2.Therapeutics-.ANTIBOITICS, STEROIDS 21-9-12

Report
Dr. Faizur Rahman
Professor of Ophthalmolgy
Peshawar Medical College
Peshawar
At the end of the session the students would
be able to:
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Know various antibiotics and steroids used in Ophthalmic
practice.
Describe the rationale of using various drugs.
Mechanism of action , effects and side effects of these
drugs.
Know drug treatment of certain diseases
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A chemical substance produced by one organism
causing the death of other bacterial cells i.e
penecillin and streptomycin.
After the introduction of synthetic agents these are
now called antibacterials.
As newer agents came up now a wide spectrum of
drugs are available called antimicrobials.
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Difference between humans and microbes is
exploited to produce substances toxic to microbes
and harmless to humans.
The selective toxicity may be relative than
absolute.
Concentration of antimicrobials must be carefully
controlled.
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INHIBIT BACTERIAL CELL WALL OR
ACTIVATE ENZYMES THAT DESTROY
BACTERIAL CELL WALL:
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PENICILLINS
CEPHALOSPORINS
BACITRACIN
VANCOMYCIN
KETOCONAZOLE
MICONAZOLE
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ALTER CELL WALL PERMEABILITY AND
LEAKAGE OF INTRACELLULAR CONTENTS
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POLYMYXINS
NYSTATIN
AMPHOTERICIN B
COLISTIMETHATE
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INHIBIT PROTEIN SYNTHESIS
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Tetracyclines
Aminoglycosides
Macrolides/Ketolides
Clindamycin
Chloramphenicol
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DRUGS THAT BLOCK SPECIFIC METABOLIC
STEPS (Foleate inhibitors)
◦ SULFONAMIDES
◦ TRIMETHOPRIM
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INHIBIT DNA DEPENDENT RNA POLYMERASE
◦ RIFAMPICIN
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INHIBIT DNA DEPENDENT DNA SYNTHESIS
◦ QUINOLONES
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ACT AS NUCLEIC ACID ANALOGUES
◦ ANTIVIRALS
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Identify the infecting organism
Empiric therapy prior to identification
Determination of susceptibility
Barriers
Patient factors.
Safety of agent
Cost of therapy.
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Chloramphenicol (Topical)
Anti-mycotics(Systemic and topical)
Aminoglycosides(Systemic and topical)
Sulphonamides(Systemic and topical)
Anti-virals (Systemic and topical)
Macrolides(Systemic)
Quinilones (Systemic and topical)
Cephalosporines (Systemic and topical)
STEROIDS
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Mineralo corticoids
 Glucocorticoids
 Androgens
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Beciomethasone
Betamethasone
Cortisone
Des oxy cortico sterone
Dexamethasone
Fludro cortisone
Hydrocortisone
Methyl prednisolone
Para methasone
Prednisolone
Prednisone
Triamcinolone
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Promote normal intermediary metabolism:
Gluconeogenesis
Stimulate protein catabolism
Stimulate lipolysis
Increase resistance to stress by:
Raising blood glucose level
Modest rise in BP
Alter blood cell levels in plasma:
Decrease in eosinophils, basophils, monocytes and
lymphocytes by redistribution from circulation to
lymphoid tissue
Increase in the number of RBC, platelets, neutrophils
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Anti inflammatory action: (Complex mechanism)
Suppression of immunity
Indirect inhibition of phospholipase A2
Alter other endocrine systems:
Decrease in ACTH and TSH
Increase in GH
Effects on other systems:
Increased production of gastric acid, pepsin
Effects on CNS
Bone loss
Myopathy
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In the treatment of ocular inflammations and
immune related ocular diseases.
Act by suppressing the formation of arachidonic
acid and other mediators by induction mediators
like phospholipaze A2 and inhibitory protein
Lipocorteins
Prevent edema, Fibrin deposition, capillary
dilatation and proliferation, Leukocyte infiltration
and subsequent scarring.
