Ocular pharmacology 1

6/1/2020 anjumk38dmc@gmail.com 1

Pharmacodynamics &
Pharmacokinetics
 Pharmacodynamics is the biological and
therapeutic effect of the drug (mechanism of
action).
 If the drug is working at the receptor level, it can
be agonist or antagonist If the drug is working at
the enzyme level, it can be activator or inhibitor

Pharmacokinetics:
 It is the
 absorption,
 distribution,
 metabolism, and
 excretion of the drug:
 A drug can be delivered to ocular tissue in various
way

Drugs delivery in eye:
Topical Periocular Intraocular Syste
mic
1 Drop Subconjunct
ival
Intracamera
l
Oral
2 Ointment Subtenons Intravitreal I/M
3 Gel Peribulbar I/V
4 Soft C.L Retrobulbar

Topical drop/ointment/gel:
 Topical drop/ointment/gel:
• Topical drop (Gutta): Simplest and more
convenient mainly for day time use one drop =
50 microliter. Conjunctival sac capacity=7-13
micro liter so, even one drop is more than
enough.

Topical drop/ointment/gel:
 Ointments increase the contact time of ocular
medication to ocular surface thus better effect. It
has the disadvantage of vision blurring. The drop
has to be high lipid soluble with some water
solubility to have the maximum effect as
ointment.
 Gel: Prolong contact time

Subconjunctival Injection
Use to achieve high concentration of drugs
and Penetrate large sized molecule

Subconjunctival Injection:
 Subconjunctival
Injection: (Fig:)
 Use to achieve high
concentration of drugs
and Penetrate large
sized molecule
Subconjunctival

Posterior Subtenon
 Subtenon injection:
• Prefer over
Subconjunctival
• Anterior Subtenon is
used to administer
steroid.
• Posterior Subtenon is
used for intermediate &
posterior uveitis.
Subtenon

Retrobulbar block
 Retrobulbar block:
• Used for:
a) Optic Neuritis
b) Papillitis
c) Previously used for
local anaesthesia for
cataract surgery

Peribulbar injection
 Now a day, it is the
most frequent
procedure for ocular
anaesthesia

Factors influencing absorption of drug
concentration and solubility: higher the
concentration better will be the penetration.
Viscosity: increases the contact time with the
cornea. Addition of methylcellulose and polyvinyl
alcohol increases the viscosity of drug.
Lipid solubility: higher the lipid solubility more
will be the penetration.

Factors influencing absorption of drug
• Surfactants: the preservatives used in ocular
preparations alter cell membrane in the cornea
and increase drug permeability e.g.-
Benzylkonium chloride (BAK) and Thiomersal.
• pH: the normal tear pH is 7.4 and if the drug pH
is different, it will cause reflex tearing.
• when an alkaloid drug is put in relatively
alkaline medium, the proportion of the
uncharged form will increase, thus more
penetration

Barrier for intraocular transport of
drugs
Corneal epithelium and stroma: most imp
Blood ocular barriers:
• blood retinal barrier
• blood aqueous barrier

Common pharmacological agents used
in ophthalmology:
1) Anti-infective agents
a) Antibacterial agents
b) Antiviral agents
c) Antifungal agents
2) Drugs affecting the pupil and accommodation:
Mydriatics and Cycloplegic agents

3) Anti-glaucoma agents
4) Anti-inflammatory and immunosuppressive
agents
a) Corticosteroid
b) Nonsteroidal anti-inflammatory drugs
c) Immunosuppressive and antimiotic drugs

5) Anti-allergic and vasoconstrictor drugs
6) Lubricating agent and artificial tear
7) Intraocular and irrigating solutions
8) Viscoelastic substances another name is ocular
viscoelastic device (OVD)
9) Anti-VEGFs agents
10)Dyes used in ophthalmology

Antibiotics is a substance (such as penicillin) that
destroys or inhibits the growth of other pathogenic
microorganisms and is used in the treatment of
external or internal infections.
While some antibiotics are produced by
microorganisms, most are now manufactured
synthetically

Classification of antibiotics:
 Antibiotics are classified several ways.
• On the basis of mechanism of action
• On the basis of spectrum of activity
• On the basis of mode of action

 The range of bacteria that an antibiotic affects
can be divided into
 narrow spectrum and
 broad spectrum.

 Narrow spectrum antibiotics act against a
limited group of bacteria, either gram positive or
gram negative. For example sodium fusidate only
acts against staphylococcal bacteria.
 Broad spectrum antibiotics act against gram
positive and gram negative bacteria. For example
amoxicillin

• Bacteriostatic” means that the agent prevents the
growth or reproduction of bacteria (i.e., keeping
them in the stationary phase of growth).
• tetracyclines, sulfonamides, spectinomycin,
trimethoprim, chloramphenicol, macrolides and
lincosamides.

