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Introduction to Pharmacology > Ophthalmic Pharmacology > Flashcards

Ophthalmic Pharmacology Flashcards

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1
Q

What are the 5 adnexal tissues of the eye? What is their purpose?

A
  1. eyelids
  2. nictitating membrane
  3. conjunctiva
  4. lacrimal glands
  5. nasolacrimal system

mechanical protection and immune surveillance

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2
Q

What are the 3 tunics of the globe?

A
  1. external, FIBROUS tunic: cornea and sclera provide rigidity
  2. middle, VASCULAR tunic: iris, ciliary body, and choroid provide blood supply, maintain IOP, and control light entry into the retina
  3. NEURAL tunic: signal transmission important for visceral function
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3
Q

What are the crystalline lens, aqueous humor (AH), and viterous humor (VH)?

A

CL - focuses light rays on the sensory retina to optimize focusing power

AH - produced by the ciliary body and occupies the space between the cornea and lens (anterior chamber) and nourishes the avascular cornea and lens

VH - occupies the space between the lens and sensory retina and maintains structural integrity of the posterior portion of the globe

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4
Q

How can the globe be subdivided?

A
  • ANTERIOR SEGMENT = structure anterior to the junction of the retina and ciliary body
  • POSTERIOR SEGMENT = structures posterior to the junction
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5
Q

What are the 2 blood-ocular barriers present in the eye? What do they do?

A
  1. blood-aqueous humor
  2. blood-retinal humor
  • impede the entrance of drugs
  • limit entrance of blood components, like WBC, RBC, proteins, and lipids (transparency of ocular media is necessary for vision)
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6
Q

How does intraocular inflammation affect the blood-ocular barriers?

A

decreases their effectiveness, allowing drugs to enter the eye

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7
Q

What innervates the eye?

A

autonomic ocular innervation
- parasympathetic (ACh)
- sympathetic (NE)

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8
Q

How do the parasympathetic and sympathetic nervous systems affect the eye?

A

PARASYMPATHETIC
- lacrimal gland secretion
- iris sphincter relaxation
- extraocular muscles controlling eye movements

SYMPATHETIC
- adnexal and orbital smooth muscle
- iris dilator muscle
- ciliary body (AH)
- iridocorneal angle structures where AH drains

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9
Q

How do the layers of the cornea affect intraocular movement of drugs?

A

CORNEAL EPITHELIUM = lipophilic
CORNEAL STOMA = hydrophilic
CORNEAL ENDOTHELIUM = lipophilic

limits movement to all but biphasic drugs

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10
Q

How are medications typically able to enter the eye?

A

can be altered by the ocular environment to import penetration
- prostaglandin analogues are converted by sterases within the cornea to improve migration through the layers

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11
Q

What are the major impediments to the penetration of systemically administered drugs into the eyes? What kinds of drugs are able to pass?

A

blood-ocular barriers

  • lipid soluble
  • low MW
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12
Q

What is the barrier to the movement of drugs between the anterior and posterior segments of the eye? What happens when this barrier is disrupted?

A

hyaloiderocapsular ligament at the junction of the posterior lens capsule and anterior vitreous

  • increases posterior movement of topically applied drugs
  • anterior movement of systemically administered drugs
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13
Q

How does the solubility of drugs affect their administration? pH?

A

BIPHASIC = topically administered
LIPOPHILIC = systemically admnistered

  • physiological pH (7-7.4) = avoids discomfort upon instillation and increases drug availability
  • nonphysiological pH formulations require buffers
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14
Q

What are the 3 most common formulations of ophthalmic drugs?

A
  1. SOLUTIONS - easier to administer in small animals and may be administered to large animals with subpalpebral lavage (volume of drops = 25µL-70µL and the palpebral fissue only holds 30µL = spillage)
  2. SUSPENSIONS - larger particles suspended in aqueous vehicles to make them minimally irritating
  3. OINTMENTS - contain drug within viscous vehicles (petrolatum, lanolin)
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15
Q

What are the 2 major advantages to using ointments over other formulations? What is a common disadvantage?

