3. ANTIMICROBIAL AGENTS
Synthetic as well as naturally obtained drugs that attenuate microorganisms.
CLASSIFICATION:
On the basis of type of organism, they inhibit-
Antibacterial- Penicillins, Aminoglycosides, Fluoroquinolones etc.
Antifungal- Amphotericin B, Fluconazole etc.
Antiviral- Acyclovir, Zidovudine etc.
Antiprotozoal- Metronidazole
Antihelminthic- Albendazole, Niclosamide etc.
4. On the basis of mechanism of action:
Inhibit cell wall synthesis- Penicillins, Cephalosporins
Cause leakage from cell membrane- Amphotericin B
Inhibit protein synthesis- Tetracyclines, Chloramphenicol
Cause misresding of m-RNA code- Aminoglycosides
Inhibit DNA gyrase- Fluoroquinolones
Interfere with DNA function- Metronidazole, Rifampicin
Interfere with DNA synthesis- Acyclovir, Zidovudin
5. On the basis of type of action
Primarily bacteriostatic Primarily bactericidal
Sulfonamides Penicillins
Tetracyclines Cephalosporins
Chloramphenicol Aminoglycosides
Fluoroquinolones
Vancomycin
6. Antibacterials
Used locally (topically and
subconjunctivally) in prophylaxis (pre and
postoperatively) and treatment of ocular
bacterial infections.
Used systemically (orally and
intravenously) for the treatment of
preseptal/orbital cellulitis
e.g. amoxycillin with clavulanate, ,
cephalosporin, vancomycin
Can be injected intravitreally for the
treatment of endophthalmitis
7. ANTIBACTERIAL AGENTS
PENICILLINS:
Bactericidal
Short half-life
Excreted mainly via kidney; a small fraction via biliary tract
Act by interfering with cell wall synthesis
Most have narrow spectrum, mainly against Gram-positive organisms
Have synergistic action with aminoglycosides
8. 3 major groups:
Penicillins effective against cocci and Gram-positive bacilli
Eg. Benzyl penicillin (non acid stable) and penicillin V (acid stable)
Penicillinase resistant penicillins
Eg. Cloxacillin and flucloxacillin
Extended spectrum penicillins
Aminopenicillins: Ampicillin, Amoxycillin
Carboxypenicillins: Ticarcillin, Carbenicillin
Ureidopenicillins: Piperacillin, Mezlocillin
9. β- LACTAMASE INHIBITORS:
Clavulanic acid:
Obtained from Streptomyces clavuligerus
Tissue distribution and elimination matches Amoxicillin
Combination- COAMOXYCLAV (Amoxycillin 250/500 mg + clavulanic acid 125 mg)
Sulbactum:
Less potent than clavulanic acid
Oral absorption inconsistent: given parenterally
Tazobactum:
Pharmacokinetics matches Piperacillin (combination- TAZOMAC : Piperacillin 4g + tazobactum 0.5g)
10. Here comes your footer
DRUGS SPECTRUM DOSE
Penicillin
derivatives
Penicillin Gram-positive organisms, Spirochetes SYSTEMIC- 4-30 million U in 24 divided doses 4-6
hourly
TOPICAL- 0.1 million U/mL (Fortified drops)
Cloxacillin Gram-positive organisms, also penicillinase
producing
SYSTEMIC-50-100mg/kg/day oral/i.v. 6 hourly
Ampicillin Gram-positive organisms, H. influenzae, E. coli,
Proteus, Salmonella, Shigella
SYSTEMIC-50-100mg/kg/day oral/i.v. 6 hourly
TOPICAL- 10 mg/mL (Fortified drops)
INTRAVITREAL- 500 mg/mL
Amoxycillin Gram-positive organisms SYSTEMIC-25-50mg/kg/day oral 8 hourly
11. CEPHALOSPORINS:
Structure and mode of action similar to penicillins (bactericidal)
Relatively resistant to staphylococcal penicillinase
Patients allergic to penicillin may develop allergy
Intraocular penetration not very good
12. DRUGS SPECTRUM DOSE
Cephalosporins
1st
Generation
Cephalexin Gram-positive organisms, penicillinase producing
staphylococci, C.diphtheriae, Clostridia, Actinomyces,
E. coli, Klebsiella, Shigella, Salmonella, Proteus, H.
influenzae
25-50 mg/kg/day oral 6 hourly
Cephazolin Gram-positive organisms, E. coli, Proteus, H.
