Principles of Pharmacokinetics and Pharmacodynamics Ocular Pharmacology

1. PRINCIPLES OF
PHARMACOKINETI
CS AND
PHARMACODYNAM
Sandeep
Kandel
Institute of Medicin
Maharajgunj Medica
Campus, Nepal

2. PRESENTATION LAYOUT
I. Pharmacokinetics
 Absorption
 Distribution
 Metabolism
 Excretion
II. Pharmacodynamics
 Signal Transduction
 Dose Response
Relationship
 Agonist and Antagonist
III. Ocular Pharmacology
 Ocular Drug Absorption
 Drug Delivery System

3. PHARMACOKINETICS AND
PHARMACODYNAMICS
The purpose of studying pharmacokinetics
and pharmacodynamics is to understand the
drug action, therapy, design, development and
evaluation
Pharmacokinetics is what the Body Does To
The Drug like how the drug is Absorbed,
Distributed, Metabolized, and Excreted by the
body – Drug disposition
Pharmacodynamics is what the Drug Does To

5. PHARMACOKINETI
CS

6. PHARMACOKINETICS
Refers to what body does to the drug
Defined as the study of the time course of drug
absorption, distribution, metabolism, and
excretion
These four pharmacokinetic properties
determine the:• Speed of onset of drug action
• Intensity of drug’s effect
• Duration of drug action

7. Absorption
Distribution
Metabolism
Elimination

8. Absorption
Drug absorption from the site of administration
permits the entry of the therapeutic agent into the
plasma
Distribution
The drug may then reversibly leave the
bloodstream and distribute into the interstitial and
intracellular fluids
Metabolism
Then the drug may be biotransformed by the
metabolism in liver, or other tissues
Elimination
Finally, the drug and its metabolites are eliminated
from the body in the urine, bile, or feces.

10. I. ABSORPTION OF
DRUGS
It is the transfer of a drug from its site of
administration to the bloodstream via one of the
several mechanisms
The rate and efficiency of absorption depend upon
following factors:
The environment where the drug is absorbed
The drug’s chemical characteristics
Route of administration (which influences the
bioavialability)

11. MECHANISM OF
ABSORPTION OF
DRUGS FROM THE GI
TRACT Passive Diffusion:
•The driving force for passive diffusion is the
concentration gradient across a membrane
separating the two body compartments
•Water soluble drugs penetrate the cell
membrane through the aqueous channels or
pores
•The lipid soluble drugs gain access to the cell
across the biological membranes due to their

12.  Facilitated
Diffusion:
Drugs enter the
cell through
specialized trans-
membrane carrier
proteins that
facilitate the
passage of large
molecules
It requires carrier molecules and can be
saturated

13.  Active Transport:
• This mode of drug entry involves specific
carrier proteins that span the membrane
and energy-dependent active transport is
driven by the hydrolysis of ATP
• It is capable of moving the drugs against
the concentration gradient ie. from low
concentration to high concentration

14. Endocytosis and Exocytosis:
•Transports the drug of exceptionally large size
across the cell membrane
•Endocytosis involves the engulfment of a drug
molecule by the cell membrane and transport
into the cell by pinching off the drug filled vesicle.
•Exocytosis is used by cells to secrete many
substances by similar vesicle formation process
•For instance, Vitamin B12 is transported across
the gut by endocytosis and neurotansmitters like
nor-epinephrine are released by exocytosis

15. DRUG DISPOSITION

16. FACTORS AFFECTING
DRUG ABSORPTION
1. Effect of pH on drug absorption
[
•Most drugs are either weak acids or weak
bases
•Acidic drugs (HA) release a proton (H+),
causing a charged anion (A-) to form
HA H+ + A–
•Weak bases (BH+) can also release an H+ and
loss of a proton produces the uncharged base
(B)
+ +

17. •A drug passes through membranes more
readily if it is uncharged, thus for weak acid,
uncharged protonated HA can permeate
through the membranes and A- cannot
•For weak bases, the uncharged B can permeate
through the membranes but the protonated form
BH+ cannot
•The ratio between the ionized and the non
ionized forms is determined by the pH at the
site of absorption and by the strength of the
weak acid or base, represented by the
ionization constant, pKa

18. 2. Blood flow to the site of absorption
•Because the blood flow to the intestine is
greater than that of stomach, the
drug from intestine is more favored
3. Total surface area available for
absorption
•With surface rich in brush border
micro-villi, the intestine has a surface area
about 1000-fold that of the stomach,
absorption of drug across the intestine

