Ocular Pharmacology

Question 1

Pharmacokinetics of topical ocular administration

Answer 1

• primary systemic absorption via nasolacrimal drainage
  
  • nasal mucosa avoids first-pass metabolims ==> systemic side-effects
• secondary systemic absorption via corneal absorption ==> aqueous humour and trabecular pathway
  
  • drugs must remain @ front of the eyeto be absorbed through the cornea
• drugs can be prepared as suspensions or gels for prolonged action

Question 2

Factors impacting rate/extent of absorption into ocular structures

Answer 2

• time drug remains in cul-de-sac and precorneal tear film
• elimination by nasolacrimal drainage
• drug binding to tear proteins
• drug metabolism by tear and tissue enzymes
• diffusion across cornea and conjunctiva

Question 3

Anatomical drug targets @ eye

Answer 3

• iris
• cornea
• ciliary body = location of aqueous humour production
• canal of schlemm
• trabecular meshwork

Question 4

General characteristics of glaucoma

Answer 4

• increase in intraocular pressure
• must decrease IOP via decrease production of aqueous humor and increase outflow.
• Normal = 10-15, >20 is bad.
• Types:
  
  • narrow angle
  • open angle
  • closed angle

Question 5

Tx strategies for narrow angle glaucoma

Answer 5

• avoid dilation ==>
• no α-1 agonists
• no muscarinic antagonists.

Question 6

Risk factors/characteristics/tx strategy for open angle glaucoma

Answer 6

• ciliary body β2 stimulation causes increase in aqueous humour production -
• Risk factors: increased IOP - prophylactic reduction of IOP reduces incidence of glaucoma
  
  • ↑ IOP
  • • family history
  • African american
  • possibly myopia
• Leading/most preventable cause of blindness
• Treatment: go after outflow in this case, reduce IOP
  
  • Give tropical drops

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Question 7

Pathophysiology/tx strategy for closed angle glaucoma

Answer 7

• Pathophysiology = mechanical blockage of the trabecular meshwork by the peripheral iris.
  
  • Blockage occurs intermittently and results in extreme fluctuations in IOP that may need to be treated as an emergency to avoid visual loss.
• Emergent eye problem
• Initial treatment is rapid reduction of IOP- pilocarpine
• Systemic medications are acetazolamide and mannitol
• Definitive treatment
  
  • Laser peripheral iridotomy
  • Avoid decongestants and anticholinergic agents while awaiting surgery

Question 8

Latanoprost: MOA, role in glaucoma

Answer 8

• MOA
  
  • prostaglandin analog
  • Increases uveoscleral outflow
• Role in glaucoma
  
  • First-line/initial treatment of open angle glaucoma
  • Increase outflow

Question 9

Latanoprost (Xalatana): Use-limiting SE/contraindication

Answer 9

• Brown discoloration of iris
• Eyelash lengthening
• Ocular irritation
• Few systemic effects

Question 10

Pilocarpine (Ocursert): MOA; role in glaucoma

Answer 10

• MOA = cholinergic agonist
• Role
  
  • Less commonly used today
  • Emergently decrease IOP in closed angle glaucoma

Question 11

Pilocarpine (Ocusert): use-limiting SE/contraindication

Answer 11

• Ciliary spasm ⇒ HA,
• Myopia
• Dim Vision

Question 12

Brimonidine (Alphagan): MOA; role in glaucoma

Answer 12

• MOA
  
  • α2 adrenergic agonist ⇒ ↓ production, ↑ outflow
  • α2 is coupled to Gi ==> less aqueous humor
  • increases uveoscleral outflow
• Role
• 2nd line along with β blockers and CAI’s in open angle glaucoma

Question 13

Brimonidine (Alphagan): use-limiting SE/contraindication

Answer 13

• Red eye and ocular irritation
• Neonates: CNS depression, hypotension, somnolence and apnea

Question 14

Timolol (Timoptic): MOA; role in glaucoma

Answer 14

• MOA
  
  • β adrenergic antagonist ⇒ ↓ production of aqueous humor
  • Can also decrease ocular blood flow, which decreases ultrafiltration required for production
• Role
  
  • 2nd line treatment in open angle glaucoma if IOP still not in target range

Question 15

Timolol (Timoptic): use-limiting SE/contraindication

Answer 15

• Depression, fatigue, bradycardia, respiraory depression
• AVOID in patients with asthma, bradycardia, COPD

Question 16

Dorzolamide (Trusopt): MOA; role in glaucoma

Answer 16

• MOA
  
  • carbonic anhydrase inhibitor ⇒ ↓ production
• Role
  
  • 2nd/3rd line treatment If not tolerant to β-blocker in open angle glaucoma

Question 17

Dorzolamide (Trusopt): use-limiting SE/contraindication

Answer 17

• Topical administration greatly decreases systemic effects:
  
  • fatigue
  • depression
  • paresthesias
  • renal stones