• Tetracycline is an example of a bacteriostatic
antibiotic. • It inhibits the bacterial ribosome, so
that no new proteins can be made. This doesn't
kill the bacteria; they already have the proteins
they need to survive for a while. However, they
can't replicate, because they would need to make
tons of new proteins in order to make a whole
new bacterial cell.

 “Bactericidal” means that it kills bacteria

a)Cell Wall Synthesis inhibitors:
b)Protein Synthesis Inhibitors
c)DNA Synthesis Inhibitors
d)RNA synthesis Inhibitors
e)Mycolic Acid synthesis inhibitors
f) Folic Acid synthesis inhibitors

• Penicillins
• Cephalosporins
• Vancomycin
 Beta-lactamase Inhibitors
Carbapenems
Aztreonam
Polymycin
Bacitracin

• Beta-lactamases are enzymes produced by
bacteria that provide multi-resistance to β-
lactam antibiotics
• such as penicillins, cephalosporins, cephamycins,
Beta-lactamase provides antibiotic resistance by
breaking the antibiotics' structure.

β-lactam.
• These antibiotics all have a common element in
their molecular structure: a four-atom ring
known as a β-lactam. Through hydrolysis, the
enzyme lactamase breaks the β-lactam ring open,
deactivating the molecule's antibacterial
properties.

 Aminoglycosides (gentamycin)
 Tetracyclines
 Macrolides
 Chloramphenicol
 Clindamycin

3) DNA Synthesis Inhibitors
• Fluoroquinolones (ciprofloxacillin)
• Metronidazole
4) RNA synthesis Inhibitors
• Rifampin

5) Mycolic Acid synthesis inhibitors
• Isoniazid
6) Folic Acid synthesis inhibitors
• Sulfonamides
• Trimethoprim

Chloramphenicol 0.5% eye drop and
ointment
• Chloramphenicol is a highly lipophilic drug with
excellent corneal penetration and broad-
spectrum coverage. Its mechanism of action is
inhibiting bacterial protein synthesis. It is
generically available in both solution and
ointment forms.

The Aminoglycosides
 Aminoglycosides are a class represented
• gentamicin,
• tobramycin, and
• neomycin.
They exert their bactericidal action through the
inhibition of bacterial protein synthesis.

Gentamicin (0.3%) and Tobramycin (0.3%)
 Both gentamicin and tobramycin perform about
the same, except that tobramycin appears to be
even less likely than gentamicin to cause any
epitheliotoxic response.
 Tobramycin is 2 -4 times more active against
Pseudomonas aeruginosa and Proteus as
compared to Gentamycin.

Fortified eye drop
 What is fortification?
• Fortification means to intensify or strengthen the
medication, to achieve adequate drug
concentration. Fortified antimicrobials are not
commercially available, thus should be, prepared
of optimal constitution in a sterile
pharmaceutical dispensary.

The Need for Fortification of Antibiotics
a) For resistant microbial keratitis, to attain
appropriate drug concentration.
b) For moderate-to-severe corneal ulcers
c) Prophylaxis after cataract surgery (Intracameral
d) For pediatric patients
e) For drugs that are available only in parenteral
form. For example - Vancomycin and
amphotericin B.

Limitations of fortification
a) High cost
b) Contamination risk
c) Since it is a preservative-free preparation, they
have short shelf-life
d) Need for refrigeration.

Aminoglycosides
• Fortified tobramycin : 14 mg/ml (1.4%)
• Fortified gentamicin : 14 mg/ml (1.4%)
• Fortified amikacin : 40 mg/ml

Cephalosporins fortified eye drop
• Fortified cefazolin : 50 mg/ml (5%)
• Fortified ceftazidime : 50 mg/ml (5%)
• Topical Vancomycin : 50 mg/ml (5%)
• Topical linezolid: 2 mg/ml (0.2%)

Antifungals eye drops
 Topical amphotericin B (0.15%)
 Topical voriconazole (1%).

General guidelines
• Selection of fortified antimicrobials must be
adapted to the type of bacteria suspected.
• Fortified drops should be prepared by a doctor or
a pharmacist inside a laminar air hood/operation
room under aseptic precautions
• Disposable syringe should be used
• Date of preparation and date of expiry should be
mentioned in prepared drops

General guidelines
• Frequency of application with storage
instructions should be explained to the patient
• Short shelf-life (preservative free)
• Since there is a risk for contamination and also it
is preservative free, it should be refrigerated and
can be kept up to 7 days at 4°C
• Shake well before instillation.

