Glaucoma

Glaucoma
clinical pharmacy department :Dr.Hemat Elgohary1-12-2016

Increased intraocular pressure (IOP)
is the most common risk factor for
the development of glaucoma
Even people with “normal” IOPS can
experience vision loss from
glaucoma.
the higher the IOP is, the greater the
risk for developing glaucoma.
Glaucoma
Leading cause of blindness worldwide
A nonspecific term used for a group of diseases that can
irreversibly damage the optic nerve
resulting in visual field loss.
clinical pharmacy department :Dr.Hemat
Elgohary
1-12-2016

Other risk factors for glaucoma.
Increasing age
African american race
Family history
Thinner central corneas
Larger vertical cup-disc ratios
Elgohary
1-12-2016

Intraocular Pressure
The inner pressure of the eye (IOP) is influenced by :
 The production of aqueous humor by the ciliary processes
 The outflow of aqueous humor through the trabecular meshwork.
Elgohary
1-12-2016

 although a more rare form of
glaucoma is associated with a
low IOP.
The Tonometry
 test to measure the IOP is based
on the pressure required to
flatten a small area of the central
cornea.
IOP of 10 to 20 mm Hg
is considered normal.
IOP of 22 mm Hg or greater
should arouse suspicion of glaucoma
1-12-2016
Elgohary

Ocular Hypertension
Ocular hypertension has been defined as :
1) An IOP exceeding 21 mm hg
2) Normal visual fields
3) Normal optic discs
4) Open angles
5) The absence of any ocular disease contributing to the elevation
of IOP.
 Only a small percentage of patients with ocular hypertension
have open-angle glaucoma.
1-12-2016
Elgohary

An ophthalmoscope
 Can examine the inside of the eye
 Especially the optic nerve
 Diagnosis of glaucoma can be applied when pathologic cupping of
the optic nerve is observed.
Elgohary
1-12-2016

Open-Angle Glaucoma
 Primary open-angle glaucoma occurs in about 1.8% of people older
than 40 years of age
glaucoma can affect other age
groups, including children.
 About 2.2 million people have glaucoma
 this number likely will increase to about 3.3 million by the year
2020 as the population ages.
Elgohary
1-12-2016

 aqueous humor outflow from the anterior chamber is
continuously subnormal primarily because of a degenerative
process in the trabecular meshwork.
In patients with
primary open-angle glaucoma (POAG)
The IOP can vary in the course of a day from normal to significantly
high pressures
Elgohary
1-12-2016

The decreased outflow appears to :
 be caused by degenerative
changes in outflow channels
 (i.e., the trabecular meshwork
and Schlemm canal)
 and tends to worsen with the
passage of time.
In rare cases,
 the outflow is normal even during a
phase of elevated IOP, and the
elevation appears to be to the result of
hyper-secretion of aqueous humor.
Elgohary
1-12-2016

 Visual field defects
 A defect in the visual field examination may be present in early
glaucoma
 but loss of peripheral vision usually is not seen until late in the
course of the disease.
 Visual field defects correlate well with changes in the optic disc and
help differentiate glaucoma from ocular hypertension in patients
with increased IOP.
 The onset of POAG usually is gradual and asymptomatic.
Elgohary
1-12-2016

Patients with :
 normal visual fields
 IOP of 24 mm Hg or greater have a 10%
 likelihood of developing glaucoma in 5 years.
Examination of the anterior chamber angle by :
Gonioscopy
using a corneal contact lens
a magnifying device (e.g., a slit-lamp microscope)
a light source
assists in differentiating between open-angle glaucoma and
angle-closure glaucoma.
Elgohary
1-12-2016

Elgohary
1-12-2016

Angle-closure glaucoma
accounts for approximately 5% to 10% of all primary glaucoma
cases.
The sole cause of the elevated IOP in angle-closure glaucoma is
closure of the anterior chamber angle.
Elgohary
1-12-2016

When patients are predisposed to angle-closure glaucoma
Their pupils should not be dilated
(e.g., During an ophthalmic examination)
And they should be taught the signs and symptoms of angle
closure.
Angle-closure glaucoma, which is :
1. A medical emergency
2. Usually presents as an acute attack
3. With a rapid increase in IOP
4. Blurring or sudden loss of vision
5. Appearance of haloes around lights
6. Pain that is often severe
Elgohary
1-12-2016

Permanent medical management
of acute or chronic angle-closure
glaucoma is difficult:
surgical procedures (e.g.,
peripheral irid-ectomies) often
are needed
Acute attacks can terminate
without treatment
But if the IOP remains high, the optic
nerve can be irreparably damaged.
Patients with chronic angle-closure generally experience a gradual
closure of aqueous humor outflow channels, and patients can be
asymptomatic until the glaucoma is in an advanced stage.
Elgohary
1-12-2016

