Therapeutic Drugs
10 Myths and Misperceptions About Therapeutic Drugs

Rethinking these controversial issues can help you steer clear of them and provide more effective care to your patients.

by Leland Carr, O.D., Portland, Ore.

In Greek mythology, a trio of bewitching maidens called the Sirens sat on a rocky shore and played enchanting music that lured mariners to their destruction.

Optometrists cling to similar myths, in a way. Like the ancient mariners, sometimes optometrists pay heed to an alluring—although misguided—voice. The "myths" we have about therapeutic drugs, while probably not destructive, can prevent us from practicing at our best.

We do it from good intentions, though. We tend to be conservative, placing great importance on protecting our patients. We emphasize safety, economics and efficacy in prescribing pharmaceuticals. While safety is good, sometimes we've gone overboard and adopted unnecessary fears and misleading myths regarding TPA practice.

Here are 10 commonly held misperceptions about using ophthalmic medications, and why you might want to rethink them.

1. Phenylephrine dilation poses a risk to hypertensives.
Not true. Clinical experience at Pacific University, the experiences of many clinicians internationally, and reports and comments by such notables as optometrist Jimmy Bartlett all reveal something quite different.

Specifically, even poorly controlled and non-compliant hypertensives experience no significant elevation in blood pressure or changes in pulse rate after instilling one or two drops of 2.5 percent phenylephrine in each eye. I've even used it safely when evaluating disc swelling in two patients in the midst of malignant hypertensive crises.

Phenylephrine is a great dilator when used to augment tropicamide, and we need not be afraid to use it. (However, you shouldn't use the 10 percent concentration in hypertensives.)

Even in cases where doctors have used 2.5 percent phenylephrine—either intentionally or inadvertently—to dilate patients taking tricyclic or MAO-inhibiting anti-depressants, I've been unable to document any ill effects.

2. We should not dilate pregnant patients.
The many hormonal changes associated with pregnancy (estrogens, progesterone, prolactin, growth hormone, melanocyte-stimulating hormone, adrenocorticotropic hormone, etc.) directly affect all areas and systems of the mother's body, including the eye and neuro-ocular tissues. These hormones—designed to influence blood and fluids, and to grow tissues and vessels for the developing fetus—can affect pre-existing conditions. Diabetic or hypertensive retinopathy, malignant melanoma, meningioma, central serous chorioretinopathy, recurrent neuritis and pseudotumor cerebri are a few of the diseases affected by pregnancy.

While all patients deserve the right to refuse dilation, it's good clinical practice to advocate dilated assessment, even during pregnancy. Millions of women worldwide have been safely dilated using 1 percent tropicamide and 2.5 percent phenylephrine without impact on themselves or their developing babies. So, we can be comfortable in recommending a truly comprehensive exam. I especially urge diabetics who become pregnant to receive thorough dilated retinal checks at least once each trimester. The blood vessel growth factors can cause diabetic retinopathy to shift into explosive growth and leakage.

3. We can't prescribe approved pharmaceuticals for off-label uses.
Another myth. However, the pharmacologic actions of the drug must make sense in treating the patient's condition. And, you must have reputable documentation to that effect. For example, if prostaglandins are known to contribute to cystoid macular edema, and ibuprofen has been shown to inhibit prostaglandin synthesis and let-down, then you can logically prescribe oral non-steroidal anti- inflammatories (NSAIDS) to treat cystoid macular edema. Be able to reference a reputable hardcover or web resource that validates or endorses the off-label use that you're planning.

4. NSAIDS don't exacerbate epithelial herpes simplex keratitis.
Despite frequent claims to the contrary, topical non-steroidals can make corneal surface simplex worse. I've witnessed simplex aggravation in nearly a dozen cases in which doctors initially treated nondescript unilateral red eyes with NSAIDS.

Typically, they've done this in combination with topical antibacterials. I've noticed that both diclofenac sodium and ketorolac can diminish the cornea's ability to hold viral infections in check. Obviously the antibacterial offers no help. Dendrites may form or multiply, and inflammatory stromal reactions typically arise.

Like topical steroids, NSAIDS provide good pain relief and controlled modulation of the inflammatory response in certain cases of simplex. The best practice, though, is to co-administer a topical antiviral to avoid enhancing the infection.

5. Never use topical steroids to treat herpes simplex eye disease.
Unprotected corneas and anterior chambers definitely can become "really hot" if you apply steroids when simplex is present. However, topical antivirals shield the cornea, and oral antivirals protect the anterior uveal tissues. In intense stromal keratitis or intense non-quieting trabeculoiridocyclitis, you need to modulate the eye's inflammatory process to preserve the clarity, structural soundness and function of the tissues. Prescribe steroids to avoid scarring, synechiae, glaucoma, cataracts and pupil destruction. However, in cases of simplex you should combine them with potent anti-virals.