influenzae
25-50 mg/kg/day i.m./i.v. 8 hourly
TOPICAL-50 mg/mL (Fortified drops)
INTRAVITREAL- 2.25 mg in 0.1 mL
2nd
Generation
Cefamandole Gram-positive organisms, E. coli, Proteus, H.
influenzae
1 gram 4 hourly i.v.
TOPICAL- 50 gram/mL (Fortified drops)
Cafaclor Gram-positive organisms, E. coli, Proteus, H.
influenzae
25-50 mg/kg/day oral 8 hourly
Cefuroxime Gram-positive and negative organisms, penicillinase-
producing N.gonorrhoeae, ampicillin-resistant H.
influenzae
30-100 mg/kg/day i.m./i.v. 8-12 hourly
14. AMINOGLYCOSIDES:
Bactericidal
Broad spectrum of activity against Gram-positive and Gram-negative
organisms
Renal and vestibular toxicity
Interfere with neuromuscular conduction- may cause paralysis in
Myasthenia gravis patients
Intravitreal injections may cause retinotoxicity
16. TETRACYCLINES:
Broad spectrum antibiotics with bacteriostatic action against both Gram-
positive and Gram-negative organisms as well as some fungi, rickettsiae and
chlamydiae.
Get deposited in growing bones- not to be used in children and pregnant or
lactating mothers
MACROLIDES:
Bacteriostatic agents with narrow spectrum against Gram-positive
organisms, Chlamydia and Toxoplasma gondii.
18. GLYCOPEPTIDES:
Very effective against nearly all Gram-positive as well as against methicillin-
resistant Staphylococcus aureus and Staphylococcus epidermidis.
toxic if used topically or subconjunctivally
VANCOMYCIN:
High systemic toxicity
Nephro and ototoxic
Used intravitreally/parenterally for treatment of endophthalmitis
19. FLUOROQUINOLONES:
Derivatives of nalidixic acid
Broad spectrum agents
1st
generation
• active mainly against Gram-negative organisms
• Eg. Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin
2nd
generation
• also active against Gram-positive and anaerobe organisms
• Eg. Levofloxacin, Lomefloxacin, Gatifloxacin, Moxifloxacin
Get deposited in growing cartilage- not recommended in children
21. CHLORAMPHENICOL:
Bacteriostatic agent
Active against bacteria, spirochaetes, rickettsiae, chlamydiae and
mycoplasmas
Widest spectrum for superficial ocular infections
Toxic to the corneal epithelium
May lead to blood dyscrasias
23. ANTI FUNGALS
Classified on the basis of molecular structure
Polyenes Imidazole Triazoles
Amphotericin B Natamycin Ketoconazole
Fluconazole Itraconazole Voriconazole
24. Polyenes
First effective antifungal used
Bind preferentially to ergosterol in fungal plasma membrane, thereby altering membrane permeability
and disruption of fungal cells
Has poor corneal penetration
Used effectively against variety of filamentous fungi Aspergillus, Candida, Histoplasma
Local hypersensitivity and corneal epithelial toxicity may occur
Prolong use may cause renal, bone marrow or CNS toxicity
25. AMPHOTERICIN B NATAMYCIN
Produced from Streptomycetes nodosus Streptomyces natalenses
Dosage •TOPICAL: 0.075-0.3% drops/hourly
•SUBCONUJNCTIVAL: 0.8-1 mg
•INTRAVITREAL: 500 μg in 0.1 mL
•SYSTEMIC: 1mg/kg in 5% dextrose 4 hourly i.v.