19. 4. Contact time at the absorption
surface
• If the drug moves across the GI tract very
quickly, as can happen with severe
is not well absorbed
5. Expression of P-Glycoprotein
•P-glycoprotein is a multidrug trans-
transporter protein responsible for
various molecules including drugs

20. BIOAVAILABILITY
Bioavailability is the fraction of administered drug
that reaches the systemic circulation
Is important for calculating drug doses for non-
intravenous routes of administration
It is determined by comparing the plasma levels
of a drug after a particular route of administration
with the plasma drug levels achieved by IV
injection, in which the total agent rapidly enters the
circulation

21. FACTORS INFLUENCING
THE BIOAVAILABILITY
In contrast to IV administration, which confers
100% bioavailability, the oral administration of drug
involves the first-pass metabolism
A. First-Pass hepatic metabolism
When the drug is absorbed across the GI tract, it
first enters the portal circulation before entering the
systemic circulation
If the drug is rapidly metabolized in the liver or gut
wall during the initial passage, the amount of
unchanged drug in the circulation is decreased

22. B. Solubility of the drug
•Very hydrophilic drug are poorly absorbed
because of their inability to cross the
cell membranes
•Paradoxically, drugs that are extremely
hydrophobic are also poorly absorbed,
because they are totally insoluble in the
aqueous body fluids
•For a drug to be readily absorbed, it must
largely hydrophobic, yet have some
in aqueous solutions
•That’s why many drugs are either weak
or weak bases

23. BIOEQUIVALENCE
Two related drug preparations are
bioequivalent if they show comparable
bioavailability and similar times to reach the
peak blood concentrations
THERAPEUTIC
EQUIVALENCE
Two similar drugs are therapeutically equal if
they are pharmaceutically equivalent with

24. II. DRUG
DISTRIBUTION
Process by which a drug reversibly leaves the
blood-stream and enters the interstitium
(extracellular fluid) and then the cells of the
tissues
A. Blood Flow:
•The rate of blood flow to the different tissue
capillaries varies widely as a result of the
unequal distribution of cardiac output to the
various organs
•Blood flow to the brain, liver and kidney is
greater compared to that of adipose tissue,

25. B. Capillary permeability:
•In the liver and spleen, a large part of the
basement membrane is exposed due to
discontinuous capillaries through which
plasma proteins can pass
•While in case of brain, the capillary
continuous that constitute the blood-brain
•So, to enter the brain, drugs must pass
the endothelial cells of the capillaries of the
or be actively transported
•Lipid soluble drugs can readily penetrate
the CNS because they can dissolve in the
membrane of the endothelial cells

26. C. Binding of drugs to plasma proteins and
tissues:
Binding to the plasma proteins:
•Reversible binding to the plasma proteins
sequester drugs into the non-diffusible form
slows their transfer out of the vascular
compartment
•Plasma albumin is a major drug binding
may act as a drug reservoir
Binding to the tissue protein:
•Numerous drugs accumulate in the tissues,
to the higher concentration of drug in the
than in the ECF and blood
•Drugs may accumulate as a result of binding

27. VOLUME OF
DISTRIBUTION
The apparent volume of distribution, Vd, can be
thought of as the fluid volume that is required to
contain the entire drug in the body at the same
concentration measured in the plasma
Where, C0 = Plasma concentration at time zero
zero
Once the drug enters the body, it has the
potential to distribute into any one of three
functionally distinct compartments of body
water or to become sequestered in a cellular site
Vd= (Amount of drug in the
body)/C0

28. Plasma compartment:
 If a drug has a very large molecular weight
binds extensively to the plasma proteins, it
large to move out through the endothelial
junctions of capillaries, thus is trapped
plasma
Extracellular Fluid:
If a drug is of low molecular weight but is
hydrophillic, it can move through the
slit junctions of the capillaries into the
fluid.
However, the hydrophillic drugs cannot
across the lipid membrane of cell to enter
water phase inside the cell
Hence these drugs distribute into a volume
is sum of plasma water and the interstitial
which constitute about 20% of total body

29. Total Body Water
If the drug has low molecular weight and
hydrophobic, it moves into interstitium
the slit junctions as well as through the cell
membranes into the intracellular fluid
Into a volume of about 60% of total body
weight ie. 42L of a 70kg individual

