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Ocular Pharmacology > Glaucoma Agents > Flashcards

Glaucoma Agents Flashcards

1
Q

which class(es) of drugs primarily inhibit the production of aqueous humor?

A
  • alpha-adrenergic agonists
  • beta-blockers
  • carbonic anhydrase inhibitors
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2
Q

which class(es) of drugs primarily increase trabecular outflow?

A
  • muscarinic agonists
  • nitrous oxide
  • rho-kinase inhibitors
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3
Q

which class(es) of drugs primarily increase uveoscleral outflow?

A

prostaglandin agonists

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4
Q

what color bottle caps do prostaglandin analogs have?

A

teal

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5
Q

what is the brand name for latanoprost?

A

Xalatan

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6
Q

what is the brand name for travoprost?

A

Travatan Z

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7
Q

what is the brand name for bimatoprost?

A

Lumigan

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8
Q

what is the brand name for tafluprost?

A

Zioptan

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9
Q

which of the prostaglandin analogs are ester prodrug(s)?

A
  • latanoprost
  • travoprost
  • tafluprost
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10
Q

what is the primary MOA for latanoprost, travoprost & tafluprost?

A

act on PGF-2α FP receptors found in ciliary muscle & iris sphincter muscle

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11
Q

which prostaglandin analog is a selective FP receptor agonist? how does it exert its ocular hypotensive effects?

A

latanoprost
- exerts its ocular hypotensive effects by increasing uveoscleral outflow by remodeling the ECM adjacent to ciliary muscle cells

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12
Q

which prostaglandin analog is a synthetic analog? it mimics the actions of what?

A

bimatoprost

- mimics the actions of prostamides

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13
Q

which prostaglandin analog has weak activity at the FP receptor?

A

bimatoprost

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14
Q

what is the MOA for bimatoprost?

A

dual mechanism of increase aqueous outflow through trabecular & uveoscleral pathway

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15
Q

which aqueous outflow pathway is pressure-sensitive?

A

trabecular

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16
Q

which aqueous outflow pathway is pressure-insensitive?

A

uveoscleral

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17
Q

what has to bind to the FP receptors to convert the prodrugs into their active form?

A

prostaglandin F2α

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18
Q

what allows prostaglandin analogs to penetrate the corneal epithelium?

A

lipophilicity

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19
Q

what converts the active form of prostaglandin analogs into free acid?

A

corneal esterases/amidases

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20
Q

what allows the free acid to bind to receptors?

A

hydrophilicity

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21
Q

which class of glaucoma medications is the first line treatment?

A

prostaglandins

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22
Q

what is the dosing for prostaglandins?

A

1 gtt qhs OU

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23
Q

when are prostaglandins most effective after administration?

A

12-24 hour period

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24
Q

what percentage of IOP lowering effects do prostaglandins have?

A

27-30%

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25
Q

which prostaglandin is used in treatment of POAG & ocular hypertension? (name generic & brand)

A

latanoprost (Xalatan)

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26
Q

Xalatan may significantly reduce IOP in patients with glaucoma associated with what condition?

A

Sturge-Weber Syndrome

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27
Q

which prostaglandin can be more effective than beta-blockers in reducing IOP in patients with pigmentary glaucoma?

A

latanoprost (Xalatan)

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28
Q

Xalatan (latanoprost) can often produce significant IOP reduction in patients with which type of glaucoma?

A

normal tension glaucoma

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29
Q

using Xalatan (latanoprost) in conjunction with which drugs can be useful due to the additive effects?

A
  • aqueous suppressant drugs

- drugs that enhance aqueous outflow through trabecular pathway

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30
Q

what is Xalatan preserved with?

A

BAK

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31
Q

when should you refrigerate Xalatan?

A

when using medication in only one eye

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32
Q

what is the brand name for latanoprost?

A

Xalatan

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33
Q

what is the brand name for travoprost?

A

Travatan

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34
Q

what preservative is in Travatan?

A

BAK

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35
Q

what is Travatan Z formulated with instead of BAK?

