medical therapy 3 Flashcards
when do we give 2 glaucoma drugs?
when pressure is not behaving
pt is dr davey - smoker (but no heart problems yet) and diabetic with some glaucoma findings. what drug do we give?
PG
second drug will be Timolol
if pressures are 35 mm hg, when do we see them?
see pt next day
if pressures are 24 mm hg, when do we see them?
3 days - 1 week
moa of osmotic drugs
Lower IOP by increasing osmotic gradient between blood and ocular fluids
◦ Administration ! blood osmolality increased by up to 20 to 30mOsm/L!loss of water from eye to hyperosmotic plasma
! Osmotic gradient between retina-choroid and
vitreous causes water transfer leading to reduction of vitreous volume
largest ocular structure
vitreous body
7 factors affecting osmotic gradient
- ocular penetration
- distribution in body fluids
- molecular weight and concentration
- dosage
- rate and route of administration
- rate of systemic clearance
- type of diuresis
when is osmotic gradient greater?
drug out of eye (did not penetrate eye)
permeability is greatly increased with what?
inflammation and congestion
Drugs entering eye rapidly produce ____ of an osmotic gradient than those that penetrate __________
◦ Ethyl alcohol enters aqueous ______, but _____ penetration in the avascular vitreous
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 avascular vitreous
Drugs restricted to extracellular fluid space (mannitol) have a greater effect on blood osmolality
! At same dose, blood osmolality is less affected by drugs distributed in total body water (urea)
Drugs restricted to extracellular fluid space (mannitol) have a greater effect on blood osmolality
! At same dose, blood osmolality is less affected by drugs distributed in total body water (urea)
Blood osmolality depends on number of milliosmoles of substance administered
◦ Drugs with low solubility require larger volumes of solution
“ Ingestion of fluids after osmotic drug use decreases blood osmolalilty
Blood osmolality depends on number of milliosmoles of substance administered
◦ Drugs with low solubility require larger volumes of solution
“ Ingestion of fluids after osmotic drug use decreases blood osmolalilty
if drug requires a lot of water to be pumped along with drug, is that good or bad?
bad –> excess water in body –> excess water in eye
Change in blood osmolality depends on total dose administered and weight of patient
! Route and rate of administration
◦ Intravenous bypasses absorption from GI tract!more rapid and greater osmotic gradient compared with oral
! Rate of systemic clearance
Change in blood osmolality depends on total dose administered and weight of patient
! Route and rate of administration
◦ Intravenous bypasses absorption from GI tract!more rapid and greater osmotic gradient compared with oral
! Rate of systemic clearance
do we want systemic clearance to be low or high?
low
indications for osmotic drug
! Short term treatment of acute and marked elevation of IOP
! Angle-closure glaucoma
! Aqueous misdirection
! Certain secondary glaucoma
whats aqueous misdirection and when does it happen?
- aqueous is going somewhere else in eye that its not supposed to be
- aqhu –> vitreous
- AC looks normal to flat, but eyeball pressure is quite high
- back of eye is elevated b/c cil body is rotated and aqhu is pushed towards vitreous –> pressure gradient in front and back of eye –> ac looks normal or shallow —> but fluid is being pushed toward back of eye
- can happen after surgeries; very rare.
- pupillary block can also make this happen
tx: lower pressure somehow
whats the natural flow of aqueous?
look it up
contraindication of osmotic drug
! Anuria
! Severe dehydration
! Frank or impending acute pulmonary edema
! Severe cardiac decompensation
! Hypersensitivity to any component of preparations
! Caution in the following patients:
◦ Cardiac, renal or hepatic diseases
◦ Congestive heart disease
◦ Hypervolemia- excess fluid in blood ◦ Electrolyte abnormalities
◦ Confused mental states
◦ Dehydration
! Oral glycerol may cause blood glucose to rise in diabetic patients **diabetic is important
◦ Dose may be lowered if IOP is not too high
◦ Terminate Intravenous (IV ) infusion when desired effect on IOP reached
◦ Stored at room temperature
◦ Higher concentrations may require slight warming – crystals may form at temperatures below room temp
◦ Should include filter
mannitol
treatment regimen
! Flavoring and pouring glycerol solution over ice improve palatability
isosorbide and dose
! Isosorbide
◦ 45% wt/vol solution
◦ 1 to 2 g/kg of body weight
◦ Osmotic effect persists up to 5 or 6 hours
◦ Two to four doses per day during the short term use
advantage of IV
fast acting; it can be stopped
disadvantage of IV
must be stored at room temp; high concentration needs warming; crystals can form (emboli)
side effects of osmotic drug
IOP rebound may be less common with glycerol and mannitol – have poor ocular penetration compared with other osmotic drugs
! Hyperglycemia in using glycerol
why is glycerol a problem?
glycerol –> glucose –> hyperglycemia
*should be avoided in diabetics
drug interactions with osmotic drugs
Drugs that may compromise renal or cardovascular status should be used with caution in combination with osmotic drugs
heart, liver, renal function
what do we need to be careful about with drugs?
