MIOTICS AND

MYDRIATICS,
DRUGS USED IN
GLAUCOMA,
OPHTHALMOLOGICAL
DIAGNOSTIC AGENTS
DR O. M. ALASIA
OCULAR PHARMACOLOGY
• Pharmacokinetics
• Study of chemical alteration of drug in the body
• 1. Absorption
• 2. Distribution
• 3. Metabolism
• 4. Excretion
 Absorption

• Absorption is the movement of the drug from its site of

administration to the target tissue (to produce the
desired effect).
• Not only the fraction of administered dose that gets
absorbed but the rate of absorption is also important.
Factors influencing absorption of drug

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 eg- Benzylalkonium 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
Factors influencing absorption of drug
Barrier for intraocular transport of drugs
Corneal epithelium and stroma: most important
Blood ocular barriers: blood retinal barrier, blood aqueous barrier
• Blink rate
• Absorption through conjunctival vessels and mucosa
• Nasolacrimal drainage of tears
 Distribution

• Once the drug is absorbed, it has the potential to

penetrate most compartments of the body known as distribution.

• Distribution largely depends on the route of administration.

Distribution

• Distribution: Topical

• Transcorneal absorption

• Accumulation in aqueous humor

• Distribution to intraocular structures

• Trabecular Meshwork

• Distribution in systemic circulation

Factors affecting distribution
Physiochemical properties of drug:
• Acidic/basic

• Binding to plasma proteins

• Binding to tissue proteins

• Relative blood flow to different tissues

 Metabolism

• Drugs are metabolized to facilitate clearance &

activate prodrugs for enhanced permeability
• Enzymatic biotransformation
Eg: Esterases, ketone reductase & phase 1 &2 oxidizing
and conjugating enzymes
Eg. 1. Dipivefrine hydrochloride - Epinephrine
2. Latanoprost (isopropyl ester)- acid
3. Nepafenac 0.1% - Amfenac
 Metabolism

• Many of the drugs metabolized and excreted via

kidneys or liver mostly
1. Timolol – Liver
2. Mannitol – kidneys
3. Acetazolamide – kidneys
4. Latanoprost (PG)- liver
5. Local anesthetics- liver/ plasma
• Routes of administration
• Topical Periocular Intraocular
• Solutions Subconjunctival Intracameral
• Gels Subtenon Intravitreal
• Ointments Peribulbar
• Contactlens Retrobulbar
MIOTICS & MYDRIATICS
Muscles of the iris:

• DILATOR PUPILLAE • SPHINCTER PUPILLAE

• Dual nerve supply. • Dual nerve supply.

• Sympathetic α1 adrenergic are • Parasympathetic muscarinic are

stimulatory while stimulatory while sympathetic are
parasympathetic are inhibitory inhibitory.
Miotics
Parasympathomimetic drugs
• Cholinergic drugs Classified as-
1. Directly acting or agonists. Eg-acetylcholine, bethanechol,
pilocarpine.
2. Indirectly acting or cholinesterase inhibitors.
a. Reversible. Eg- physostigmine, neostigmine, edrophonium.
b. Irreversible. Eg- ecothiophate iodide, demecarium,
diisopropylfluro phosphate.
3. Dual action: having both muscarinic and weak cholinesterase
action. Eg carbachol.
4. Reactivation of acetylcholinesterase: pralidoxime.
• Five types of muscarinic receptors

• The M1 receptors are located in the nervous system.

• The M2 receptors are located in the heart, and slow the heart
rate and force of contraction.

• The M3 receptors are located at the endothelial cells of blood vessels and cause vasodilatation, lungs causing
bronchoconstriction the smooth muscles of the GIT to increase intestinal motility and dilating sphincters, glands
to stimulate secretion in salivary glands, detrusor muscle and urothelium of the bladder, causing contraction. They
are present in the ciliary muscle and the iris.

• The M4 receptors: Postganglionic cholinergic nerves, possible CNS effects

• The M5 receptors: Possible effects on the CNS

Stimulation of the M3 receptors in the eye
causes-
1. Contraction of the pupil (miosis) and alters the relationship
of the iris with thee lens behind and the anterior chamber
angle in front.
2. They contract the longitudinal fibres of the ciliary body and
cause opening of the trabecular meshwork and increase
the aqueous outflow.
3. They cause contraction of the circular muscles of the ciliary
body thus causing the zonules to relax and allow the lens
to assume a more spherical shape (accommodation).
 Pilocarpine hydrochloride

• It is a parasympathomimetic alkaloid obtained from the leaves of

tropical South American shrubs from the genus Pilocarpus. It is a
nonselective muscarinic receptor agonist.

• It was introduced in 1877 for the treatment of glaucoma.

• When applied topically it is largely degraded in the cornea. Only 3%

enters the aqueous.

