage forms: 500 or 875mg tablets BID 125 or 250mg/5cc pediatric suspension

62 Augmentin Amoxacillin/Clavaulanate Broad spectrum penicillin (Staph, Strep, Hemophilus Effective against penicillinase producersclavulanate blocks High therapeutic index Bacteriocidal Low GI side-efffects Safe in pregnancy Watch out for allergy Cheap***

63 Plan B: The cephalosporins Mechanism: Same as penicillin Bacteriostatic Low toxicity 3% allergic to pen are allergic to Ceph. Better penicillinase resistance than penicillins

64 Know your generations First Generation: Good GR (+) activity against penicillinase producers/poor Gr (-) activity especially Hemophilus (children) Cefadroxil: Duricef-PO Cephazolin: IV- Ancef- Keratitis Cephalexin: PO-Keflex Cephadrine: PO- Velosef

65 ivity, s Cefaclor: PO-Ceclor Cefuroxime: PO-Ceftin Third Generation: Reduced GR (+) activity (Staph sp) with marked Gr (-) activity Cefixime: PO- (Suprax) Cefpodoxime: PO - Vantin Cefprozil: PO - Cefzil

66 Pre-Septal Considerations JAMA 2013 Dec. Dual cohorts of 95,000 each, older adults (mean 76) who were users of Calcium Channel Blocker s Clarithromycin (inhibitscyp3a4 which can cause increased CCB levels) vs: Azithromycin ( non inhibitor) Measured for 30 days post treatment Risk for hospitalization 0.44% vs 0.22% due to acute kidney injury All cause mortality 1.02% vs.0.59%

67 Erythromycin (E-Mycin) Formulations 250mg, 500mg tablets Dosages 250mg, 500mg q.i.d., b.i.d

68 Azithromycin (Zithromax) Formulations 250mg, 500mg 600mg tablets: suspension 100mg/5ml, 200mg/ml Z-PAK six 250 mg tablets, TRI- PAK three 500mg tablets Dosages 1 gm one dose administration for Chlamydia: 500mg q.d. followed by 250mg q.d for four days

69 Fluoroquinolones Levofloxacin (Levaquin) Ciprofloxacin (Cipro) Gatifloxacin (Tequin) Moxifloxicin (Avelox)

70 Levofloxacin (Levaquin) Formulations 250mg, 500mg and 750mg tablets 25mg/ml oral suspension Dosages 250mg to 750mg q.d.

71 Ciprofloxacin (Cipro) Formulations 100mg, 250mg, 500mg, 750mg and 1000mg tablets Dosages 500 mg to 750mg b.i.d.

72 Gatifloxacin (Tequin) Formulations 200mg and 400mg tablets Dosages 400mg q.d.

73 Moxifloxicin (Avelox) Formulations 200mg and 400mg tablets Dosages 400mg q.d.

74 Corticosteroids

75 STEROIDS INHIBIT PROSTAGLANDIN AND LEUKOTRIENE ACTIVITY BY BLOCKING ACTION OF ENZYME PHOSPHOLIPASE A2.

76 Clinical Case Examples Scleritis Severe anterior uveitis Posterior uveitis Inflammatory preseptal cellulitis Progressive thyroid eye disease DLK

77 Steroids 99 % topical use in eye care Medrol Dose Pack most common Pred Forte Generic since January 2009 Lotemax/ Alrex & Durezol

78 Prednisone (Deltason) Formulation 2.5mg, 5mg, 10mg, 20mg and 50mg tablets; 5mg/5ml solution/syrup Dosage Varies based on condition

79 Methylprednisolone (Medrol) Formulation 2mg, 4mg, 8mg, 16mg, 24mg and 32mg tablets Medrol Dose Pak 21 4mg tablets Dosage Varies based on condition

80 Clinical Case Examples Scleritis Dermatitis Severe anterior uveitis Posterior uveitis Inflammatory preseptal cellulitis Progressive thyroid eye disease DLK

81 Interesting Facts In steroid responders, onset of IOP elevation occurs after about two weeks of use Time of onset often longer for systemic steroids Complex pathophysiologic factors result in increased resistance to aqueous outflow

82 Steroids 99 % topical use in eye care Medrol Dose Pack most common Pred Forte Generic since January 2009 Lotemax/ Alrex & Durezol

