This document provides an overview of HEENT disorders therapeutics, focusing on glaucoma. It defines glaucoma and discusses the two main types: open-angle glaucoma and closed-angle glaucoma. For each type, it covers risk factors, pathophysiology, clinical presentation, diagnosis, and treatment goals and approaches. Treatment typically begins with medications to lower intraocular pressure and may progress to laser therapy or surgery if medication is not effective. The document provides detailed information on evaluating and managing both chronic open-angle glaucoma and acute angle-closure glaucoma.

1. HEENT disorders therapeutics
By: Tsegaye Melaku
[B.Pharm, MSc, Clinical Pharmacist]
06, January, 2017
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et
+251913765609
Glaucoma
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2. Learning objectives
Upon completion of the chapter, you will be able to:
Identify risk factors for the development of primary open-angle
glaucoma (POAG) and acute angle-closure glaucoma.
Compare and contrast the pathophysiologic mechanisms responsible
for open-angle glaucoma and acute angle-closure glaucoma.
Compare and contrast the clinical presentation of chronic open-angle
glaucoma and acute angle-closure glaucoma.
List the goals of treatment for patients with POAG, and acute angle-
closure glaucoma.
Choose the most appropriate therapy based on patient specific data.
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3. Background: Anatomy and Physiology
The eye is separated into two segments
by the lens (anterior and posterior
segment)
Anterior segment of the eye is
separated by the iris into 2 (posterior
and anterior chambers).
Ciliary body(ring-like structure) :
Surrounds and supports the lens,
Produces and secretes neutral fluid
called aqueous humor.
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4. 4
Aqueous humor flow
Ciliary body posterior chamber pupil (to provide oxygen and nutrition to the
avascular lens and cornea) anterior chamber trabecular meshwork  Schlemm’s
canal  episcleral venous system.

5. 5

6. Introduction: Glaucoma
Glaucoma: spectrum of ophthalmic disorders x-zed by
neuropathy of the optic nerve and loss of retinal ganglion cells.
Its effect:
Permanent deterioration of the visual field
Potentially total vision loss.
It is often, but not always, eye pressure related.
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9. Epidemiology
2nd leading cause of blindness after cataracts.
60.5 million people have glaucoma in 2010 in US.
By 2020: reach 80 million people worldwide.
2.22 million people are affected by POAG, and by 2020 increase
to 3.36 million.
Prevalence of POAG increases with age & rare in <40 yrs.
Prevalence of angle-closure glaucoma is lower than POAG.
POAG is a “silent disease,” with patient’s not experiencing vision loss
until late in the disease process.
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10. Classification
According to anterior chamber angle findings and the presence or
absence of disease (states) causing elevated IOP and accompanying
factors.
2 types: Open angle (most common) and closed angle.
Primary glaucoma
Open angle (OAG)
Angle closure (With/Without pupillary block)
Congenital glaucoma
Secondary glaucoma
Open angle (Pre-trabecular/Trabecular/Post-trabecular)
Angle closure (Without /With pupillary block)
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11. Primary glaucoma: cannot be attributed to a preexisting ocular or
systemic disease.
Open-angle, closed angle, and congenital
Secondary glaucoma: attributed to preexisting ocular or systemic
disease.
Neovascular, traumatic, uveitic, steroid-responsive, and
pseudoexfoliative glaucoma.
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12. Open-Angle Glaucoma
Bilateral,
Genetically determined disorder constituting 60% to 70% of all
glaucomas
90% to 95% of primary glaucomas.
An increased IOP is not required for diagnosis of POAG.
Sxs do not present until substantial visual field constriction occurs.
Prognosis: excellent when it is discovered early and treated adequately.
Medical treatment are an effective
Medications will control IOP successfully in 60% to 80% of patients over
a 5-year period
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13. Risk Factors for Open Angle Glaucoma
Identified without an eye
examination
Age
Family history
High myopia
Previous eye trauma
Steroid use
Identified by an eye examination
Intra-ocular pressure
Central corneal thickness
Optic disc structure
Intra-ocular pathology
Pseudo-exfoliation.
Vascular and inflammatory disease
Congenital abnormalities

14. Risk Factors for Angle Closure Glaucoma
Age
Family history
Hypermetropia (long sightedness)
Anterior chamber (AC) morphology
Shallow AC, narrow AC angles