A

ionic buffered compound (sofZia)

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36
Q

what adverse effect was reduced when comparing Travatan Z (sofZia preservative) & Travatan (BAK preservative)?

A

conjunctival hyperemia

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37
Q

what is the brand name for tafluprost?

A

Zioptan

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38
Q

which prostaglandin is the only non-preserved IOP lowering agent?

A

Zioptan

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39
Q

what is the brand name for bimatoprost?

A

Lumigan

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40
Q

Lumigan is formulated with what as a buffer? what preservative is used?

A
  • citrate phosphate buffer

- BAK preservative

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41
Q

which prostaglandin is indicated as the primary therapy for IOP reduction in open-angle glaucoma & ocular hypertension?

A

Lumigan

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42
Q

Lumigan is formulated as what percent solution?

A

0.01%

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43
Q

what is the brand name when bimatoprost is formulated as 0.03% solution? what does it treat?

A

Latisse → treats hypertrichosis of eyelashes

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44
Q

these ocular side effects are from which class of glaucoma medications?

  • increased eyelid pigmentation
  • iris color darkening
  • conjunctival hyperemia
  • allergic reaction
  • punctate corneal erosions
  • corneal pseudodendrites
  • anterior uveitis
  • cystoid macular edema
  • pruritis
A

prostaglandins

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45
Q

which prostaglandin has the greater chance of causing conjunctival hypermia?

A

Lumigan (bimatoprost)

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46
Q

what are the contraindications of prostaglandins?

A
  • history of uveitis or prior incisional ocular surgery

- previous episodes of herpes simplex keratitis

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47
Q

prostaglandins should be used cautiously after cataract surgery in patients with a high risk factor of primarily developing what?

A

cystoid macular edema (CME)

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48
Q

beta-blockers have what colored bottle caps?

A

yellow, sometimes blue

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49
Q

name the non-cardioselective beta-blockers

A
  • timolol
  • levobunolol
  • metipranolol
  • carteolol
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50
Q

name the selective beta-blockers

A
  • betaxolol
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51
Q

which beta-blocker is most commonly used?

A

timolol

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52
Q

which beta blocker comes as a suspension?

A

betaxolol

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53
Q

which beta-blocker has intrinsic sympathomimetic activity (ISA)?

A

carteolol

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54
Q

beta-1 receptors are involved with?

A

cardiac rate, rhythm & force

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55
Q

beta-2 receptors are involved in what?

A

pulmonary function

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56
Q

what is the MOA of beta-blockers?

A

block beta-2 receptors on the postsynaptic neuron at the ciliary body epithelium → prevents production of aqueous fluid

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57
Q

which glaucoma medication is the second most commonly used to treat glaucoma?

A

timolol

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58
Q

what percentage of IOP lowering effects does timolol have?

A

~25%

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59
Q

which glaucoma medication is known to have relatively rapid development of tolerance? what is this referred as?

A

timolol → “escape”

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60
Q

what else has also been described in timolol besides “escape”?

A

long-term “drift”/drug tolerance

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61
Q

what is the dosing for timolol?

A

BID or QD

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62
Q

when dosing timolol QD, when is the best time to instill the drops?

A

in the morning

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63
Q

IOP lowering effects of timolol are additive to what therapies?

A
  • outflow agents (eg, pilocarpine)

- inflow agents (eg, CAIs & alpha-agonists)

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64
Q

why are beta-blockers not as effective during the night?

A

supine position causes 50% reduction of aqueous when we sleep

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65
Q

along with prostaglandins, what is the most effective ocular hypotensive agent in patients with POAG & ocular hypertension?

A

timolol

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66
Q

which glaucoma medication is used as a prophylactic after laser iridotomy, posterior subcapsulotomy & cataract surgery?

A

timolol

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67
Q

in Timoptic XE, what type of vehicle is in the formulation? what is the name of the vehicle?

A

Gelrite → viscosity agent

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68
Q

Isatol is formulated with potassium sorbate, what does it do?