Isolate Antibiotic & concentration
Empirical
treatment
Fluoroquinolones monotherapy or
cefuroxime + 5% ‘fortified’ gentamicin
duo therapy 1.5%
Gram-positive
cocci
Cefuroxime 0.3% Vancomycin
Gram-negative
cocci
Fluoroquinolones or Varies with
preparation Ceftriaxone
Gram-negative
rods
Fortified’ genta or 1.5% Fluoroquinolones
or Varies with preparation ceftazidime
Kanski 179 (9th edition)

Fortified tobramycin or fortified
gentamycin 14 mg/ml (1.4%)
Preparation: 2 ml parenteral antibiotic (40 mg/ml)
is added to 5 ml commercially available gentamicin
ophthalmic solution (0.3%)
Concentration: 15 mg/ml (1.5%)
Shelf-life: Up to 14 days if refrigerated.
CALCULATION:
Gentamycin (0.3%) 5 ml contains: 15 mg
2 ml injection gentamycin contains: 80 mg
So 7 ml contains 95 mg
 1 ml contains 95/7 = 13.57mg =14 mg=1.4%

Cephalosporins: cefazolin, cefuroxime, or
ceftazidime
 Preparation: 500 mg parenteral antibiotic is
diluted with 2.5 ml sterile water and added to 7.5
ml of preservative-free artificial tears:
 Concentration: 50 mg/ml (5%)
 Shelf-life: 24 hours at room temperature; at least
4 days if refrigerated
(Kanski: 179)

Apparent treatment failure of CU
• It is important not to confuse ongoing failure of
re-epithelialization with continued infection.
Drug toxicity, particularly following frequent
instillation of fortified aminoglycosides,
 may give increasing discomfort,
 redness and
 discharge despite the eradication of infection.
(Kanski 9th edition P: 180)

Preparation of antifungals: Topical
amphotericin B (0.15%)
 Method: Add 10 ml of distilled or sterile water to
parenteral 50 mg of amphotericin B powder for
injection. Draw 3 ml of this and add to 7 ml of
artificial tear eye drops
 Shelf-life: Refrigerate and shake well before
instillation
 Storage: should not be exposed to light. The
drops should be inspected at each visit for any
turbidity, which may indicate contamination or
drug precipitation.

Calculation: Topical amphotericin B (0.15%)
 10 ml contains: 50 mg
 3 ml contain: 15 mg
 Make it 10 ml by addition of 7 ml artificial tear
 So 10 ml contain 15 mg that is 0.15%

Topical voriconazole eye drops (1%)
 Method: Voriconazole powder (200 mg) was
reconstituted with 20 ml of water for injections
in order to obtain 20ml.
 So 1 ml contains 10 mg voriconazole solution: So,
Voriconazole eye drops (1%)
 Storage: Refrigerate at 4°C and shake well before
instillation

2mg
 Begin with a 500 mg ampoule
 Add 10 ml water for injection (WFI) or saline and
dissolve thoroughly (for a 250 mg vial add 5 ml
WFI or saline, for a 1 g vial add 20 ml WFI or
saline)
 Draw up 1 ml of the solution, containing 50 mg of
Antibiotic
 Add 1.5 ml WFI or saline giving 50 mg in 2.5 ml

2mg
 2.5 ml contain 50 mg
 1 ml contains 20 mg
 0.2 ml contain 4 mg
 0.1 mg contains 2 mg

0.4mg
 Presentation: vial contains 500 mg of amikacin
in 2 ml of solution
 Use a 3 ml syringe to draw up 1 ml of amikacin
solution then add 1.5 ml of WFI
 Inject 0.4 ml of the solution, containing 40 mg of
antibiotic, into a 10 ml syringe and dilute to 10
ml (giving 4 mg per ml)

• Draw up about 0.2 ml (excess to facilitate
priming) into a 1 ml syringe. When ready to
inject, fit the needle to be used, and discard all
but 0.1 ml (contains 0.4 mg of antibiotic) for
injection

0.4mg
 2 ml contain: 500 mg
 So, 1 ml contain: 250 mg (now make it 2.5 ml by add
1.5 ml WFI)
 2.5 ml contain 250 mg
 1 ml contain 100 mg
 0.4 ml contain 40 mg (now add 9.6 ml WFI)
 10 ml contain 40 mg
 1 ml contain 4mg of Amikacin

Ocular pharmacology 1

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