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Long acting/ Short acting/ Depot
Very potent
Potent
Moderately potent
Mild
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Impaired wound healing/ Easy Bruising
Negative calcium balance/ Osteoporosis
Increased appetite/ Hyperglycemia/ Diabetes Mellitus
Euphoria/ Depression/ Psychosis
Hypertension
Edema (Sodium and water retension)/ Weight Gain
Peptic ulcers/ GI Hemorrhage/ GI Perforation
Hypokalaemia (Potassium depletion)
Hirsutism /Acne/ Coetaneous striae/ Amenorrhea
Myopathy (Gluconeogenesis)
Avascular Bone necrosis (Neck of femur)
Decreased Immunity
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Cataract (PSC)
Steroid induced Glaucoma
Retinal Micro-Aneurysms
Papilloedema
Delayed Wound Healing
Mild Blephroptosis
Immune Suppression-Secondary Infections
◦ CANDIDA, TOXOPLASMOSIS, CMV, HSV,
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Topical
Intralesional
Subconjunctival
Subtenon
Periocular
Intravitral
Intracameral
Systemic
oral
iv
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Prenisolone (Topical and systemic)
Dexamethasone (Topical and systemic)
Betamethasone (Topical and systemic)
Hydrocortisone (Systemic only)
Loteprednol (Topical only)
( No IOP Rise)
Flouromethalone (Topical only) ( No IOP Rise)
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Intra lesional in hemangioma and chalazion
Iv in optic neurirtis
Oral in dysthyroid ophthalmopathy. Corneal
transplant
Intravitreal in CRVO
Topical postoperative, uveitis, corneal transplant
Intracameral Per-op in children
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The patient with orbital cellulitis should be promptly hospitalized for
treatment. Hospitalization should be continued until the patient is
afebrile and is clearly improved clinically.
Symptomatic; antipyretic, NSAIDS
Antimicrobials ;
◦ Ceftazidime 1 g tds , I/M
◦ Metronidazole 500mg tds, PO
◦ Vancomycin in case of allergy to the above mentioned
Surgical intervention in case of local abscess or unresponsive cases
Consultation with ENT specialist, neurosurgeon & paediatrician if
required
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Specifically identified pathogens identified on
cultures.
Intravenous antibiotic therapy should be continued
for 1-2 weeks and then followed by oral antibiotics
for an additional 2-3 weeks.
Fungal infection requires intravenous antifungal
therapy along with surgical debridement.
Surgical drainage of an orbital abscess is indicated
if any of the following occurs:
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A decrease in vision occurs.
An afferent pupillary defect develops.
Proptosis progresses despite appropriate antibiotic
therapy.
The size of the abscess does not reduce on CT scan within
48-72 hours after appropriate antibiotics have been
administered.
If brain abscesses develop and do not respond to antibiotic
therapy, craniotomy is indicated.
SAFE strategy developed by WHO for trachoma:
 Surgery:
◦ To prevent blindness & limits progression of corneal
scarring.
◦ Can improve vision.
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Antibiotics:
◦ Azithromycin—1 G single dose (adults).
◦ Children: 20mg/kg single dose
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Erythromycin 250 mg QID for 4 weeks. (children
125mg/kg).
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Tetracycline 250 mg QID for 4 weeks.
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Topical tetracycline 1% 0.5 inch ribbon BD for 6 weeks.
Facial cleanliness:
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◦ Reduces risk & severity of trachoma.
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Environmental change:
◦ Improved water supply & household sanitation.
◦ Personal & community hygiene.
◦ Adequate housing & water & sewage system.
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Topical Tetracycline.
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Oral Erythromycin 25mg/kg body weight 12
hourly for 14 days.
Caution:
Examine mother & father for chlamydial urethritis/
cervicitis and treat.
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Broad spectrum antibiotics
Analgesics
Drainage if abscess formation
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Initial treatment: Broad spectrum topical
antibiotics (Fortified)
Dual therapy: Aminoglycoside & cephalosporin.
Mono therapy: Fluoroquinolone.
