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Introduction to Pharmacology > Ophthalmic Pharmacology > Flashcards

Ophthalmic Pharmacology Flashcards

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
Q

What is the purpose of medical treatment of glaucoma?

A
  • decrease aqueous humor production
  • increase aqueous humor drainage
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26
Q

Topical administered ocular hypotensives:

A
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27
Q

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?

A

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
Q

What 4 carbonic anhydrase inhibitors are used to treat glaucoma? How do they work?

A

Dorzolamide, Brinzolamide, Methozolamine, Acetozolamide

decrease AH production by blocking the carbonic anhydrase system in the ciliary body epithelium

29
Q

When can carbonic anhydrase inhibitors be used in an emergency? What is a common adverse effect?

A

treatment of acute glaucoma every 15-30 mins

topical = local ocular discomfort
- no systemic side effects

30
Q

What 3 prostaglandin analogues are used to treat glaucoma? How do they work? How are they able to enter the eye?

A

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
Q

What species are prostaglandin analogues not used in? Why?

A

cats - ocular hypotensive effects are mediated by EP receptors, not FP

32
Q

What are the possible side effects to prostaglandin analogue treatment of glaucoma? What is usage contraindicated in?

A

inflammation - conjunctival hyperemia and moderate to marked miosis

most cases of secondary glaucoma (obstruction of AH drainage)

33
Q

What 2 hyperosmotic agents are used to treat glaucoma? What do they cause?

A
  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
Q

In what 3 situations is usage of hyperosmotic agents to treat glaucoma contraindicated?

A
  1. anterior uveitis
  2. cardiovascular disease, renal disease, DM
  3. glycerol can induce vomiting at high doses
    (usage is limited in veterinary medicine)
35
Q

What happens in acute glaucoma?

A

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
Q

What 2 parasympathomimetics are used to treat glaucoma? How do they work?

A

pilocarpine (direct), demecarium bromide (indirect)

increase outflow by inducing miosis, thus widening the iridocorneal angle (ICA) and increasing AH outflow

37
Q

What is a common side effect of Pilocarpine? When is usage to treat glaucoma contraindicated?

A

(parasympathomimetic)
acidic pH causes irritation following topical administration

induces miosis - patients with uveitis and/or pupillary block glaucoma

38
Q

Why is antiinflammatory therapy important in ophthalmic pharmacology? When are topical and systemic antiinflammatories used?

A

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
Q

How do corticosteroids work as antiinflammatory ocular therapy? What are 2 possible adverse effects? When are topicals contraindicated?

A

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
Q

How do nonsteroidal antiinflammatory agents (NSAIDs) work? How do they compare to topical corticosteroids? What is a common side effect?

A

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
Q

What causes most ocular infections?

A

pathogenic effects of normal ocular surface bacteria

42
Q

What is the main characteristic of normal ocular bacteria? What is an exception?

A

predominantly Gram-positive

Pseudomonas aeruginosa is Gram-negative and a potent ocular pathogen

43
Q

When are antibacterials used prophylactically in ocular infections? Therapeutically?

A

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
Q

What 3 aminoglycosides are used for ocular infection? What is their spectum like?

A

Tobramycin, Gentamycin, Neomycin (topicals, ointments)

principally Gram-negative, but does have restricted efficacy against Gram-positive Staphylococcus aureus

45
Q

When are aminoglycosides typically used? What are common side effects of gentamycin ane neomycin?

A
  • 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
Q

What tetracycline is used for ocular infections? What is its spectrum like? In what 2 ways is it most useful?

A

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
Q

What fluoroquinolones are used for ocular infections? What is their spectrum like?

A

norfloxacin, ofloxacine, cirpofloxacin, levofloxacine, morifloxacin, gatifloxacin, besifloxacin

wide-spectrum affecting G- and G+ bacteria

48
Q

When are fluoroquinolones used for ocular infections? side effect is common in cats?

A

prophylaxis or therapy for ocular surface and intraocular infections

parenteral administration may cause retinal degeration with aged cats most susceptible

49
Q

What lincosamide and macrolide are commonly used for ocular infections? What is the spectrum like? When are they used?

A

erythromycin ointment; clindamycin and azithromycin orally

G+ efficacy, especially Chlamydophila felis and Mycoplasma spp.

prophylaxis or therapy for ocular surface infections

50
Q

What are the 2 most frequent indication for antifungal agent usage in ocular infection? When are these infections most common?

A
  • 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
Q

What 2 polyenes are commonly used for ocular fungal infections? What is the spectrum like? What are they used for?

A

natamycin, amphotericin B

broad spectrum

poor penetration to cornea with intact epithelium —> used in confirmed ulcerative keramycosis (good in inflammed epithelium)

52
Q

What azoles are commonly used for ocular fungal infections? What is their spectrum like? When is it most commonly used?

A

voriconazole, miconazole, itraconazole, ketoconazole, fluconazole

broad spectrum against filamentous fungi

ulcerative and nonulcerative keratomycosis

53
Q

What side effect is Fluconazole most commonly associated with?

A

(azole antifungal)

prolonged recovery in horses recovering from anesthedia

54
Q

What is the most common viral infection treated by antiviral agents? How does this typically manifest?

A

feline herpesvirus-1

ocular surface disease in cats

55
Q

What 2 pyrimidine analogs are used as ocular antivirals? How are they used?

A

trifluridine, idoxuridine

exert action on DNA synthesis —> only active when the virus is replicating
- can be used for corneal and/or conjunctival ulceration

56
Q

What purine analogs are used as ocular antivirals? What are they specifically used to treat?

A

vidarabine, cidofovir, famciclovir, acyclovir, valocyclovir

treats FHV-1 and keratitis in horses due to EHV-2

57
Q

What are 2 common side effects of pyrimidine analogs? When is usage of acyclovir and valacyclovir contraindicated?

A
  1. topical irritation
  2. nasolacrimal punctual occlusion

CATS - life-threatening toxicities to kidney and bone marrow

58
Q

What are lacrimogenics? What kind of drug is most commonly used as one? What are possible adverse effects?

A

drugs that increase tear production

parasympathomimetic - pilocarpine

PARASYMPATHETIC OVERSTIMULATION - excessive salivation, lacrimation, urination, defecation

59
Q

What do dogs with neurogenetic keratoconjunctivitis sicca (dry eye) lack?

A

neurological input to lacrimal gland

60
Q

What are mydriatics and cycloplegics?

A

MYDRIATIC: dilate pupil —> diagnostic procedures

CYCLOPLEGIC: paralyze ciliary body musle —> anterior uveitis

61
Q

What drugs are used as mydriatics and cycloplegics? When are they most commonly used? What are 2 possible side effects?

A

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
Q

What 2 parasympatholytics are used as mydriatics and cycloplegics? How do they work? What affects efficacy?

A

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
Q

What are 3 possible side effects of parasympatholytics used as mydriatics and cycloplegics?

A
  1. salivation
  2. reduction in aqueous tear film production
  3. photophobia due to mydriasis
64
Q

What 4 local anesthetics are commonly used on the eyes? Why are they used?

A
  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
Q

What are 3 possible side effects of local anesthetics on the eye?

A
  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

Introduction to Pharmacology (39 decks)

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