Lecture 11 Medical management of glaucoma part 2-OBB's/A2A's/CAI's/cholinergics Flashcards
Which OBB (ocular beta blocker) medication was FDA approved in 1978 which changed how glaucoma was managed?
a) propranolol
b) practolol
c) timolol
d) metoprolol
c) timolol. (Propranolol was developed in 1964 to treat systemic hypertension and angina, as an OBB, however, it anesthetized the cornea. Practolol was developed which did not anesthetize the cornea but caused immunological problems such as occulomucocuataneous syndrome. Metoprolol is a current oral beta blocker therapy)
(T/F) Beta blockers became the primary therapy for glaucoma after the FDA approval of timolol and up until 1996 when the prostaglandin analog called latanoprost showed to be more effective.
true
*Match the following regarding beta blockers:
1) beta-1
2) beta-2
3) beta-3
a) receptors found in bronchial muscle, blood vessels, and uterus
b) receptors found in mammals for mediation of lipolysis
c) receptors found in heart
1) beta-1–c) receptors found in heart
2) beta-2–a) receptors found in bronchial muscle, blood vessels, and uterus
3) beta-3–b) receptors found in mammals for mediation of lipolysis
*think beta-1=heart b/c you have 1 heart, beta-2=lungs b/c you have 2 lungs
Which one of the following statements regarding beta-blockers is FALSE?
a) stimulation of beta-1 receptors causes bradycardia (decreased heart rate) and decreased cardiac contractility
b) stimulation of beta-2 receptors causes dilation of bronchi and blood vessels
c) beta-3 has recently been identified in mammals for mediation of lipolysis
d) all of the above are true
a) stimulation of beta-1 receptors causes bradycardia (decreased heart rate) and decreased cardiac contractility. (FALSE–stimulation of beta-1 causes tachycardia (increased heart rate) and increased cardiac contractility.
(T/F) Ocular beta blockers (OBB’s) are also known as beta-adrenoreceptor agonists
false— OBB’s are aka beta-adrenoreceptor ANTAGONISTS (they block the receptor, an agonist would aid in the stimulation of the receptor)
(T/F) OBB’s are “competitive” inhibitors
true
(T/F) A non-selective OBB would effect BOTH beta-1 and beta-2, whereas, a selective OBB would effect EITHER beta-1 or beta-2.
true–keep in mind a high enough dose of a selective beta blocker could affect both beta-1 and beta-2
- How do OBB’s reduce IOP (what is the mechanism of action)?
a) decrease aqueous production
b) increase aqueous outflow through the trabecular pathway only
c) increase aqueous outflow through the uveoscleral pathway only
d) OBB’s help with both aqueous production and outflow
a) decrease aqueous production (by as much as 50%)–there is no effect on aqueous outflow.
(T/F) The mechanism by which OBB’s reduce aqueous production is still not clear, however, there are 2 hypothesis’s: classic and alternative hypothesis.
true.
1) Classic= OBB’s, through a cascade of events, eventually block cAMP which is required to produce aqueous.
2) Alternative=OBB’s interfere with the tonic stimulation needed to produce aqueous.
*Keep in mind there is evidence against the CLASSIC hypothesis, some studies have shown IOP to decrease in response to cAMP and regarding the ALTERNATIVE, this is just speculation.
Which one of the following is NOT an indication for OBB’s?
a) ocular hypertension
b) Primary or secondary open angle glaucoma
c) angle closure glaucoma
d) all of the above are indications for OBB use
d) all of the above are indiactions for OBB use
- Which one of the following is NOT a contraindication regarding the use of OBB’s?
a) pt’s with pulmonary disease (COPD)
b) pt’s with bradycardia (less than 60 bpm resting)
c) pt’s with sulfa allergies
d) pt’s with hypersensitivity to beta-blockers
c) pt’s with sulfa allergies (sulfa allergies is a contraindication with CAI’s–carbonic anhydrase inhibitors)
(T/F) OBB’s are typically given BID (twice daily) but can be given QD (once daily) to minimize side effects
true.