Oral antibiotics:
Atropine.
Systemic analgesics.
• Acyclovir 3% ointment x 5 times daily
• Trifluorothymidine 1% drops 2-hourly
• Debridement if non-compliance or no response
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Polyenes:
Natamycin 5%: Filamentous fungi.
Amphotericin B: Filamentous fungi.
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Imidazole:
Miconazole 1%: Candida, Aspergillus.
Systemic: Itraconazole, Ketoconazole.
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Pyramidine:
Flucytosine 1%: Candida.
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Topical:
Propamidine Isothionate 0.1% (Brolene),
Dibromopropamidine Isothionate 0.15%,
Miconazole 1%.
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Systemic:
Ketoconazole.
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Intravitreal antiboitics
Subconjuntival antibiotics.
Topical antibiotics.
Role of systemic antibiotics.
Role of steroids.
Role of vitrectomy.
Cycloplegics and analgesics.
Drug Treatment of Glaucoma
To prevent further damage to the eye by
lowering IOP & to ultimately prevent
blindness
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Plasma Expanders
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Urea
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Mannitol
20% IV solution.
Dose: 1-2g/kg or 5 ml/kg body weight.
Up-to 60 drops/min over 20-30 min.
Peak of action: within 30 min.
Duration of action: up-to 6 hrs.
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Diuretics
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IV Acetazolimide
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50% solution.
Oral agent with a sweet & sickly taste.
Pure lemon should be added to avoid nausea.
Dose:1-2g/kg or 2-4ml/kg body weight.
Peak of action: Within 1 hr.
Duration of action: Upto 3 hrs.
Metabolized to glucose in the body.
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Oral agent with a minty taste.
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Dose: Same as for glycerol.
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Metabolically inert & can be given to diabetics
without insulin cover.
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Mechanism Of Action:
1- POAG: Stimulation of longitudinal muscle of
ciliary body---pull on scleral spur---widening of
trabecular spaces---lowering of IOP.
2- PACG: Opening the angle by pulling the
peripheral iris away from the trabeculum.
Indications:
 POAG.
 Acute ACG.
 Many secondary glaucomas.
Good additive effect with beta blockers.
Response:
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Blue eyes: Max. response.
Dark eyes: Relatively low response.
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Pilocarpine(1%,2%,3%,4%):
One-half inch ribon at bed time.
Induced myopia & miosis lasts only during sleep.
Corneal haze in 20%, rarely affects VA.
 Pilocarpine sustained-release (Ocusert Pilo-20 & Pilo-40):
Polymer containing adsorbed pilocarpine.
Inserted in upper fornix---7 days.
Pilo-20: Equivalent to pilocarpine 1% drops.
Pilo-40: Equivalent to pilcarpine 2-4% drops.
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Parasympathomimetic muscarinic agonist, also a
weak chloinesterase inhibitor.
Onset of action: Within 40 min.
Duration: 12 hrs.
Dose: 8 hourly.
Good alternative to pilocarpine in resistant cases.
0.01% intraocular solution for miosis during
surgery.
Epinephrine
Dipivefrin
Clonidine
Apraclonidine
Brimonidine
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Epinephrine 0.5, 1%, 2%
Mechanism Of Action: Increases both trabecular &
uveoscleral outflow via beta agonist activity
mediated by cyclic AMP.
Tripple response: Conj. decongestion, slight
mydriasis & reduction of IOP.
Onset of action: Within 1 hr.
Duration of action:12 - 24 hr.
Indications: POAG, ocular hypertension.
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Dipivefrin (0.1%)—(Propine)
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Prodrug: Converted to adrenaline after absorption.
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Penetration 17 times greater than adrenaline.
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Duration of action same.
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IOP lowering effect is comparable with 1%
adrenaline.
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Fewer side effects.
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Twice daily dose.
Wash out period: 3.3 wks.
Peak effect at 2 hrs.
Duration of action 12 hrs.
Comparable to Timolol.
Nonresponder: Less than 10%.
No tachyphylaxis.