30. III. DRUG CLEARANCE BY
METABOLISM
The major routes involved in drug elimination are
•Hepatic Metabolism
•Elimination in Bile
•Elimination in Urine
Metabolism leads to products with increased
polarity, which will allow the drug to be eliminated
Clearance(CL):
It estimates the amount of drug cleared from the
body per unit of time
CL= 0.693 × Vd/t1/2
Where, t1/2 = The drug’s elimination half time
Vd = Apparent volume of distribution

31. KINETICS OF
METABOLISM:
First Order Kinetics:
• When the rate of drug metabolism and elimination is
directly proportional to the concentration of free drug,
and first order kinetics is observed
• Hence, with every half life the drug concentration
reduces by 50%
Zero Order Kinetics:
• With few drugs like aspirin, ethanol and phenytoin, the
doses are very large
• Therefore, the rate of metabolism remains constant over
time. This is called zero order kinetics, clinically
referred to as Non-linear kinetics

32. REACTIONS OF DRUG
METABOLISM
The kidney cannot efficiently eliminate
lipophillic drugs that readily crosses cell
membrane and are reabsorbed in the distal
convoluted tubules.
Therefore, the lipophillic agents must be
metabolized into more polar substances in the
liver using two general sets of reactions:
Phase I Phase II

33. PHASE I REACTION
Converts lipophilic molecules into more polar
molecules by introducing or unmasking a polar
functional group such as –OH or –NH2
Most frequently catalyzed by the Cytochrome
P450 system
Various reactions like, Amine oxidation, alcohol
dehydrogenation and etc, do not involve P450
systems

34. PHASE II REACTION
Consists of the conjugation reactions
Subsequent conjugation of Phase I metabolites
with an endogenous substrate, such as Glucuronic
acid, Sulfuric acid, Acetic acid or an amino acid
results in polar and therapeutically inactive
compounds
Glucuronidation is the most common and most
important conjugation reaction

35. IV. DRUG CLEARANCE BY
THE KIDNEY
Most important
route of
elimination of drug
from the body
Involves three
processes:
• Glomerular filtration
• Active Secretion
• Passive
Reabsorption

36. GLOMERULAR
FILTRATION
Drugs enter the kidney
through renal arteries,
which divide to form a
glomerular capillary
plexus
Free drug flows through
the capillary slits into the
Bowman’s Space as part
of the glomerular filtrate
Lipid Solubility and pH
do not influence the
passage of drugs into
the glomerular filtrate

37. PROXIMAL TUBULAR
SECRETION
Drugs that were not transferred into the
glomerular filtrate leave the glomeruli through the
efferent arterioles, which divides to form capillary
plexus around the proximal tubule
Secretion primarily occurs in the proximal
tubules by two energy-requiring active transport
systems:
One for Cations
One for Anions

38. DISTAL TUBULAR
REABSORPTION
As drug moves toward the distal convoluted
tubule, its concentration increases and exceeds
that of peri-vascular area
If the drug is uncharged then it may diffuse out of
the nephric lumen into the systemic circulation

39. ION TRAPPING
The manipulation of the pH of urine to increase
the ionized form of drug to minimize the amount
of back diffusion and hence increasing the
clearance of the undesirable drug
Weak acids can be eliminated by method of
Ion Tapping by alkalinization of urine while weak
base can be eliminated by the acidification of
the urine

40. DRUG CLEARANCE BY
OTHER ROUTES
Other routes of drug elimination mainly include
via intestines, the bile, the lungs, and the breast-
milk in the lactating mother
The feces are primarily involved in elimination
of unabsorbed orally ingested drugs
The lungs are primarily involved in the
elimination of anesthetic agents
Excretion of drugs into milk, sweat, saliva,
tears, hair, and skin occurs only to a small

41. TOTAL BODY
CLEARANCE
The total body clearance, CLtotal, is the sum of
the clearances from various drug metabolizing
and drug eliminating organs.
CLtotal= CLhepatic+ CLrenal+ CLpulmonary+ CLother

42. BIOLOGICAL HALF-LIFE
OF A DRUG
The time required for one-half of an
administered drug to disappear from the blood
plasma
 As the drug molecule leaves plasma it can be
eliminated from the body, or it can be
translocated to another body fluid compartment
such as the intracellular fluid or it can be
destroyed in the blood
As repeated doses of a drug are administered