Most OBB”s can be prescribed BID (twice daily), however, there are 3 exceptions that are only prescribed QD (once daily). Which one of the following is NOT one of those exceptions?
a) Istalol-qam
b) timolol-qpm
c) timoptic XE or GFS gel-qd
d) betagan-qd
b) timolol-qpm. (Timolol is usually prescribed BID because it has a maximum effect of 12 hours and the pm dose is weaker at reducing IOP below baseline levels)
- gels are only qd because of improved bioavailability, meaning the drug can stay longer on the eye and more drug can be absorbed
- istalol is only qd because it is formulated with potassium sorbate which enhances bioavailability
Which one of the following is the most commonly used OBB today?
a) propranolol
b) practolol
c) timolol
d) metoprolol
c) timolol (timolol maleate is more common than timolol hemihydrate)
Most OBB’s contain the preservative BAK. Which 3 of the following do NOT contain BAK?
a) Timoptic unit dose–preservative free
b) Timoptic XE–Benzododecinum bromide 0.012%
c) Timolol GFS–Benzododecinum bromide 0.012%
d) Betagan-preservative free
a) Timoptic unit dose–preservative free
b) Timoptic XE–Benzododecinum bromide 0.012%
c) Timolol GFS–Benzododecinum bromide 0.012%
d) Betagan-preservative free (FALSE, betagan is not preservative free, it contains BAK)
- Which one of the following is NOT true regarding OBB’s?
a) Timolol is non-selective
b) Betaxolol is a selective beta blocker that can be used in pt’s with pulmonary disease
c) Gels, such as Timoptic XE have increased systemic absorption because they do not drain as fast as drops
d) Betaxolol is less effective compared to timolol
- c) Gels, such as Timoptic XE have increased systemic absorption because they do not drain as fast as drops (this is FALSE, gels decrease systemic absorption because systemic absorption happens in the nasolacrimal duct and gels do not drain thru the lacrimal ducts as readily as the drops)
- more selective=less effective
Which one of the following is NOT true regarding Timolol?
a) onset of action is 30 minutes following instillation of drops
b) peak action 2 hours
c) maximal effect can persist for 12 hours
d) IOP lowering persists for 24 hours
e) all of the above are true
e) all of the above are true
(T/F) Timolol is usually prescribed BID, however, there is doubt regarding its efficacy on the PM dose since it does not seem to reduce IOP below baseline levels as in AM doses.
true
Which of the following is NOT true regarding “short term escape”?
a) It does not happen in all pt’s
b) it is a decrease in efficacy of timolol over time (several weeks)
c) it is a response of beta receptors to constant antagonists
d) There may be a down regulation of beta receptors in target tissue
d) There may be a down regulation of beta receptors in target tissue (false–there may be an UP REGULATION of beta receptors in target tissue)
Which of the following is NOT true regarding “long term drift”?
a) efficacy decreased over months to years
b) Its recommended to do a washout to restore levels
c) We do not know for sure if the cause is lack of efficacy or poor adherence
d) all of the above are true
d) all of the above are true
(T/F) A washout period is where a glaucoma pts stop their medication for a period of 4 weeks or up to 6 weeks (for dark irises) in an attempt to counteract long term drift.
true. (IOP lowering effects may persist for 2 weeks after discontinuation of meds. For darker irises, you may have to do for a little longer because the medications can stick longer to iris pigments.)
(T/F) The preservatives found in OBB’s, such as BAK, are necessary to break the epithelial barrier for better absorption.
true
Which one of the following is NOT true regarding Istalol?
a) it is timolol maleate 0.5%
b) it is formulated potassium sorbate and has enhanced bioavailability
c) it has lower BAK concentration
d) it is used BID
d) it is used BID (false, it is only used QD because of its enhanced bioavailability)
Between a solution and a suspension, which needs to be shaken well?
a suspension. (particles in a suspension settle down to the bottom) Any suspension prescribed must say “shake well” on the label.