A
  1. ability to administer lipid-soluble drugs
  2. achieves longer contact time with less drainage through the nasolacrimal system

oily residue frequently remains

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16
Q

What 4 ways of injection can drugs be given in the eyes?

A
  1. SUBCONJUNCTIVAL - space between conjunctiva and sclera; drugs penetrate through the sclera and cornea or absorbed in conjunctival vasculature
  2. INTRACAMERAL - anterior chamber, allowing movement within the intraocular environment and draining with AH
  3. INTRAVITREAL - vitreous, long-term reservoir
  4. PERIBULBAR/RETROBULBAR - behind globe, anesthetics to provide akinesia and analgesia
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17
Q

Why is intracameral administration of ophthalmic drugs less common?

A

associated with a high risk of iatrogenic damage and intraocular drug toxicity

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18
Q

Why are ophthalmic drugs given topically?

A

enables high levels of medication to be reached locally into the conjunctiva, cornea, and anterior chamber without systemic exposure and adverse drug reactions/interactions

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19
Q

In what 3 situations is systemic (parenteral/oral) administration of ophthalmic drugs indicated?

A
  1. eyelid - restricted penetration of topical medication and extensive vascularization
  2. orbital disease - restricted penetration of topical medication and extensive vascularization
  3. posterior segment disease - allows passage of corneal and hyaloidecapsular barriers
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20
Q

What maintains intraocular pressure?

A

balance between production and drainage of AH

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21
Q

How is aqueous humor produced? What happens next?

A

produced in ciliary bodies and is actively secreted by carbonic anhydrase and cAMP-mediated mechanisms

AH flows anteriorly through the pupil and drains out of the eye at the iridocorneal angle (ICA)

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22
Q

In what 2 ways is aqueous humor drained?

A
  1. CONVENTIONAL outflow through the trabecular meshwork into sclera vessels**
  2. UNCONVENTIONAL (uveoscleral) outflow drains the remainder via absorption by the posterior sclera
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23
Q

What is glaucoma characterized by? What are 4 outcomes?

A

increased intraocular pressure

  1. retinal damage
  2. optic nerve damage
  3. vision loss
  4. discomfort
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24
Q

What is glaucoma always caused by? What are the 2 types of glaucoma?