Good additivity to beta blockers, CAIs & miotics.
No vasoconstrictive effect in retinal tissues.
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Prophylaxis of post-laser IOP spike.
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Property of neuroprotection in animal models.
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SIDE EFFECTS:
Ocular: Follicular conj., contact dermatitis, ocular
irritation & hyperemia.
Systemic: Bradycardia, hypotension, apnea in
neonates.
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Pharmacokinetics:
Highly selective alpha-2 agonist.
Easy penetration to cornea.
Lower access to CNS: Less lipophilic, rapid
metabolism, short plasma half life.
Reduce allergic reaction: Not produce hapten.
Mechanism Of Action: Reduce IOP by initial
decreasing aqueous production followed by increase in
uveoscleral flow.
OCULAR
 Irritation.
 Lacrimation.
 Allergic BC.
 Adrenochrome
pigmentations.
 Cystoid macular
edema.
 Pupillary dilatation.
SYSTEMIC
 Headache.
 Palpitations.
 Tachycardia.
 Hypertensive crisis.
 Anxiety.
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Mechanism Of Action:
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Decrease aqueous secretion with little effect on
episcleral venous pressure.
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10% unresponsive.
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First choice medication for POAG.
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Non-selective or cardioselective.
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Contralateral effect.
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0.25% and 0.50% BD.
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Timolol LA 0.25% and 0.50%.
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Digital pressure over eyes after medication
(3minutes) to reduce systemic absorption.
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0.5% BD.
Cardio-selective.
Ocular hypotension < Timolol & Levobunolol &
similar to Carteolol.
IOP reduction 6 mm Hg.
Less effective than Timolol in post-cataract surgery
increase in IOP.
Increases retinal blood flow.
Superior visual fields protection.
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Non selective.
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Onset of action: Within 1 hr.
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Peak of action: 2-6 hr.
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Duration: 24 hr.
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Dose: Usually OD.
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Potent as Timolol.
Non-selective.
 More selective action on the eye than cardiopulmonary
system. (less bradycardia than Timolol).
 Efficacy similar to Timolol.
Metipronolol (0.1%, 0.3%)
 Non-selective.
 Similar properties to Timolol.
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Latonoprost (Latep)
Travoprost (Travatan)
Unoprostone (UF-021)
Bimatoprost (Lumigan)
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Prodrug derived from pulmonary metabolite of PGF2
alpha.
Efficacy:
14-17% less than Latanoprost & comparable to
Timolol.
Dose: 0.15% BD.
Inhibit activity of endothelin-1 & may improve ocular
blood flow.
Side effects: Conj. hyperemia, corneal epithelial
defects.
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Synthetic PGF2 alpha analog.
Dose: 0.004% OD.
Widest temperature storage range.
Efficacy:
7-8mm Hg IOP reduction (upto 33%)—start after 2 hr,
peak at 12hr.
6-7mm Hg IOP reduction with Timolol.
Higher mean IOP reduction & responder rate than
Latanoprost.
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Synthetic analog of endogenous prostamides.
Receptor profile: Controversial---no prodrug?
no binding to PG receptors?
Mechanism Of Action: Increase trabecular outflow
(35%) & uveoscleral outflow (50%).
Dose: 0.03% OD.
Efficacy:
33% (7-8mm Hg) IOP reduction.
Better diurnal control & less PG-like side effects than
Latanoprost.
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Topical as well as systemic
Acetazolamide 250mg Tablets (AZM)
Brinzolamide Drops (Azopt)
Dichlorphenamide 50 mg
Methazolamide 50 mg
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1) Timolol/ Dorzolamide (Cosopt)
2% dorzolamide & 0.5% timolol maleate.
Efficacy: 25-30% IOP reduction (less than separate
therapies).
2) Latanoprost/ Timolol (Xalacom)
0.005% latanoprost & 0.5% timolol,OD
3) Timolol/ Brimonidine (Combigan)
4) Timolol/ Pilocarpine.
THANK YOU

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