*Pretreat with 25mg hydrocortisone
TOPICAL: 5% ophthalmic suspension/hourly
interval followed by gradual tapering
Topical suspension should be shaken well
before use
Indications Aspergillus, Candida, Cryptococcus and
mucormycosis
Candida, Histoplasma and Actinomycetes
Considered superior but has to be reconstituted
and has low shelf life
DOC
Easily available in solution form
Trade names Amphocin, Fungizone Natamet, Nataone, NataAid
26. Clotrimazole
Chlorinated imidazole derivative
Broad antifungal activity more active in treatment of aspergillus infections
DOSAGE:
1% topical ophthalmic drops and ointment
Topical drops are instilled hourly followed by gradual tapering
Ointment is applied 4 times a day
Adverse reactions include ocular irritation and punctate keratopathy
27. Fluconazole
Most effective against yeast species Candida and Cryptococcus
DOSAGE:
0.3% solution
Every 4 hour interval with gradual tapering
Has faster and deeper penetration
Highly effective in fungal keratitis with deep abscess
Adverse reactions are minimal irritation and transient burning of the eyes
28. Itraconazole
Shares a similar pharmacokinetic profile with fluconazole
Used in Aspergillius infections, has moderate effects against Candida
DOSAGE:
1% ophthalmic solution
8 times a day is the recommended dosage
29. Voriconazole
Indicated for use in the treatment of fungal keratitis caused by
Aspergillus spp., Fusarium spp.,Candida spp. and Scedosporium
apiospermum
PREPARATION:
Lyophilized form
enhances drug stability and solubility
30 mg powder reconstituted with 3 mL to get 10 mg/mL
(1% solution)
ADVERSE EFFECTS:
it may cause serious hepatic reactions
30. ANTI VIRAL DRUGS
Anti viral drugs are activated to triphosphate by viral and cellular thymidine
kinases (TK)
This active metabolite then inhibits DNA/RNA replication by competitive
inhibition and direct incorporation into viral DNA resulting in chain termination
Oral Acyclovir- 800 mg, 5 times/day
ADVERSE EFFECTS:
Blurring of vision, dizziness, drowsiness, tremors, severe allergic reactions, hematuria
Acyclovir and Ganciclyovir ointment are available for topical use
31. ACYCLOVIR (3%) GANCICYCLOVIR (0.15%)
Indications • Primary HSV keratitis, dendritic ulcers
• Herpes zoster and varicella infections
• Acute retinal necrosis syndrome
Adverse effects • Vision blurred,irritation,Punctate keratitis
• Conjunctival hyperemia
• Erythema of eyelid, SPK
• Dry eye, Foreign body sensation
Dosage 5 times a day, followed by tapering
Acyclovir vs Gancicyclovir Ganciclovir ophthalmic gel 0.15% is a new dosage form recently approved by
the FDA for the treatment of acute herpetic keratitis (dendritic ulcers).
Better penetration than acyclovir with lesser side effects
Trade name ACIVIR OINTMENT® VIRSON GEL®
32. LOCAL ANAESTHETICS
Topical: (drops/jelly)
E.g. Proparacaine 0.5%, Lignocaine 2%
Uses: applanation tonometry, goniscopy,removal of corneal foreign bodies,
removal of sutures, examination of patients, cataract surgery
Adverse effects: toxic to corneal epithelium, rarely allergic reactions
33. Orbital infiltration:
Peribulbar
Retrobulbar
cause anesthesia and akinesia for intraocular surgery
e.g. Lidocaine 2%, Bupivacaine 0.25%-0.5%
34. ANTINEOPLASTIC AGENTS
These are used in chemotherapy of ocular tumours
some are used to decrease the fibroblastic response in ocular surgeries
CLASSIFICATION:
Alkylating agents:
eg. Carboplatin
Antimetabolites:
eg. Methotrexate, Azathioprine, 5- Fluorouracil
Natural products:
Plant products: eg. Vincristine, Etoposide
Microorganism product: eg. Mitomycin C
35. DRUG GROUP MECHANISM USED IN DOSES
Carboplatin Alkylating agent-
Platinum co-
ordination complex
Alkylation of nucleic
acid resulting in cross
linking/ abnormal base
pairing of DNA strands
Ocular tumours 560 mg/m2 BSA (body
surface area) i.v.