A

increases lipophilicity

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69
Q

which formulation of timolol maleate is preservative free?

A

Timoptic Ocudose

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70
Q

which beta-blocker is metabolized by dihydrobunolol?

A

levobunolol

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71
Q

what is the primary mechanism of levobunolol?

A

decrease in production of aqueous humor

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72
Q

levobunolol contains which viscosity agent & which preservative?

A
  • viscosity agent → polyvinyl alcohol

- preservative → BAK

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73
Q

what is the dosing for levobunolol?

A

QD

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74
Q

which beta-blocker is metabolized by des-acetyl-metipranolol

A

metipranolol

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75
Q

what increases during treatment with topical metipranolol?

A

retinal perfusion pressure & blood flow

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76
Q

what is the primary metabolite of carteolol?

A

8-hydroxycarteolol

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77
Q

because carteolol possesses intrinsic sympathomimetic activity, it may be used in patients with glaucoma coexisting with what condition?

A

pulmonary disease

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78
Q

which glaucoma medication is used for chronic treatment of elevated IOP in patients with ocular hypertension & open-angle glaucoma?

A

carteolol

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79
Q

which beta-blocker is less effective than levobunolol or timolol?

80
Q

betaxolol has the ability to block what & where? what does it suggest?

A

sodium & calcium channels in vascular tissue & retinal ganglion cells → suggests that it may have potential as a neuroprotective agent

81
Q

what allows betaxolol to be used successfully in patients with coexisting glaucoma & pulmonary disease?

A

its relative cardioselectivity

82
Q

what is betaxolol formulated with what that is believed to increase drug residence time in the eye?

A
  • polyacrylic polymer

- cationic exchange resin

83
Q

what are the cardiovascular side effects of beta-blockers

A
  • bradycardia
  • exercise induced tachycardia
  • conduction arrhythmias
  • hypotension
  • Raynaud’s phenomenon
84
Q

which class of glaucoma medications have these pulmonary side effects?

  • average decrease of 25% in FEV1 in patients w/ COPD
  • bronchoconstriction/bronchospasm
  • asthma
  • dyspnea
A

beta-blockers

85
Q

why do beta-blockers have CNS side effects?

A

less blood throughout the body

86
Q

what gastrointestinal side effects do beta-blockers have?

A
  • diarrhea

- nausea

87
Q

what ocular side effects do beta-blockers have?

A
  • allergic blepharoconjunctivitis
  • dry eye/decreased TBUT
  • corneal anesthesia
  • macular edema (aphakics)
  • macular hemorrhage/retinal detachment
  • uveitis
  • cataract progression
88
Q

what systemic side effect do beta-blockers have?

A

masking of hypoglycemia

89
Q

beta-blockers are contraindicated in patients with?

A
  • bronchial asthma or history of it
  • severe chronic obstructive pulmonary disease (COPD)
  • bradycardia
  • severe heart block
  • cardiac failure
  • caution in patients w/ diabetes
  • children & infants
90
Q

beta-adrenoreceptor blockage may mask signs & symptoms of what condition(s)?

A
  • thyrotoxicosis

- acute hypoglycemia

91
Q

in beta-blockers, which drug(s) should you avoid for best IOP control?

92
Q

when cost is an issue, which beta-blocker(s) are preferred?

A
  • generic timolol
  • metipranolol
  • carteolol
93
Q

when comfort is an issue, which beta-blocker(s) is preferred?

94
Q

when hypercholesterolemia is an issue, which beta-blocker(s) is preferred?

95
Q

when preservative (BAK) allergy is an issue, which beta-blocker(s) is preferred?

A
  • Timoptic XE
  • Timoptic GFS
  • Timoptic Ocudose
96
Q

when COPD is an issue, which beta-blocker(s) is preferred?

A
  • betaxolol

- carteolol

97
Q

when pregnancy is an issue, which beta-blocker(s) is preferred?

A

avoid all (category C)

98
Q

adrenergic agonists have what color bottle cap?

99
Q

what drugs are classified as adrenergic agonists?