15. Etiology
Imbalance between the amount of internal (intraocular) fluid produced
and the amount that drains away.
OAG:
Optic nerve to ischemia (a reduced or dysregulated blood flow),
excitotoxicity, autoimmune reactions  
Apoptosis of the retinal ganglion cells, which results in axonal
degeneration and finally permanent loss of vision.
ACG:
Primary for ≤5%
Inherited shallow anterior chambers
Mechanical blockage trabecular meshwork by the peripheral iris.
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Closed-angle glaucoma
 Topical anticholinergics
 Topical sympathomimetics
 Systemic anticholinergics
 Heterocyclic antidepressants
 Low-potency phenothiazines
 Antihistamines
 Ipratropium
 Benzodiazepines (low risk)
 Theophylline (low risk)
 Vasodilators (low risk)
 Systemic sympathomimetics (low risk)
 Central nervous system stimulants (low risk)
 Serotonin selective reuptake inhibitors
 Imipramine
 Venlafaxine
 Topiramate
 Tetracyclines (low risk)
 Carbonic anhydrase inhibitors (low risk)
 Monoamine oxidase inhibitors (low risk)
Open-angle glaucoma
 Ophthalmic corticosteroids (high risk)
 Systemic corticosteroids
 Nasal/inhaled corticosteroids
 Fenoldopam
 Ophthalmic anticholinergics
 Succinylcholine
 Vasodilators (low risk)
 Cimetidine (low risk)
Drugs that May Induce or Potentiate Increased IOP

17. 17

18. Open-Angle Glaucoma (OAG)
Often referred to as the "sneak thief of sight.“
Pressures in the 20 to 30 mm Hg range for yrs before any disease
progression is noticed in the optic disk or visual fields.
Optic nerve damage in POAG can occur at a wide range of IOPs.
Iris adheres to the trabecular meshwork  continuously increased
IOP  "creeping" angle closure
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19. Open Angle Glaucoma
 Obstruction at the level of the trabecular
meshwork
 Progressive loss of visual field over time from
periphery to center
 Presence of hollowed out optic disc (‘cupping’)
due to retinal ganglion cell death
 Open anterior chamber angle
 Majority of patients have IOP > 21 mmHg,
asymptomatic

20. Closed-Angle Glaucoma
Mechanism of IOP elevation is clearer than that of POAG.
In CAG, a physical blockage of trabecular meshwork is present.
In many cases, single or multiple episodes of excessively high IOP (>40
mm Hg) result in optic nerve damage.
Very high IOP (>60 mm Hg) may result in permanent loss of visual field
within a matter of hours to days.
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21. How increased IOP cause optic nerve damage
It Produce the death of retinal ganglion cells and their axons.
Pressure-sensitive astrocytes and other cells in the optic disk supportive
matrix may produce changes and remodeling of the disk, resulting in
axonal death.
Vasogenic theories: optic nerve damage results from insufficient blood
flow to the retina secondary to the increased perfusion pressure
required in the eye, dysregulated perfusion, or vessel wall abnormalities,
  degeneration of axonal fibers of the retina.
Another theory suggests that the IOP may disrupt axoplasmal flow at the
optic disk.
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23. Clinical pictures
General
 Mostly asymptomatic.
 POAG is a chronic, slowly progressive(>50 yrs of age)
 CAG associated with symptomatic acute episodes.
Symptoms
 POAG: None until substantial visual field loss occurs.
 CAG: Non-symptomatic/prodromal symptoms (blurred or hazy vision with halos
around lights headache) may be present.
 Ocular pain, or discomfort, nausea, vomiting, and diaphoresis.
Signs
 POAG: Disk changes and visual field loss; IOP can be normal or elevated (>21
mm Hg.
 CAG: Hyperemic conjunctiva/optic disk, cloudy cornea, shallow anterior
chamber,; IOP 40 to 90 mm Hg
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27. Diagnosis/Examination
Physical & history
Eye pain (sudden and severe eye pain)
Headache, nausea and vomiting, reduced visual
acuity, photophobia, and irisopsia*.
Blurred vision (corneal edema and uveitis)
Visual field defects
Bulbar conjunctival hyperemia
Slit-lamp microscopy
Conjunctivae, anterior chamber, iris, lens, etc.,
are observed
Anterior chamber angle and ocular fundus.
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*A visual defect in which colored circles are seen around lights.