PRIMARY OPEN-ANGLE GLAUCOMA
Therapeutic Agents for Treatment of
Primary Open-Angle Glaucoma
 Historically, β-adrenergic blockers have been the most commonly
prescribed first-line agents for the treatment of POAG.
 In recent years, prostaglandin analog use has reached, if not
exceeded, β-adrenergic blocker use.
 All of the ophthalmic β-
blockers currently on the
market are available in
generic formulation
 allowing for cost-effective
treatment.
 generic versions of
prostaglandin analogs are
not yet available
 the cost be prohibitive for
some patients, depending
on their insurance plans
Elgohary
1-12-2016

β -ADRENERGIC BLOCKERS
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1-12-2016

 block the β-adrenergic receptors in the ciliary epithelium of the
eye
 lower IOP primarily by decreasing aqueous humor production.
 β-blockers decrease IOP by 20% to 35% depending on :
1. The strength used
2. The frequency of administration.
Elgohary
1-12-2016

Timolol (Timoptic)
 Nonselective β1- and β2-adrenergic antagonist
 one of the most commonly prescribed glaucoma
medications.
Because Timolol was the first ocular β-
adrenergic blocker marketed
marketed ophthalmic β-blockers usually are
compared with Timolol for safety and
effectiveness.
Elgohary
1-12-2016

 Monocular administration of
Timolol has resulted in equal
bilateral IOP reduction and can
reduce the cost of therapy and
side effects for some patients.
 Concentrations or dosages exceeding one drop of Timolol
0.5% twice daily (BID) DO NOT produce further significant
decreases in IOP.
 Therapy usually is initiated with a 0.25% solution administered
as one drop BID.
Elgohary
1-12-2016

An escape phenomenon
 or tachyphylaxis, can occur with timolol.
 Timolol has been associated with a modest reduction of
resting pulse rate (5–8 beats/minute)
 worsening of heart failure
 adverse pulmonary effects (e.g., dyspnea, airway
obstruction, pulmonary failure).
S.E
 After chronic administration in susceptible individuals,
timolol can cause corneal anesthesia.
 Although uveitis has been reported in patients receiving
ophthalmic timolol, a cause-and-effect relationship has not
been established.
Elgohary
1-12-2016

 Systemic absorption after topical administration does occur, but
it may not be significant in the majority of patients.
Care should be taken when timolol is used
in patients with:
 Sinus brady-cardia
 Heart failure
 Pulmonary disease.
 Systemic side effects could be exaggerated in
Elderly patients secondary to :
 inadvertent overdosing associated with poor
administration technique .
Elgohary
1-12-2016

Timolol ophthalmic gel-forming solution, is
administered once daily.
The ophthalmic vehicle, gellan gum(gelrite), is a
solution that forms a clear gel in the presence of
monovalent or divalent cations.
This ion-activated gelation :
prolongs pre-corneal residence time
increases ocular bioavailability
allowing timolol to be administered once
daily.
Timoptic xe is comparable to timoptic solution in
lowering IOP.
Timoptic XE
Elgohary
1-12-2016

 Levobunolol 0.5% and 1% are
comparable to timolol in lowering IOP.
 The incidence of adverse reactions,
including decreases in heart rate, are
also comparable to that for timolol.
Levo-buno-lol (Betagan)
 Nonselective β-adrenergic antagonist
 approved for either once daily or BID
administration
Elgohary
1-12-2016

Metipranolol is associated with:
 a greater incidence of stinging or burning on administration
 granulomatous anterior uveitis.
Meti-prano-lol (OptiPranolol)
 Nonselective β-adrenergic blocking agent
 Metipranolol 0.1% to 0.6%, is comparable to
timolol 0.25% to 0.5% in reducing IOP.
 Like timolol, metipranolol produces corneal
anesthesia,which occurs within 1 minute of
instillation and returns to baseline after 10
minutes.
 As a result of these side effects, the use of metipranolol is limited.
Elgohary
1-12-2016

Carteolol 1% and Timolol 0.25% administered BID are equally
effective in reducing IOP.
Carteo-lol (Ocupress)
nonselective β-adrenergic blocking agent with
partial β-adrenergic agonist activity
Theoretically
should minimize the bronchospastic,
bradycardic, and hypotensive effects associated
with other ocular β-adrenergic blockers.
no clinical differences were seen when the cardiovascular
and pulmonary function effects of carteolol were compared
with those of timolol.
Elgohary
1-12-2016

Betaxolol is slightly less
effective than timolol in IOP
reduction
more patients tend to need
adjunctive therapy with
betaxolol.
Beta-xo-lol (Betoptic)
selective β1-adrenergic blocker.
This cardio-selective property may result in less adverse effects
on pulmonary function than nonselective β-adrenergic blockers
in patients with reactive airway disorders.
Elgohary
1-12-2016

1-12-2016
Elgohary
Timolol, and possibly all other Ḃ-blockers, have
minimal IOP-lowering efficacy during sleep.