• It is available in 0.12%, 0.25%, 0.5%, 1%, 2%, 3% ,4%, 6%.

 • Pilocarpine ocular therapeutic system (ocusert)
is available as ocusert P-40 or P-20 or
incorporated into soft contact lenses.
• Is also available in a polymer vehicle as a gel
that prolongs the duration of action.
• The ocusert releases 3 times the dose for 1 hour
and then declines to required value over 6
hours.
• Are to be placed in the cul de sac before
sleeping, so that the induced myopia wanes
away by morning.
Uses:
1. It causes complete miosis on intracameral administration. Used in
cataract Rx after lens extraction, in penetrating keratoplasty, iridectomy,
etc.
2. 0.12% is used diagnostically to confirm Adie’s tonic pupil. In this
condition there is defective parasympathetic innervation to the iris and
ciliary body due to post ganglionic denervation. The affected muscles
exhibit hypersensitivity to pilocarpine and hence contract, while normal
iris does not react to this low concentration.
3. 0.25% to 6% are used in the management of primary open angle
glaucoma. It is contraindicated in acute angle closure glaucoma because
it cause anterior movement of lens iris diaphragm.
4. As it causes increase in tear secretion and punctal stenosis as side
effects, it is used in aqueous tear deficiency (ATD) dry eye. Due to
increased salivation and lacrymal secretion it is used in Sjgrens’s
syndrome and also for dry eye and xerostomia as an effect of radiation
therapy for head and neck cancer.

5. Used to differentiate pharmacological mydriasis from neurological

mydriasis. In pharmacological as the receptors are saturated, the pupil
will remain dilated while in third nerve palsy or Adie’s tonic pupil it will
constrict even with very dilute solution.
6. Used to reduce glare in patients with intra ocular lens Implantation.

7. Pilocarpine is used to stimulate sweat glands in a sweat test to measure

the concentration of chloride and sodium that is excreted in sweat. It is
used to diagnose cystic fibrosis.
Adverse effects

1. Contraction of the ciliary body can cause traction on the pars plana as well
causing retinal tear or rhegmatogenous retinal detachment.
2. Catarctogenesis.
3. Drug induced contraction of the ciliary body causes increased convexity of
the lens and shifts the lens forward. Hence causes induced myopia. This causes
brow ache.
4. Reduced vision during night time due to miosis. Reduced field of vision.
5. Higher concentration use causes miotic iris cysts
6. Increased lacrimal secretion and punctal stenosis can cause epiphora.
7. Increased bleeding during surgery.
8. It causes break down of the blood aqueous barrier hence can cause
severe fibrinous iridocyclitis post operative. Hence it is contraindicated
in uveitic glaucoma.
9. Posterior synechiae formation.
10. It is known to cause idiosyncratic reaction, allergic reaction,
pseudopemphigoid.
11. Systemic- salivation, diarrhoea, urinary urgency, vomiting,
bronchospasm, bradycardia, diaphoresis, flushing.
12. Succinyl choline should be avoided in patients who have used these
drugs recently.
Acetylcholine Carbachol
• Used only intracamerally as It is 100 times effective and
it is not active if used topically. longer acting than acetylcholine.
• Available as a powder. Fresh • Lesser fluctuations in IOP.
solution has to be prepared. Effect last upto 8 hours.
When given intracamerally it • ADR- corneal clouding, bullous
causes miosis in seconds. keratopathy, iritis, injection, ciliary
• Rapidly degraded by spasm, retinal detachment.
cholinesterases in aqueous. • Topical- 0.75%, 1.5%, 2.5%, 3%.
3 times a day
Hence v short acting
• Intracameral- 0.01%
Physostigmine Demecarium
• Acetylcholinesterase inhibitor. • Same as physostigmine.
• Also used for accommodative
• Same actions, uses. esotropia. 0.125% once a day for 3-4
weeks. Miosis may interfere.
• Used in patients who fail to respond
to directly acting cholinergic agents. • Prolonged action. Twice daily usage.
Severe ADR.
• 0.25-0.5% up to 4 times a day. Eye
ointment also available. • 0.125% twice a day.
• Avoid overdosing.
 Echothiophate
• Depresses plasma & erythrocyte cholinesterase.
• Irreversible acetylcholinesterase inhibitor
• Used in subacute or chronic angle closure glaucoma.
• Topical solution is prepared by reconstituting powder form.
Concentrations available are 0.03, 0.06, 0.125 and 0.25%.
• Tolerance may develop on chronic use.
• As it is an insecticide it is also used for lice infestations of the eye
lashes
 Mydriatics
•Mydriatics are agents which dilate the pupil and cycloplegics are agents
which cause paralysis off the ciliary body.
• Two classes of mydriatics are available-
1. Adrenergic agonists- adrenaline, cocaine, phenylephrine,
hydroxyamphetamine.
They cause pupillary dilatation, increase in aqueous outflow, decreased
aqueous formation, and relaxation of ciliary muscles.
2. Cholinergic antagonists- tropicamide. Causes mydriasis and
cycloplegia.
Adrenaline (epinephrine) Cocaine
• Causes mydriasis. • Alkaloid
• 1:1000 solution used. • 2% and 4% solution.
Repeated in 5 minutes. • Toxic to corneal epithelium
• Used for open angle (hence increased penetration).
glaucoma. • Inhibits the action of
• Can be used with procaine and amine oxidases and hence
atropine in severe iritis. reduces the uptake of NE.
• Used to diagnose Horner’s
syndrome.
Horner’s syndrome.