28. Keratoconjunctiva: Corneal edema
Anterior chamber: screening for shallow anterior chamber (PACG)
Iris: if bulged markedly in an anterior direction shows presence of
pupillary block
Neovascularization of the iris, iridial atrophy, and iridial nodules.
Lens: abnormal size or shape(lens swelling, spherophakia, etc.) and
abnormal lens position (lens luxation, lens subluxation, etc.).
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Slit-lamp microscopy

29. Tonometry [1,2,3]
Measure the internal pressure of the
eye
Gonioscopy
Recognize the various structures
composing the anterior chamber angle
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1
2
3

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Gonioscopy

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Ophthalmoscopy[1,2]
Detection of morphological changes in the
optic disc or retinal nerve fiber layer. 1
2

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Perimetry
For visual field

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RECEPTOR ACTIVATION WILL: TO LOWER IOP,
AIM FOR:
IRIS, Circular
Fibers
mAchR : Constrict Pupil  Activity
IRIS, Radial Fibers 1 R : Dilate Pupil  Activity
CILIARY MUSCLES mAchR : Contract for Accommodation
2 R : Relax for Far Vision
 Activity
Activity
Treatment[1]
Treatment Rationale
Lower IOP by:
(1) Decreasing Production of Aqueous Humor
(2) Increasing Outflow of Aqueous Humor

34. Treatment [2]
Goal of therapy for OAG
Prevent further loss of visual function;
Minimize adverse effects of therapy
Maintain general health, and quality of life;
Maintain IOP at or below a pressure at which further optic nerve
damage is unlikely to occur;
Educate and involve the patient in the management of their disease.
Targeted at decreasing IOP.
Preserve visual function by controlling the elevation in IOP
Prevent damage to the optic nerve,
Manage or prevent an acute attack of angle closure.
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NB: Bold : more for ACG

35. An initial target IOP to be set at least 25% lower than the patient’s
baseline IOP.
Not simply obtain an IOP in the range of 10 to 21 mm Hg.
The target IOP can be set lower (30% to 50% of baseline IOP)
Who already have severe disease,
Risk factors for disease progression, or
Have normal-tension glaucoma (NTG)
Initial IOP control can be achieved by medical, laser, surgical, or both.
Medical treatment is the most commonly selected therapeutic modality.
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36. Rx of OAG
Initiated in a stepwise manner.
Starting with lower concentrations of a single, well-tolerated topical
agent.
Medications:
Non-selective β-blockers,
Prostaglandin analogs (latanoprost, travoprost, and bimatoprost),
α2-agonist: brimonidine,
Combination: timolol/dorzolamide or timolol/brimonidine.
Pilocarpine and dipivefrin: 3rd line
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37. Start monotherapy in one eye (except for patients with very high IOP or
advanced visual field loss)
A monocular trial of medication is recommended when possible.
To evaluate drug efficacy and tolerance.
Initial response to therapy is typically done 4 to 6 weeks after the
medication is started.
Once IOPs reach acceptable levels, the IOP is monitored every 3 to 4
months.
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38. Rapid reduction of the IOP to preserve vision and to avoid surgical or
laser iridectomy on a hypertensive, congested eye mandatory.
Iridectomy (laser or surgical) is the definitive treatment.
Produces a hole in the iris
Permits aqueous humor flow to move directly from the posterior
chamber to the anterior chamber, opening up the block at the
trabecular meshwork.
Drug therapy: Pilocarpine, hyperosmotic agents, and a secretory inhibitor
(β-blocker, α2-agonist, prostaglandin analog, or topical/systemic CAI)
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Rx of ACG

39. Drugs that decrease aqueous production
Beta-Blockers [levobunolol, timolol, carteolol, betaxolol]
-Mechanism: Act on ciliary body to  production of aqueous humor
-Administration: Topical drops to avoid systemic effects
-Side Effects: Cardiovascular (bradycardia, asystole, syncope), bronchoconstriction
(avoid with 1-selective betaxolol), depression
Alpha-2 Adrenergic Agonists [apraclonidine, brimonidine]
-Mechanism:  production of aqueous humor
-Administration: Topical drops
-Side Effects: Lethargy, fatigue, dry mouth [apraclonidine is a derivative of clonidine
(antihypertensive) which cannot cross BBB to cause systemic hypotension]
Carbonic Anhydrase Inhibitors [acetazolamide, dorzolamide]
-Mechanism: Blocks enzyme production of bicarbonate ions (transported to posterior
chamber, carrying osmotic water flow), thus  production of aqueous humor
-Administration: Oral, topical
-Side Effects: malaise, kidney stones,

40. Drugs that increase aqueous outflow
Nonspecific Adrenergic Agonists [epinephrine, dipivefrin]
-Mechanism:  uveoscleral outflow of aqueous humor
-Administration: Topical drops
-Side Effects: Can precipitate acute attack in patients with narrow iris-corneal angle,
headaches, cardiovascular arrhythmia, tachycardia
Parasympathomimetics [pilocarpine, carbachol, echothiophate]
-Mechanism:  contractile force of ciliary body muscle,  outflow via TM
-Administration: Topical drops or gel, (slow-release plastic insert)
-Side Effects: Headache, induced miopia.
Prostaglandins [latanoprost]
-Mechanism: May  uveoscleral outflow by relaxing ciliary body muscle
-Administration: Topical drops
-Side Effects: Iris color change