A

decreased aqueous humor drainage

  1. PRIMARY - inherent abnormality in the drainage angle
  2. SECONDARY - obstruction of aqueous humor flow within or from the eye
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25
What is the purpose of medical treatment of glaucoma?
- decrease aqueous humor production - increase aqueous humor drainage
26
Topical administered ocular hypotensives:
27
What 2 β-blockers are used to treat glaucoma? What is thought to be their mechanism of action? In what animals should their use be avoided?
Timolol, Betaxolol decrease AH production by interacting with cAMP or Na+/K+ ATPase small dogs and cats, especially with cardiovascular disease (β receptors in heart)
28
What 4 carbonic anhydrase inhibitors are used to treat glaucoma? How do they work?
Dorzolamide, Brinzolamide, Methozolamine, Acetozolamide decrease AH production by blocking the carbonic anhydrase system in the ciliary body epithelium
29
When can carbonic anhydrase inhibitors be used in an emergency? What is a common adverse effect?
treatment of acute glaucoma every 15-30 mins topical = local ocular discomfort - no systemic side effects
30
What 3 prostaglandin analogues are used to treat glaucoma? How do they work? How are they able to enter the eye?
Latanoprost, Bimatoprost, Travoprost decrease IOP by increasing uveoscleral (nonconventional) AH outflow through the activation of FP receptors they're prodrugs - administered form is converted by cornea esterases
31
What species are prostaglandin analogues not used in? Why?
cats - ocular hypotensive effects are mediated by EP receptors, not FP
32
What are the possible side effects to prostaglandin analogue treatment of glaucoma? What is usage contraindicated in?
inflammation - conjunctival hyperemia and moderate to marked miosis most cases of secondary glaucoma (obstruction of AH drainage)
33
What 2 hyperosmotic agents are used to treat glaucoma? What do they cause?
1. mannitol - (with water depravation) to treat acute primary glaucoma 2. glycerol - long-term management causes serum to become hyperosmotic to intraocular fluids, allowing it to move from the AH to the VH
34
In what 3 situations is usage of hyperosmotic agents to treat glaucoma contraindicated?
1. anterior uveitis 2. cardiovascular disease, renal disease, DM 3. glycerol can induce vomiting at high doses (usage is limited in veterinary medicine)
35
What happens in acute glaucoma?
drainage of AH becomes impeded with the pupil is dilated because the folding of the iris occludes the drainage angle, causing IOP to increase
36
What 2 parasympathomimetics are used to treat glaucoma? How do they work?
pilocarpine (direct), demecarium bromide (indirect) increase outflow by inducing miosis, thus widening the iridocorneal angle (ICA) and increasing AH outflow
37
What is a common side effect of Pilocarpine? When is usage to treat glaucoma contraindicated?
(parasympathomimetic) acidic pH causes irritation following topical administration induces miosis - patients with uveitis and/or pupillary block glaucoma
38
Why is antiinflammatory therapy important in ophthalmic pharmacology? When are topical and systemic antiinflammatories used?
minimizes the secondary effects of inflammation and preserves ocular structure/function - TOPICAL = ocular surface inflammation (conjunctivitis, keratitis), anterior segment inflammation (anterior uveitits) - SYSTEMIC = posterior uveitis, where topicals cannot reach
39
How do corticosteroids work as antiinflammatory ocular therapy? What are 2 possible adverse effects? When are topicals contraindicated?
inhibition of arachidonic acid cascade 1. long-term topical administration can lead to corneal deposits 2. systemic absorption may occur, causing endocrine imbalances - in the presence of corneal ulcers because they sill inhibit the reepithelialization of the wound and lead to infections
40
How do nonsteroidal antiinflammatory agents (NSAIDs) work? How do they compare to topical corticosteroids? What is a common side effect?
inhibit production of PG through the blockage of cyclooxygenase-1 and cyclooxygenase-2 - less effective - safer to use in the presence of corneal ulceration inhibits the reepithelialization of cornea ---> acute corneal melts
41
What causes most ocular infections?
pathogenic effects of normal ocular surface bacteria
42
What is the main characteristic of normal ocular bacteria? What is an exception?
predominantly Gram-positive Pseudomonas aeruginosa is Gram-negative and a potent ocular pathogen
43
When are antibacterials used prophylactically in ocular infections? Therapeutically?
PROPHYLACTIC: superficial, uncomplicated corneal ulcers; indicated in association with surgical procedures in which the conjunctiva in involved THERAPEUTIC: infected, complicated corneal disease, bacterial endophthalmitis
44
What 3 aminoglycosides are used for ocular infection? What is their spectum like?
Tobramycin, Gentamycin, Neomycin (topicals, ointments) principally Gram-negative, but does have restricted efficacy against Gram-positive Staphylococcus aureus
45
When are aminoglycosides typically used? What are common side effects of gentamycin ane neomycin?