• It is caused due to a lesion in the oculosympathetic

pathway.
• Characterised by ipsilateral miosis, ptosis and
anhidrosis.
• The light reflex is normal in these patients but the
pupil is slow to redilate in dim light.
It can be tested pharmacologically as

Step 1: Instill 2 drops of 4% cocaine in both eyes.

It inhibits reuptake of nor epinephrine from the post ganglionic segment.

Hence causes mydriasis. But in Horner’s there is no NE. Hence no dilatation.

Post cocaine anisocoria of 1mm is diagnostic.

Apraclonidine has weak α1 agonistic action. In normal eyes it has little effect
on pupil. But in Horner’s syndrome there is supersensitivity and the pupil
dilates.
 Step 2:
• once diagnosis is established, hydroxyamphetamine is used to localize
the lesion.

•Normal pupil dilates with hydroxyamphetamine. If the Horner’s pupil

does not dilate means lesion is in the postganglionic segment. But if it
does dilate lesion is in the preganglionic segment.
Phenylephrine hydrochloride

• Causes pupil dilatation and conjunctival vasoconstriction causing

blanching.
• Action can be reversed by thymoxamine 0.1%.
• 2.5 and 10% concentrations. 2.5% used most commonly.
• Sufficient mydriasis occurs in 15-30 mins, maximum dilation in 45-60
mins and remains for 4- 6 hours.
• Since sphincter pupillae muscles are stronger than dilator, mydriasis
caused by phenylephrine is largely overcome by light reflex.
Adverse effects
 Ocular- transient stinging, blurring, • Brow ache.
rarely maculopathy in aphakic • Reflex bradycardia
patients. • Stroke.
 Systemic- • Myocardial infarction.
• Palpitations.
• Tachycardia. 10% solution contains 5mg
• Extrasystoles. of drug per drop. Systemic
• Arrhythmias. dose for hypotension is 50-
• Hypertension. 100 micro gram
• Headache
Contraindicated in

• Narrow angle glaucoma.

• Hypertensives.
• Type 1 diabetes mellitus.
• Aneurysms.
• Cardiac diseases.
• Old debilitated patients
• Patients on reserpine, TCAs MAO inhibitors or cocaine.
• Infants. As it increases BP (dose per unit weight is high)
Hydroxyamphetamine hydrobromide

• Indirect acting adrenergic agent.

• It releases nor- epinephrine from post
ganglionic nerves.
•Minimal cycloplegia.
•1% concentration equivalent to 2.5%
phenylephrine.
•25-40 minutes for max dilatation. Lasts 4-6
hours.
 Uses

•To dilate the pupil for ocular examination.

• To differentiate post ganglionic Horner’s syndrome from preganglionic

Horner’s syndrome.
Post ganglionic lesions fail to dilate.
 Tropicamide
•Blocks the effect of acetylcholine released.

•Causes both mydriasis and cycloplegia.

•0.5 or 1% acts within 20-30 minutes and effect lasts for 6-8 hours.

•Mydriasis is more pronounced. It prevents pupil constriction in response to

indirect ophthalmoscopy and retinal photography.

•Independent of iris pigmentation.

 Uses
• Since it has no vasopressor action it can be used safely in cardiac
patients.

• It is the first choice of mydriatic because it is rapid acting, short acting,

and strong intensity of action.

•Commonly used as a combination with phenylephrine or

hydroxyamphetamine.
Mydriatics and cycloplegics Uses

•Atropine, homatropine, scopolamine and

cyclopentolate are cycloplegics that are used in
uveitis or acute anterior segment inflammation to
reduce the formation of posterior synechiae.
• They also reduce the permeability of blood aqueous
barrier and help to reduce inflammation apart from
causing cycloplegia.
• They can be used as occlusion therapy for
amblyopia.
DRUGS USED IN GLAUCOMA
• Glaucoma- ancient meaning (Greek) clouded or blue green colors