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42. 42

43. β-Blocking Drugs
Lower IOP by 20% to 30%
1st line
Timolol, levobunolol, metipranolol, carteolol, and betaxolol
Local effects: dry eyes, corneal anesthesia, blepharitis, blurred
vision
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44. α2-Adrenergic Agonists
MOA: decrease the rate of aqueous humor production (some increase in
uveoscleral outflow, brimonidine).
Brimonidine (0.2%) , Apraclonidine
Effective for prevention or control of postoperative or post-laser
treatment increases in IOP
Apraclonidine: high incidence of loss of control of IOP (tachyphylaxis)
and a more severe and prevalent ocular allergy rate.
Reduce IOP by 18 -27% at peak (2 to 5 hrs) and by 10% at 8 to
12 hrs
Side effects: lid edema, eye discomfort, foreign-object sensation,
itching, dizziness, fatigue, somnolence, dry mouth
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45. Prostaglandin Analogs
MOA: increase the uveoscleral and, to a lesser extent, trabecular outflow
of aqueous humor.
Latanoprost, travoprost, and bimatoprost
If the patient does not respond to trovaprost or latanoprost, a switch to
bimatoprost, more effective (differences in receptor sites).
Nocturnal control of IOP is improved compared with timolol.
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46. Topical and systemic CAIs agents
MOA: decrease ciliary body aqueous humor secretion.
Inhibit aqueous production by blocking active secretion of sodium and
bicarbonate ions from the ciliary body to the aqueous humor.
Topical CAIs: Dorzolamide and Brinzolamide
 Well tolerated, reduce IOP by 15% to 26%
 S/Es: transient burning and stinging, ocular discomfort and transient blurred
vision, tearing, and, rarely, conjunctivitis, lid reactions, and photophobia.
Systemic CAIs: Acetazolamide, Methazolamide
 Reduce IOP by 25% to 40%
Systemic and topical CAIs should not be used in combination
Should be used with caution for patients with sulfa allergies, sickle cell
disease, respiratory acidosis, pulmonary disorders, renal calculi, electrolyte
imbalance, hepatic disease, renal disease, diabetes mellitus
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47. Parasympathomimetic Agents
MOA: reduce IOP by increasing aqueous humor trabecular outflow.
Pulling open the trabecular meshwork secondary to ciliary muscle
contraction reducing resistance to outflow.
They may also reduce uveoscleral outflow.
Work well to decrease IOP, but their use decreased
Local ocular adverse effects and/or frequent dosing requirements.
Pilocarpine
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48. Drugs Used in the Treatment of glaucoma
Drug Pharmacologic
Properties
Dose Form Strength (%) Usual Dose Mechanism of
Action
β-Adrenergic blocking agents
Betaxolol Relative β1-
selective
Solution 0.5 1 drop twice a day All reduce aqueous
production of ciliary
body
Suspension 0.25 1 drop twice a day
Carteolol Nonselective,
intrinsic
sympathomimetic
activity
Solution 1 1 drop twice a day
Levobunolol Nonselective Solution 0.25, 0.5 1 drop twice a day
Metipranolol Nonselective Solution 0.3 1 drop twice a day
Timolol Nonselective Solution 0.25, 0.5 1 drop q day–2x/day
Gelling
solution
0.25, 0.5 1 drop every day
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49. Carbonic anhydrase inhibitors
Brinzolamide Suspension 1 Two to three times a
day
All reduce
aqueous humor
production of
ciliary bodyDorzolamide Solution 2 Two to three times a
day
Acetazolamide Tablet 125 mg, 250 mg 125–250 mg two to
four times a day
500 mg/vial 250–500 mg
Capsule 500 mg 500 mg twice a day
Methazolamide Tablet 25 mg, 50 mg 25–50 mg two to
three times a day
Prostaglandin analogs
Latanoprost Solution 0.005 1 drop every night Increases aqueous
uveoscleral
outflow and to a
lesser extent
trabecular outflowBimatoprost Solution 0.03 1 drop every night
Travoprost Solution 0.004 1 drop every night
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50. Monitor and Evaluate
Clinical signs and symptoms and investigations
Safety and effectiveness
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28/04/2009 E.C