- prophylaxis for therapy for ocular surface infection - limited in patients with deep corneal infections - GENTAMYCIN = chemical ablation of ciliary body in chronically glaucomatous eyes GENTAMYCIN = low pH makes it irritating NEOMYCIN = allergic and hypersensitivity reactions common
46
What tetracycline is used for ocular infections? What is its spectrum like? In what 2 ways is it most useful?
oxytetracycline formulated with polymyxin B affects both Gram-negative and Gram-positive bacteria 1. prophylaxis for ocular surface infections 2. increased corneal epithelial wound healing
47
What fluoroquinolones are used for ocular infections? What is their spectrum like?
norfloxacin, ofloxacine, cirpofloxacin, levofloxacine, morifloxacin, gatifloxacin, besifloxacin wide-spectrum affecting G- and G+ bacteria
48
When are fluoroquinolones used for ocular infections? side effect is common in cats?
prophylaxis or therapy for ocular surface and intraocular infections parenteral administration may cause retinal degeration with aged cats most susceptible
49
What lincosamide and macrolide are commonly used for ocular infections? What is the spectrum like? When are they used?
erythromycin ointment; clindamycin and azithromycin orally G+ efficacy, especially Chlamydophila felis and Mycoplasma spp. prophylaxis or therapy for ocular surface infections
50
What are the 2 most frequent indication for antifungal agent usage in ocular infection? When are these infections most common?
- treatment of fungal infections of the cornea (keratomycosis) in horses - intraocular infection with systemic mycotic organisms in dogs warm, humid climates ---> Aspergillus sp. and Fusarium spp. (filamentous)
51
What 2 polyenes are commonly used for ocular fungal infections? What is the spectrum like? What are they used for?
natamycin, amphotericin B broad spectrum poor penetration to cornea with intact epithelium ---> used in confirmed ulcerative keramycosis (good in inflammed epithelium)
52
What azoles are commonly used for ocular fungal infections? What is their spectrum like? When is it most commonly used?
voriconazole, miconazole, itraconazole, ketoconazole, fluconazole broad spectrum against filamentous fungi ulcerative and nonulcerative keratomycosis
53
What side effect is Fluconazole most commonly associated with?
(azole antifungal) prolonged recovery in horses recovering from anesthedia
54
What is the most common viral infection treated by antiviral agents? How does this typically manifest?
feline herpesvirus-1 ocular surface disease in cats
55
What 2 pyrimidine analogs are used as ocular antivirals? How are they used?
trifluridine, idoxuridine exert action on DNA synthesis ---> only active when the virus is replicating - can be used for corneal and/or conjunctival ulceration
56
What purine analogs are used as ocular antivirals? What are they specifically used to treat?
vidarabine, cidofovir, famciclovir, acyclovir, valocyclovir treats FHV-1 and keratitis in horses due to EHV-2
57
What are 2 common side effects of pyrimidine analogs? When is usage of acyclovir and valacyclovir contraindicated?
1. topical irritation 2. nasolacrimal punctual occlusion CATS - life-threatening toxicities to kidney and bone marrow
58
What are lacrimogenics? What kind of drug is most commonly used as one? What are possible adverse effects?
drugs that increase tear production parasympathomimetic - pilocarpine PARASYMPATHETIC OVERSTIMULATION - excessive salivation, lacrimation, urination, defecation
59
What do dogs with neurogenetic keratoconjunctivitis sicca (dry eye) lack?
neurological input to lacrimal gland
60
What are mydriatics and cycloplegics?
MYDRIATIC: dilate pupil ---> diagnostic procedures CYCLOPLEGIC: paralyze ciliary body musle ---> anterior uveitis
61
What drugs are used as mydriatics and cycloplegics? When are they most commonly used? What are 2 possible side effects?
sympathomimetics: EPI, phenylephrine - prior to intraocular surgery - diagnose Horner's 1. ocular surface irritation 2. systemic hypertension (limited used in patients with cardiovascular disease)
62
What 2 parasympatholytics are used as mydriatics and cycloplegics? How do they work? What affects efficacy?
tropicamide, atropine induce anticholinergic blockade of iris sphincter an ciliary body muscles iridal pigmentation ---> pigments are reservoirs for drugs, which slow down onset and prolong duration in heavily pigmented eyes
63
What are 3 possible side effects of parasympatholytics used as mydriatics and cycloplegics?
1. salivation 2. reduction in aqueous tear film production 3. photophobia due to mydriasis
64
What 4 local anesthetics are commonly used on the eyes? Why are they used?
1. 0.5% proparacaine 2. 0.5%, 1% tetracaine 3. butacaine 4. dibucaine provide corneal and conjunctival anesthesia for routine diagnostic and therapeutic procedures (cytology collection, surgery)
65
What are 3 possible side effects of local anesthetics on the eye?
1. proparacaine causes transient tear film instability ---> repeated dosing may result in epithelial keratitis 2. inhibit blood vessel formation and corneal epithelialization 3. TOPICAL - contraindicated as therapy for any ocular surface disease

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