• Glaucoma- blindness coming from advancing years

• Second leading cause of blindness

• Glaucoma is a group of disorders characterized by a progressive optic neuropathy

resulting in a characteristic appearance of optic disc and specific pattern of
irreversible visual defects that are associated frequently but not variably with
increased IOP (less than 21 mm Hg)

• All types of glaucoma lead to death of retinal ganglion cells (RGCs)

 Aqueous Humor Dynamics
• Aqueous is continuously produced by the ciliary body (2-3µl/minute)

• Aqueous flow from the posterior chamber through the pupil into the anterior
chamber

• Aqueous filters largely through the trabecular meshwork (90%) and canal of
Schlemm---episcleral venous plexus and into systemic circulation

• Aqueous also exits to a smaller extent through the ocular venous system (10%)
Types of Glaucoma
• Congenital glaucoma

• Primary glaucoma
---open angle
---closed angle
• Secondary glaucoma-
Lens induced, traumatic or steroid induced

• Absolute glaucoma
Therapeutic Goal

• Lower IOT by
-Reduction of aqueous humor secretion
-Promoting aqueous drainage
• Lowering of IOT retards the progression of optic nerve damage even in
normal/low i.o.t.
 Sites of action of ocular hypotensive
drugs
 Open angle/wide angle/chronic simple
glaucoma
• Genetically predisposed degenerative disease affecting patency of trabecular
meshwork
• Meshwork becomes less efficient at draining
• IOP builds up progressively
• Damage of the optic nerve
• Has no symptoms in its early stages after middle age
• Ocular hypotensive drugs– reduce formation of AH, increase drainage or protect
optic nerve
Available Drugs
• Beta-adrenergic blockers: Timolol, Betaxolol, Levobunolol, Carteolol,
Metipranolol
• Alpa-adrenergic agonists: Dipiverfrine, Apraclonidine and
Brimonidine
• PG analogue: Latanoprost, Travoprost and Bimatoprost
• Carbonic anhydrase inhibitors: Acetazolamide and dorzolamide
• Miotics: Pilocarpine and Physostigmine
 Beta- adrenergic blocker in glaucoma-MOA
• Topical beta-adrenergic blockers have been the 1st line of drugs PG F2a are
preferred now
• Contrast to miotics—no effects on pupil size, tone of ciliary muscle and outflow
facility
• Lower IOP by reducing aqueous formation
-Down regulation of adenylcyclase due to B2 receptor blockade in ciliary
epithelium
-Reduction of blood flow
• Advantages over miotics—produce less ocular side effects, lipophilic and weak
anaesthetic (corneal hyposthesia and damage)
Beta- adrenergic blockers ----contd
• Ocular side effects: mild and infrequent
-stinging, redness, dryness
-corneal hypoesthesia
-blurred vision
-blepharoconjunctivitis
• Systemic adverse effects: major limitation of use
-nasolacrimal duct
-life threatening bronchospasm-COPD and asthma
-bradycardia, heart block and CHF-ADRs
-inner canthus pressure-5min
 Individual Drugs
• Timolol (0.25-0.5% eye drops): non-selective-Beta1+beta2
-no LA or sympathomimetic action
-decreased IOT by 20-35%- 1 hour to 12 hours
-smooth and well sustained action after chronic dosing –high level of clinical safety
-30% patients response

• Betaxolol (0.5%)
-selective beta1 blocker-less bronchopulmonary, probably less cardiac, central and metabolic
effects
-exert protective effect on retinal neurons
-less efficacious in decreasing IOT than Timolol (Beta2)

• Levobunolol: once daily dosing alt. to Timolol

-ocular and systemic side effects similar to timolol
 Alpha-adrenergic agonists
• MOA
-Alpha1 constrict cilliary body—reduced aqueous secretion
-alpha2 in ciliary epithelium reduce aqueous secretion
-secondary role in enhancing drainage of aqueous mainly through uveoscleral
ouflow and also trabecular outflow
• Dipiverfrine (0.1%)
-adrenaline-ocular smarting, reactive hyperemia
-prodrug of adrenalin—Adr. Decrease IOT by increasing uveoscleral outflow,
increase trabecular outflow (Beta2), decrease aqueous production (alpha1 + alpha2)
-not used now due to systemic effects and ocular intolerance
-maybe used as an add-on therapys
 Alpha-adrenergic agonists---contd
• Apraclonidine (0.5-1%): Clonidine congener
-No CNS production
-decreased IOT by approx. 25%
-ADRs: itching, lid dermatitis, follicular conjunctivities, mydriasis, eyelid retraction,
dryness of mouth and nose, etc.
-use of restricted to short term control of IOT spikes (trabecloplasty or iridotomy).

