DRUGS USED FOR GLAUCOMA

Dr. Theodorus, MMedSc

Staf Bagian Farmakologi
FK Unsri
GLAUCOMA
INTRODUCTION
- Glaucoma is a disease of the optic nerve
- Nerve damage in glaucoma causes
typical pattern of vision loss
- Elevated intraocular pressure is a
risk factor, but not required for glaucoma
to occur
- 13,5% of global blindness (5.1 million)
- Aging demographics will increase the problem
(those over age 80 are up to 10 times as likely to
develop glaucoma than those under 40)
1. TIMOLOL (maleate)
A beta1 and beta2 (non-selective)
blocker
It is white, odorless, and soluble in
water and alcohol
Stable at room temperature
Ophtalmic solution is supplied as a
sterile, isotonic, buffered
Benzalkonium is added as
preservative



TIMOLOL (maleate)
MECHANISM OF ACTION
- The precise mechanism of the ocular
hypotensive action of timolol is not clearly
established
- Its predominant action maybe related to
reduced aqueous formation or the rate of
synthesis aqueous humor
- Effective in lowering intraocular pressure
- Short duration of action
TIMOLOL (maleate)
PHARMAKOKINETIC
- well absorbed into circulation even
not significant
- plasma concentration is estimated
to be about 5-10 ng/ml
- can be found in milk of nursing
mother

TIMOLOL (maleate)
INDICATION
- Patient with open-angle glaucoma
- Patient with aphakic glaucoma
- Some patient with secondary
glaucoma
- Other patient with elevated intra-
ocular pressure
- As additional drug


TIMOLOL (maleate)
CONTRAINDICATION
- Bronchial asthma
- Severe chronic obstructive pulmo-
nary disease
- Sinus bradycardia
- Second and third degree atrio-
ventricular block
- Cardiac failure
- Cardiogenic shock
- Hypersensitivity
TIMOLOL (maleate)
SIDE EFFECTS
- Muscle weakness
- Severe respiratory reaction
- Cardiac reactions
- CNS: headache, depression
- GI tract: nausea
- Masked symptoms of hypoglycemia
in insulin dependent diabetes
- Visual disturbance, ocular irritation,
diplopia, ptosis
- Alopecia
TIMOLOL (maleate)
DRUG INTERACTION
- The concomitant use with digitalis and
calcium antagonis may cause prolonging
atrioventricular conduction time
- Close observation when this drug is
administered to patients receiving
reserpine due to hypotension
- Can cause mydriasis if this drug given
together with epinephrine
a. BETAXOLOL
A Selective beta1
A white, crystalinne powder and
soluble in water
A sterile isotonic solution
Benzalkonium is added as
preservative


BETAXOLOL
Exhibit fewer cardiovascular side efects
than timolol
Better tolerated than timolol in patients
with reactive airway disease and asthma

SIDE EFFECTS
Brief local discomfort, occasional tearing
Systemic: insomnia, depression (rare)
b. LEVOBUNOLOL
A beta1 and beta2 ( non selective) blocker
Sterile solution, colorless
Benzalkonium is added as preservative

SIDE EFFECTS
Local: Transient burning/stinging
Cardiovascular: may resemble timolol
CNS: ataxia, dizzines, lethargy
Dermatologic: urticaria, pruritus (rare)

2. PILOCARPINE
Natural alkaloids
Cholinomimetic or cholinergic agents
Miotics, direct - acting
A dominant muscarinic action
Sweat glands are sensitive to this
drug
Benzalkonium is added as
preservative
PILOCARPINE
MECHANISM OF ACTION
Acts on a subtype muscarinic reseptor
(M3) causing the muscle to contract
and produce miosis. This opens the
trabecular meshwork through
increased tension on the scleral spur.
This action facilitates the rate that
aqueous humor leaves the eyes to
decrease intraocular pressure
PILOCARPINE
PHARMACOKINETIC
- Onset of action 10 to 30 minutes
and the duration 4 8 hours
- Causes pupillary constriction,
spasm accommodation, and a
transitory rise in intra ocular
pressure
- Causes marked diaphoresis in man
- Gastric glands are stimulated to secrete
juice
PILOCARPINE
INDICATION
- Chronic simple glaucoma or open-
angle glaucoma
- Chronic angle-closure glaucoma
- Acute (angle-closure) glaucoma
- Pre and postoperative intraocular
tension
- Mydriasis caused by mydriatic or
cyclopegic agents
PILOCARPINE
CONTRAINDICATION
- Hypersensitivity
- Where constriction is undesirable
( acute iritis and uveitis, secondary
glaucoma, acute inflammatory
disease of the anterior chamber)
- Safety and efficacy for children
have not been established
- Pregnancy: category C
PILOCARPINE
SIDE EFFECTS
- Cloudy vision, transient stinging
and burning, tearing, ciliary spasm,
detached retina
- Hypertension, bronchial spasm and
pulmonary edema, sweating, salivation
- Headache, nausea, vomiting,
diarrhea (rare)

PILOCARPINE
DRUG INTERACTION
There have been reports that both
these drug (pilocarpine with non
steroid anti-inflammatory drugs), if
using together; have been ineffective
a. ACETYLCHOLINE CHLORIDA
Aqueous solution of acetylcholine is
unstable
Miotics, direct acting
Short duration

INDICATION
Miosis. To produce complete miosis
in second after delivery of the lens in
cataract surgery, keratoplasty, iridectomy
and other anterior segment surgery
Acetylcholine chlorida
SIDE EFFECTS
- Corneal edema, clouding,
decomposition
- Bradycardia, hypotension, flushing,
breathing difficulties, sweating
3. EPINEPHRINE
A direct-acting sympathomimetic
Act on and receptors
The most potent vasopressor drugs
Topical application: causes conjunctival
decongestion (vasoconstriction), transient
mydriasis, and reduction in intraocular pressure
Available as epinephrine bitartrate and
hydrochloride: both therapeutically equal
Benzalkonium is added as preservative