Prostaglandin analogs
Elgohary
1-12-2016

Latanoprost (Xalatan)
travoprost (Travatan)
bimatoprost (Lumigan)
Elgohary
1-12-2016

These agents often are prescribed as first-line agents for the
treatment of POAG because they are :
1) At least as effective as the β-blockers
2) Can be administered once a day
3) Are associated with minimal systemic adverse effects.
Latanoprost and travoprost are analogs of
prostaglandin F2α , and they lower IOP by
serving as selective prostaglandin F2α -
receptor agonists.
Bimatoprost is a synthetic prostamide analog.
The prostaglandin analogs(PGAs) increase uveo-
scleral outflow of aqueous humor and, thereby,
decrease IOP.
Elgohary
1-12-2016

the nocturnal control of IOP with latanoprost was
superior to that with timolol.
Latanoprost
Latanoprost 0.005% should be:
dosed once daily
in the evening
because the IOP-lowering effects of latanoprost might actually
be inferior when administered more frequently.
Approved for the initial treatment of POAG or ocular hypertension.
When administered once daily in the evening, latanoprost is at
least as effective as timolol in decreasing iop.
When the effectiveness of latanoprost 0.005% once daily was
compared with timolol 0.5% BID, the IOP-lowering effects of
latanoprost were superior to those of timolol.
Elgohary
1-12-2016

Systemic side effects are minimal with latanoprost
local reactions are relatively common.
1. iris pigmentation
2. eyelid skin darkening
3. eyelash lengthening ,thickening, pigmentation, and
misdirected growth
4. conjunctival hyperemia
5. ocular irritation
6. superficial punctate keratitis
Latanoprost can gradually increase the amount of brown pigment
in the iris by increasing the melanin content in the stromal
melanocytes of the iris.
Elgohary
1-12-2016

The nature and severity of adverse events are not affected by the
increased pigmentation of the iris.
This pigment change occurs in 7%
to 22% of patients and is most
noticeable in those with green-
brown, blue/gray brown,or
yellow-brown eyes.
The onset of increased iris pigmentation usually is noticeable
within the first year of treatment and can be permanent.
Elgohary
1-12-2016

Latanoprost has additive effects when administered with :
β-blockers (e.g., timolol)
carbonic-anhydrase inhibitors (e.g.,dorzolamide)
α2-adrenergic agonists (e.g., brimonidine,apraclonidine).
When added to existing therapy, latanoprost
decreases IOP an additional 2.9 to 6.1 mm Hg.
As a result,latanoprost is a good adjunctive ophthalmic agent for
patients who are unable to adequately lower their IOP with
single-agent therapy.
Elgohary
1-12-2016

 The complementary IOP-lowering effects of latanoprost are
comparable with those of brimonidine
 (at least a 15% reduction in IOP)
 brimonidine (an α2-adrenergic agonist) in a comparative study
was associated with fewer adverse effects on the quality of life.
in patients inadequately controlled on β-adrenergic
blocking agents
watery or teary eyes
and cold hands and
feet were reported
more frequently in
latanoprost treated
patients.
Elgohary
1-12-2016

Travoprost
 Travoprost (Travatan Z) is US Food and Drug
Administration (FDA)–approved for the
reduction of elevated IOP and ocular
hypertension in patients who are intolerant
or who fail to respond to other agents.
 Travoprost is used as a first-line agent in clinical practice because
it is more effective than timolol and at least as effective as
latanoprost.
 The mean IOP reduction with travoprost in African American
patients was 1.8 mm Hg greater than in non–African American
patients.
Elgohary
1-12-2016

 Travoprost, as adjunctive therapy to timolol in patients not
responding adequately to timolol alone, reduced IOP an additional
6 to 7 mm Hg.
 The side-effect profile of travoprost is similar to that for
latanoprost, including increased iris pigmentation and eyelash
changes.
Local irritation may be less because it is free of
the preservative benzalkonium chloride.
Elgohary
1-12-2016

Bimatoprost
 once daily or BID achieved lower target IOPs
than did timolol BID.
 Bimatoprost BID, however, was less effective
than bimatoprost once a day.
 Iris pigmentation changed in 1.1% of
bimatoprost treated patients.
Elgohary
1-12-2016

Side effects
 were similar between treatment groups
 conjunctiva hyperemia was more common ( p <0.001) in
bimatoprost treated patients.
Overall, the side effect profile of bimatoprost appears to
be similar to that for latanoprost and travoprost.
 The local side effects seen with other PGAs also appear to be
relatively common with bimatoprost.
Elgohary
1-12-2016

