Ocular Pharmacology Exam 1

must be resuspended by shaking to provide an accurate dosage of drug and the degree of resuspension varies among preparations and patients

Colony forming unit
A measure of viable bacteria numbers

reduce IOP by increasing uveoscleral outflow

QD HS (once at night)
excellent IOP reduction at night

MOST COMMONLY used mode of delivery for topical ocular medications , more easily instilled, interfere less with vision, and have fewer potential complications

Minimum inhibitory concentration
the lowest conc of a drug that produces no apparent bacterial growth

prostaglandins

inferior conjunctival sac

1. Staphylococcus (gram +)
2. Streptococcus (gram +)
3 Pseudomonas (gram -)
4 Enterobacteria (gram -)

1. HYPEREMIA
2. PERIORBITAL SKIN DARKENING
3. punctate keratopathy
4. INCREASED EYELASH GROWTH
5. blurred vision
6. dry eye
7. iris pigmentation
8. A/C reaction

a. High local concentrations of drug can be obtained with the use of small quantities of medication, so that adverse systemic effects are avoided.
b. High tissue concentrations can be obtained with drugs that poorly penetrate the epithelial layer of the cornea or conjunctiva. This method is useful in patients who do not reliably use topical medication.
c. Drugs can be injected at the conclusion of surgery to avoid the necessity of topical or systemic drug therapy.

1.H. Flu (82%)
2.Strep pneumonia
3.Staph Aureus

1. secondary inflammatory glaucoma
2. anterior segment inflammation (uveitis)

use cautiously in patients with previous outbreaks of HSV keratitis

a. anterior sub-tenon’s injections: (of corticosteroids) used in the treatment of severe uveitis
b. posterior sub-tenon’s injections: treatment of chronic equatorial and mid zone posterior uveitis including macular inflammation

Trimethoprim

1. Xalatan: 3-5 weeks
2. Travatan Z: 2 weeks
3. Lumigan: few days

a. Retrobulbar: directly into the muscle
b. Peribulbar: the needle avoids the intraconal space! Placing one or two injections of local anesthetic around the globe but NOT directly into the muscle cone (the anesthetic injected around the globe eventually infiltrates to provide the anaethesia)

Liposomes:
1. bioerodible and biocompatible systems consisting of microscopic vesicles composed of lipid bilayers surrounding aqueous compartments.
2. demonstrated prolonged drug effect at the site of action but with reduced toxicity.

Lumigan
-different receptors
-synthetic prostamide
-occurs naturally in ocular tissues

a. injection of viscoelastic substances into the AC chamber during a cataract extraction and glaucoma filtering surgeries to protect against loss of endothelial cells and flat AC

Sulfa and PABA are very similar structurally. Pus contains PABA. therefore, if there is pus present (mucopurulent d/c), there is a lot of PABA around, and the PABA competes with sulfa so the sulfa can't get to the appropriate receptors and inhibit the bacteria's growth.

1. Xalatan
Latanoprost 0.005%

2. Travatan Z
Travoprost 0.004%

3. Lumigan
Bimatoprost 0.03% and 0.01%

1. selectively eradicate neovascuar membranes while producing minimal damage to normal retinal and choroidal tissues (good for choroidal neovascularization associated with ARMD that is difficult to treat with traditional laser because the normal retinal tissues will be destroyed, destroying central vision)
2. IV administration of veteporfin for 10 minutes (a potent photosensitizing eye)
3. 5 minutes after, nonthermal light at 689nm applied to abnormal tissues for 83 seconds
4. When activated by light, verteporfin causes the production of singlet oxygen and free radicals that produce cell death and occlusion of abnormal vessels

BAK alone, bactericidal activity starts with in 5 mins
-reduces the tear break up time by 1/2
zymar has BAK

1. Xalatan
NO PRESERVATIVES

2. Travatan Z
Sofzia- more gentle than BAK

3. Lumigan
BAK roughs up epithelium to enhance corneal penetration

NOT commercially available
-No approved indication, could be investigational use
-None commonly used!

they have durasite or xanthum gum which increases contact time of drug

Lumigan

-Accepted for medical use
-strict limitations due to recognized high abuse and dependency potential
-Rx should be signed by practitioners and cannot be refilled
- Cocaine, Oxycodon with Acteaminaphen

the drugs have different solubility properties

short term:
PF-2 receptor stimulation

long term:
changing the ground substance in the cellular matrix of the ciliary meshwork

-Significant but less abuse and dependency potential than that of schedule 1 and 2
-these may contain limited quantities of certain narcotics
-Example: Tylenol III, aspirin with codein

prostaglandin analogs

Penicillans
Cephalosporin
bacitracin
vancomycin

-Relatively low abuse potential and limited dependency potential
-Whereas schedule 2 RXs must be written, RXs for schedule 3 and 4 drugs may be verbal and may be refilled up to 5X in 6 months if authorized by the prescriber
-Example:Propoxyphen with acetaminaphen