EPINEPHRINE
MECHANISM OF ACTION
- It is believed IOP (IntraOcular
Pressure) reduction is primarily due
to reduced aqueous production and
increased aqueous outflow
- The duration of decrease in IOP is
12 to 24 hours
EPINEPHRINE
PHARMACOKINETICS
- Onset < 1 hour
- Peak plasma : 4 8 hour
- Duration : 24 hour
- Crosses placenta; passes into
breast milk

EPINEPHRINE
INDICATION
- Open-angle glaucoma
- Chronic simple glaucoma

CONTRAINDICATION
- Hypersensitivity
- Narrow or shallow angle glaucoma
- Aphakia patients
- Special risk patients: diabetes, hypertension, heart
disease, cerebral arteriosclerosis
- For elderly: use with caution
- Children: Safety and efficacy have not been
established
EPINEPHRINE
SIDE EFFECTS
- Local: Transient stinging and burning;
eye pain/ache, browache, allergic lid
reactions, conjunctival or corneal
pigmentation, localized adrenochrome
deposits in conjunctiva and cornea
(prolonged use)
- Systemic: Headche, palpitation,
tachycardia, extrasystole, hypertension,
cardiac arrhytmia
EPINEPHRINE
DRUG INTERACTION
Timolol, apraclonidine and atropine has an
additive effect (synergistic) with
epinephrine
Increased sympathomimetic with
imipramine
Decreased vasopressor effects with
chlorpromazine and phenotiazines
Do not use while wearing soft contact
lenses

4. CARBONIC ANHYDRASE
INHIBITORS
Carbonic anhydrase is an enzyme found in
many tissues of body including the eye
Carbonic anhydrase exists as a number of
isoenzymes
Acetazolamide (prototype of this agent),
dichlorphenamide and metazolamide are
given systemically; DORZOLAMID is used
topically
Originally introduced as diuretics, but their
effect on intraocular pressure does not
depend upon diuresis




CARBONIC ANHYDRASE
INHIBITORS
MECHANISM OF ACTION
- This drug reduces the rate of aqueous
humor formation; intra- oculary pressure in
patients with glaucoma is correspondingly
reduces
- Inhibition of carbonic anhydrase in the
cilliary processes of the eye decreases
aqueous humor secretion, presumably by
slowing formation of bicarbonate ions with
subsequent reduction in sodium and fluid
transport
CARBONIC ANHYDRASE
INHIBITORS
PHARMACOKINETICS
- Carbonic Anhydrase inhibitors are widely
distributed throughout the body
- When used topically: this reach the
systemic circulation and accumulate in
RBCs. Extensive distribution to RBCs yields
a long half-life
- Plasma protein binding is moderate (33%)
- The absorpsion of this drug does not
appear to be reduced by food
- Primarily excreted unchanged in the urine


CARBONIC ANHYDRASE
INHIBITORS
INDICATION
- Primary open-angle glaucoma
- Others chronic glaucoma refractory
to other drug
CONTRAINDICATION
- Renal and liver disease
- Obstructive pulmonary disease
- Pregnancy
- Efficacy and Safety in children have not
been established
- Do not administered this drug while wearing contact
lenses
CARBONIC ANHYDRASE
INHIBITORS
SIDE EFFECTS
- For topical used: have not been fully
evaluated
- Ocular stinging, burning or discom-
port immediately following adminis-
tration (33%)
- signs and symptoms of ocular aller-
gic reactions (10%)
- Blurred vision
- Headhe, skin rashes, asthenia/fatigue
CARBONIC ANHYDRASE
INHIBITORS
DRUG INTERACTION
- Can cause salicylate intoxication in
patients receiving aspirin
- Interfere with the action of methe-
namine
- Drug induced osteomalacia has
been reported with the simultane-
ous use of phenytoin

5. LATANOPROST
Selective Prostaglandin F2 analog
Protect from the light, may be stored at
room temperature
Is a lipophilic prodrug
Is converted into the active latanoprost by
ester hydrolysis of latanoprost
Benzalkonium is added as preservative

LATANOPROST
MECHANISM OF ACTION
- The primary mechanism by which
most of PGs reduce IOP is by
increasing outflow, especially
through the uveoscleral outflow
pathway
- Other mechanism maybe the relaxa-
tion of the cilliary muscle
- PGs do not reduce aqueous humor

LATANOPROST
PHARMACOKINETICS
- Latanoprost si absorbed through
cornea where the latanoprost ester
product is hydrolyzed to biologically
active acid.
- Peak concentration will be reached
2 hours after application
- Reaching systemic circulation is
primarily metabolized by the liver
- The metabolites are mainly eliminated via
the kidney
LATANOPROST
INDICATION
- Open- angle glaucoma
- Ocular hypertension
- Pigment dispersion syndrome

CONTRAINDICATION
- Allergic or sensitive to these drugs
- Pregnancy and nursing women
- Safety and efficacy in children have not
been established
- DO NOT ADMINISTERED LATANOPROST WHILE
WEARING CONTACT LENSES
LATANOPROST
SIDE EFFECTS
- Eyelash change (the most frequent)
- Eye irritation, conjunctiva hyper-
emia
- Iris color change (brownish)
- Uveitis
- Cystoid macular edema
- Common cold (4%)
- Pain in muscle/joint/back
- Rash/allergic skin reaction
LATANOPROST
DRUG INTERACTION
- Addictive to the effect of other ocu-
lar hypotension agent including
timolol, pilocarpine and oral carbo-
nic anhydrase inhibitors