Pharmaceutical Agents

The Prescription/Patient Compliance

Jill C. Autry

THE PRESCRIPTION DOS AND DONT’S: PRESCRIBING GUIDELINES (SEE FIGS. 5-1, 5-2 AND 5-3 AND TABLES 5-1 AND 5-2)

Do write legibly.
Do check drug spelling; many drug names look alike.
Do include dosage form, quantity, and strength of medication.
Do specify length of treatment on acute care prescriptions.
Do use the most economical size package on chronic care prescriptions.
Do make sure the patient understands all special instructions, for example
- Refrigeration
- Shake suspensions
- Proper instillation techniques
Do specify the symptoms that require “as needed” treatment, for example
- Itch
- Pain
- Redness
Do use only metric measurement. DO NOT use household or apothecary measurement systems.
Do not preprint your DEA number on your prescription pad.
Do use tamper resistant prescription pads where required by law.
Do not leave prescription pads unattended on counter tops.

IMPROVING PATIENT COMPLIANCE

One of the most difficult things that any physician faces in managing the patient with chronic disease, be it systemic hypertension, elevated cholesterol, diabetes, or, as in ophthalmic cases, glaucoma and dry eye, is patient compliance with drug therapy.

Use the following recording and education sheets to assist your patient to utilize their medications more effectively (Figs. 5-4, 5-5 and 5-6).

Ophthalmic Dyes

Jill C. Autry

Ophthalmic dyes are among the most useful diagnostic agents used in the management and detection of disorders of the visual system. The most common uses of these agents and their properties are listed in Tables 5-3, 5-4, 5-5, 5-6, 5-7 and 5-8 and Figure 5-7.

Anesthetic Agents

Jill C. Autry

Clinical procedures that may induce patient discomfort should always include the use of an appropriate anesthetic agent. These drugs can vary in their ability to decrease pain, duration of effect, and potential to induce allergic and toxic reactions. It is important to select the most appropriate agent with adequate efficacy and minimal adverse effects (Tables 5-9, 5-10, 5-11, 5-12 and 5-13). If a patient
reports an allergy to an anesthetic agent in one chemical class, an agent from the alternate class can be considered with caution. For example, if a patient reports an allergy to tetracaine (an ester compound), a compounding pharmacist can prepare topical lidocaine (an amide compound) for ocular use.

Figure 5-1. Sample drug record—diagnostic.

Figure 5-2. Sample drug record—therapeutic.

Figure 5-3. Sample consent form.

TABLE 5-1 Lati Abbreviations Commonly Used in Ophthalmic Prescription Writing

Latin	Abbreviation	Meaning
Ad	Ad	Up to, to
Admove	Admov.	Apply
Alternis horis	Alt. hor.	Every other hour
Ante	A	Before
Ante cibos	ac	Before meals
Bis in di’e	bid	Twice a day
Capsula	caps	Capsule
Cum	[C with bar above]	With
Diebus alternis	Dieb. alt.	Every other day
Gram	g, gm	Gram
Gutta	gt, gtt	A drop
Hora	h	An hour
Hora somni	hs	At bedtime
Nocte	noct.	At night
Oculo utro	O.U.	Each eye
Oculus dexter	O.D.	Right eye
Oculus sinister	O.S.	Left eye
Per os	po	By mouth
Pro re nata	prn	When needed
Quaque	q	Each, every
Quaque hora	qh	Every hour
Quater in di’e	qid	Four times a day
Recipe	Rx	Take, you take
Signatura	Sig.	Write, you write
Sine	[s with bar above]	Without
Solutio	Sol.	Solution
Tabella	tab	Tablet
Ter in di’e	tid	Three times a day
Unguentum	ung.	Ointment
Ut dictum	Ut dict.	As directed
Unus	i	One
Duo	ii	Two
Tres	iii	Three
Quattour	iv	Four
Quinque	v	Five

TABLE 5-2 A “Minimum List” of Dangerous Abbreviations, Acronyms, and Symbols Has Been Approved by Joint Commission (Beginning January 1, 2004, the Following Items Must Be Included on Each Accredited Organization’s “Do Not Use” List)