43. STEADY STATE
When the amount of drug in the plasma has built
up to a concentration level that is therapeutically
effective and as long as regular doses are
administered to balance the amount of drug being
cleared the drug will continue to be active
 The time taken to reach the steady state is about
five times the half life of a drug
Sometimes a loading dose may be administered
so that a steady state is reached more quickly then
smaller maintenance doses are given to ensure
that the drug levels stay within the steady state

45. PHARMACODYNA
MICS

46. PHARMACODYNAMICS
Pharmacodynamics describes the actions of a
drug on the body and the influence of drug
concentrations on the magnitude of the
response
Drug-receptor complex initiates alterations in
the biochemical and/or molecular activity of a
cell by a process called signal transduction

47. I. SIGNAL
TRANSDUCTION
Drugs act as signals and their receptors act as
signal detectors
A. The Drug Receptor Complex:
Cells have different types of receptors, each of
which is specific for a particular ligand and produce
an unique response
Receptors has ability to recognize a ligand and
couple or transduce this binding into a response by
causing a conformational change or a biochemical
effect
Recognition of drug by receptor is analogous to the

48. B. Receptor State:
Classically, the binding of a ligand was thought
to cause receptors to change from an inactive
state to an activated state
However, recent studies suggest that receptors
exist in two states, inactive and active, that are
in reversible equilibrium with one another
In absence of agonist, the equilibrium mainly
favors the inactive state
Drugs acting as agonists bind to the active
state of receptor and thus rapidly shift the
equilibrium from inactive to activated state

49. C. MAJOR RECEPTOR FAMILIES
Pharmacology defines receptor as any biologic
molecule to which a drug binds and produce a
measurable response
Thus, enzymes, nucleic acids and structural
proteins can be considered to be pharmacologic
receptors
However, the richest source of therapeutically
exploitable pharmacologic receptors are the
proteins

50. PHARMACOLOGIC
RECEPTORS
Ligand-Gated Ion Channels
G Protein-Coupled
Receptors
Enzyme-Linked Receptor
Channels
Intracellular Receptors

51. TRANSMEMBRANE LIGAND
GATED ION CHANNELS
It is responsible for the regulation of the flow of
ions across the cell membranes
Response to these receptors is very rapid
These receptors mediate diverse functions
including neurotransmission, cardiac conduction,
and muscle contraction
For example: generation of an action potential
and activation of contraction in the skeletal
muscle

52. TRANSMEMBRANE G
PROTEIN-COUPLED
RECEPTORS
Comprises a single alpha-helical peptide that has
seven membrane-spanning regions
Important processes mediated by G Protein-
Coupled Receptors include neurotransmission,
olfaction and vision
The extracellular domain of this receptor usually
contains the ligand binding area
Intracellularly, these receptors are linked to a G
Protein having three subunits, an α subunit that

53. Binding of appropriate ligand activates the G
protein so that GTP replaces GDP on the α
subunit
Dissociation of G protein occurs, and both the α -
GTP subunit and beta-gamma subunit interact
with other cellular effectors which further activates
second messengers responsible for other actions
within the cell

54. SECOND MESSENGERS
These are essential in conducting and
amplifying signals coming from G-Protein
Coupled receptors
A common pathway turned on by Gs and other
types of G proteins, is the activation of adenyl
cyclase by α GTP subunits, which results in the
production of cAMP- a second messenger that
regulates protein phosphorylation

55. ENZYME LINKED
RECEPTORS
Consists of a protein that spans the membrane
once and may form dimers or multisubunit
complexes
Also have cytosolic enzyme activity as an
integral component of their structure
Metabolism, growth and differentiation are
important biological functions controlled by these

56. INTRACELLULAR
RECEPTORS
Ligand must be sufficiently lipid soluble so as to
diffuse into the cell to interact with this receptor
Steroid hormones exert their action on target via
this receptor mechanism
Binding of the ligand to its receptor activates the
receptor and the activated ligand-receptor
complex migrates to the nucleus, where it binds to
specific DNA sequence, resulting in the regulation
of gene expression
Other targets of intracellular ligands are
structural proteins, enzymes, RNA and ribosomes