A
  • apraclonidine

- brimonidine

100
Q

what is the brand name for apraclonidine?

101
Q

what is the brand name for brimonidine?

A

Alphagan P

102
Q

alpha receptors have been identified where in relative to sympathetic nerve activity?

A

on presynaptic nerve terminals & post-junctionally in ciliary body

103
Q

activation of the presynaptic alpha-2 receptors does what?

A

inhibits neurotransmitter release → causes decrease in norepinephrine

104
Q

activation of postsynaptic ciliary body alpha-2 receptors does what?

A

reduces intracellular levels of cyclic adenosine monophosphate (cAMP)

105
Q

in relation to glaucoma, what may be mediated via alpha-2 receptor activity?

A

reduced aqueous production

106
Q

which adrenergic agonist is a selective alpha-2 receptor agonist?

A

apraclonidine

107
Q

generic brimonidine is preserved with what?

108
Q

Alphagan P is formulated with what preservative? what does it do?

A

Purite → disappears when it encounters light

109
Q

which adrenergic agonist is 30x more selective for alpha-2 receptors?

A

Alphagan-P

110
Q

at the post-junction ciliary body, stimulation of beta-2 does what?

A

increases aqueous production

111
Q

at the post-junction ciliary body, stimulation of alpha-2 does what?

A

decreases aqueous production

112
Q

at the post-junction of the iris dilator muscle, how does apraclonidine cause dilation?

A

it is more alpha-2 selective but still binds to alpha-1 on the postsynaptic iris dilator muscle

113
Q

at the post-junction iris dilator muscle, how does brimonidine prevent dilation?

A

it is way more alpha-2 selective vs alpha-1 → preventing release of NE → prevents binding to alpha-1 receptors on iris dilator muscle

114
Q

what is the primary MOA of Iopidine & Alphagan P?

A
  • both lower IOP by decreasing aqueous production

- brimonidine also increases aqueous outflow via uveoscleral pathway

115
Q

apraclonidine (Iopidine) has additional ocular hypotensive effects by?

A

influencing ocular blood flow

116
Q

how does apraclonidine affect vascular tone?

A
  • may also stimulate alpha-1 receptors in vascular smooth muscle → causing vasoconstriction
117
Q

what is the dosing of apraclonidine (Iopidine)?

A

TID x 3 months

118
Q

1.0% apraclonidine is indicated for?

A

controlling/preventing postsurgical IOP elevations after ant seg laser surgery & short-term IOP control of open-angle glaucoma before filtering procedures

119
Q

which glaucoma medication is used to lower IOP in initial treatment of an acute angle closure glaucoma?

A

apraclonidine

120
Q

apraclonidine 1.0% has also been used for what?

A

prophylaxis of postercyclopledgic spikes in IOP

121
Q

are apraclonidine & brimonidone used as monotherapy or as an additive?

122
Q

brimonidine may be used to improve vision function under what condition in which patients?

A

under scotopic conditions in patients who had refractive surgery

123
Q

what is the most common ocular side effects of adrenergic agonists?

A

conjunctival blanching

124
Q

apraclonidine has a 40% rate of causing what ocular side effect?

A

contact dermatitis

125
Q

what are the systemic (dose-related) side effects of adrenergic agonists?

A
  • dry mouth
  • dry nose
  • tachyphylaxis
  • shortness of breath
126
Q

what CNS side effects do alpha adrenergic agonists have?

A
  • fatigue
  • lethargy
  • headache
127
Q

adrenergic agonists are contraindicated in patients taking what medication?

128
Q

adrenergic agonists should be cautioned in patients with what condition?

A

severe cardiovascular disease (ie, HTN)

129
Q

adrenergic agonists should be cautioned/avoided in which age group?

A

young children, especially those weighing < 20 kg & those younger than 6 y/o

130
Q

what pregnancy category is brimonidine? apraclonidine?

A
  • brimonidine → category B

- apraclonidine → category C

131
Q

carbonic anhydrase inhibitors (CAIs) have what bottle cap color?