 Eyelash lengthening
 Thickening
 darkening or pigmentation
is seen after 8 to 16 weeks of use.
 the FDA approved the cosmetic use
of bimatoprost solution
Latisse
 Latisse solution is applied with an
applicator to the base of the upper
eyelashes for the treatment of
hypotrichosis (inadequate eyelashes).
Elgohary
1-12-2016

α2-Adrenergic Agonists
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1-12-2016

 Apraclonidine (Iopidine)
 brimonidine (Alphagan)
Are selective α2-adrenergic agonists similar to clonidine.
Elgohary
1-12-2016

 Less lipophilic than clonidine and brimonidine
 Does not cross the blood–brain barrier as readily
Apraclonidine
Theoretically
 has fewer systemic side effects
1. Hypotension
2. Decreased pulse
3. Dry mouth
Apraclonidine 1%
 indicated to control or prevent post-surgical
elevations in IOP after Argon laser
trabeculoplasty or iridotomy.
Elgohary
1-12-2016

Common ocular side effects include
1. Burning
2. Stinging
3. Blurring
4. conjunctival follicles
5. An Allergic like reaction consisting of hyperemia, pruritus,
edema of the lid and conjunctiva, and foreign body sensation.
The 0.5% apraclonidine solution
 is indicated for short-term adjunctive therapy in patients on
maximally tolerated medical therapy.
Long-term IOP control
should be monitored closely in patients taking α2-
adrenergic agonists because tachyphylaxis can occur.
Elgohary
1-12-2016

 It may also be used as adjunctive therapy in
patients not responding to other agents.
Brimonidine
 more highly selective for α2-adrenergic receptors than clonidine
or apraclonidine
Theoretically,
 should be associated with fewer ocular side effects.
 α2-Adrenergic agonists appear to lower IOP by decreasing the
production of aqueous humor and by increasing uveo-scleral
outflow.
 Brimonidine is an alternative first-line agent in
the treatment of POAG.
Elgohary
1-12-2016

α2-Adrenergic agonists should be used with caution in patients
with :
1. cardiovascular disease
2. orthostatic hypotension
3. Depression
4. renal or hepatic dysfunction
Although ocular side effects are less common with brimonidine
than with apraclonidine, systemic side effects are more common
with brimonidine e.g.
1. dry nose and mouth
2. mild hypotension
3. decreased pulse
4. Lethargy
Elgohary
1-12-2016

Brimonidine (Alphagan P)
Is available with purite as a preservative, which:
 facilitates drug delivery into the eye
 allowing use of a lower drug concentration.
 The IOP-reduction effects (peak and trough) of
brimonidine 0.2% BID are 14% to 28%.
 Although the approved dosing schedule of
brimonidine is Three Times A Day (TID),
brimonidine 0.2% BID lowers IOP comparably to
timolol 0.5% BID,and both are slightly better
than betaxolol 0.25% BID.
Elgohary
1-12-2016

 The IOP-lowering effect of brimonidine also may be
comparable with that of latanoprost; however,
conflicting efficacy and tolerability results in clinical
studies may be related to differences in study design.
 is as equally tolerable and effective as the combination
brimonidine
and timolol
dorzolamide
and timolol.
The combination of
Elgohary
1-12-2016

The FDA-approved combines
 α2-adrenergic agonist (brimonidine
tartrate 0.2%)
 β-adrenergic blocker (timolol maleate
0.5%).
Combigan ophthalmic
Elgohary
1-12-2016

Topical carbonic anhydrase
inhibitors
Elgohary
1-12-2016

 Although CAIs have been used orally for many years in the
treatment of elevated IOPs, they have been replaced by the
topical ophthalmic CAIs
Carbonic anhydrase
 occurs in high concentrations in the ciliary processes and retina
of the eye.
resulting in a 40% to 60% decrease in aqueous humor secretion.
Bicarbonate
production
Carbonic anhydrase inhibitors (CAIs)
 lower IOP by  Bicarbonate
 Sodium
 water
the
posterior
chamber
Elgohary
1-12-2016

 Dorzol-amide (Trusopt)
 Brinzol-amide (Azopt)
 which are safer and better tolerated.
 Topical CAIs are excellent alternatives to β-blockers in the
initial management of elevated IOPs, and are effective as
adjunctive agents.
Elgohary
1-12-2016

Brinzolamide 1%
 TID reduces IOP comparably to that achieved with
dorzolamide 2% TID and to betaxolol 0.5% BID,
but slightly less than timolol 0.5% BID.
 The IOP-reduction effects (peak and trough) of
dorzolamide 2% TID are 16% to 25%.
 Brinzolamide and dorzolamide are approved for
TID dosing; however, BID dosing may be
adequate.
 Dorzolamide provides additional IOP-lowering
effects when added to existing β-blocker
therapy.
Elgohary
1-12-2016

