Medical Management Of Glaucoma-2 Flashcards
1
Q
Beta 1 receptors found where
A
Heart
Stimulation causes increase HR, cardiac contraxtiltiy and atropoventricualr conduction
2
Q
Beta 2 receptors found where
A
Located in bronchial muscle,. Blood vessles and uterus
Stimulation causes dilation of bronchi and blood vessels
3
Q
Beta 3 receptors found wher
A
Recently identified in mammals
Mediation of lipolysis
4
Q
Topical ocular BBlockers (OBB)
A
B adrenergic antagonsits are competitive inhibitors
Classifications
- selective (B1 or B2)
- non selective (both B1 ands B2)
5
Q
Selectivity of BBlockers
A
Selectivity is relatively at high concentrations selective B adrenergic act on all beta receptors
6
Q
MOA of OBB
A
Reduction in aqueous formation
- no change in outflow facility
- aqueous formation can decrease as much as 50%
- exact mechanisms still not clear (despite 30 years of use)
- two hypothesis: classic and alternate
7
Q
Classic hypothesis of OBB
A
Inhibits B adreneriv agonsits from binding its receptors, cannot act as a second messenger with cAMP, reduced production of aqueous from CB
8
Q
Alternate mechanisms of OBBs
A
- ciliary process are under continuous tonic stimulation to produce aqueous (medicated by epinephrine)
- B blocker interfere with tonic stimulation
- this is a speculative hypothesis
- no anatomical basis identify yet
9
Q
Indications of OBB
A
- lowering IOP ocular hypertension and open angle glaucoma
- may be used stand alone or in combination with other drugs
- secondary glaucoma
- angle closure glaucoma
10
Q
Contraindications of OBB
A
- relative or absolute contraindication in patients with pulmonary disease, bronchial asthma, severe COPD. Betaxolol (selective OBB is not contraindicated for above disease)
- any pateitn with sinu bradycardia (less than 60 beats restin), overt CHF
- any patient that develops either heart or Leung problems after starting OBBs
- patient hypersensitivity to drug or any components
11
Q
Any one with less than ____- beats per minute or with ______ should not be on OBB
A
60BPM
CHF
12
Q
Treatment regimen for OBB
A
- used once or twice daily
- twice daily may lower IOP greater than once daily
- more and more practictioners used qd and increase to BID if needed (to minimize side effects)
- all OBBs twice daily
13
Q
Exception to using OBB twice a day
A
Isatalol qam
Timoptic XE or GFS (gels) qd
Betagan qd
14
Q
Timolol
A
- available as timolol maleate or hemihydrate 0.25 and 0.5%
- commonly used 0.5%
- non selective beta adrenergic antagonist
- no corneal anesthesia (like propranolol)
- greater efficacy than pilocarpine
- lowers IOP in normals, ocular hypertensive and glaucoma patients
15
Q
Most commonly used OBB
A
Timolol maleate 0.5%
16
Q
Selectivity of timolol
A
Non selective
17
Q
Timolol used as an alternative
A
Good alternative for PGs
18
Q
Onset of action for timolol
A
30m following instillation
19
Q
Peak action of timolol
A
2 hours
20
Q
Maximal effect of timolol persists for how long
A
12 hours
21
Q
IOP lowering of timolol persist for
A
24 hours
22
Q
Timolol in pateitns with systemic BBlockers
A
Don’t put them on it If they are already on an oral BBcloker
23
Q
When should we use timolol
A
AM
-reduces IOP below baseline
Timolol PM dose foes not reduce it below baseline levels
This casts doubt on its efficacy on PM dosing
24
Q
Short term escape: timolol
A
- not in all pateitns
- efficacy of timolol decreases over time (several weeks)
- repsosne of beta receptors to constant antagonsits
- there may be an up regulation of beta receptors in target tissue
Important-no in all patients!