83 STEROIDS ORAL vs IV ADMINISTRATION INITIAL DOSE - 1mg/kg/day STANDARD TAPER INITIAL THERAPY 2-3 DAYS, THEN TAPER AS INDICATED FOR CLINICAL RESPONSE ALTERNATE DAY THERAPY- LONG TERM Tx- DOUBLE DOSE QOD THROUGH TAPER

84 Steroids Oral vs. IV administration Initial dose determination (1mg/kg/day) Standard taper vs. alternate day therapy Standard taper - start initial dose, monitor in 2-3 days, then taper as appropriate for clinical response Alternate day therapy - for longer term therapy (more than 2-3 weeks), give double dose every other day, continue pattern throughout tapering process Prednisone - Initial dose typically in mg range as per above

85 Steroids vs.immunomodulation Ashcroft DM; BMJ Mar 2005 Meta-analysis 25 trials Tacrolimus (Protopic) / Pimecrolimus (Elidel) vs. Potent and Mild steroids Tacrolimus = Potent steroid > Mild Pimecrolimus< Potent Steroid FDA Black Box Recommended use: Facial area( steroid atrophy) Pulse therapy Intolerant of steroids

86 IOP after DSEK Price,FW AJO eyes/38 patients Mean CCT 701 microns Pnemotonometry: 20.3 mmhg +/-4.5 mmhg Pascal: 19.8 mmhg +/- 4.4 mmhg Goldmann: 15.9 mmhg +/- 4.9 mmhg If IOP is elevated with Goldmann it is probably real

87 NSAID S IBUPROFEN KETOROLAC INDOMETHACIN NAPROXEN TRAMADOL CELEBREX

88 NSAID S CLINICAL APPLICATIONS ANALGESIA ANTI-INFLAMMATORY MUSCULOSKELATAL/ MYOSITIS ACUTE GOUT DYSMENNORRHEA CME

89 NSAID S CORNEAL OPACITIES( WHORL) TINNITUS FLUID RETENTION EPISTAXIS BREAST CHANGES ANEMIA/BLEEDING CONSTIPATION

90 NSAID S CLINICAL APPLICATIONS ANALGESIA ANTI-INFLAMMATORY MUSCULOSKELATAL/ MYOSITIS ACUTE GOUT DYSMENNORRHEA CME

91 NSAIDS, H Pylori and Gastric Ulcers Lancet 2002 Jan 5; 359: NSAID users Peptic ulcer disease 42 % H Pylori patients 26% of non-infected patients Peptic ulcer disease 36 % of NSAID users 8% of non users Risk of bleeding ulcer (6.1x> in H Pylori on NSAIDS0

92 Narcotic Agents Effective for severe acute pain Patient response variability due to individual sensitivity of opioid receptors No addiction likely with short term use Dosage varies with drug used and patient Adverse effects is usually the limiting factor in usage

93 Narcotic Agents Hydrocodone (Schedule III) (Lortab, Vicodin) mg tid-qid with acetaminophen

94 Narcotic Agents 6 times more potent than codeine Less gastrointestinal problems Less sedation?? euphoria

95 Important notification for patients Drowsiness Dizziness Blurred vision Nausea/vomiting/constipation Take with food to avoid GI distress Avoid Etoh or other CNS agents Breathing distress

96 Contraindications Bronchial asthma COPD Emphysema Pregnancy Hypersensitivity Prior addiction Renal/Liver dysfunction H/O Etoh use, Concurrent use of CNS agents(tricyclic antidepressants, Phenothiazines)

97 Narcotic agents Directly affect opioid receptor Agonist, partial agonist, or mixed Bind to opioid receptors in brainstem, corticol areas and spinal cord Mimic endorphins, producing a morphine like effect whether natural or synthetic

98 Narcotic Agents Effective for severe acute pain Patient response variability due to individual sensitivity of opioid receptors No addiction likely with short term use Dosage varies with drug used and patient Adverse effects is usually the limiting factor in usage

99 Narcotic Agents Hydrocodone (Schedule III) (Lortab, Vicodin) mg tid-qid with acetaminophen

100 Narcotic Agents 6 times more potent than codeine Less gastrointestinal problems Less sedation?? euphoria

101 Important notification for patients Drowsiness Dizziness Blurred vision Nausea/vomiting/constipation Take with food to avoid GI distress Avoid Etoh or other CNS agents Breathing distress

102 Contraindications Bronchial asthma COPD Emphysema Pregnancy Hypersensitivity Prior addiction Renal/Liver dysfunction H/O Etoh use, Concurrent use of CNS agents(tricyclic antidepressants, Phenothiazines)