The combined use of topical dorzolamide
and oral acetazolamide does not result in
additive effects and might increase the risk
of toxicity.
 An ophthalmic solution of dorzolamide
hydrochloride and timolol maleate is
marketed as Cosopt.
The topical CAIs are well tolerated with few systemic side effects.
The most common adverse effects with dorzolamide are :
1. ocular burning
2. Stinging
3. discomfort and allergic reactions
4. bitter taste
5. superficial punctate keratitis.clinical pharmacy department :Dr.Hemat
Elgohary
1-12-2016

These drugs should not be used in patients with renal or
hepatic impairment.
Brinzolamide dorzolamide
causes less burning and
stinging of the eyes, because
its pH more closely resembles
that of human tears.
Both are sulfonamides and may cause the same types of
adverse reactions attributable to sulfonamides.
Elgohary
1-12-2016

PILOCARPINE
 (Isopto Carpine) historically was an initial treatment of
choice, but with the introduction and widespread use of
newer agents, pilocarpine has fallen out of favor.
M.O.A
 direct-acting cholinergic (parasympatho-mimetic) causes
contraction of ciliary muscle fibers attached to the trabecular
meshwork and scleralspur make it open to enhance aqueous
humor outflow.
 There also may be a direct effect on the trabecular meshwork.
 Pilocarpine causes miosis by contraction of the iris sphincter
muscle, but the miosis is not related to the decrease in IOP.
 Therapy usually is begun using lower concentrations (1%), one
drop four times a day (QID).clinical pharmacy department :Dr.Hemat
Elgohary
1-12-2016

CARBACHOL
 reserved as a third-line agent in patients who are
unresponsive or intolerant to initial medications.
 In addition to having direct cholinergic effects,
carbachol is more resistant to cholinesterase than
pilocarpine.
Added benefits include:
 increased release of acetylcholine from parasympathetic nerve
terminals
 weak anticholinesterase effect.
 Carbachol is administered TID.
Elgohary
1-12-2016

Anticholinesterase agents
If control of IOP is not achieved with :
 optimal use of other topical monotherapy
 combination therapy agents
 anticholinesterase agents may be prescribed as a last topical
therapy option.
Acetylcholine
cholinesterase
Destruction
Anticholinesterase
Elgohary
1-12-2016

Echo-thio-phate iodide
 Echothiophate iodide (Phospholine Iodide), an irreversible
cholinesterase inhibitor
 primarily inactivates pseudo cholinesterase and secondarily
inhibits true cholinesterase.
 may be used if maximal doses of other agents and combination
therapy are ineffective.
 has a long duration of action that affords good control of IOP
 miosis and myopia are significant side effects.
 Concentrations higher than 0.06% are associated with a significant
increase in subjective complaints (e.g., brow ache).
Elgohary
1-12-2016

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Elgohary

Combination Therapy
Elgohary
1-12-2016

 In general, drugs with different pharmacologic actions have at
least partially additive effects in lowering IOP in the treatment
of glaucoma.
 Drugs with similar pharmacologic actions (i.e., from the same
pharmacologic class) should not be combined
because dose-related adverse effects are more likely
and the incremental increase in benefits is likely to be
more modest.
Timolol and other β-adrenergic blocking drugs have additive IOP
lowering effects when used in combination with :
1. miotic agents
2. prostaglandin analogs
3. α2-agonists
4. CAIs.
Elgohary
1-12-2016

For example, the IOP-lowering effect is greater when Timolol is
used in combination with:
1. pilocarpine
2. Dorzolamide
3. Brimonidine
4. travoprost.
Latanoprost has additive effects when administered with:
1. timolol
2. Dorzolamide
3. α2-adrenergic agonists
Elgohary
1-12-2016

These advantages include :
improved adherence because of a reduction in the number of
dosages and bottles
eliminating the need to instill two separate drugs 5 to 10 minutes
apart to prevent a washout effect from the second medication
improving safety and tolerability by limiting the exposure to the
benzalkonium chloride preservative
a cost savings for the patient by potentially eliminating a copay
for one of the medications.
 The trend toward the development of fixed-combination
products offers many advantages in the treatment of POAG.
Elgohary
1-12-2016

These investigational agents include
 Timolol/latanoprost (xalacom)
 Timolol/travoprost (duotrav, extravan)
 Timolol/bimatoprost.
There are two β-adrenergic blocker combination products
currently on the market
 timolol/dorzolamide (Cosopt)
 brimonidine/timolol (Combigan).
The IOP-lowering effects of timolol/dorzolamide (Cosopt)
are comparable to or greater than those of latanoprost
monotherapy.
Several other combination products are under investigation for
POAG, which will offer a wide range of options for patients.
Elgohary
1-12-2016