1. iris: miosis
2. ciliary body: accommodation and TM opening
3. trabecular meshwork: aqueous outflow increase
4. ciliary meshwork: aqueous outflow decrease

Polymixin B
Gramicidin

these have lower abuse potential
-cough suppressants and anti-diarrheals

Pilocarpine
1. direct acting cholinergic agonst
2. increase trabecular meshwork outflow

Tetracycline 30s
Macrolide 50s
aminoglycosides 30s
Chlororamphenicol

a. Beginning 1971, optometry laws began to permit the use of drugs for diagnosis & tx
- rhode island

MIOSIS

Pyrimethamine
Sulfonamide
Trimethoprim

-the practitioner is held to the same standard that a reasonable practitioner would have acted under the same or similar circumstance
-uses expert witness testimony and “body of evidence” set by the professional community

1%, 2%, 4%
QID (BID if a part of poly therapy)
GREEN CAP

Fluoroquinolones
Inhibits topoisomerase II and IV

-based on what a reasonable patient must know rather than what the practicioner must divulge
-what would a prudent person in the patient’s position have done if they had sufficient information to make a decision
-does NOT require an expert testimony
-it is CHEAPER to defend yourself in this standard

1. UVEITIC GLAUCOMA (INFLAMMATORY)
2. neovascular glaucoma
3. aphakia
4. retinal detach
5. posterior subcapsular cataract present
6. pre-presbyopia

inhibits DNA synthesis

a. The indication is why you would use a drug; you can find it on the drug or company website, FDA.gov, etc
b. The indication is determined by FDA trials following animal and lab studies (Phase 3 is VERY focused and leads to labeling a drug!)

1. any patient with primary angle closure glaucoma prior to laser surgery
2. acute pupil block angle closure

Those viruses do NOT have lipid envelopes (ex – Adenovirus)

a. Using a prescription drug for a purpose NOT stated specifically in its indication

1. Brimonidine tartrate (P is the Purite preservative)
2. TID
3. PURPLE

HSV: 400mg, 5x a day for 7-10 days
HZV: 800mg, 5x a day for 7-10 days

Look over in notes

1. decreases aqueous production (possibly increasing uveoscleral outflow)
2. reduces the production of norepinephrine and decreasing sympathetic tone

HSV: 1 g PO BID
HZV: 1 g PO TID

Some patients may have access to drugs in phase 3 trials even if they are not “in” the trial

1. drowsiness
2. fatigue
3. dry mouth

*no effect on BP, pulse or pulmonary function
*most significant in smaller people and kids

• Purine analogue to guanine that is specific to viral cells
• Inhibit DNA synthesis
• Short half life bc of poor GI absorption
• Common side effects mostly GI

DO NOT USE WITH MAO INHIBITOR

does not appear to have IOP lowering effects at night/during sleep

1. beta blockers--->except topical bb ok with cardiac pacemakers
2. Alpha agonists

• Prodrug of acyclovir
• Hydrolized by esterases in GI tract, converting valacyclovir to acyclovir, therefore making more bioavailable

1. bradycardia
2. COPD/Asthma/Emphysema
3. Myasthenia gravis
4. Cerebrovascular insufficiency
5. Greater than first degree heart block

Systemic anti-inflammatory drugs

-prodrug of penicyclovir
-Inhibits DNA synthesis
• Well-absorbed orally
• Active against HSV 1 & 2 and HZV

Timolol (non selective)
0.25% (BLUE)
0.50% (YELLOW)
BID

topical Beta blockers

Prophylaxis against secondary bacterial infection of conj and cornea

1. Betaxolol
2. may still exacerbate asthma
3. weaker (BID)
4. may increase nerve perfusion

phenylephrine

-Bind to ergosterol
increase cell membrane permeability
-fungistatic in low doses

1. Carteolol 1% (Ocupress)
2. intrinsic sympathomimetic activity and transient agonist activity
3. can be used on atheletes

i. hyperosmotic agents (ex – glycerine)
ii. systemic corticosteroid therapy
iii. topical beta blockers

• aka antimetabolites
• Block thymidine synthesis in some fungi
• Impairs DNA synthesis
• Fungistatic – Flucytosine

uveitic glaucoma

1. Cyclopentolate
2. Topical beta blockers

• Impair ergosterol in cell membrane, increasing cell membrane permeability
• Fungistatic
• Resistance is increasing
• More interactions with other systemic drugs in this category