6. Topical fluoroquinolones are non-toxic or minimally toxic.
To get an effective antibacterial kill, a massive loading-dose of these agents is vital. This means that keratoconjunctivitis or ulcer patients should use many drops during the first several hours of treatment. A minimum of drops at 10-15 minute intervals over 2-3 hours is advised to build to bactericidal concentration. This will indeed cause toxicity.

If you don't notice high levels of sodium fluorescein (+) staining at the 24- or 48-hour follow-ups of patients under treatment with fluoroquinolones, then they are not using their drops often enough.

7. Fluoroquinolones replaced fortified antibiotics for corneal ulcers.
Fluoroquinolones have significantly simplified our management of bacterial keratitis. Still, we should not think of them as a cure-all for corneal ulcers. There are cases in which fluoroquinolones just won't work. I have personally managed or consulted on at least a dozen cases that involved fluoroquinolone-resistant corneal ulcers. In each case, scrapings, cultures and sensitivities confirmed what we already knew clinically: The bugs were resisting the drugs. Culprits in these episodes included Strep. pneumoniae, Pseudomonas aeruginosa and Staph. epidermidis.

While ofloxacin, and especially ciprofloxacin, are often effective, we must remain vigilant, especially since fluoroquinolone resistance appears to be increasing. Many cases still need fortified antibacterial eye drops. Timely referral to an anterior segment or ocular infectious disease specialist is also important, since these cases can become complicated.

Also remember that fortifying tobramycin eye drops with tobramycin and vancomycin intravenous powders may be the perfect key to preventing a perforating corneal ulcer and endophthalmitis.

8. Over-prescribing has boosted drug-resistant bacterial strains.
The real culprit in drug resistance is not the topical Rx. Rather, it's the overuse of systemic drugs that has increased resistant pathogens.

Unnecessary use of oral Cipro (ciprofloxacin) and oral and injectable Floxin (ofloxacin) have selected for microbes that can now resist Ciloxan (ciprofloxacin) and Ocuflox (ofloxacin), respectively. In short, don't rush to use big-gun oral antibiotics when not necessary. Use potent systemic agents only on a true "when-needed" basis.

9. Occlusion doesn't impact systemic absorption of eye drops.
Punctal occlusion won't eliminate systemic transit of a topical eye drop. However, it can prolong drug contact with the ocular surface, increase penetration through the cornea and result in higher-level buildup within the aqueous. This is true for either digital occlusion (using the fingertips) or the use of collagen or silicone plugs. An alternative method: Instruct the patient to keep the eyes closed for five minutes after instillation.

An additional advantage to punctal occlusion: Any of the drug that assimilates systemically does so gradually and over a longer period. This results in a "zero bolus" impact and a diluted effect on the body.

I cannot overstate my appreciation of punctal occlusion in treating nasty infections or inflammations of the cornea, conjunctiva or anterior segment. This is a good technique for boosting the therapeutic impact in these areas of the eye while reducing the systemic effects.

10. You cannot test for bilateral afferent pupillary defects (APD).
While this isn't a drug myth, it is an ocular disease myth and deserves exposure. Recall that a swinging-flashlight test relies on a unilateral pathway problem where unequal light stimulus (afferent loop) reaches the mid-brain centers that trigger pupil constriction within both eyes when light enters one of them.

In a positive test, one eye appears to dilate as light is directed into it. This is because the consensual response (light into opposite eye) is a stronger constriction than what you see during the direct response (light into the eye directly observed). A swinging-flashlight test works because the afferent signal for the two eyes is asymmetric, and this is the situation when one pathway is diseased. So, bilateral anterior pathway disorders (both optic nerves inflamed, for example) would produce symmetrically poor afferent signals, cancel each other out and fail to reveal a positive APD. We would see poor direct responses and poor consensual responses in each eye.

Still, there is a useful test for confirming bilateral afferent problems. Assuming that both iris sphincters are intact and responsive, and that both third nerves are conducting motor (efferent) signals to those sphincters, the patient with bilateral optic nerve disease will demonstrate a brisk and normal bilateral pupil constriction upon near point stimulation. This will be in stark contrast to the bilateral pupil sluggishness you'll see when you shine a light into either eye alone, or into both eyes together. Often referred to as a "dissociated pupil response" (strong to near; poor to light), you'll also observe this in cases of neuro-syphilis with Argyll Robertson pupils. In those cases, however, the pupils are notoriously abnormal in other ways.

You may suspect bilateral optic nerve disease if the swinging-flashlight test reveals all these findings: Pupils seem relatively normal in size and shape; the patient's brightness sense is down; color sensitivity is bilaterally poor; acuity is down or "not quite right" in both eyes; and optic disc colorations are suspicious. But don't forget to look for a brisk near response in two eyes that fail to respond normally to light.

Our conservatism in using therapeutic pharmaceutical agents certainly adds to safety, but better that we continue to investigate controversial issues rather than cling to timeworn "myths." After all, in Homer's The Odyssey, Odysseus and his men managed to pass by the Sirens safely. Even in mythology, there's a way to overcome myths.

Dr. Carr is the dean and clinical professor at Pacific University College of Optometry.