Glaucoma Agents Flashcards
If bicarbonate is in pH below it’s pKa will it be mostly ionized or non-ionized?
Non-ionized (In component form)
If bicarbonate is in pH above it’s pKa will it be mostly ionized or non-ionized?
Ionized (Acid form)
True or false, the acidosis caused by CAIs is part of the mechanism of action to lowering IOP
False
What are the systemically administered CAIs?
Acetalzolamide (Diamox)
Methazolamide (Neptazane)
What are the topically administered CAIs?
Dorzolamide (Trusopt) 2%
Brinzolamide (Azopt) 1%
Cosopt; 2% dorzolamide and 0.5% timolol
Describe the ocular effects with CAIs
DECREASE IN IOP VIA DECREASING AQUEOUS PRODUCTION
Metabolic acidosis
What effect will CAIs have on a normal non-glaucoma patient’s eye?
None
What’s the normal dose and onset for Diamox?
125-250mg 4X a day; 3-4 hours for max effect lasting 6-12 hours
What’s the normal dose for Diamox Sequels?
500mg 1-2x a day; lasts 18-24 hours
How long does Diamox need to take effect if given by IV?
30 minutes, lasts 2-4 hours
What’s the max effectiveness for oral methazolamide?
Taken 2x a day, after 7-8 hours for max effect and duration is 10-14 hours
Describe the toxicities seen with CAIs
Very common, dropout is 20-30% Parathesia; tingling/pins and needle sensation in the extremities that also can cause abnormal taste Headache, fatigue, dizziness, drowsy GI; Irritation, upset, cramping, weight loss, NVD, anorexia Muscle weakness and decreased libido Lethargy, depression and malaise Diuresis via K+ depletion Renal and colic stones Transient myopia Rarely aplastic anemia
What are the contraindications for CAIs?
SULFA DRUG ALLERGY Renal dysfunction Hypokalemia Liver cirrhosis Severe COPD (can develop respiratory alkalosis and be unable to maintain increased respiratory rate) Renal calculi (kidney stone) Pregnancy Do not use for chronic non-congestive angle closure
With topical dorzolamide, do you see the drift effect seen with beta blockers like Timolol?
No
How does the brinzolamide (azopt) suspension compare to the use of the topical drop dorzolamide?
Brinzolamide 1% suspension taken 2-3x day equals 2% dorzolamide 3x day
Less dose and systemic toxicity
What two drugs are in cosopt and how does cosopt’s efficacy compare to the agents comprising it alone?
2% dorzolamide and 0.5% timolol
More effective than either agent alone
Describe ocular toxicities with dorzolamide
Short term keratitis/mild irritation
Burning, blurry vision, FBS, ocular allergies less likely with brinzolamide
What is a possible corneal toxicity with dorzolamide or other similar topical CAIs?
Corneal edema or even corneal decomposition
If your patient has a history of an intraocular surgery such as a corneal transplant, what concern would arise from selecting a topical CAI?
Corneal endothelium compromise
Describe some systemic toxicities with dorzolamide
Sulfa allergy
Bitter taste
Headache
Concern with patients with compromised/history of compromised liver and/or kidney
Between a topical CAI (Dorzolamide) and a beta blocker (Timolol) which has better diurnal control of IOP?
Topical CAI
Name the class of drug that is now the gold standard for newly diagnosed glaucoma patients
Prostaglandin Analogs
Describe the MOA for Latanoprost
PGF2a analog; prodrug until esterases at cornea convert to active drug to then work at proper receptor
Increases UVEOSCLERAL OUTFLOW, as well as causing substantial remodeling of TM to reduce resistance to outflow via increasing MMP production to break down the TM’s extracellular matrix
What kind of tolerance/drift/absorption effects are present with Latanoprost (other prostaglandins)
No tolerance develops
IOP well controlled (equal to or better than Timolol 2x day)
No drift
No effect from iris color, age, race, sex, previous treatments, or type of glaucoma to be treated
Describe some toxicities with Latanoprost (Xalatan) and other prostaglandins
HYPEREMIA OF CONJUNCTIVA Blurred vision, stinging eyes (related to increased inflammation due to stimulating prostaglandin receptors) FBS, punctate keratopathy Cystoid macular edema Corneal pseudodendrites (herpes simplex) Seemingly no systemic toxicities
Describe the permanent and non-permanent cosmetic toxicity seen with Latanoprost and other prostaglandins
Permanent - Increase in Iris melanin formation (darker eye)
Non-permanent - thicker and longer eyelashes
What are the contraindications for Latanoprost and other prostaglandins?