Which one of the following is NOT true regarding Betaxolol?
a) It is a non-selective beta blocker
b) It is only available in a suspension, not a solution
c) It is less effective than timolol
d) Lower CNS effects compared to timolol
a) It is a non-selective beta blocker (false- it is selective therefore it can be used in pt’s with pulmonary disorders)
- Also, Betaxolol may posses calcium channel blocker properties which would give it neuroprotective (protecting ganglion cells) effects–but this is only speculation
Which OBB has a side effect of corneal anesthesia?
a) timolol
b) istalol
c) propranolol
d) betaxolol
c) propranolol
Which one of the following is NOT a common local side effect of OBB’s?
a) decreased tear production and goblet cell density
b) dry eye symptoms
c) ocular cicatrical pemphigoid
d) blurring with gels forms
e) all of the above are
e) all of the above are (also, blurring happens with gel forms of anything, not just OBB’s)
(T/F) Metipranolol is associated with granulomatous uveitis
true
Systemic side effects are a concern with OBB’s. When the drops drain into the nasolacrimal ducts they can be absorbed systemically. explain the systemic effects of OBB’s.
OBB eye drops never reach levels of an oral dose. A typical oral dose of beta blocker is 20-60mg. systemic levels from eyedrops reach 6% of a 20mg oral dose. This is the equivalent to the “trough levels”, rather than the “peak levels” of an oral beta blocker.
Which one of the following is NOT a CNS adverse effect of OBB’s?
a) sexual dysfunction: decreased libido in women and men, impotence in men
b) anxiety/depression
c) fatigue/sleep disturbances
d) confusion/memory loss
e) all of the above are CNS adverse effects
e) all of the above are CNS adverse effects (**Betaxolol has fewer CNS side effects)
Which one of the following statements regarding beta blockers is NOT true?
a) a non-selective beta blocker or selective beta blocker that blocked beta-1 would lower heart rate and blood pressure
b) You should always check blood pressure and pulse on pt’s prescribed or on OBB’s
c) Pulmonary effects are due to blocking beta-2 receptors
d) betaxolol should not be used on pt’s with lung diseases
d) betaxolol should not be used on pt’s with lung diseases (false, betaxolol is safe for pts with pulmonary disease because it is selective and does not block beta-2)
(T/F) OBB’s can affect lipid metabolism
true. Normal volunteers showed a 12% increase in triglycerides and a 9% decrease in HDL. (but Dr. Davey says this data is inconclusive b/c not all studies show this)
Which one of the following is not a contraindication listed of OBB’s?
a) cardiovascular disease
b) pulmonary disease
c) hepatitis
d) diabetes
c) hepatitis. (keep in mind, OBB’s can mask signs of hypoglycemia in diabetic pt’s and put them at risk for diabetic coma)
Which one of the following is TRUE?
a) clonidine is an example of a carbonic anhydrase inhibitor
b) Dorzolamide is an example of an alpha-2-agonists
c) mannitol is an example of a cholineric
d) brimonidine is an example of an osmotic drug
e) all of these are false
e) all of these are false
Match the following:
1) prostaglandin analog
2) alpha-2-agonist
3) beta blocker
4) carbonic anhydrase inhibitor
5) cholinergic
6) osmotic
a) clonidine
b) mannitol
c) pilocarpine
d) timolol
e) acetazolamide
f) latanaprost
1) prostaglandin analog–f) latanoprost
2) alpha-2-agonist–a) clonidine
3) beta blocker–d) timolol
4) carbonic anhydrase inhibitor–e)acetazolamide
5) cholinergic–c) pilocarpine
6) osmotic–b) mannitol
Which of the following is NOT true regarding why apraclonidine is better than clonidine?
a) apraclonidine has a wider therapeutic index
b) apraclonidine is less alpha-2 selective
c) apraclonidine is more hydrophillic
d) apraclonidine does not penetrate eyes and blood brain barrier
b) apraclonidine is less alpha-selective (false: it is more alpha-2 selective
Which of the following is NOT a mechanism of action for apraclonidine?