• Brimonidine (0.2%): newer clonidine congener, more selective to alpha2

-more lipophilic than apraclonidine
-decreased IOT by 20-27% by decreased aq. Production and increased uveoscleral flow.
-uses both in short term (post surgery) and long term therapy in glaucoma—add on
therapy
 Prostaglandin analogues
• Low concentration of PGF2α analogues decrease IOT by:
-increase uveoscleral outflow (increase ciliary tissue permeability and vascular
permeability)
-trabecular outflow less marked
-down regulation of ciliary body COX-2 in wide angle glaucoma – a role of PG in aq.
Humor dynamics.
• Latanoprost (0.005% eye drop)
-topically IOT decrease 25-35% well sustained
-decrease IOT in normal pressure glaucoma
-ocular irritation and pain
-good efficacy, once daily application and absence of systemic complications-first
choice in open glaucoma
-other ADRs: blurring of vision, iris pigmentation, thickening and darkening of eye
lashes, etc.
• Travoprost and bimatoprost: similar efficacy with latanoprost
 Carbonic anhydrase
inhibitors
• Carbonic anhydrase present within ciliary epithelial cells generates HCO-3 ion
secreted into aq. Humour.
• Inhibition of carbonic anhydrase-limits generation of HCO-3 ion---reduction of
aq. Humour.
• Acetazolamide:
-orally-0.25 gm 6-12 hrly
-used to supplement ocular hypotensive drugs for short term indication like
angle closure, before and after surgery/laser therapy
-long term use when IOP not controlled by topical drugs
• Side effects: systemic s/e-parastheisa, anorexia, hypokalemia, acidosis, malaise,
depression (on long term use)
• Dorzolamide: 2% eye drop topical -20% efficacy
 miotics
• Last option because of several draw backs-myopia, diminution of vision,
headache
• Pilocarpine
-causes miosis by contraction of iris sphincter muscle—removes pupillary
block and reverses obliteration of iridocorneal angle
-contraction of ciliary muscle---pulls on scleral spur and improves
trabecular patency
-max of 10-20% IOP reduction- 0.5% to 4% solution
 OAG—current appraoch
• Monotherapy with Latanoprost or a topical beta-blocker
• If not target attained-change to alternative drug or both together
• Brimonidine/dorzolamide (or dipivefrine) used whent above two
contraindicated
• Acetazolamide and mitotics-last options
Angle closure (narrow angle, acute congestive)
Glaucoma
• Emergency situation occurring in person with narrow iridocorneal angle and
shallow interior chamber
• IOT raised after it is being precipitated by mydriasis
• IOT rises rapidly to very high levels (40 -60 mmHg)
• Marked congestion of eyes and severe headache
• Failure to lower IOT ---loss of sight
• Definite treatment---surgery (iridotomy/laser therapy)
 Therapy of closed angle Glaucoma
1. Hypertonic mannitol (20%) 1.5-2g/kg or glycerol (10%):
-IV infusion-decongest eye by osmotic action
-Glycerine 50%- retention enema
2. Acetazolamide (0.5g) IV followed by oral BD started concurrently
3. Miotic: if above reduced the IOP—topical pilocarpine 1-4% every 10 mins
initially and then at longer intervals
4. Topical beta blocker: Timol 0.5% 12 hrly in addition
5. Latanaprost (0.005%)/Apraclonidine (1%) may also be added

Chronic narrow angle: mitotic/other drugs for longer period

PHARMACOLOGICAL DIAGNOSTIC
AGENTS
 OUTLINE
• INTRODUCTION
• ROUTES OF OPTHALMIC DRUG ADMINISTRATION
• FACTORS INFLUENCING DRUG PENETRATION
• CLASSES OF OPHTHALMIC DIAGNOSTIC AGENTS
• MYDRIASIS AND THE RISK OF ANGLE CLOSURE GLAUCOMA
• CYCLOPLEGICS
• MYDRIATICS
• ANESTHETICS
• OPTHALMIC DIAGNOSTIC DYES
 INTRODUCTION

In order the make proper diagnoses of eye conditions, proper

investigations need to be carried out. Some of these investigations
require the use of some medications and diagnostic agents to facilitate
proper examination of ocular structures which will thereby lead to proper
identification of the ocular defect. These agents and medications are
known as ocular diagnostic agents.
ROUTES OF OPHTHALMIC
DRUG ADMINISTRATION
TOPICAL PERIOCULAR INTRAOCULAR
SYSTEMIC
SOLUTIONS SUB CONJUNCTIVA INTRACAMERAL
ORAL
OINTMENTS SUB TENDON INTRAVITREAL
INTRAVENOUS
GELS PERIBULBAR
INTRAMUSCULAR
CONTACT LENS RETROBULBAR
FACTORS AFFECTING DRUG
PENETRATION INTO OCULAR TISSUE
• Drug concentration and solubility: the higher the concentration
the better the penetration e.g pilocarpine 1-4% but limited by
reflex tearing.
• Viscosity: addition of methylcellulose and polyvinyl alcohol
increases drug penetration by increasing the contact time with
the cornea and altering corneal epithelium
• Lipid solubility: because of the lipid rich environment of the
epithelial cell membranes, the higher lipid solubility the more
the penetration
Amphipathic- epithelium/endothelium----lipophilic
stroma---hydrophilic
FACTORS AFFECTING DRUG
PENETRATION INTO OCULAR TISSUE
• Surfactants: the preservatives used in ocular
preparations alter cell membrane in the cornea and
increase drug permeability e.g. benzyalkonium and
thiomersal
• pH: the normal tear pH is 7.4 and if the drug pH is
much different, this will cause reflex tearing.
• Drug tonicity: when an alkaloid drug is put in
relatively alkaloid medium, the proportion of the
uncharged form will increase, thus more penetration
• Molecular weight and size.
DISTRIBUTION