57. PHARMACOLOGIC
RECEPTORS

58. CHARACTERS OF
SIGNAL TRANSDUCTION
1.Ability to amplify small signals:
Firstly, a single ligand-receptor complex can
interact with many G proteins, thereby
the original signal by manyfold
Secondly, the activated G proteins persists for
longer duration to amplify the signals
2. Desensitization of Receptors:
When the repeated administration of a drug
in a diminished effect, the phenomenon is
tachyphylaxis
In this process, the receptors are still present
the cell surface but are unresponsive to the

59. II. DOSE RESPONSE
RELATIONSHIP
As the concentration of drug increases, the
magnitude of its pharmacologic effect also
increses
Plotting the magnitude of the response against
the increasing dose of drug produces the graded
drug-dose response curve, that generally has a
shape of a rectangular hyperbola
The two important properties of the drug
defined in the graph are its efficacy and
potency

60. 1. Potency
It is an amount of drug required to produce an
effect of a given amplitude
The concentration of drug producing an effect
of 50% of the maximum is commonly
designated as EC50
2. Efficacy
It’s the ability of the drug to elicit a response
when it interacts with a receptor
A drug with greater efficacy is more important
than drug potency
Maximal efficacy assumes that all the
receptors are occupied by the drug and no
increase in the response will be observed if
more drugs is added

61. III. AGONISTS
Binds to a receptor and produces a biological
response which may mimic the response of an
endogenous ligand
A. Full Agonist:
If a drug binds to a receptor and produces a
maximal biological response it is known as a full
agonist
B. Partial Agonist:
Have efficacies greater than zero but less than
that of full agonist
The unique feature of partial agonist is that,
under appropriate conditions, a partial agonist

62. C. Inverse Agonist
They reverse the constitutive activity of
receptors and exert the opposite
pharmacological effect of receptor agonist

63. IV. ANTAGONISTS
Antagonist are the drugs that decrease or
oppose the actions of another drug or
endogenous ligand
An antagonist has no effect if an agonist is not
present
If both the antagonist and the agonist bind to the
same receptor then they are said to be
competitive
An antagonist may act at a completely separate

65. V. THERAPEUTIC INDEX
The therapeutic index of the drug is the ratio of
the dose that produces toxicity to the dose that
produces a clinically desired response in the
population of the individuals
Where , TD50=the drug that produces toxic effect in
effect in half the population
population
ED50=the drug that produces a therapeutic
effect in half the population
TI=TD50/ED50

66. OCULAR
PHARMACOLOGY

67. MECHANISMS OF OCULAR
DRUG ABSORPTION
Drugs can be administered in many different
topical forms, including solutions, gels and
ointments.
The efficacy of treatment is usually dependent
on intraocular penetration, which depends on:
1) Permeability of the drug across the
cornea
2) Anatomical and physiological influences
of the local environment, including
lacrimation, tear drainage and the

68. ROUTES OF
ADMINISTRATION
Conjunctiva
Topical administration into the inferior
the conjunctiva is by far the most common
of ocular drug delivery
Both lacrimation and blinking profoundly
influence the residence time of fluid in the

69. CLINICAL CORRELATION
The conjunctival sac has a capacity of
approximately 15–30 μL (dependent on blinking)
and the natural tear film volume is 7–8 μL
 The tears turn over at approximately 16% per
minute during a normal blink rate of 15–20
blinks per minute
 Most solution applicators deliver between 50
and 100 μL per drop, so a substantial amount of
drug will be lost through overspill on
administration

70. After its transport through the epithelium, in the
subconjunctival stroma, which is a highly vascular
conjunctiva owing to the rich superficial venous plexus and
lid margin vessels, drugs may be absorbed in significant
concentrations into the circulation
After administration into the inferior fornix, drugs drain
directly through the nasolacrimal duct into the nose, where
measurable systemic absorption of drugs via the nasal
and nasopharyngeal mucosa occurs
Restricting the entry of a topically applied ophthalmic
dose into the nasal cavity by nasolacrimal occlusion for
5 min, or by making appropriate alterations to the vehicle
(i.e. from solution to ointment) increases ocular absorption

71. PRECORNEAL
TEAR FILM
AND CORNEA
The pH of normal tears varies between 6.5 and
7.6, while many drug delivery systems are often
formulated at pH of less than 7
Any alteration in the components of the tear film
will result in instability of the tear film and a
reduced conjunctival residence time of the drug.
At the same time alteration in the pH of the tear
film may affect the ionization of the drug and thus
its diffusion capacity.