25
Long term drift: timolol
- over months to years
- control of IOP not as good as once
- washing out and re starting helps restore levels
- lack of efficacy or poor adherence? We dont know for sure
26
Washout period of timolol
- IOP lowering effects may persist for 2 weeks
- aqueous flow up to 6 weeks
- clinically a 4 week washout period is considered acceptable
27
Gels vs drops for timolol
Gels
- improve bioavailability
- decreases systemic absorption
- once a day dose instead of BID-compliance/adherence may be better
- blurs vision if left over in morning
- timoptic XE preserved with benzododecinium bromide (not BAK)
28
Istalol
- timolol maleate 0.5%
- formulated with potassium sorbate
- claims to enhance bioavailability so once a day
- lower BAK concentration
- most visits IOP difference is within 1.0mmHg between groups 95% CL
- all visits within 1.5mmHg (compared to twice daily)
29
Why is istalol once daily
Formulated with potassium sorbate. Claims to enhance bioavailability, so only needed once daily
30
Betaxolol hydrochloride
- selective BBlocker
- initially 0.5% solution (1985)
- later 0.25% suspension of resin coated beads (gradual release)-betoptic S (suspension)
- betaxolol solution is not longer available ion USA
31
Is betaxolol solution available in US
No
32
Clinically a _____ wash out period is considered acceptable
4 week wash out
33
Why do we use betaxolol suspension (betoptic S) instead of solution
- causes less ocular irritation compared to solution
- less effective when compared to timolol
- advantage it is selective BBlocker- can be used in patients with pulmonary disease
34
Local side effects of betaxolol
- propranolol-corneal anesthesia
- other OBBs no such effect
- discomfort, burning stinging. Factors like active molecule, pH, preservative and vehicle
- preservative-BAK. BAK helps with penetration fo OBBs, sensitivity not uncommon
- ocular cicatricial pemphigoid
35
Purpose of BAK in betaxolol
Helps with penetration of OBBS
36
Problems with BAK in OBBs
- decreased tear production
- decreased goblet cell density
- dry eye systmpoms
37
Betaxolol and blurring
Transient blurring with gel form (all gels not exclusively problem with OBBS)
38
Granulomatous uvetiits and meripranaolol
Associated with it
39
Why is betaxolol suspension not well liked
Because you have to shake it for a long time
40
Systemic side effects of OBBs
Enter systemic circulation via nasolacrimal system
-almost like IV dose of medication
Does not approach oral dose
41
Typical oral dose of BBlockers
20-60mg P.O.
- first pass hepatic metabolism
- 50% approx 10-30mg
Peak plasma values 50-103ng/mL
Trough plasma values 0.8-7.2 Ng/mL
42
Two drops of timolol plasma level ranges
5-9.6 ng/mL
43
CNS adverse effects
- detailed history is required
- anxiety, depression, fatigue, lethargy, confusion, sleep disturbance, memory loss and dizziness
- sexual dysfunction
- decreased libido men and women
- impotence in men
44
CNS side effects are fewer with which OBBs
Betaxolol
45
Cardiovascular adverse effects of OBBs
-blocking beta 1 receptors interferes with normal sympathetic stimulation of heart
BBlockers
- lower HR
- lower BP
- decreased myocardial contractility
- slowed conduction time
46
Topical OBBs and cardiovascular side effects
- decreased HR and significant bradycardia
- reduce BP. ALWAYS CHECK BP and pulse rate on patients RXed or on OBBs
- timoptic XE and other gels less effect;gels stay in the eye and decrease systemic absorption
47
What type of OBBs if better for having less cardiovascular effects
Gels
| -they stay in the eye and decrease systemic absorption
48
Pulmonary adverse effects of BBlockers
- most problems were early on due to lack of experience with OBBs
- 12 deaths in first 8 years; 50% of these had pulmonary disease
- pulmonary effects due to blockade to B2 receptors
- betaxolol has been used safely in patients with pulmonary disease
49
Should we give someone BBlockers if they have cardiovascular disease
Contraindicated
| -may worsen BP-potential worsening orthostatic hypotension, cerebrovascualr disease, peripheral vascular disease
50
Should we give someone BBlocker with pulmonary disease
Use with caution
51
If someone on OBBs develop cardiovascular or pulmonary diases while on it
Alter medications
| -may relieve symptoms/conditions
52
BBlockers interaction with diabetes
BBclockers alter some of the symptoms of hypoglycemia- so masks effect
A true problem in insulin dependent pateitns
53
Adrenergic agents
Clonidine
Apraclonidine
Brimonidine
54
Clonidine
Lowers IOP well but
- causes sedation
- systemic hypotension
- narrow therapeutic index
55
Pharmacology apraclondine
More hydrophilic
- does not penetrate eyes and BBB
- more A2 selective