1. nocturnal hypotension
2. aqueous formation decreases in the evening so beta blockers have less effect

i. Monoamine oxidase inhibitors
ii. Tricyclic antidepressants

• Inhibit glucan synthesis, weaken cell wall of some fungi
• Newer class of drugs including capsofungin, micafungin, anidulafungin

1. bicarbonate make the eye hypertonic and drawing in fluid into the eye
2. by blocking bicarbonate production, it blocks osmosis into posterior chamber
3. blocks aqueous formation

Systemic drugs
only 2 safe ones are E-mycin and penicillans

1. Fluconazole: mainly effective against yeasts
2. Miconazole: relatively good activity against yeast

1. sulfa allergies
2. sickle cell disease
3. hypokalemia
4. renal disease (kidney stones)
5. liver disease

Topical Timolol

Acetazolamide
125, 250, 500 SR
1000mg QD p.o.
indicated post surgically and for acute angle closure (250mg)

i. Topical ocular sulfonamides
ii. Carbonic anhydrase inhibitors

Methazolamide
range: 25mg BID-50mg TID
much better tolerated than diamox

a. Cardiac glycosides – Cardiac depression
b. Quinidine – Cardiac depression
c. Beta adrenergic agonists – Cardiac depression & bronchospasm
d. Xanthines - Bronchospasm

1. Dorazolamide 2%
2. Orange Cap
3. TID
4. Hyperemia due to low pH of drug

1. keep medications out of childrens reach
2. advise pt to wipe away excess drug from lids after instillation
3. Avoid overdosing
4.Confirm the dosage of infrequently used drugs before prescribing before administering them
5.Consider the potential adverse effects of a drug relative to its potential diagnostic or therapeutic benefit. Warn patients so that they can get an informed consent
6. consult with primary care physician
7.Recognize adverse drug reactions

1. Brinzolamide Suspension 1%
2. TID
3. ORANGE
4. significantly more comfortable and better tolerated than Trusopt

Tx of ocular infxns

A/E= Bone marrow suppression
and fatal aplastic anemia

uveitic glaucoma

clinical circumstance: Open angle glaucoma

A/E:Decrease cardiac rate, syncope, exercise intolerance, bronchospasm, emotional, psychiatric disorder

1. compromised corneal endothelium
2. sulfa allergies
3. renal stones Hx

tx of open angle glaucoma

A/E:Dry mouth, CNS effect including fatigue and lethargy

1. latanoprost
2. pilocarpine
3. timolol
4. betaxolol
5. carteolol
6. brimonidine (0.2% and 0.15%)
7. COSOPT

Treatment of open angle glaucoma when succinyl choline is used as skeletal muscle relaxant during surgery requiring general anesthesia

A/E: Prolonged apnea

A: SAFE for humans
B: SAFE for animals or fail to demonstrate risk in humans
C: AE in animals or NO HUMAN TRIALS
D: TRIALS SHOW HARM TO HUMANS
X: CONTRAINDICATION!!

Overdosage in treatment of acute angle closure glaucoma

A/E Nausea, vomiting, sweating, tremor, bradycardia

1. hypersensitivity or toxicity reactions
2. superinfections
3. facilitate resistance

Overdosing for cycloplegic rxn

A/E: Hallucinatory behavior

a. Pediatric dose = adult dose x (weight(kg)/70) or adult dose x (weight(lb)/150)

1. rash, fever, itching anaphylaxis, bronchospasm
2. nausea, vomiting, diarrhea
3. disruption of normal flora
4. kidney, liver, and other drug interaction
5. OTOTOXICITY

8-10mcl

1. produce enzymes
2. change bind site
3. blocks entry or pump back out

30

NEVER USE ANTIBIOTICS BELOW THERAPEUTIC DOSE

50mcl or .05ml

1. minimum inhibitory concentration
2. if MIC is higher than blood, bacteria is RESISTANT
3. if MIC is lower than blood, bacteria is SUSCEPTIBLE

.5-2.2mcl/min

1. Penicillins
2. Cephalosporins
3. Macrolides
4. Fluoroquinolones
5. Tetracyclines

QD or BID

a. Increased ocular drug absorption
b. Because lacrimation is reduced, the drug is not rapidly diluted by the tears which prolongs the time next to the corneal surface
i. This is where most of the absorption occurs
c. The total tear film for these patients is less than normal, so the drop of a medication is not diluted as much as usual

Amoxicillin and Clavulanate
500mg BID x 7 days

kids active against H.flu

1. Reflex tearing prevents adequate absorption of the drug at the ocular surface
2. These drugs are formulated at high concentration to offset the dilution and washout that occur from tear flow.
3. Patients with dry eyes that do not tear readily can absorb greatly exaggerated doses of topically applied medications.