72. TRANSPORT OF DRUGS
ACROSS CORNEA
The epithelium of the
cornea represents the most
important barrier to the drugs
via this route.
 First, the stratified cellular
epithelium is bound by
desmosomes between the
lateral borders of the
superficial cells.
Second, the corneal
epithelium is hydrophobic so
will allow only lipid-soluble

73. Bowman’s membrane, an acellular
collagenous sheet, shows similar drug
penetration characters with the stroma
In contrast, the stroma, which accounts for
90% of the corneal substance, permits ionized
water-soluble drugs to pass more efficiently than
lipid-soluble drugs.
Finally, transport across the single-layer
endothelium of the cornea is relatively free
because it contains gap junctions that permit
good penetration of most drugs into the
aqueous humour.
Hence to exhibit better ocular penetration
many topical eye medications are weak bases,

74. CILIARY BODY
Drugs are usually limited by the apically tight
junctions of the non-pigmented cells of the ciliary
epithelium
Systemic drugs enter the anterior and posterior
chambers largely by passing through the ciliary
body vasculature and then diffusing into the iris,
where they can enter the aqueous humor
The ciliary body is the major ocular source of
drug metabolizing enzymes

75. LENS
The lens can be viewed primarily as a barrier to
rapid penetration of drugs from aqueous to vitreous
humor
Hydrophilic drugs of high molecular weight cannot
be absorbed by the lens from the aqueous humor,
because the lens epithelium is a major barrier to
entry
Lipid-soluble drugs, however, can pass slowly
into and through the lens Cortex
After the lens removal following cataract surgery
more rapid exchange can occur between aqueous

76. VITREOUS
Vitreous can serve both as a major reservoir for
drugs and as a temporary storage depot for
metabolites
RETINA AND OPTIC NERVE
Tight junctional complexes (zonula occludens) in
the retinal pigment epithelium prevent the ready
movement of antibiotics and other drugs from the
blood to the retina and vitreous
The barrier protects against the entry of a wide
variety of metabolites and toxins and is effective
against most hydrophilic drugs, which do not cross

77. REMOVAL OF DRUGS
AND METABOLITES
The bloodstream is responsible for removing
drugs and drug metabolites from ocular tissues
The two circulatory pathways in the eye—the
retinal vessels and the uveal vessels—are fairly
different
The retinal vessels can remove many drugs,
metabolites, and such agents as prostaglandins
from the vitreous humor and retina, apparently by
active transport
The uveal vessels remove drugs by bulk
transport from the iris and ciliary body

78. BIOAVAILABILITY OF
OCULAR DRUGS
Precorneal fluid dynamics
Drug binding to tear proteins
Conjunctival drug absorption
Systemic drug absorption
Resistance to corneal penetration
Drug binding to melanin
Intraocular drug metabolism

79. OCULAR DRUG
DELIVERY SYSTEM
The corneal epithelium presents a considerably
greater barrier to hydrophilic than to lipophilic
drugs (10 : 1)
Corneal epithelial permeability increases during
ocular inflammation increasing the absorption of
drugs, like dexamethasone
Penetration of anionic sodium fluorescein, a
hydrophilic agent, only in cases epithelial
breakdown is also suggestive of lipophilic nature
of corneal epthelium
Preservatives such as benzalkonium chloride
have also been shown to enhance the ocular

80.  [
For a drug to penetrate optimally, it must be
able to exist in both ionized and un-ionized
forms.
Drugs will be buffered by the precorneal tear
film and any alteration in the pH will change the
ratio of ionized to un-ionized forms of the drug
 [
Once absorbed into the eye, drugs may be
bound to melanin within the pigment epithelium
of the iris and the ciliary body, which may in turn
reduce its bioavailability and also retard its
clearance
Similarly, after penetrating into the eye, drugs
may be rendered inactive by intraocular

81. DRUG VEHICLES
AFFECT DRUG
DELIVERY1. Solutions
Solutions are a common mode of delivery because
cause less blurring of vision than ointments
They are easily administered and achieve high
concentrations
Possess a short contact time and are quickly washed
at a rate proportional to the volume instilled
 Polyvinyl alcohol or methylcellulose added to the
increases the viscosity and/or lowers the surface
and will thus prolong contact time.
Ophthalmic suspensions, particularly steroids,
assumed to have the drug particles that persist in the
conjunctival sac which gives rise to a sustained-
effect