Set	Item	Abbreviation	Potential problem	Preferred term
1.	1.	U (for unit)	Mistaken as zero, four or cc.	Write “unit.”
2.	2.	IU (for international unit)	Mistaken as IV (intravenous) or 10 (ten).	Write “international unit.”
3.	3. 4.	q.d., Q.O.D. (Latin abbreviation for once daily and every other day)	Mistaken for each other. The period after the Q can be mistaken for an “I” and the “O” can be mistaken for “I.”	Write “daily” and “every other day.”
4.	5. 6.	Trailing zero (X.0 mg) [Note: Prohibited only for medication-related notations]; Lack of leading zero (.X mg)	Decimal point is missed.	Never write a zero by itself after a decimal point (X mg), and always use a zero before a decimal point (0.X mg).
5.	7. 8. 9.	MS MSO4 MgSO4	Confused for one another. Can mean morphine sulfate or magnesium sulfate.	Write “morphine sulfate” or “magnesium sulfate.”
Effective April 1, 2004 (if your organization does not already have additional “do not use” items in place), each organization must identify and apply at least another three “do not use” abbreviations, acronyms, or symbols of its own choosing. (Revised 11/3/03.)

Figure 5-4. Patient medication instruction sheet.

Figure 5-5. Medication refill request form.

Figure 5-6. Missed appointment record sheet.

TABLE 5-3 Common Uses of Ophthalmic Dyes

FLUORESCEIN

Lacrimal testing (TBUT, Jones test)

Detection of corneal epithelial defects

Detection of penetration of globe (Seidel’s sign)

Applanation tonometry

Contact lens/corneal fitting relationship

Retinal angiography

LISSAMINE GREEN

Dry eye evaluation

FLUOREXON

Evaluation of soft contact lens fit

ROSE BENGAL

Dry eye evaluation

Herpes simplex keratitis

INDOCYANINE GREEN

Angiography

TABLE 5-4 Properties and Characteristics of Fluorescein

CHEMICAL PROPERTIES
C₂H₁₂O₅Na
Molecular weight = 376.27
Orange-red powder
Yellow in solution
Fluorescence
	Yellow-green with blue light in weak alkali solution
	Peak absorption: 465-490 nm
	Peak emission: 520-530 nm
	Fluorescence increases with greater concentrations up to 0.001%
Fluorescence increases with greater pH up to pH 8
At very high concentrations:
	Quenching occurs
	It dimerizes and polymerizes
	Emission shifts to longer wavelengths
CLINICAL CHARACTERISTICS
Stains epithelial defects bright green
Diffuses into intercellular spaces
Will not stain devitalized cells nor mucus
Tear film appears yellow-orange
Can exhibit:
	Pseudoflare
	Fisher-Schweizer mosaic
	Negative staining
Promotes growth of Pseudomonas in solution
Will stain soft contact lenses

TABLE 5-5 Characteristics of Fluorexon

N₁ N-bis (carboxymethyl)-aminoethyl-fluorescein tetra-sodium salt
Molecular weight = 710
Stains epithelial defects, devitalized cells, and mucin (less than fluorescein or rose bengal)
Fluorescence
	Less brilliant than fluorescein
	Does not increase linearly with increasing concentration
Does not stain most soft contact lenses
May stain high water (>60%) contact lenses
Promotes the growth of Pseudomonas

TABLE 5-6 Characteristics of Rose Bengal

4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein sodium

Stains devitalized cells and mucin a brilliant red

Stains the nucleus more than cytoplasm

Higher concentrations stain more distinctly and highlight more subtle defects

Stings upon instillation

Antiviral properties

Stains a line along the ciliary margin on conjunctival tarsus in normal eyes

TABLE 5-7 Comparative Staining Characteristics of Fluorescein, Rose Bengal, and Fluorexon

	Epithelial defects	Devitalized cells	Mucin
Fluorescein	++	0	+
Rose bengal	0	++	++
Fluorexon	+	+	+
Lissamine green	0	++	+

TABLE 5-8 Topical Products

Product	Concentration	How supplied
FLUORESCEIN
Fluorescein (Alcon, Iolab)	2%	1, 2, and 15 mL
Fluorocaine (Akorn)	0.25% fluorescein sodium, 0.1% proparacaine hydrochloride, 0.01% thimerosal preservative	5 mL
Flucaine (Pharmafair, Inc)	0.25% fluorescein sodium, 0.50% proparacaine hydrochloride, 0.01% thimerosal preservative (povidone, boric acid polysorbate 80)	5 mL
Fluress (Sola/Barnes-Hind)	0.25% fluorescein sodium, 0.4% benoxinate hydrochloride, 1% chlorbutanol, povidone buffers	5 mL
Ful-Glo (Sola/Barnes-Hind)	0.6-mg strips	300 strips
Fluor-1-Strip (Wyeth-Ayerst)	9-mg strips (boric acid polysorbate 80, 0.5% chlorbutanol)	300 strips
Fluor-1-Strip AT (Wyeth-Ayerst)	1-mg strips (boric acid polysorbate 80, 0.5% chlorbutanol)	300 strips
Fluorets (Akorn)	1-mg strips	100-1,300 strips
FLUOREXON
Floresoft (Holles)	0.35%	0.5-mL pipettes
LISSAMINE GREEN	1-mg strips	100 strips
ROSE BENGAL
Rose Bengal 1% (Akorn) Americil	1% solution (povidone, sodium borate, PEG P-isoc tylphenolio, 0.01% thimerosal)	5 mL
Rose Bengal (Sola/Barnes-Hind)	1.3-mg strip	100 strips
Rosets (Smith & Nephew)	1.3-mg strip	100 strips