a) decreases aqueous production
b) improves trabecular outflow
c) decreases episcleral venous pressure
d) all of the above are true
d) all of the above are true
Name 2 uses of apriclonidine
1) to prevent post laser treatment spikes
2) adjunctive therapy
*usually used as 2nd line med, not primary
Which one of the following is in order of less alpha-2 selective to highly alpha-2 selective?
a) apraclonidine, clonidine, brimonidine
b) apriclonidine, brimonidine, clonidine
c) clonidine, apraclonidine, brimonidine
d) brimonidine, clonidine, apraclonidine
c) clonidine, apraclonidine, brimonidine
Which of the following is the mechanism of action for brimonidine?
a) decreases aqueous production
b) improves trabecular outflow
c) decreases episcleral venous pressure
d) all of the above are true
a) decreases aqueous production
(T/F) Alpha-2-agonists are also called adrenergic agents
true
Which dosing is correct for alpha-2-agonists?
a) once daily (QD)
b) twice daily (BID)
c) three times daily (TID)
d) four times daily (QID)
c) three times daily (TID) based on effect present present at lower amounts at 8 hours
Brimonidine can be used as primary or secondary line of therapy for which kind of glaucoma?
a) normal tension glaucoma
b) ocular hypertension glaucoma
c) psuedoexfoliation glaucoma
d) primary or secondary open angle glaucoma
b) ocular hypertension glaucoma
Which one of the following is the main contraindication of using alpha-2-agonists?
a) using in combination with beta-blockers (OBB”s)
b) using in combination with carbonic anhydrase inhibitors (CAI’s)
c) using in combination with monoamine oxidase inhibitors (MAOI’s)
d) all of the above are contraindications
c) using in combination with monoamine oxidase inhibitors (MAOI’s). MAOI’s are a common category for anti-depressants. If your pt says they take anti-depressants, do not prescribe an alpha-2-agonist because there is a high likelihood it is an MAOI.
- combigan is a combo drug of alpha-2-agonist (brimonidine) and a beta blocker (timolol)
- simbrinza is a combo drug of alpha-2-agonist (brimonidine) and CAI (brinzolamide)
Which of the following is NOT an adverse reaction to alpha-2-agonists?
a) red eye (hyperemia), dryness, burning, stinging
b) conjuntival follicles/ocular allergic reactions/ocular pruritis (itching)
c) headache, foriegn body sensation, fatigue/drowsiness
d) all of the above are all adverse reactions of alpha-2-agonists
d) all of the above are all adverse reactions of alpha-2-agonists
Which of the following is NOT true regarding neuroprotection?
a) in theory: any method that prevents or slows the death of neurons is considered neuroprotective
b) because all glaucoma meds lower IOP which slows the death of ganglion cells, in theory, they can all technically be considered to be neuroprotective
c) none of the drugs approved for use in glaucoma have indication of neuroprotection
d) There are only 2 criteria that need to be met to be deemed neuroprotective
d) There are only 2 criteria that need to be met to be deemed neuroprotective (false–there are 4 criteria)
1) the agent must have a target in the retina
2) it must be neuroprotective in animal models
3) it must reach neuroprotective concentrations in posterior segment after dosing (IOP lowering agents probably do not reach the back of the retina in sufficient quantities)
4) it must be shown to be neuroprotective in controlled clinical trials (this is the one we do not have)
summary: we cannot call IOP lowering agents neuroprotective
(T/F) A cholinergic drug, such as pilocarpine, is considered to be a miotic and can help lower IOP.
true. when you constrict the pupil, you can unfold meshwork and widen schlemm’s canal
Which one of the following is the main indication for a cholinergic drug, such as, pilocarpine?
a) primary open angle glaucoma
b) psuedoexfoliation glaucoma
c) normal tension glaucoma
d) angle closure glaucoma with pupillary block
d) angle closure glaucoma with pupillary block
Which one of the following is the mechanism of action of pilocarpine?
a) decreases aqueous production
b) increases aqueous outflow
c) both a and b
b) increases aqueous outflow via contraction of ciliary muscles which cause pupil to get smaller to open up angle
Which dosing is correct for cholinergics?