TRANS- CORNEAL ABSORPTION

ACCUMULATION IN AQUEOUS HUMOR

DISTRIBUTION YO INTRAOCULAR STRUCTURES

DISTRIBUTION TO SYSTEMIC STRUCTURES

METABOLISM

Drugs are metabolized to facilitate clearance &

activate prodrugs for enhanced permeability
Enzymatic biotransformation of ocular drugs
significant Eg: Esterases, ketone reductase & phase 1
&2 oxidizing and conjugating enzymes
Ex: Development of prodrugs for enhanced ocular
permeability
1. Dipivefrin hydrochloride - Epinephrine
2. Nepafenac 0.1%- Amfenac
ELIMINATION

Many of the drugs metabolized and excreted via

kidneys or liver mostly
For Example:
1. Timolol – Liver
2. Mannitol – kidneys
3. Acetazolamide – kidneys
4. Latanoprost (PG)- liver
5. Local anesthetics- liver/ plasma
CLASSES OF OPHTHALMIC DIAGNOSTIC
AGENTS
• CYCLOPLEGICS

• ANAESTHETICS

• MYDRIATICS

• DYES
WHY USE DIAGNOSTICS

• Ocular media and fundus examination

• Enhancing retinal photography; optical coherence
tomography
• Refraction through cataracts when pupils are small
• Cycloplegic refraction
• Techniques where anesthesia is required
• For the differential diagnosis in various ocular
pathological conditions such as corneal abrasions,
congestion, micro aneurysm, blood vessel
proliferations in retina and ischemia etc
PRECAUTIONS

Although the risk of inducing an attack of acute glaucoma is evidently low, the
eye care provider should nevertheless take precautions to further
enhance the care they give to their patients.
1) Check anterior chamber angles before dilating. If
obviously almost closed then reconsider dilating
2) Check intraocular pressure (IOP) before dilating
3) If angles narrow, then check IOPs again
4) If angles narrow, warn patients of symptoms of
attack (pain, hazy vision, nausea)
 CYCLOPLEGICS
Cycloplegics are used to induce paralysis of the ciliary muscles of the
eye resulting in loss of accommodation.
Cycloplegics work by binding to effector sites in the ciliary muscle
thereby blocking action of acetylcholine.
Pupillary dilation is an (unwanted) side effect and its onset precedes
cycloplegia.
The eye caregiver should ensure there are no angle anomalies before
instillation of cycloplegic drop.
Cycloplegics are most often used in children in the presence of
esotropia or esophoria or when latent hypermetropia is suspected.
Another use is to impose penalization of a dominant eye in amblyopia
 MECHANISM OF ACTION
• Innervation of the ciliary body cause contraction of the ciliary
muscle to induce accommodation
• Cholinergic receptors in the human eye found in the iris
sphincter and ciliary body are of the muscarinic type.
• Muscarinic agonist at the receptors constricts the pupil, contracts
ciliary muscle thereby reducing Intraocular pressure and induce
accommodation.
• Cycloplegic drugs are anticholinergic thereby causing
antagonizing effect at the muscarinic receptors leading to
pupillary dilation and paralysis of accommodation.
EXAMPLES OF CYCLOPLEGIC DRUGS

• ATROPINE

• CYCLOPENTOLATE

• TROPICANAMIDE

• SCOPOLAMINE

• HOMATROPINE
 ATROPINE

• Atropine is a strong cycloplegic agent.

• Binds to and inhibits muscarinic acetylcholine receptors, producing a wide range of anticholinergic
effects

• Atropine Sulphate is used 0.5% and 1% as eye drops;

and 1% eye ointment.

• Muscarinic antagonist.

• Peak effect of the drug is in 2-3 days.

• Duration is 7-10 days.

 TROPICAMIDE

• Tropicamide (Midriacyl) is also a short duration cycloplegic available

in 0.5% and 1% solutions.

• A non-selective muscarinic antagonist that binds to all subtypes of

muscarinic receptors.