Predisposing Factors
Elgohary
1-12-2016

 CASE 1
 QUESTION 1:
 Tonometry measured an IOP of 36 mm Hg in both eyes.
 Ophthalmoscopy revealed physiologic cupping of the optic discs in both eyes
 visual field examination revealed a nerve fiber bundle defect consistent with
glaucoma.
 Pupils were normal in both eyes,
 Gonioscopy indicated that anterior chamber angles were open in both eyes.
 There were no signs of cataract formation.
 M.H., a 52-year-old African American woman with brown
eyes, presented for routine ophthalmic examination.
 Visual acuity without correction was 20/40 right eye and
20/80 left eye.
 M.H. related a positive family history for glaucoma and presently is being
treated for hypertension, chronic heart failure (CHF), chronic obstructive
pulmonary disease, and asthma.
Elgohary
1-12-2016

Her medications include the following:
 Amitriptyline, 75 mg at bedtime
 Chlorpheniramine, 4 mg every 6 hours as needed (PRN)
 Lisinopril, 10 mg once daily
 Furosemide, 40 mg BID
 Nitroglycerin, 0.3 mg sublingual PRN
 Fluticasone/salmeterol 250 mcg/50 mcg dry powder inhaler, one
inhalation twice daily
 Albuterol 90 mcg metered-dose inhaler, 1-2 puffs QID PRN
 Tiotropium bromide inhaler, 18 mcg inhaled once daily
 Findings on examination indicate that M.H. has POAG.
 What other factors may predispose M.H. to an increased IOP?
Elgohary
1-12-2016

1. POAG is thought to be determined genetically, and M.H. has a
positive family history.
2. The disease is more prevalent and aggressive in African
Americans.
3. In addition, she is taking several medications that have been
associated with increases in IOP.
Elgohary
1-12-2016

 The IOP is always measured before this procedure, so the use
of these agents would not have influenced the IOP readings in
M.H.
Anticholinergic Drugs
 Most reports dealing with drug-induced increases in IOP
center around precipitation of angle-closure glaucoma by
ophthalmic mydriatic or cycloplegic agents (anticholinergics).
 In patients with open-angle glaucoma, topical anticholinergics
can significantly increase resistance to aqueous humor outflow
 As part of any routine ophthalmic examination, the pupils are
dilated with a mydriatic or cycloplegic agent (unless otherwise
contraindicated).
Elgohary
1-12-2016

 If systemic anticholinergic agents are administered in doses
sufficient to cause pupillary dilation, the risk of precipitating
angle-closure increases.
 these agents will aggravate open-angle glaucoma unless the
amount reaching the eye is sufficient to cause cycloplegia.
 literature documentation of POAG exacerbation by these agents
is scarce, medications with anticholinergic side effects should be
considered. e.g.:
1. Antihistamines
2. Benzodiazepines
3. Disopyramide
4. Phenothiazines
5. Tricyclic antidepressants
6. Tiotropium
Elgohary
1-12-2016

Therefore, it is highly unlikely that these medications
contributed to her increased IOP
M.H.is receiving:
1. Chlorpheniramine as needed
2. Amitriptyline at bed-time
3. Tiotropium bromide once daily
 but her pupil examination is normal with no evidence of
mydriasis or cycloplegia.
Elgohary
1-12-2016

 These have no proven adverse influences on IOP in patients with
either normal eyes or eyes with open-angle glaucoma.
Adrenergic Drugs
Adrenergic agents may produce minimal pupillary dilation. , Such
as :
1. Central nervous system stimulants
2. Vasoconstrictors
3. Appetite suppressants
4. Bronchodilators
the use of salmeterol and albuterol in M.H. is also an
unlikely source of the increased IOP.
Elgohary
1-12-2016

Other Drugs
 Conclusive evidence for the production of angle-closure
glaucoma by vasodilators is lacking, although slight increases in
IOP have been reported.
Use of nitroglycerin as needed in M.H. is not a cause for concern.
 There have been isolated reports of other medications causing
mydriasis in glaucoma patients.These include:
1. Muscle relaxants (carisoprodol)
2. Monoamine oxidase inhibitors
3. Fenfluramine
4. Ganglionic blocking agents
5. Salicylates
6. Oral contraceptives
Elgohary
1-12-2016

 Succinylcholine
 Ketamine
 Caffeine
Have been associated with increases in IOP.
If M.H. requires administration of any other
medications associated with increases in IOP, the
risk of potential adverse effects can be minimized by
routine follow-up.
Elgohary
1-12-2016