1. internal hordeolum, preseptal cellulitis, decryocystitis, orbital blow out
2. 250mg QID x 7days

corneal epithelium-both
corneal stroma-both
aqueous humor-hydrophillic
Iris-lipophillic
Lens-lipophillic

Amoxicillin

Look up

SYSTEMIC DRUG ONLY
combine with probenecid to decrease kidney elimination

*topical yield high incidence of allergy

miosis-->can be accomplished by endogenous or exogenous acetylcholine or by cholinergic stimulation

1. disrupt cross linking in cell wall, so it works well against gram POSITIVE
2. bactericidal
3. category B!!

1. FIRST GENERATION
2. 500mg BID x 7days

b. Mydriasis can be accomplished by an adrenergic stimulant, such as epinephrine (which acts on the dilator musculature), or by an antagonist to acetylcholine (which allows relaxation of the sphincter

1. binds to 50s
2. resistance developing by altering binding site on ribosome

a. Aqueous humor is formed by the CILIARY BODY and occupies the posterior and anterior chambers
b. It flows from the posterior chamber through the pupil and then slowly circles in the anterior chamber, circulated by the THERMAL DIFFERENTIAL between the cornea and the deeper ocular tissues

erythromycin
QID (mg varies with adult/child)

20%

1. B: azithromycin and erythromycin
2. C: clarithromycin (DO NOT USE IN PG WOMEN)

Ciliary body

250-500mg BID x 7 days

used for respiratory tract infections and skin infections (gram + plus H.flu)

aldose-reductase inhibitors

Z PAC:
Two 250mg QD on day one
then 250mg QD 2-5 days

Zithromax Tripak:
Three 500mg, one per day (ADULTS ONLY)

Zmax:
SINGLE 2g dose with extended release

a. Lens acts as a barrier b/w aqueous and vitreous, so this barrier is removed after cataract surgery.
b. Drug concentrations increase in retinal tissue after lens is removed, compared to before cataract surgery

500mg BID x 1 week

a. The retina is a developmental derivative of the neural tube wall and can be viewed as a direct extension of the brain; it is not surprising that the blood–retinal barrier somewhat resembles the blood–brain barrier in form and function.
b. Histamine does not alter the vascular permeability of the retina but does affect that of all other ocular tissues.
i. The retina closely resembles the brain with respect to this trait.
c. The barrier protects against the entry of a wide variety of metabolites and toxins and is effective against most hydrophilic drugs, which do not cross the plasma membrane

500mg QD x 1 week

a. The retinal vessels can remove many drugs, metabolites, and such agents as prostaglandins from the vitreous humor and retina, apparently by ACTIVE TRANSPORT.

400mg BID x 1 week

By the iris and ciliary body via bulk transport aka uveoscleral outflow

1. nausea/vomiting/diarrhea/ab pain
2. phototoxicity
3. should not be used in kids under 18 yr, pregnant women, or in pts with CNS disorders

• When the metabolite of a drug is more active at the receptor site than is the parent form, the drug is often termed a prodrug
• A prodrug must metabolize predictably to the effective drug form before it reaches the receptor site

• The greatest advantage of prodrugs is the potential to add groups that mask features of the drug molecule that prevent penetration or have other undesirable effects.
• Prodrug design can be a useful way of increasing penetration of a therapeutic

Placed in the eye and then becomes inactivated with less side effects

example:
Loteprednol etabonate is an active metabolite of a prednisolone-related compound that predictably and rapidly undergoes transformation by enzymes in the eye to an inactive form associated with fewer side effects.

a. Bioavailability describes the amount of drug present at the desired receptor site.
a. A time sufficient to produce the desired action. The dose level producing a response that is 50% of maximum is termed the ED50
b. An effective dose level must be present for a time sufficient to produce the desired action.
c. The requirements for concentration and time to achieve ED50 differ widely, depending on the mechanism of action of the drug and the desired response.

1. Stability
2. Osmolarity
3. Active Ingredients
4. Preservatives

• The quaternary surfactants benzalkonium chloride (BAC) and benzethonium chloride are preferred by many manufacturers because of their stability, excellent antimicrobial properties in acid formulation, and long shelf life.
• They exhibit toxic effects on both the tear film and the corneal epithelium and have long been known to increase drug penetration

-toxicity maybe increased with inc in acidity
-reduces tear breakup time by 1/2
- neither protects corneal epi or promotes oily stable tear surface

b. The first is a device of low permeability filled with drug (Ocusert), which has been discontinued.
c. The second is a polymer that is completely soluble in lacrimal fluid, formulated with drug in its matrix (Lacrisert).
d. Both systems can be made to approach zero-order kinetics.
e. However, patient acceptance has been poor.