• For young adults 3 to 4 drops of the 1% solution, separated by a few

minutes, will bring about full cycloplegia in about 30 minutes.

• Recovery occurs within6-8 hours.

 CYCLOPENTOLATE

• Short duration cycloplegic agent available in 0.5%

and 1% solutions.
• Muscarinic antagonist

• Cycloplegia occurs within 30 to 45 minutes

and persists for as long as 24 hours.

• For children aged 6 to 16, one drop of 1% solution

• For adults one drop of 0.5% solution.

 SCOPOLAMINE

• Short duration cycloplegic agent

• A competitive inhibitor at postganglionic muscarinic receptor site of the

parasympathetic nervous system

• Available in 0.25% solution

• Onset of action occurs within 30-60mins

• Effect wares off within 7 days

SIDE EFFECTS

• Blurring of vision

• Difficulty with near work

• Photophobia

• Dry mouth

• Flushing of the face

• Fever
CONTRAINDICATIONS

• Abnormally shallow anterior chamber

• Dislocation or subluxation of the

crystalline lens.

• Patients using pilocarpine for treatment

of glaucoma

• An intraocular lens in the anterior

chamber or iris supported type.
MYDRIATICS
Mydriatics dilate the pupil to facilitate a
more thorough examination of the fundus,
lens periphery and vitreous. They are mostly used
on elderly patients, as older pupils are usually smaller
pupils and lens opacities and abnormal
retinal conditions are not uncommon.

MODE OF ACTION: The pupil dilator muscle is

innervated by the sympathetic nervous system
and sympathomimetic drugs such as phenylephrine
will cause a contraction of the dilator muscle
causing mydriasis. Sympathomimetic drugs also have
little effect on accommodation.
SYMPATHOMIMETIC
MYDRIATICS
• Phenylephrine is the only sympathomimetic mydriatic in
regular use. It is available in a variety of strengths but
2.5% and 10% are most often used.

• Mydriasis commences in 10mins and is maximal in

30minutes. Mydriatic effect can last for up to several
hours.

• There is little doubt that sympatomimetics produce less

effect on accommodation than antimuscarinics and some
authors like (Kanski 1969) suggest that phenylephrine
produces dilation without any cycloplegic effect at all.
ANTIMUSCARINIC MYDRIATICS

• Tropicamide
1. Tropicamide is the antimuscarinic mydriatic of choice
Today

2. It is available in 0.5% and 1.0% strengths. The

weaker solution is most often used for mydriasis
and the stronger solution for cycloplegia.

3. Tropicamide is popular for quick onset and short

duration. ( 10-30mins onset and 6-8 hours
duration)
CYCLOPENTOLATE

• The mydriatic concentration of cyclopentolate is 0.1%

compared with 0.5% and 1.% for cycloplegia. However
this strength is no longer available for use and if
cycloplentolate is used for dilation then there will be a
significant amount of cycloplegia accompanying its
use.
 HOMATROPINE

• At one time Homatropine was the principal mydriatic. Its mydriatic

effect commences at 10-20mns and is maximal in 20-40mins.
• Acts by blocking muscarinic receptors and cholinergic signal pathways.
Hence inhibit the response of the iris sphincternuscle and cause the
pupil to be unresponsive to light. It inhibits the accommodation
muscles of the cillary body to cholinergic stimulation.

• Recovery takes the same time as cyclopentlate if miotic is not used but
can be as prolonged as three days.
CYCLOPLEGIC AND MYDRIATICS
DRUG FORMULATION INDICATION ONSET OF ACTION
DURATION OF
ACTION
ATROPINE 0.5%, 1% & 2% Solution. Cycloplegia OA; 30-40 mins
1% ointment mydriasis Mydriasis-15 days
Cycloplegia -120mins
HOMATROPINE 2% & 5% solution Cycloplegia SAME AS ABOVE
Mydriasis

SCOPOLAMINE 0.25% solution Cycloplegia Mydriasis 7days

Mydriasis Cycloplegia 30-60 mins

CYCLOPENTOLATE 0.5% solution Cycloplegia OA; 15-30 MINS

Mydriasis Mydriasis 1 day
Cycloplegia 20-45 mins

TROPICAMIDE 0.5% & 1% solution Cycloplegia OA;15-30mins

ANESTHETICS

• Anesthetics are chemical agents that

reversely block transmission of nerve
impulses along sensory fibres.
DESIRED PROPERTIES OF A TOPICAL
ANESTHETIC

• Non- irritating, safe and painless

• Must be water soluble
• Rapid onset of action
• Durtion of action appropriate to the operation to be performed
• Non-toxic
• No local after effect (nerve damage or necrosis)
• Must be effective regardless its application to tissue or mucous
membrane
GENERATION OF ACTION POTENTIAL

• Sensory information passes along nerve fibres through electrical impulses or action
potential (AP).