82. 2. Semisolids (ointments)
Ointments consist of any one or a combination
hydrocarbons, mineral oils, lanolin and polymers
as polyvinyl alcohol, carbopol and methylcellulose
Drugs applied by this method provide an
the duration of action because of reduced
reduced drainage and prolonged corneal contact
Give rise to blurring of the vision and an
incidence of contact dermatitis
Lid Scrub:
 After several drops of the antibiotic solution or
detergent, such as baby shampoo, are placed on
end of a cotton-tipped applicator, the solution is
to the lid margin with the eyelids either opened or
closed

83. 3. Slow-release preparations
Ocular Inserts
Controlled-release delivery systems deliver a
bioactive agent to the target site at a controlled
concentration over a desired time course.
 Ocular inserts are flexible, elliptical devices,
consisting of three layers. The two outer coats of
ethylene vinyl acetate enclose an inner coat of
drug/alginate mix.
Collagen shields
The collagen bandage shields prolong contact
between drug and cornea
Drugs can be incorporated into the collagen
absorbed on to the shield during rehydration, or
applied topically over a shield when in the eye
the shield releases the drugs gradually into the
film

84. Soft contact lens
 In this case the polymer of the contact lens
hydrophilic and thus water-soluble drugs are
absorbed into the lens
 The lens is hydrated once placed on to the
cornea and so releases the drug until
is reached between drug concentration in the
contact lens and in the conjunctival sac
Intravitreal inserts
Has gained increasing impetus following
successful trial evidence supporting
drug administration for macular
vascular occlusions and CMV viral retinitis

85. INTRACAMERAL AND
INTRAVITREAL
ADMINISTRATION
The treatment of many ocular disorders is
hampered by poor penetration into the eye
Intracameral administration involves delivering
a drug directly into the anterior chamber of the
eye
The treatment of bacterial endophthalmitis is
often inadequate unless vitrectomy and
intravitreal antibiotics are used

86. PERIOCULAR
ADMINISTRATION
When higher concentrations of drugs,
particularly corticosteroids and antibiotics, are
required local injections into the periocular tissues
can be considered
Includes subconjunctival, sub- Tenon’s,
retrobulbar, and peribulbar administration
Subconjunctival Injection:
Offer an advantage in the administration of
drugs, such as antibiotics, with poor intraocular
penetration

87.  Greatest clinical benefit of the sub-conjunctival route is
in the treatment of severe corneal disease, such as
bacterial ulcers
Sub- Tenon’s Injection:
Anterior sub-Tenon’s injections of corticosteroids are
occasionally used in the treatment of severe uveitis
Posterior sub-Tenon’s injection of corticosteroids is
most often used in the treatment of chronic equatorial
and mid-zone posterior uveitis, including inflammation of
the macular region
 Cystoid macular edema after cataract extraction and
diabetic macular edema are treated occasionally with

88. Retrobulbular Injection:
Originally developed to anesthetize the globe for
extraction
However antibiotics, vasodilators, corticosteroids,
alcohol have also been administered through this
Currently, retrobulbar anesthetics are frequently
retrobulbar corticosteroids are used occasionally and
retrobulbar alcohol or phenol is rarely administered
intractable ocular pain in blind eyes
Peribulbular Injection:
The procedure consists of placing one or two
of local anesthetic around the globe but not directly
the muscle cone

89. ADVANCED OCULAR
DELIVERY SYSTEM
New Ophthalmic Delivery System(NODS) is a
method of administering a drug as a single unit
volume within a water-soluble preservative-free
form
Particulates: Microspheres and nanoparticles
represent promising particulate polymeric drug
delivery systems for ophthalmic medications
Liposomes are vesicles composed of lipid
membranes enclosing an aqueous volume
Iontophoresis is a method of drug delivery that
utilizes an electric current to drive a polar drug

90. DRUGS ADMINISTERED
SYSTEMICALLY ALSO
PENETRATE THE EYE
Carbonic anhydrase inhibitors (acetazolamide
and dichlorphenamide), are administered orally or
intravenously to reduce intraocular pressure.
Systemic antibiotics, like ciprofloxacin, are found
to have the ability to reach intraocular infections.
Similarly, both non-steroidal anti-inflammatory
drugs and steroids penetrate the eye when given
orally.
Conversely, drugs applied topically may also
reach the systemic circulation and affect the
contralateral eye.

91. INSTILLING TOPICAL
OCULAR SOLUTIONS

92. PRESCRIPTION

94. REFERENCES