Figure 5-7. Common corneal fluorescein patterns.

TABLE 5-9 Physiochemical and Pharmacologic Properties of the Injectable Local Anesthetics

	Physiochemical properties			Pharmacologic properties
Agent (Trade Name)	pK_a (25°)	Partition coefficient^*	Percent protein binding (%)	Onset (min^†	Relative potency	Duration (h†)	Concentration (%)
ESTERS Procaine (Novocain)	8.9	0.02	6	Slow (15-25)	1	Short (0.5-1)	1-2
Tetracaine (Pontocaine)	8.5	4.1	76	Slow (20-30)	8	Long (3-5)	0.25
AMIDES
Prilocaine (Citanest)	7.9	0.9	55	Fast (5-15)	2	Moderate (1-3)	1-3
Lidocaine (Xylocaine)	7.9	2.9	64	Fast (5-15)	2	Moderate (1-3)	0.5-2
Mepivacaine (Carbocaine)	7.6	0.8	78	Fast (5-15)	2	Moderate (1-3)	1-2
Bupivacaine (Marcaine)	8.1	27.5	96	Moderate (10-20)	8	Long (3-5)	0.25-0.75
Etidocaine (Duranest)	7.7	141	94	Fast (5-15)	6	Long (3-5)	0.5-1
^*Partition coefficient is a measure of lipid solubility. ^†Onset and duration times seen with epidural injection.
Modified from Covino BG. Pharmacology of local anesthetics. Ration Drug Ther 1987;21:1-9, and Local anesthetics. In: Facts and Comparisons, St. Louis: Lippincott, 1990: 691-694.

TABLE 5-10 Commonly Used Topical Ocular Anesthetics

Drug (Trade Name)	Concentration (%)	Onset (s)	Duration (min)	*Maximum dose^ (drops^†**
Benoxinate (Fluress)^‡	0.4	20	10
Cocaine^§	1.0-10	30	12	20 mg (about 5 drops to each eye of a 4% solution)
Proparacaine (various) (Fluoracaine)^‡ (I-Parescein)^‡	0.5	15	14	10 mg (about 20 drops to each of a 0.5% solution)
Tetracaine (various)	0.5	20	10	5 mg (about 10 drops to each eye of a 0.5% solution)
(Pontocaine eye)^\|\|
^Suggested maximum total topical doses. (Based on theoretical calculations from Lyle WM, Page C. Possible adverse effects from local anesthetics and the treatment of these reactions. Am J Optom Physiol Opt* 1975;52:736.) ^†Assumes approximately 20 drops/mL of solution. ^‡Combined with 0.25% fluorescein sodium. ^§Must be prepared from a powder. ^\|\|Ointment, 0.5%.

TABLE 5-11 Central Nervous System Toxicities of Local Anesthetics

EARLY EXCITATORY EFFECTS

Restlessness

Anxiety

Dizziness

Tinnitus

Miosis

Tremors

Convulsions

DEPRESSIVE EFFECTS (MAY OR MAY NOT BE PRECEDED BY THE EXCITATORY SYMPTOMS)

Drowsiness

Sedation

Generalized CNS depression

Unconsciousness

Coma

Apnea and respiratory depression

Death from respiratory arrest

TABLE 5-12 Cardiovascular Symptoms of Toxicity from Local Anesthetics

Hypertension and tachycardia (associated with the CNS excitatory phase)

Myocardial depression

Decreased cardiac output

Peripheral vasodilation

Hypotension

Bradycardia

Methemoglobinemia (seen only with prilocaine)

Heart block

Ventricular arrhythmias

Circulatory collapse

TABLE 5-13 Ocular Toxicity from Acute Administration of Topical Ocular Anesthetics

Mild stinging, burning

Vasodilation

Shortening of the tear breakup time

Decreased reflex tearing

Decreased blinking

Corneal edema

Decreased epithelial mitosis and migration

Slowed epithelial healing

Punctate epithelial keratitis

Epithelial desquamation

Allergic reactions of the lids and conjunctiva

Dilating Agents and Procedures

Jill C. Autry

Of all the tests that we, as primary eyecare providers, perform to assess the ocular health of our patients, there is probably no more important test than the dilated fundus examination.