• When the nerve is at rest the interior has a negative charge and the exterior has a positive
charge.

• An AP is generated by an influx of sodium ions into the interior of the nerve giving it a
positive charge (depolarisation)

• The nerve fibre is returns to its normal state (repolarization) by efflux of potassium ions.

• AP is generated by a successive depolarization and repolarization of adjacent regions.

MECHANISM OF ACTION FOR
TOPICAL ANAESTHETIC (TA)
INDICATIONS FOR USE

• Foreign Body Removal

• Contact Lens Fitting

• Gonioscopy

• Schirmer's Test

• Ocular Surface Examinations with Fluorescein

ANAESTHETICS

•Among the topical anaethetics the most

widely used are proparacaine hydrochloride 0.5% (Alcaine),
benoxinate0.5% and tetracaine 0.5%

•The instillation of a drop of one of these drugs renders the cornea

insensitive within 15secs

•Reapplication will enhance the anaesthetic

effect.
OPTHALMIC DIAGNOSTIC DYES

• The use of diagnostic dyes represents one of the most efficient,

objective and directly visible means we have of identifying and
tracking ocular structures at the cellular level.

• They particularly are useful as both diagnostic modalities and as

therapeutic adjutants in both anterior and posterior segment disorders.
OPHTHALMIC DYES

Dyes used in eye care include:

•Fluorescein

•Lissamine Green

•Rose Bengal

•Indocyanine Green
FLUORESCEIN

• Fluorescein is made water-soluble dye molecules which diffuse into the

intercellular spaces between living cells.

• Absorbs light in blue wavelength and emits green fluorescence

INDICATIONS

• Tear film break up time(TBUT)

• Corneal epithelial defects & corneal ulcers.

• Applanation tonometry –Goldmann

• tonometer/Perkins hand-held tonometer

• Seidel's test: Concentrated fluorescein dye (Bleb/Perforation)

• Jones dye test for assessment of lacrimal passage functional potency.

• Fundus fluoroscein angiography: 10%-20% i/v

SIDE EFFECTS

• Allergic Reaction

• Vomiting

• Sneezing

• Discoloration of skin and urine

CORNEAL EPITHELIAL DEFECT

APPLANATION TONOMETER

SEIDELS TEST POSITIVE

FLUORESCEIN STRIPS
ROSE BENGAL

•It is a derivative of fluorescein.

•Unlike fluorescein, it is a true histological stain which binds strongly
and selectively to cellular components stains dessicated or devitalised
tissue.

•Research on rose bengal has revealed that it's blocked from staining the
ocular surface where molecules such as mucins, albumin, or even an
artificial tear compound such as carboxymethylcellulose are present.
Thereby making ideal in cases like keratoconjunctivitis sicca.
INDICATIONS

• Used in evaluation of Conjuctiva and Corneal Surface

• Ideal for evalutation of pathologies such as: herpetic corneal epithelial

dendrites, superficial punctate keratitis, Meibomian gland dysfunction,
and dysplastic or squamous metaplastic cells of conjunctival squamous
neoplasms
SIDE EFFECTS

• Stinging on instillation which may become severe

• Dose dependent toxic effect on human corneal epithelial cells in vitro

that is further enhanced by light exposure

• Intrinsic cellular toxicity

• SJOGREN’S KERATOCONJUNTIVITIS SICCA

• Rose Bengal Strips

• DRY EYE
LISSAMINE GREEN

• Lissamine green is one of the top three dyes used in the eye clinic. It is
known to stain membrane damaged or devitalised cells only.

• Stains the edges of the dendritic ulcer while fluorosceine stains the
central bed.

• There is no stinging or discomfort such as that associated with rose

bengal.

• Like rose bengal, the dye is known to localize in the cell nucleus.
• Lissamine green Strip

• Eye stained with Lissamine Green

• DRY EYE
INDOCYANINE GREEN (ICG)

• Used for retinal angiography. Provides a better visualisation of the choroidal (rather
than retinal) vasculature. In addition to visualising choroidal neovascularisation, it
may also be helpful in assessment of inflammatory disease and choroidal tumours.
• Tightly bound to plasma proteins, thus becomes confined to vascular system. Does
not leak through the fenestrations of the Choroidal Capillaries. Therefore perfect
for imaging the choroidal vasculature
• Absorbs light at about 805 nm and emits 835nm infrared radiation. These
frequencies penetrate retinal layers allowing ICG angiography to image deeper
patterns of circulation than Fluorescein Angiography..
• Administration - 40mg in 2ml intravenous:
• Contra-indications - pregnancy, renal impairment, iodine allergy.
• Side-effects - nausea and vomiting, sneezing and pruritus, staining of stool, severe
allergic reaction.
THANK YOU