a) once daily (QD)
b) twice daily (BID)
c) three times daily (TID)
d) four times daily (QID)
d) four times daily (QID) based on the fact that miosis only lasts 4-8 hours
Which of the following is NOT true regarding pilocarpine?
a) drug binds to iris pigment: use 2% for light irises and 6% for dark irises
b) it takes 75 minutes for pupil to constrict once pilocarpine is instilled
c) it contains BAK and EDTA
d) The pilocarpine gel should should be used at bedtime
e) pilocarpine nitrate strengths range from 0.5% to 4% and pilocarpine hydrochloride ranges from 0.5% to 6%
b) it takes 75 minutes for pupil to constrict once pilocarpine is instilled (false, it takes between 10 and 30 minutes. It has a max IOP reduction time of 75 minutes)
Which one of the following is NOT a side effect of Pilocarpine?
a) stinging/burning
b) vision decrease
c) eyebrow (temporal or supraorbital) headache/ciliary spasm
d) risk of hyphema and failure with surgeries
e) all of the above are side effects of pilocarpine
e) all of the above are side effects of pilocarpine
(T/F) Pilocarpine can cause “long term escape”, a decreased efficacy of lowering IOP with long term use
true, but mechanisms are not clear
(T/F) Pilocarpine has an extremely high risk of systemic toxicity
false, systemic toxicity is actually very rare. Signs to look out for would be : sweating, salivation, overactive GI. *Atropine is the pharmacological antagonist for pilocarpine
(T/F) pilocarpine can be combined with drugs that decrease aqueous humor production but should NOT be used in combination with prostaglandin analogs because PG’s increase the spaces in the ciliary muscle.
true
Which one of the following is NOT a contraindication associated with pilocarpine?
a) risk/history of retinal detachment
b) intraocular congestion, such as, uveitis
c) anyone whom pupil size and accommodation is an issue
d) all of the above are contraindications associated with pilocarpine
d) all of the above are contraindications associated with pilocarpine
Which one of the following is NOT true regarding the mechanism of action of carbonic anhydrase inhibitors (CAI’s)?
a) CAI’s cause reduction in bicarbonate ions in posterior chamber
b) there is a subsequent prevention of Na+ movement and hence water outflow prevention
c) CAI’s work primarily on increasing aqueous outflow
d) all of the above are true
c) CAI’s work primarily on increasing aqueous outflow (false–CAI’s decrease aqueous production)
Which one of the following is NOT true regarding contraindications of CAI’s?
a) CAI’s are not to be given to pt’s with sulfa allergies
b) CAI’s are not to be given to pt’s susceptible to diabetic ketoacidosis
c) CAI’s are not to be given to pt’s with hepatic insufficiency
d) CAI’s are not to be given to pt’s with COPD
e) all of the above are true
e) all of the above are true
Which one of the following is not considered a side effect of CAI’s?
a) numbness/depression
b) anorexia/nausea
c) flatulence/diarrhea
d) all of the above are side effects of CAI’s
d) all of the above are side effects of CAI’s
The max dose for acetazolamide is ____mg ____.
The max dose for methazolamide is ____mg ____.
The max dose for acetazolamide is 250mg QID.
The max dose for methazolamide is 150mg BID.
(T/F) Diamox (acetazolamide) comes in an immediate release 250mg and a slow release 500mg
true
Which 2 of the following are topical CAI’s only?
a) acetazolamide
b) methazolamide
c) dorzolamide
d) brinzolamide
c) dorzolamide
d) brinzolamide
*these can be BID or TID but TID has better IOP reduction
(T/F) The order of glaucoma management:
1) 1st try a PG
2) doesnt work–try an a-2 agonist, b-blocker, or CAI (dont bother trying a different PG)
3) doesnt work–try 2 of these: combo of a-2 agonist, b-blocker, or CAI
4) doesnt work–try laser and one of these: a-2 agonist, b-blocker, or CAI
5) doesnt work–try invasive surgery: trabeculectomy
true