◦ Osmotic drugs are mainstay in treatment for what?
◦ Therapy directed at lowering IOP and opening anterior chamber angle
what happens when vitreous dehydrates?
lens and iris move posteriorly –> deepens AC
when IOP elevates, what happens to iris sphincter?
nonreactive due to relative ischemia
Rapid reduction of IOP by osmotic drugs may relieve this ischemia ! sphincter function, miosis, opening of anterior chamber angle
Oral isosorbide or glycerol easier to administer in an office setting compared with what?
Oral isosorbide or glycerol easier to administer in an office setting compared with IV mannitol
_____ may cause less nausea and vomiting than glycerol and not metabolized to glucose
Isosorbide may cause less nausea and vomiting than glycerol and not metabolized to glucose
However nausea already present in patients with angle closure and may not be able to retain oral medications
Highly elevated IOP
◦ Glaucoma requiring control of IOP until underlying
problem corrected
◦ Use of isosorbide avoids large calorie load intake ingested with glycerol therapy
◦ Uveitic and posttraumatic glaucoma ◦ Preoperatively in eyes with extremely high IOP that
require glaucoma surgery
! Aqueous misdirection (explain to students) ◦ Osmotic drugs temporarily dehydrate the vitreous
Highly elevated IOP
◦ Glaucoma requiring control of IOP until underlying
problem corrected
◦ Use of isosorbide avoids large calorie load intake ingested with glycerol therapy
◦ Uveitic and posttraumatic glaucoma ◦ Preoperatively in eyes with extremely high IOP that
require glaucoma surgery
! Aqueous misdirection (explain to students) ◦ Osmotic drugs temporarily dehydrate the vitreous
the poorer the penetration of drug, is that beneficial or not?
beneficial
Glycerol dosage
Glycerol ◦ Onset of action 10 to 30 minutes ◦ Maximal effect in 45 to 120 minutes ◦ Duration of action 4 to 5 hours ◦ 80% of metabolism occurs in liver – 10%-20% occurs in kidney
problem with glycerol
◦ Produces 4.34 cal/g – diabetic patients may develop hyperglycemia and ketosis
◦ Nausea and vomiting following ingestion – problem in therapy of acute glaucoma and perioperative use
Isosorbide
Isosorbide
◦ Similar to glycerol in onset of action, time to
maximal effect and duration of effect
◦ No caloric load
◦ Less likely than glycerol to produce nausea and vomiting – more likely to produce diarrhea
ethyl alcohol
◦ Oral dose for lowering IOP 2 to 3 mL/kg of body weight of a 40% to 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 increase osmotic gradient
Metabolized and increased caloric load
! Hypotonic diuresis may cause dehydration
! Central nervous system side effects, nausea and vomiting
limit short- and long-term use
calorie load is an effect of which two drugs?
ethyl alcohol and glycerol
carbs 4 cal/g (glycerol)
fat 9 cal/g
alcohol ?
7 cal/g
mannitol
◦ Osmotic diuretic – drug of choice when IV
osmotic drug required for lowering IOP ◦ Onset of action 10 to 30 mins
◦ Peak effect in 30 to 60 mins
◦ Duration of action 4 to 6 hours ◦ Distributed in extracellular water ◦ Poor ocular penetration
◦ Large volume of IV fluid required due to limited solubility
◦ Cardiac or renal disease require caution
◦ Osmotic effect is less pronounced
◦ Distributed in total body water
◦ Penetrates eye more readily – especially when inflamed
◦ Greater rebound of IOP
urea
which is the drug of choice for osmotic agents?
IV mannitol
any oral drug may just come out of pt
orally- choose isoscorbate
which drug is most ideal?
none! this is the last ditch effort to decrease iop; side effects are not good for all of them
why cant we just pull the fluid out of AC?
doesnt mean body will stop producing aqhu; if we suddenly drop it –> will potentially cause more physiological side effects we dont want
can optometrists in cali handle peds glaucoma
no were not allowed to
General Considerations
◦ Infrequently diagnosed
◦ Occasional preexisting glaucoma
◦ Consider potential for systemic effects
◦ Concern extends to developing child
◦ Little literature demonstrating adverse events of topical medications during pregnancy
glaucoma pregnancy general considerations

! Mild decrease in IOP compared to pressure before pregnancy
! Episcleral venous pressure decreases due to changes in mother’s hemodynamics
! Metabolic acidosis – affects aqueous production and decreases IOP
! Average decrease of 1.5mm Hg during pregnancy
iop during pregnancy
teratogenicity
Prostoglandin analogs for ophthalmic use are in same class of prostoglandins that may cause abortion when administered as periuterine injection
Dosage used to stimulate abortion is equivalent of 400 cc of latanoprost as formulated for ocular use
◦ Caution is advised
what are all the fda classes?