- wide therapeutic index
56
MOA of apraclonidine
- decreased aqueous production
- improves TM outflow
- decreases EVP
57
Uses of apraclonidine
- FDA approved to prevent post laser treatment spikes in IOP
| - adjunctive therapy-TID
58
Brimonidine
- highly A2 selective drug
- MOA: reduction of aqueous flow
- peak effectiveness in 2 hours
- effect present at lower amount at 8 hours
- thus TID
59
Indications of brimonidine
- prophylactic- to avoid postlaser IOP spike
| - primary or secondary therapy glaucoma and ocular hypertension
60
Contraindications of brimonidine
- allergy to drug
| - contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy
61
Adverse reactions to brimonidine
- conkinctival follicles, ocular allergic reactions, and ocular pruritis (itching)
- HA, blurring, FB sensation, fatigue/drowsiness
- oral dryness
- ocular hyperemia, burning and stinging
62
Combigan
Brominidine and timolol-BID
63
Cosopt
Dorzolamide and timolol-BID
64
MOA of rhokinase inhibitor
-changes to TM-cytoskeletal modulating drugs
65
Netradusil Rhopressa
- another class of ROCK inhibitor-small molecule
- alter TM cells
- Alters NE transporter (NET). NEY inhibitor lower aqueous production
- changes EVP
66
Rhopressa vs lotanaprost
- diff-IOP approx 1mmHg
- conjunctival hyperemia 52-57%
- conjunctival hemorrhages 5-6%
- increased lacrimation 5-7%
67
Summary of Rhopressa
- shows promise as a second line drug to PGA
- roclatan-shows IOP lowering effect better than latanaprost and Rhopressa
- side effects conjunctival hyperemia
- cornea issues-erosions, change in endothelium, and cornea verticillata
68
How often do you take Rhopressa
Once a day at bedtime
69
Brinzolamide + brimonidine
Does better than individual drugs
| Simbrinza
70
Cholinergic drugs for glaucoma
Pilocarpine
| Mainly angle closure glaucoma with pupillaryblock
71
MOA of pilocarpine
Anatomic relationship between anterior tendons of ciliary muscles and
- scleral spur
- peripheral cornea
- TM
- inner wall of Schlems canal
72
Contraction of ciliary muscle in atropine causes
Unfolding of meshwork
| Widening of sclemss canal
73
How to use pilocarpine in angle closure with pupillary block
1-2% two-three X in 30 minutes
74
Types of pilocarpine
- pilocarpine nitrate (0.5% QID)
- pilocarpine hydrochloride (0.5%)
- preservative BAK and EDTA
- pilocarpine gel-bed time
75
Pharmacokinetics of pilocarpine
Absorbed by cornea
Drug binds to iris pigment
Light iris-2%
Dark iris-6% may be needed
76
Dose effect varies with strength in pilocarpine
```
1% drug
10-30 minutes-miosis
Max IOP reduction 75 minutes
Mitosis lasts 4-8 hours
IOP lowering 4-14 hours
```
77
Side effects of pilocarpine
Singing
Burning
Prolonged use-raise of failure with surgery
Risk of hyphema during surgeries
Ciliary spasm, temporal, or supraoribital HA and induced myopia
-BC of drug induced contraction of ciliary muscle
Mitosis vision decreased
Intent miropsis and constant accommodation
-increase risk of pupillary block
78
Long term escape of pilocarpine
Decreased efficacy of lowering IOP with long term use
- mechanisms unclear
- increasing problem in drainage mechanisms
79
Systemic toxicity of pilocarpine
Extremely rare
If it occurs
-sweating and salivation
-GI over activity
Atropine is antagonsits for it
80
Contraindications of pilocarpine
- risk/Hx of RD
- intraocualr congestion like uveitis
- any one whom pupil size and accommodative is an issue
81
CAI
Members of sulfonamide family
82
If someone has a sulfa allergy, what drug should we not use to treat glaucoma
CAI
83
MOA of CAI
Reduction of bicarbonate ions in posterior chamber
| -subsequently prevents Na+ movement and hence water movement
84
CAI types and dose
Acetazolamide max dose 250mg QID
| Methazolamide max dose 150mg BID
85
Contraindications of CAI
- Sulpha allergies
- DM patients susceptible to ketoacidsosis
- patients who have hepatic insufficiency and cannot tolerate the increase in serum ammonia
- patients with chronic obstructive pulmonary disease, in whom increased retention of carbon dioxide can cause potentially fatal narcosis from a combination of both renal and respiratory acidosis
86
Side effects of CAI
- many well known ocular and systemic side effects occur with administration of all the CAIs
- these include numbness, parathesias, malaise, anorexia, nausea, flatulence, diarrhea, depression, decreased libido, poor tolerance of carbonated beverages, myopia, hirsuotims, increased serum rate, and, rarely, thrombocytopenia and idiosyncratic asplastic anemia
87
Topical CAIs
Dorzolamide
Brinzolamide
BID or TID
Three times daily gives better reduction in IOP appx 1mmHg
88
Carbonated beverages and CAIs
Leaves a metallic taste in the pateitns mouth. They cannot tolerate it