132
Q

what are the oral carbonic anhydrase inhibitors?

A
  • acetazolamide (Diamox)

- methazolamide (Neptazene)

133
Q

what are the topical carbonic anhydrase inhibitors?

A
  • dorzolamide (Trusopt)

- brinzolamide (Azopt)

134
Q

formation of what is an essential component of aqueous production?

A

bicarbonate

135
Q

carbonic anhydrase is found in which anterior segment structure?

A

ciliary processes

136
Q

production of what in where plays a key role in aqueous humor formation?

A

production of bicarbonate in ciliary epithelium

137
Q

what is the MOA for carbonic anhydrase inhibitors?

A

inhibits production of bicarbonate & acts on decreasing sodium entry into posterior chamber by decreasing fluid movement across nonpigmented ciliary epithelium → resulting in a decrease of aqueous production & IOP (aqueous suppressant)

138
Q

which carbonic anhydrase inhibitor is given in angle-closure attacks? in what dose?

A

acetazolamide → 125 & 250mg tablets

139
Q

which carbonic anhydrase inhibitor comes as a suspension?

A

brinzolamide

140
Q

Cosopt is a combination of which glaucoma medications? what drug class do each belong to?

A

dorzolamide (CAI) + timolol (beta-blocker)

141
Q

which carbonic anhydrase inhibitor is the most widely used & orally administered?

A

acetazolamide

142
Q

what is the dosing for acetazolamide (Diamox)?

A
  • 250 mg q6h

- 500 mg sustained release capsule BID

143
Q

why do you need relatively large doses of acetazolamide to produce a signoficant plasma level of unbound drug?

A

majority of it binds to plasma proteins in the blood

144
Q

why should you be cautious of giving acetazolamide to patients with kidney issues?

A

drug is not metabolized → it is excreted by the kidneys

145
Q

why is acetazolamide often reserved for short-term use?

A

significant adverse reactions

146
Q

which glaucoma medication may also produce a partial/complete resolution of macular edema in patients w/ CME, retinitis pigmentosa & chronic intermediate uveitis (pars plantis)? why?

A

acetazolamide → diuretic

147
Q

is acetazolamide or methazolamide more potent?

A

methazolamide

148
Q

does acetazolamide or methazolamide have higher lipid & water solubilities?

A

methazolamide

149
Q

is acetazolamide or methazolamide less toxic to the kidneys?

A

methazolamide

150
Q

what is the dosing for methazolamide (Neptazane)

A

25-100 mg TID

151
Q

which carbonic anhydrase inhibitor do many authorities believe should be the first to be used for glaucoma therapy?

A

methazolamide

152
Q

these common systemic side effects are for which glaucoma medications?

  • numbness & tingling of extremities & perioral region
  • metallic taste
  • GI irritation
  • metabolic acidosis
A

oral carbonic anhydrase inhibitors

153
Q

what are the two main uncommon systemic side effects of oral CAIs?

A
  • hypokalemia

- aplastic anemia

154
Q

what are the ocular side effects of oral CAIs?

A

transient myopia

155
Q

carbonic anhydrase inhibitors should be avoided in patients with a known hypersensitivity to what?

A

sulfonamides

156
Q

oral CAIs are contraindicated in patients with what conditions?

A
  • clinically significant liver disease
  • renal disease
  • severe COPD
  • certain secondary glaucomas
157
Q

topical CAIs alter aqueous humor composition by?

A
  • lowering pH
  • decreasing bicarbonate levels
  • increasing posterior chamber ascorbate levels limited to the eye receiving dose
158
Q

what allows dorzolamide to have increased corneal & scleral penetration?

A

addition of an alkyl amino group enhances lipid & water solubility of the drug

159
Q

when dorzolamide is used as a monotherapy, what is the usual dosing?

160
Q

how does dorzolamide lower IOP?

A

decreasing aqueous humor secretion & production

161
Q

dorzolamide has an additive effect when used in conjunction with which glaucoma medication? which class is it in?