! Class A – established safety record ! Class B – animal safety data but no human
data to confirm
! Class C – either animal studies with adverse effects or no human or animal data
! Class D – clear risks
! Class X – known to cause birth defects and should never be used during pregnancy
whats the only drug that falls in class b? what other class are the other drugs?
brimonidine
class c
glaucoma medical therapy in pregnancy
if infant is abnormal (renal/hepatic fxn problem), timolol from breast milk can affect them
Few studies in literature
! Any medication with any degree of systemic absorption must be assumed to have measurable level in breast milk
! Study – timolol 0.5% and betaxolol in breast milk
◦ Level of timolol was not of concern if infant has normal renal and hepatic function
◦ Infants must be monitored carefully
general considerations for baby drinking timolol breastmilk
General Considerations
◦ More vulnerable to side effects – reduced
body mass and blood volume
◦ Unable to verbally describe side effects
Prostaglandin analogs (pediatric patients) “ Study of 31 eyes – 19% had 34% reduction in IOP
“ Majority did not respond to therapy
! Juvenile-onset open-angle glaucoma was more likely to respond –anatomy of angle more closely approximating that in adult
! Sturge-Weber – between 17% and 28% responded
“ response rate is low in pediatric population
“ If responsive - very effective and offers good 24- hour control
Prostaglandin analogs (pediatric patients) “ Study of 31 eyes – 19% had 34% reduction in IOP
“ Majority did not respond to therapy
! Juvenile-onset open-angle glaucoma was more likely to respond –anatomy of angle more closely approximating that in adult
! Sturge-Weber – between 17% and 28% responded
“ response rate is low in pediatric population
“ If responsive - very effective and offers good 24- hour control
which majority did not respond to therapy
pediatric patients, b/c theyre eyes are not as developed like adults
beta blockers and pediatric pts
beta blockers
◦ 29% had definitive improvement
◦ 32% had modest or equivocal improvement
◦ 39% demonstrated no improvement
◦ As in adults, systemic level of timolol can be found in pediatric patients after topical dosing, but much higher levels
Lower levels of metabolic enzymes may also prolong half-life of medications in children by a factor of ______
Lower levels of metabolic enzymes may also prolong half-life of medications in children by a factor of 2 to 6
Children older than 5 – Avg. decrease of 6 beats per minute in resting pulse rate
◦ no observable change in younger than 5
Lower concentration 0.25% timolol rather than 0.5% is preferred in __________
Lower concentration 0.25% timolol rather than 0.5% is preferred in younger
4
! Carbonic anhydrase inhibitors (CAI)
◦ Oral CAI administration can cause ______________
◦ Oral acetazolamide is well tolerated at doses of ______mg/kg per day (divided 2x or 3x daily)
“ Reduces IOP
“ Improves corneal edema
4
! Carbonic anhydrase inhibitors (CAI) ◦ Oral CAI administration can cause growth
retardation and metablolic acidosis
◦ Oral acetazolamide is well tolerated at doses of 5 to 15 mg/kg per day (divided 2x or 3x daily)
“ Reduces IOP
“ Improves corneal edema
Children _______ years – systemic administration of acetazolamide and topical dorzolamide effective at lowering IOP (36% vs. 27%)
◦ Topical treatment is ________ – rate of side effects lower
Children 3 to 12 years – systemic administration of acetazolamide and topical dorzolamide effective at lowering IOP (36% vs. 27%)
◦ Topical treatment is preferred – rate of side effects lower
Management of glaucoma in reproductive-age women includes consideration of a second patient that does not need medication (fetus)
! Therapy should not harm the unborn or breast- feeding child
! Pediatric glaucoma is mostly managed surgically – medical therapy can temporarily decrease IOP to facilitate surgery by clearing the cornea and permit certain operations
! Medications used in glaucoma were mainly developed and tested primarily in adults
! Side effects can be very different for small children
Management of glaucoma in reproductive-age women includes consideration of a second patient that does not need medication (fetus)
! Therapy should not harm the unborn or breast- feeding child
! Pediatric glaucoma is mostly managed surgically – medical therapy can temporarily decrease IOP to facilitate surgery by clearing the cornea and permit certain operations
! Medications used in glaucoma were mainly developed and tested primarily in adults
! Side effects can be very different for small children
alternative glaucoma med and do they work?
◦ Ginkgo biloba ◦ Bilberry
◦ Taurine
◦ Magnesium
◦ Vitamin B12
! Vitamin C (ascorbate) may lower IOP by osmotic
effect
! Available medicine does not support use of alternative medicines for glaucoma therapy