Hypersensitivity to drug or drug components (Sulfa)
What are some cautions for prescribing for Latanoprost and other prostaglandins?
Ocular inflammation
Or a history of aphakia, pseudoaphakia with torn posterior capsule or cystoid macular edema
What is the name for the “synthetic prostamide analog”?
Bimatoprost (Lumigan) 0.03%, 0.01%
For the treatment of glaucoma with Bimatoprost (lumigan) would it help to go from 0.01% to 0.03%?
Not really, both concentrations seem to be equally effective but the 0.01% tends to have less toxicities (by a bit)
What is the name for the formulation of Bimatoprost (lumigan) used for cosmetics?
Latisse 0.03% for hypotrichosis (eyelash ‘deficiency’)
Compare Latanoprost (Xalatan) with Travoprost (Travatan) in terms of MOA.
MOA for Latanaprost (Xalatan) and Travaprost (Travatan) are the same; PGF2alpha analog
Describe Travatan Z
Travaprost (Travatan) uses a different preservative and is ‘preservative free’ by being less irritating to the cornea.
Compare Latanoprost (Xalatan) with Tafluprost (Zioptan) in terms of MOA and preparation
Both are still prostaglandin analogs; PGF2alpha.
Tafluprost is used as a single drop dispensing with no preservatices
Describe Neuroprotectin as a method to treat glaucoma
Newer method tested in animal models, Nitrogen Oxide Synthesis Inhibitors; decreases cell apoptosis –> protecting neurons from dying in glaucoma
Describe the A2 agonist Brimonidine (alphagan) in the treatment of glaucoma
Seemed to help in cases of retinal ischemia in preventing cell death in animal studies
What is Aminoguanidine being used to treat in animal studies?
Glaucoma
Describe Memantine (used to treat Alzheimer’s) in the treatment of glaucoma
NMDA receptor blocker; prevent excessive glutamate on NMDA receptor to prevent excitotoxicity (apoptosis from excessive stimulation)
Shown to decrease nerve cell loss in retina and LGN in monkeys
Describe Resveratrol in the treatment of glaucoma; and mention where it can be found.
Antioxidant found in abundance in red wine
Decreases cell death IN VIVO; perhaps neuroprotective in nature
Describe the general MOA and name the prototypical Hyperosmotic Agent used for treating glaucoma
Agents that cause greatly increased plasma osmolarity and effectively dehydrate body tissues like the eye (mainly vitreous) and CSF
Mannitol
Describe the use of hyperosmotic agents
Used for acute angle closure glaucoma and pre/post surgery
Describe the toxicities seen with the use of all Hyperosmotic Agents
Decreased CSF volume causing headache
Dry mouth and increased thirst
Nausea and Vomiting
Hyperosmotic coma from excessive CNS dehydration
Congestive Heart Failure and/or Pulmonary Edema from increased cardiac load
Muscle cramping and weakness if given IV
Which is the drug of choice for IV hyperosmotics?
Mannitol; takes 30-60 minutes for peak efficacy lasting 6-8 hours
Describe the Glycerin (Osmoglyn)
Oral hyperosmotic, max effect in 5 hours
Caution for diabetic patients as this has a caloric value (super sweet sugar water)
Briefly, describe the IOP lowering effects of Ethanol and Marijuana
EtOH - Osmotic effect like osmotic diuretics
Marijuana - Possible cannabinoid receptor action to lower IOP, or may just be the lowering of BP in general causing lower IOP. Not terribly effective due to requiring constant use for IOP reduction. (Might be fun though)
