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Lecture 32: Ocular Pharmacology
Timothy Beer (Modified by Dave Reilly 2013)
Ocular Antihypertensives (Glaucoma)
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**Prostaglandin Analogs: the #1 drug of choice for glaucoma
o
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MOA
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Upregulate matrix metalloproteinasesincreased uveoscleral outflow
Almost all the other glaucoma drugs are about “turning off the faucet” (aka decreasing aqueous
production).
o Clinical Use
 Drug of choice for glaucoma
 Once daily dosing
o Clinical Efficacy
 Produces a greater reduction in intraocular pressure (IOP) than beta-blockers
o Side Effects (not too bad, overall)
 Turns hazel eyes brown (15%), by increasing size (not number) of melanocytes
 Hypertrichosis (lengthening of the lashes)
 Eye redness (so bedtime dosing is preferred)
 Periorbital skin darkening
 Uveitis (prostaglandins are pro-inflammatory)
 Reversible Cystoid macular edema
o Agents
 Xalatan
**Beta-blockers: NOT the drug of choice for glaucoma
o MOA
 Antagonize circulating catecholamines at B1 and B2 receptors at ciliary body epithelium  decreased
aqueous production
o Clinical Use
 In the past, 75% of glaucoma patients used beta-blockers
 No longer the drug of choice
 Can be used adjunctively to prostaglandin analogs
o Side Effects
o
o
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Carbonic Anhydrase Inhibitors
Dorzolamide
o
o
o
o
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 Decreased HR and BP
 Shortness of breath
 Fatigue
 Depression
 Decreased libido
 Adverse effect on lipid profiles
Contraindications
 Asthma or other pulmonary disease
 Bradycardia
 Myasthenia gravis
Agents
 Carteolol
 Non-selective beta-blocker
 Decreased side effects
 Decreased adverse effects on lipid profiles
 Betoptic S
 Cardioselective B1-blocker
 Less breathing problems
MOA

Inhibit carbonic anhydrase in pigmented and non-pigmented epithelium of ciliary body  decreased
aqueous humor production
 Note: these drugs are sulfonamide derivatives
Clinical Use
 Used short-term emergently (orally)
 Drops can be used adjunctively with a B-blocker (Timolol)
Side Effects
 Systemic effects
 Metallic taste
 Tingling
 Renal stones
 Metallic acidosis
 Ocular effects
 Burning eyes
 Eye redness
 Induced myopia (near sightedness) – ciliary body swells and pushes lens apparatus forward =
lengthens distance between retina and lens = near-sighted.
Contraindications
 Sulfa allergy – can cause serious reaction in pt w/ true sulfa allergy.
 Renal stones
 Liver or kidney disease
 Addison’s disease
 Adrenal insufficiency
 Thiazide diuretics
 Steroids
 Digitalis
 Aspirin
Anticholinergics (Mydriatics/Cycloplegics)
o
MOA
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Block effect of acetylcholine
Paralyze the parasympathetic iris sphincter and circular muscle of ciliary body
Move the lens-iris diaphragm
Stabilize the blood-aqueous barrier
o
o
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o
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Alpha Adrenergic Agonists (Sympathomimetics)
o
o
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Clinical Use
 Used to for dilation (eye exam)
Side Effects
 Atropine toxicity (Hot as a hare, red as a beet, dry as a bone, blind as a bat and mad as a hatter)
Contraindications
 Predisposed individuals with narrow angle
 Can precipitate angle-closure attack
Agents
 Atropine
MOA
 Decrease aqueous production
Side Effects
 Allergic reaction (redness, itching)
 Allergic conjunctivitis
 Dry mouth/nose, syncope, eyelid retraction, mydriasis
Contraindications
 **MAOIs
 **Children
Agents
 Alphagan P
 Iopidine
Miotics (Cholinergic agents): Pilocarpine, Carbachol
o
o
o
MOA

Activates the M3 cholinergic receptors on pupillary constrictor muscle - Causes dramatic miosis which
stetches the iris away from the outflow tract = increased outflow.
Side Effects
 Pilocarpine toxicity (salivation, lacrimation, sweating, N/V/D, bronchiolar spasm, pulmonary edema
 Worsens parkinson’s disease
RARELY USED ANYMORE. Essentially only pts that have been on them forever, and in emergency/surgical setting
**Anti-VEGF (Angiogenesis Inhibitors)
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Indications
o Any ocular disease associated with neovascularization, including:
 Macular degeneration
 Diabetic retinopathy
 Retinal vein occlusions
o GREAT DRUG!!!!!!!!!
Side Effects (mostly d/t route of administration- injection)
o Blurred vision
o Redness of the eye
o Sensitivity to light
o Increased intraocular pressure
o Cataract
o Infection
o Retinal detachment
o Allergic reaction
o Possible increased risk of thromboembolic events**
Agents
o Ranibizumab
 Recombinant monoclonal antibody targeting VEGF-A
o Bevacizumab
Antiinflammatory Agents
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Ocular Complications Associated with Steroids
o Steroid-induced glaucoma
o Cataract
o Delayed wound healing, enhanced microbial or fungal proliferation, punctate keratopathy
Antibiotics
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In contact lens wearers, use fluoroquinolone, because it covers Pseudomonas!!!!!!!
The Logistics of Using Medicated Eye Drops
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After taking drops, close eyes and rest for a second, don’t blink
o Increases contact time
o Reduces systemic side effects
The best time interval between eye drops is 5 minutes
Major draining is through the inferior punctum – for maximum exposure you want to occlude the puctate to avoid loss
of drug through the naso-lacrimal system.
o Punctal occlusion = reduce systemic toxicity, avoid tasting the drops. Always occlude in pregnancy and when using
-blockers!
What if you think you miss getting the drop in?
o Re-dose IMMEDIATELY. You cannot overdose as long as you do it right away. The cul-du-sac of the eye can only
hold so much, the rest will overflow onto the cheek. The longer you wait the more time the med has to work on
the eye, which means if you didn’t miss, you might overdose.
PRACTICAL CLINICAL PEARLS
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5 minutes between drops
punctual occlusion!!
Immediate redosing if necessary
Chill the drops!
Ask about eye meds!!
Cap color is helpful
Fluoroquinolones for contact lens wearers needing topical antibiotic.
High Yield Receptors
Muscarinic (acetylcholine) M3: pupillary constriction, ciliary body constriction (accommodation), aqueous production from
ciliary body.
1 receptor: Pupil dilation
 receptors: increase aqueous humor production from the ciliary body, (but also increases aqueous outflow at the trabecular
meshwork)