medical therapy 3

Question 1

when do we give 2 glaucoma drugs?

Answer 1

when pressure is not behaving

Question 2

pt is dr davey - smoker (but no heart problems yet) and diabetic with some glaucoma findings. what drug do we give?

Answer 2

PG

second drug will be Timolol

Question 3

if pressures are 35 mm hg, when do we see them?

Answer 3

see pt next day

Question 4

if pressures are 24 mm hg, when do we see them?

Answer 4

3 days - 1 week

Question 5

moa of osmotic drugs

Answer 5

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

Question 6

largest ocular structure

Answer 6

vitreous body

Question 7

7 factors affecting osmotic gradient

Answer 7

1. ocular penetration
2. distribution in body fluids
3. molecular weight and concentration
4. dosage
5. rate and route of administration
6. rate of systemic clearance
7. type of diuresis

Question 8

when is osmotic gradient greater?

Answer 8

drug out of eye (did not penetrate eye)

Question 9

permeability is greatly increased with what?

Answer 9

inflammation and congestion

Question 10

Drugs entering eye rapidly produce ____ of an osmotic gradient than those that penetrate __________
◦ Ethyl alcohol enters aqueous ______, but _____ penetration in the avascular vitreous

Answer 10

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

Question 11

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)

Answer 11

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)

Question 12

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

Answer 12

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

Question 13

if drug requires a lot of water to be pumped along with drug, is that good or bad?

Answer 13

bad –> excess water in body –> excess water in eye

Question 14

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

Answer 14

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

Question 15

do we want systemic clearance to be low or high?

Answer 15

low

Question 16

indications for osmotic drug

Answer 16

! Short term treatment of acute and marked elevation of IOP
! Angle-closure glaucoma
! Aqueous misdirection
! Certain secondary glaucoma

Question 17

whats aqueous misdirection and when does it happen?

Answer 17

• 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

Question 18

whats the natural flow of aqueous?

Answer 18

look it up

Question 19

contraindication of osmotic drug

Answer 19

! 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

Question 20

◦ 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

Answer 20

mannitol

Question 21

treatment regimen

Answer 21

! Flavoring and pouring glycerol solution over ice improve palatability

Question 22

isosorbide and dose

Answer 22

! 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

Question 23

advantage of IV

Answer 23

fast acting; it can be stopped

Question 24

disadvantage of IV

Answer 24

must be stored at room temp; high concentration needs warming; crystals can form (emboli)

Question 25

side effects of osmotic drug

Answer 25

IOP rebound may be less common with glycerol and mannitol – have poor ocular penetration compared with other osmotic drugs ! Hyperglycemia in using glycerol

Question 26

why is glycerol a problem?

Answer 26

glycerol --> glucose --> hyperglycemia *should be avoided in diabetics

Question 27

drug interactions with osmotic drugs

Answer 27

Drugs that may compromise renal or cardovascular status should be used with caution in combination with osmotic drugs

Question 28

heart, liver, renal function

Answer 28

what do we need to be careful about with drugs?

Question 29

◦ Osmotic drugs are mainstay in treatment for what?

Answer 29

◦ Therapy directed at lowering IOP and opening anterior chamber angle

Question 30

what happens when vitreous dehydrates?

Answer 30

lens and iris move posteriorly --> deepens AC

Question 31

when IOP elevates, what happens to iris sphincter?

Answer 31

nonreactive due to relative ischemia Rapid reduction of IOP by osmotic drugs may relieve this ischemia ! sphincter function, miosis, opening of anterior chamber angle

Question 32

Oral isosorbide or glycerol easier to administer in an office setting compared with what?

Answer 32

Oral isosorbide or glycerol easier to administer in an office setting compared with IV mannitol

Question 33

_____ may cause less nausea and vomiting than glycerol and not metabolized to glucose

Answer 33

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

Question 34

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

Answer 34

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

Question 35

the poorer the penetration of drug, is that beneficial or not?

Answer 35

beneficial

Question 36

Glycerol dosage

Answer 36

``` 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 ```

Question 37

problem with glycerol

Answer 37

◦ 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

Question 38

Isosorbide

Answer 38

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

Question 39

ethyl alcohol

Answer 39

◦ 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

Question 40

calorie load is an effect of which two drugs?

Answer 40

ethyl alcohol and glycerol

Question 41

carbs 4 cal/g (glycerol) fat 9 cal/g alcohol ?

Answer 41

7 cal/g

Question 42

mannitol

Answer 42

◦ 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

Question 43

◦ Osmotic effect is less pronounced ◦ Distributed in total body water ◦ Penetrates eye more readily – especially when inflamed ◦ Greater rebound of IOP

Answer 43

urea

Question 44

which is the drug of choice for osmotic agents?

Answer 44

IV mannitol any oral drug may just come out of pt orally- choose isoscorbate

Question 45

which drug is most ideal?

Answer 45

none! this is the last ditch effort to decrease iop; side effects are not good for all of them

Question 46

why cant we just pull the fluid out of AC?

Answer 46

doesnt mean body will stop producing aqhu; if we suddenly drop it --> will potentially cause more physiological side effects we dont want

Question 47

can optometrists in cali handle peds glaucoma

Answer 47

no were not allowed to

Question 48

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

Answer 48

glaucoma pregnancy general considerations

Question 49

 ! 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

Answer 49

iop during pregnancy

Question 50

teratogenicity

Answer 50

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

Question 51

what are all the fda classes?

Answer 51

! 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

Question 52

whats the only drug that falls in class b? what other class are the other drugs?

Answer 52

brimonidine class c

Question 53

glaucoma medical therapy in pregnancy

Answer 53

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

Question 54

general considerations for baby drinking timolol breastmilk

Answer 54

General Considerations ◦ More vulnerable to side effects – reduced body mass and blood volume ◦ Unable to verbally describe side effects

Question 55

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

Answer 55

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

Question 56

which majority did not respond to therapy

Answer 56

pediatric patients, b/c theyre eyes are not as developed like adults

Question 57

beta blockers and pediatric pts

Answer 57

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

Question 58

Lower levels of metabolic enzymes may also prolong half-life of medications in children by a factor of ______

Answer 58

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

Question 59

Lower concentration 0.25% timolol rather than 0.5% is preferred in __________

Answer 59

Lower concentration 0.25% timolol rather than 0.5% is preferred in younger

Question 60

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

Answer 60

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

Question 61

Children _______ years – systemic administration of acetazolamide and topical dorzolamide effective at lowering IOP (36% vs. 27%) ◦ Topical treatment is ________ – rate of side effects lower

Answer 61

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

Question 62

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

Answer 62

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

Question 63

alternative glaucoma med and do they work?

Answer 63

◦ 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