This section provides a quick reference to the procedures and medications that will improve the efficiency of this all-important procedure (Tables 5-14 and 5-15).

Prior to dilation, the clinician must assess the potential for angle closure. This can be done by gonioscopy or by the slit-lamp estimation procedure as seen in Table 5-16. Of course, patients most likely to develop angle closure are older, phakic patients with emmetropic to hyperopic prescriptions. See also Tables 5-17 and 5-18.

TABLE 5-14 Indications for Dilation

1.	Any new patient
2.	Established patient every 2-4 y
3.	Any patient with flashes or floaters
4.	Unexplained vision loss
5.	Any patient with progressive retinal disease (e.g., macular degeneration, diabetic retinopathy)
6.	Any patient with systemic disorders that can affect the eye (e.g., systemic hypertension)
7.	History of ocular trauma
8.	History of chronic uveitis
9.	Any child under 6 y (with cycloplegia)
10.	Once yearly if history of ocular surgery
11.	Moderate to high myopia:
	a. 3-7 D of myopia—at least every 2 y
	b. >8 D of myopia—at least yearly
12.	Any patient with history of peripheral retinal degeneration
13.	Any patient with developing cataract
14.	All hyperopes or anisometropes (include cycloplegic refraction)

TABLE 5-15 Mydriatic Pharmaceuticals for Dilation

Drug		Maximal dilation	Duration
PARASYMPATHOLYTIC AGENTS
Tropicamide
	0.5%	20-40 min	4-8 h
	1.0%		6-8 h
Cyclopentolate
	0.5%	30-60 min	12-24 h
	1.0%		12-36 h
Homatropine
	2.0%	40-60 min	24-72 h
	5.0%		36-72 h
Scopolamine
	0.25%	20-30 min	3-7 d
Atropine
	1.0%	30-40 min	7-10 d
SYMPATHOMIMETIC AGENTS
Phenylephrine
	2.5%	20-30 min	4-6 h
	10%
Hydroxyamphetamine
	1%	25-35 min	4-6 h

TABLE 5-16 Van Herick Filtration Estimation Guide

A/C depth at limbus compared to corneal thickness at limbus	Estimated grade of angle
1/2-1	Grade 4
1/4-1/2	Grade 3
=1/4	Grade 2
<1/4	Grade 1
CLOSED	Grade 0

TABLE 5-17 Examination Procedures in Relation to the DFE

I.	Perform these procedures prior to dilation:
	1. Case history
	2. Best corrected acuity
	4. Near-point accommodation and stereopsis
	5. External evaluation and pupil testing
	6. Biomicroscopy
	7. Tonometry
	8. Gonioscopy if indicated
II.	Perform these procedures during dilation:
	1. Color vision
	2. Visual field
	3. Frame selection
	4. Patient education
III.	Perform these procedures after dilation:
	1. Repeat retinoscopy and subjective to R/O latent hyperopia
	2. Binocular indirect ophthalmoscopy
	3. Slit lamp of lens and vitreous chamber with 60, 78, or 90 D lens

TABLE 5-18 Example of the “Round-Robin” Approach to Patient Scheduling for Dilation

Morning schedule^*	Procedure
8:30-8:55 AM	Predilation examination of new patient A
8:55-9:20 AM	Predilation examination of new patient B
9:20-9:30 AM	Dilated exam and dismissal of patient A
9:30-9:40 AM	Brief follow-up examination of patient C (e.g., contact or glaucoma IOP recheck)
9:40-9:50 AM	Dilated exam and dismissal of patient B
9:50-10:15 AM	Predilation examination of new patient D
10:15-10:40 AM	Predilation examination of new patient E
10:40-10:50 AM	Dilated exam and dismissal of patient D
10:50-11:00 AM	Follow-up examination of patient F
11:00-11:10 AM	Dilated exam and dismissal of patient E
11:10-11:35 AM	Predilation examination of new patient G
11:35-11:50 AM	Follow-up examinations as needed and return morning phone calls
11:50-noon	Dilated exam and dismissal of patient G
^*Afternoon schedule may repeat morning or use for specialty appointments. Examination times may vary from doctor to doctor. Delegation of tests and an adequate number of examination rooms is necessary to follow this type of scheduling.