Vincristine Vinca alkaloids Arrest the cell cycle in
mitotic phase by
disrupting mitotic
spindle
Ocular tumours 1.5 mg/m2 BSA i.v.
Etoposide Epipodophyllotoxins Arrests cells in G2
phase and inhibits DNA
topoisomerase II
Ocular tumours 150 mg/m2 BSA i.v.
5-Fluorouracil Antimetabolite-
Pyrimidine
antagonist
Iinhibition of
pyrimidine synthesis
To prevent excessive
scarring in postoperative
period (eg. pterygium
surgery, trabeculectomy)
25 mg/mL topical
Mitomycin C Antibiotic alkylating
agent
cross linking of DNA as
well as an inhibition of
RNA and protein
synthesis
After pterygium and
glaucoma surgery
(trabeculectomy) to reduce
scarring and recurrence
Ocular surface neoplasias
0.2-0.5 mg/mL (0.02%-
0.05%) solution topical
36. ANTIOXIDANTS
Oxidative damage plays a major role in development of many ophthalmic
conditions; viz.
Senile cataract, age related macular degenerations (ARMD), diabetic retinopathy etc.
Mechanism of oxidative damage:
Free radicals and reactive oxygen species are main culprits
Attack proteins (enzymes), neurotransmitters, nucleic acids, phospholipids, retinal
pigment epithelium, lens tissue
Antioxidants react rapidly with free radicals and reactive oxygen species
Act as scavengers for free radicals
38. PREPARATIONS:
Various standardised antioxidant combinations, available in form of
capsules; eg.
i) Zn 30mg, Cu 1.5mg, Se 60 μg, Mn 5mg, vit.A 6000 IU, vit.B2 20 mg, vit.C
200 mg, vit.E 60 IU
ii) mixed carotenoids, i.e. α-carotene, β-carotene, cryptoxanthin, leutin,
zeaxanthin
39. Major role of various antioxidant elements:
Zinc: integral part of two endogenous antioxidant enzymes viz. catalase and
superoxide dismutase
Copper: cofactor for superoxide dismutase
Selenium: cofactor for glutathione peroxidase
Vitamin C: directly reacts with and scavenges free radicals; major function is
protection of lens from oxidative damage
Vitamin E: intercalates into cell membrane and protects cellular constituents
against free radicals
40. Carotenoids: major action is to suppress lipid peroxidation (responsible for
generation of free radicals)
Lutein and zeaxanthin: only carotenoids found in the retina and lens of the eye.
They help reduce risk of developing age-related cataracts and macular
degeneration
Astaxanthin: The most powerful of the carotenoids, by far. Astaxanthin can
penetrate into every part of the cell
42. ANTI VEGF
Anti Vascular Endothelial Growth factors
VEGF stimulates both angiogenesis and increased vascular permeability
Major angiogenic factor implicated in the pathogenesis of neovascular and
exudative eye diseases
Anti VEGFs inhibit VEGF and thus evolution of the disease
49. TOPICAL IMMUNE THERAPY
Relatively new concept
To treat iatrogenic inflammation following any type of intraocular surgery
To make up the decreased levels of ocular immunoglobulins vital for ocular
defence system against external infections
50. WHY REQUIRED:
In immediate postoperative period (≈7 days) there is significant decrease in
globulin levels of tears
There is increase in tear secretion following surgeries, resulting in dilution of
immunoglobulins
There is physical breach in the continuity of ocular tissue, predisposing to
infections
51. DOSAGE:
Available as:
Topical solution (ASPAC)
0.1% each of IgG and IgA and 0.05% of IgM
1-2 drops 3-4 times/day for 7-14 days
ADVERSE EFFECTS:
Only occassionaly- transient burning sensation, stinging, conjunctival
injection, hypersensitivity reactions (rarely)