 CASE 1, QUESTION 2:
 What is the best initial therapeutic treatment in M.H.?
Initial Therapy
 Topical β-blockers or PGAs are the initial agents of choice in the
treatment of POAG .
 Their efficacy is well documented in numerous studies, and side
effects are well characterized.
 Brimonidine (Alphagan) and Topical CAIS are alternative first-line
agents.
Elgohary
1-12-2016

 Betaxolol
 β1-adrenergic blocker
 better tolerated than the nonselective β-
adrenergic blocker in patients with reactive
airway disease
 should be considered when topical β-blocker
therapy is indicated in patients such as M.H.
 Timolol or other nonselective β-adrenergic blockers should
not be initiated for M.H. because of her history of asthma
Elgohary
1-12-2016

 Betaxolol 0.25%
 suspension BID would be reasonable for the
initial treatment of M.H.’s glaucoma.
 adverse pulmonary and cardiac side effects can occur
with betaxolol
M.H. should be followed up closely for these adverse effects
ocular burning and stinging
 have been associated more frequently with betaxolol and
metipranolol than with other topical β-blockers
 the 0.25% suspension is better tolerated than the 0.5%
solution and is as effective.
Elgohary
1-12-2016

 Although brimonidine, topical CAIS, and latanoprost may not
exacerbate her asthma or CHF
 They can cause localized side effects and Brimonidine can cause
systemic hypotension and lethargy.
 Brimonidine, a topical CAI
 PGA (e.g.,latanoprost)
 Are acceptable alternatives
to betaxolol as initial
therapy.
Elgohary
1-12-2016

 CASE 1, QUESTION 3:
 Betaxolol 0.25% suspension, one drop in both
eyes BID, is ordered for M.H.
 How should M.H. be instructed regarding the
proper use of her betaxolol and expected
therapeutic side effects?
 rest that hand on her forehead to minimize the
risk of inadvertent eye injury caused by sudden
unexpected movement of the hand.
 M.H. should be instructed to
hold the inverted betaxolol
bottle between her thumb and
middle finger
1
2
Elgohary
1-12-2016

 The patient should look up and administer the drug into the
pouch of the eye.
 The index finger is left free to depress the bottom of the
container, releasing one drop for the dose.
3
 The lower eyelid should be drawn downward with the index
finger of the opposite hand or pinched between the thumb and
index finger to form a pouch.
4
5
Elgohary
1-12-2016

 Patients must be encouraged to continue regular use of their
medications for effective treatment of glaucoma.
 Chronic glaucoma is a silent disease and often not associated
with symptoms; therefore, the continuation of therapy should
be encouraged continuously in patients, especially when side
effects to drug therapy can be encountered.
Elgohary
1-12-2016

1-12-2016
Elgohary
 Betaxolol is best administered every 12 hours
BECAUSE this schedule of administration is consistent with its
duration of action.
 Systemic side effects are rare with betaxolol e.g.:
1. Bradycardia
2. heart block
3. CHF
4. pulmonary distress
5. central nervous system
 but M.H. should be instructed to report any of these
effects to her primary-care provider.

CASE 1, QUESTION 4:
 How much would occlusion of the nasolacrimal ducts
(punctal occlusion) by M.H. influence systemic
absorption or alter the therapeutic effects of betaxolol?
Elgohary
1-12-2016
Nasolacrimal, or punctal, occlusion
is a technique that can decrease the amount of drug absorbed
systemically.
Nasolacrimal occlusion

1-12-2016
Elgohary
Occlusion of the puncta
(through the application of slight pressure with the finger to the
inner corner of the eye closest to the nose for 3 to 5 minutes during
and after drug instillation)
1. can minimize systemic absorption of ophthalmic medications
(e.g.,betaxolol)
2. decrease the incidence of side effects
3. improve medication effectiveness.

When a single drop of ophthalmic timolol 0.5% was instilled into
the eyes of patients at various times before cataract surgery and
the nasolacrimal duct was occluded for 5 minutes, drug levels in
the aqueous humor were significantly greater in patients who
had their nasolacrimal ducts occluded than those who did not.
The average measured maximal aqueous humor timolol
concentration of 1.66 mcg/mL in the occlusion group was
significantly greater than 0.85 mcg/mL in the non-occlusion
group.
Elgohary
1-12-2016
The area under the curve was 1.7 times greater in
patients who used the technique of naso-lacrimal
occlusion, and the duration of action was
prolonged.