Diagnostic Agents and Procedures for the Management of Accommodative Disorders

Jill C. Autry

The use of diagnostic pharmaceuticals during the examination procedure is necessary in a number of situations. This section provides information regarding the appropriate use of pharmaceutical agents for the diagnosis of accommodative disorders (Tables 5-19, 5-20, 5-21, 5-22, 5-23 and 5-24 and Fig. 5-8) and accommodative esotropia (Table 5-25 and Fig. 5-9).

TABLE 5-19 Indications for Cycloplegic Refraction

1. Strabismus (particularly esotropia)

2. Amblyopia

3. Anisometropia

4. Pseudomyopia

5. Hyperopia associated with esophoria or a lag of accommodation

6. Unstable end point on static retinoscopy

7. For the uncooperative child during static retinoscopy

8. Preparation for refractive surgery

Ophthalmic Lubricants

Jill C. Autry

Ophthalmic lubricants represent the cornerstone of the management of ocular surface disease. New formulations of these all-important products have recognized the importance of limiting preservative toxicity while enhancing epithelial cell growth. Tables 5-26, 5-27, 5-28, 5-29 and 5-30 list the most common products.

TABLE 5-20 Comparison of Cycloplegic Agents

Drug	Dosage	Onset of cycloplegia	Duration of cycloplegia
Tropicamide 1%	1 drop, repeat after 5 min	20-30 min	4-8 h
Cyclopentolate 0.5% 1.0%, 2%	1 drop, repeat after 5 min	20-45 min	8-24 h
Homatropine 5%	1 drop, repeat after 5 min	30-60 min	24-48 h
Scopolamine 0.25%	1 drop, repeat after 20 min	30-60 min	5-7 d
Atropine
0.5% ointment	1/4”ointment at bedtime for 3 d prior to exam	30-60 min	10-14 d
1.0% solution	1 drop tid × 1 d prior to exam

TABLE 5-21 Efficiency of Cycloplegics

Drug	% Efficiency
1% Atropine	100
1% Cyclopentolate	92
1% Tropicamide	80
5% Homatropine	54

TABLE 5-22 Ocular Side Effects of Cycloplegic Agents

Allergic contact dermatitis

Angle-closure glaucoma

Elevation of IOP with open angles

TABLE 5-23 Dose-related Systemic Side Effects of Atropine

Dose	Effects
0.5-2 mg (1-4 drops 1% solution)	Tachycardia
	Dry mouth
	Mydriasis/cycloplegia
5 mg (10 drops 1% solution)	The above plus:
		Speech disturbance
		Restlessness
		Confusion
		Hot, dry skin
		Decreased GI motility
		Urinary retention
>10 mg (over 20 drops 1% solution)	The above plus:
		Hyperexcitability
		Hallucination
		Coma
		Convulsion
		Death

TABLE 5-24 Side Effects Associated with Topical Cholinesterase Inhibitors

OCULAR
Ciliary body
	Accommodative spasm^*
	Anterior movement of the lens-iris diaphragm
	Breakdown of the blood-aqueous barrier
	Decreased anterior chamber depth
Conjunctiva
Drug-induced cicatrizing conjunctivitis
Hyperemia
Corneal toxicity
Increased intraocular pressure (paradoxical)
Lens
	Cataract formation^† (particularly anterior subcapsular cataracts)
Lids
	Allergic blepharoconjunctivitis
	Depigmentation of the skin (reversible)
	Twitching of orbicularis oculi
Pupil
	Iris cysts^*
	Miosis
Retina
	Increased peripheral vitreoretinal traction
SYSTEMIC
Cardiac
Arrhythmia
Bradycardia
Gastrointestinal^*
	Abdominal cramps
	Diarrhea
	Nausea
Headache
Pulmonary
	Bronchospasm
	Upper respiratory congestion
Lacrimation
Reduced plasma cholinesterase levels
	Reduced breakdown of succinylcholine, procaine, and tetracaine
Rhinorrhea
Urinary incontinence
^*More common in children. ^†More common in elderly.

TABLE 5-25 Characteristics of Accommodative Esotropia

1. Type of onset: Gradual and intermittent
2. Time of onset: Typically 2.5-4 y of age with a range from 4 mo to 7 y
3. Typically large angle of 25-40 degrees
4. Concomitant
5. Normal correspondence
6. Seldom have significant amblyopia
7. Refractive type:
	Normal AC/A
	Hyperopia between 2.00 and 7.00 D, with mean of 4.50 D
8. Nonrefractive type:
	High AC/A ratio (>6:1)
	Hyperopia between 0.50 and 4.50 D, with mean of 2.00 D
9. Can have a combination of refractive and nonrefractive components