A

timolol → beta-blocker

162
Q

the use of dorzolamide prevents IOP spikes after undergoing what?

A
  • YAG laser
  • argon laser trabeculoplasty
  • laser iridotomy
163
Q

which topical CAI is a suspension that has high affinity for carbonic anhydrase II isoenzymes?

A

brinzolamide

164
Q

what is the dosing for brinzolamide?

165
Q

which topical CAI doesn’t sting as much upon instillation? why?

A

brinzolamide → pH is closer to our eye’s pH

166
Q

what is the primary ocular side effect of topical CAIs?

167
Q

what systemic side effects do oral CAIs have?

A

bitter taste

168
Q

topical CAIs are contraindicated in patients with what conditions?

A
  • allergy to sulfonamides
  • caution in patients with severe renal & hepatic impairment
  • avoid in patients taking oral CAIs
169
Q

cholinergic agonists are also known as?

A
  • miotics
  • parasympathomimetics
  • cholinomimetics
170
Q

how are cholinergic agonists classified?

A
  • direct-acting

- indirect-acting

171
Q

what is the MOA for direct-acting cholinergic agonists?

A

activate cholinergic receptors at the neuroeffector junctions of iris sphincter muscle & ciliary muscle

172
Q

what is the MOA for indirect-acting cholinergic agonists?

A

inhibit cholinesterase → increases amount of acetylcholine at the cholinergic receptors

173
Q

what is the only formulation of cholinergic agonists still used today?

A

pilocarpine

174
Q

what color bottle caps do cholinergic agonists have?

175
Q

which type of glaucoma are cholinergic agonists used to treat?

A

open angle glaucoma

176
Q

what is the MOA of cholinergic agonists for treating open angle glaucoma?

A

contraction of longitudinal fibers of the ciliary muscles inserted into the scleral spur → opens up trabecular pores → increased drainage

177
Q

is pilocarpine direct-acting or indirect-acting?

A

direct acting

178
Q

the cholinomimetic action of pilocarpine on smooth muscle muscarinic receptors results in what?

A

contraction

179
Q

what are the intraocular smooth muscle response with pilocarpine?

A
  • pupillary constriction
  • spasm of accommodation
  • reduction of IOP
180
Q

what affects pilocarpine’s ocular hypotensive response?

A

ocular pigmentation

181
Q

long-term therapy with pilocarpine may cause what? how?

A

permanent miosis → loss of iris radial muscle tone & from fibrosis of the sphincter muscle

182
Q

what is the usual dosage of pilocarpine?

183
Q

pilocarpine is indicated to treat which type of glaucoma?

A

acute angle-closure glaucoma

184
Q

what is administered before pilocarpine in an acute angle-closure attack?

A
  • apraclonidine

- beta-blockers

185
Q

pilocarpine is also useful for which surgery? why?

A

laser iridotomy → to facilitate stretching of iris

186
Q

which types of glaucomas is pilocarpine contraindicated in?

A
  • neovascular

- uveitic

187
Q

what color bottle caps do rho-kinase inhibitors have?

188
Q

although netarsudil (Rhopressa) is a triple action ROCK/NET inhibitor, what is it’s primary action?

A

improves TM outflow & lowers episcleral venous presure

189
Q

Rhopressa is indicated to lower IOP in which types of glaucoma?

A

open-angle glaucoma & ocular hypertension

190
Q

what is the recommended dosage of Rhopressa?

191
Q

what is the most common side effect of Rhopressa?

A

conjunctival hyperemia

192
Q

what is the novel prostaglandin? what is its brand name? what color is the bottle cap?

A

latanoprost bunod (Vyzulta) → teal

193
Q

what is the MOA for Vyzulta?

A
  • latanoprost acid targets uveoscleral pathway

- nitric oxide targets trabecular meshwork

194
Q

how does Vyzulta affect the uveoscleral pathway?

A

widens the space to increase outflow

195
Q

how does Vyzulta affect the trabecular meshwork?

A

relaxes the trabecular meshwork to increase outflow

Ocular Pharmacology (9 decks)

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