1-12-2016
Elgohary
Nasolacrimal occlusion
Is effective and can maximize drug benefits
Because
a lower concentration of an ophthalmic
formulation can be used
the dose can be administered less
frequently .

 only 55% achieved
comparable IOP
reductions
when nasolacrimal ducts
were not occluded.
Elgohary
1-12-2016
Pilocarpine 1% and 2%
 significantly decreased IOP at 6, 8, and 12 hours after
instillation when the technique of nasolacrimal
occlusion was applied.
 Carbachol 1.5% and 3%
 The combination of carbachol 1.5% with timolol 0.25%
every 12 hours
 Were maximally beneficial with nasolacrimal occlusion.
 reduced IOP by 15%
 maintained at 24 hours
 in 92% of patients
when nasolacrimal occlusion was used
Timolol

1-12-2016
Elgohary
pilocarpine 2% and carbachol 1.5% can be administered every
12 hours rather than the usual TID or QID regimens needed
Timolol can be administered every 24 hours if the nasolacrimal
occlusion technique is used.
maximal drug effect can be achieved with a reduced frequency
of administration and at about half of the drug concentrations
typically used.
Nasolacrimal occlusion should be incorporated into patient
counseling for instillation of all eye drops.
When nasolacrimal occlusion is used

 Alternative Therapy
 CASE -1, QUESTION 5:
Two weeks after initiation of therapy
 M.H. returns to clinic for a follow-up evaluation.
 Her IOP measures 32 mm Hg in the right eye and 30 mm Hg
in the left eye.
 She denies non-adherence and has no complaints of
intolerable side effects.
 How should therapy be altered?
 Are there alternative dosage forms or drugs that can be
used?
 Betaxolol may not be as effective as other ocular β-blockers.
 Therefore, adjunctive therapy may be required.
Elgohary
1-12-2016

Elgohary
1-12-2016
M.H.should be evaluated to determine whether she has been
using the technique of nasolacrimal occlusion
M.H. should be again instructed on the technique of
nasolacrimal occlusion and the importance of this technique in
achieving the maximal therapeutic effect of her therapy
If not,
After the initiation of therapy, patients should be seen for a
follow-up evaluation within about 2 weeks.

 Patients who are experiencing unstable reductions of IOP should
be followed up within 4 months.
 Stable patients usually are evaluated every 6 to 12 months.
Elgohary
1-12-2016
 If M.H. has been adherent to therapy and has been occluding
her nasolacrimal ducts
 a new course of action is needed because her IOP still is
elevated
When the goal of therapy has not been achieved
1. the drug concentration of the ophthalmic formulation can be
increased
2. adjunctive therapy (e.g., brimonidine, a topical CAI, a PGA)
can be initiated
3. an alternative first-line agent can be selected.

 Adverse Effects
Several weeks later
 dorzolamide 2% solution, one drop both eyes BID, is added
to M.H.’s betaxolol therapy.
Two weeks later,
 M.H. returns for a follow-up evaluation and complains of
bilateral stinging and foreign body sensation.
 Her IOP measures 30 mm Hg in the right eye and 29 mm
Hg in the left eye.
What are the possible causes of her side effects and poor
response to therapy?
Elgohary
1-12-2016

1-12-2016
Elgohary
These granules can drop into a patient’s eyes when instilling the
medication, leading to local side effects, such as stinging and
foreign body sensation
The exposure of dorzolamide to the outside
environment may result in the aggregation of dry white
granules on the tip of thedorzolamide bottle.
Such foreign bodies may cause enough discomfort to induce
non-adherence, resulting in a poor response to therapy.
These granules may be rinsed off of the tip with sterile
water.
M.H. should be questioned about the presence of dry
white granules on the tip of her dorzolamide bottle.

These complaints may also be a side effect from the medications,
regardless of the granule presence.
Ocular burning, stinging, and discomfort were reported in one-
third of patients in dorzolamide clinical trials.
M.H.’s administration technique should also be assessed to
determine whether she is administering the two drugs at least 5
to 10 minutes apart so that the first drug is not washed away by
the second drug.
Elgohary
1-12-2016
This should be a consideration when assessing her response to
therapy.

 After further discussions with M.H., it is determined that she
has not been adherent to her dorzolamide therapy because
of intolerable side effects.
 The dorzolamide is discontinued and replaced with
travoprost 0.004% one drop both eyes once a day at
bedtime.
 Why might this drug selection be especially appropriate for
M.H.?
 What patient education information should be provided to
M.H. about travoprost side effects?
Elgohary
1-12-2016

Prostaglandin analogs are first-line agents and are appropriate in
patients who are not responding to or are having intolerable side
effects from other medications.
Travoprost is an ideal choice for M.H., because African Americans
respond especially well to travoprost.
M.H. still needs to be informed about the PGA- induced potential
for hyperpigmentation of the iris, which may be permanent.
She also needs to be educated on the possibility of eyelid skin
darkening and increased thickness, length, and pigmentation of
her eyelashes, which all may or may not be reversible.
These side effects might not be as cosmetically concerning to
M.H., because she has brown eyes and will be instilling travoprost
eye drops into both eyes.clinical pharmacy department :Dr.Hemat
Elgohary
1-12-2016

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