Medical Managemtn Of Glaucoma-3 Flashcards
Osmotic drugs intro
- infrequently used for reduction of IOP
- more effective in short term treatments
- preoperative preparation
- initial treatments of acute and extreme elevation of IOP. Angle closure glaucoma, secondary glaucoma
MOA of osmotic agents
lower IOP by increasing osmotic gradiaent between blood and ocular fluids
-administration: blood osmalility increased by up to 20-30mOsm/L: loss of water from eye to hyperosmoistic plasma
Osmotic gradient between retina choroid and vitreous causes water transfer leading to reduction of vitreous volume
Factors affecting osmotic gradient
- Ocular penetration
- Distribution in body fluids
- Molecular weight and concentration
- Dosage
- Rate and route of administration
- Rare of systemic clearance
- Type of diuresis
Ocular penetration of osmotic agents
- drugs entering eye rapidly produce less of an osmotic gradient than those that penetrate slowly or not at all
- ethyl alcohol enters aqueous rapidly, but slow penetration in the avascuarl vitreous
Permeability of osmotic agents
Permeability is greatly increased with inflamamtion and congestion
Distribution of body fluids: osmotic agents
- drugs restricted to extracellular fluid space (mannitol) have a greater effect on blood osmolarity
- at same dose, blood osmolarity is less affected by drugs distributed in total body water (urea) Urea no longer utilized
Concentration issues and osmotic agents
Drugs with low solubility require larger volumes of solution
-ingestion of fluids after osmotic drug use decreases blood osmolarity
Dosage of osmotic agents
-change in blood osmolalitly depends on total dose admintered and weight of patient
Route and rate of administration
-IV bypasses GI absorption: more rapid and greater gradient compared with oral
Rate of systemic clearance
Indications for osmotic agents
- short term treatment of acute and marked elevation of IOP
- angle closure glaucoma
- aqueous misdirection
- certain secondary glaucoma
Contraindications of osmotic agents
- Anuria
- severe dehydration
- frank or impending acute pulmonary edema
- severe cardiac decompensation
- hypersensitivity to any component of preparations
- caution in: cardiac, retinal or hepatic diseases, CHF, hypervolemia, electrolyte imbalance, confused mental statues, dehydration
- oral glycerol may cause blood glucose to rise in diabetic patients
Treatment regiment of osmotic agents
-flavoring and pairing glycerol solution over Ice improve palatabiltiy
Isosorbide
- 45% wt/vol solution
- 1-2 g/kg of body weight
- osmotic effect persists up to 5-6 hours
- 2-4 doses per day during the short term use
Treatment Regimen of mannitol (osmotic agents)
- does may be lowered if IOP is not too high
- terminate IV infusion when desired effect on IOP reached
- stored at room temp
- higher concentrations may require slight warming-crystals may form at temporatures below room temp
- should include filter
Side effects of osmotic drugs
- IOP rebound may be less common with glycerol and mannitol-have poor ocular penetration compared with other osmotic drugs
- hyperglycemia in using glycerol
Side effects of osmotic drugs
Ocular
- IOP rebound
- intraocualr heme
- increased GI activity
- CNS problems
- CHF, PE, and angina
-hyperglycemia
Hypersensitivity
Drug interactions of osmotic drugs
-drugs that’s may compromise renal or cardiovascular status hsould be used with caution in combintastion with osmotic drugs
Angle closure glaucoma and osmotic agents
- therapy directed at lowering IOP and opening AC angle
- osmotic drugs are mainstay in treatment
- vitreous dehydration allows lens and iris to move posteriorly-deepening of AC chamber
- iris sphincter often nonreactive due to relative ischemia when IOP elevated
Rapid reduction of IOP by osmotic drugs may relieve this ischemia-sphincter function, iosis, opening of AC angle
Which is easier to administer for angle closure glaucoma in the office for osmotic agents
Oral isosorbide or glycerol
Benefit of isosorbide for angle closure vs glycerol
Less nausea and vomiting and not metabolized to glucose
-however nears already present in pateitns with angle closure and may not be able to retain oral medications
Osmotic drugs used for secondary glaucoma
- highly elevated IOP
- glaucoma rewriting control of IOP until underling problem corrected
- use of isosorbide avoids large calorie load intake ingested with glycerol therapy
- uveitis and post traumatic glaucoma
- preoperatiely in eye with extremely high IOP that require glaucoma surgery
Aqueous misdirection
-osmotic drugs temporarily dehydrate the vitreous
Glycerol onset of action
10-30m
Max effect: oral glycerol
45-120m
Duration of action of oral glycerol
4-5 hours
Metabolism of oral glycerol
80% in liver, 10-20% occurs in kidney
Oral glycerol and diabetics
Produces 4.34cal/g
Diabetics may develop hyperglycemia and ketosis
Problems with oral glycerol
Nausea and vomiting following ingestion-problem in therapy of acute glaucoma and perioperative use
Oral isosorbide
- similar to glycerol in onset of action, time to max effect and duration of effect
- no caloric load
- less likely than glycerol to produce nausea and vomittin-more likely to produce diarrhea
Which osmotic agent has a caloric load
Oral glycerol
Oral ethyl alcohol
- oral dose for lowering IOP 2-3mL/kg of body weight of a 40-50% solution
- rapidly absorbed
- distribution in total body water and rapid penetration of eye limit degree and duration of osmotic gradient
- alcohol induces hypotonic diuresis-prolong and increased osmotic gradient
- increased caloric load
- dehydration
- CNS effects
IV mannitol
- drug of choice when IV osmotic drugreuwired for lowering IOP
- onset 10-30m
- peak effect 30-60m
- duration of action 4-6 hours
- distribution in extracellular water
- poor ocular penetration
- large volume of IV fluid required due to limited solubility
- cardiac or renal disease require caution
Does generic work as well as brand name
In theory yet but it actually depends
Issues with generics
- drop size-may not be equivalent
- variability of active ingredient
- environmental exposure such as heat
- reaction with plastic containers
Heat stress test
Latanaprost
-significant decreased compared to brand name in active ingredient
Dorzolamide/timolol
-resistant to heat changes
BAK concentrations at 50C was decreased
Particulate matter and heat: generic vs brand name
- at 25C, particulate matter increased in generic
- at 50X, both generic and brand name showed increased inarticulate matter
Loss of efficacy of brand name vs generic
Baseline drop
- 38.6% with Dalmatian
- 22.7% with generic latanaprost
- 86% loss of efficacy change from Dalmatian to latanaprost
- 3% increase efficacy change from generic to brand name
Summary of generic vs brand name
- brand name offers more tighter control of the drug related issues
- some drug is better than no drug and generics are here to stay
Medications and glaucoma: chronic drug use and preservatives
- chronic drug uses and its effect on future surgical outcomes?
- chronic combination therapies-significant risk factor for failure of trabeculectomy
Preservative effect?
Inflamamtion leading to failure of future procedures
Summary of preservatives
- preservative free better solution given the understanding we have
- non BAK preservatives may be a good trade off although not totally problem free
- PGs dont need preservatives for drug penetrations
- some drug is better than no drug, preserves medications have a role to play in glaucoma maagnentms
