International journal of pharmaceutical compounding
W O U N D C A R E
Wound Care of a
Diabetic Foot Ulcer
Tom Wynn, RPh
narrowing of the blood vessels in the feet and legs. Poor circu-lation in combination with the high-pressure areas on the bot-
Chad Thompson, PharmD
tom of the foot can lead to callous formation in the patient
who has diabetes. If not addressed, the callous can lead to an
ulcer. The ﬁnal stage can be gangrene of the toes and possibleamputation if not treated.1 Thus, treatment of wounds in the
patient with diabetes must address both rapid granulation and
It has been clearly demonstrated that wound care is one of
increased circulation. Circulation can be maintained using a
the foremost concerns of patients with diabetes. Poor wound
topical nifedipine preparation.14 In addition, the use of pen-
care can lead to the loss of toes, feet, ﬁngers and, in some cas-
toxifylline enhances vascular permeability, which increases cir-
es, a limb.1 A variety of therapies exist to help ensure the
culation and increases penetration of medication and nutrients
proper healing of a wound, to include surgeries using vascular
reconstruction techniques to create new arterial pathways that
Finally, maintaining proper nutrition is very important. Not
can increase blood ﬂow to the wound.2 In addition, the use of
only is proper glucose control important for wound healing
growth factors such as keratinocyte-2 and interleukin-6 is be-
but the intake of adequate amounts of vitamins and minerals
ing studied.3 These therapies appear promising but they are
also plays a key role. It has been documented17 that deﬁcien-
expensive; therefore, many patients are left to use the few
cies in zinc, vitamin C and other nutrients may inﬂuence
commercially available topical gels such as Regranex (0.01%
becaplermin) to achieve some relief.
Case reports and articles4-15 dating back to 1989 have sug-
gested alternatives to these treatments. These alternatives in-
On June 23, 2003, our pharmacy consulted with a 65-year-
clude compounded topical products, which can consist of
old woman who had a wound on her right foot. The wound
phenytoin, misoprostol, metronidazole, or some combination
was located on the pad underneath the big toe. It had a large
of the three, and nifedipine. These case reports tend to show
callous surrounding a deep wound that was 4 cm long and 2 cm
positive outcomes with the use of these products with little to
wide. The patient stated that she had little success using com-
no adverse effects. The effectiveness of these topically applied
mercially available products for wound care over the past year.
medications can be traced to their mechanisms of action:
After discussing possible alternatives with the patient and her
promotes granulation in a wound while providing
physician, a decision was made to compound a wound care gel
antimicrobial effects and counteracting inﬂammation.4
formulation for the treatment of this patient’s wound. Prior to
is a synthetic prostaglandin that accelerates
the application of any gel, the foot was inspected for venous
return and measurements of the wound were taken.
exerts an antimicrobial effect to assist in
Using a formulation from the International Journal of Phar-
)8 as a guide, two preparations
blocks the calcium inﬂux into smooth muscles,
were compounded. The ﬁrst was a preparation of phenytoin
thereby decreasing the vascular tone, which in turn increas-
3% and misoprostol 0.0024% gel, which was used for wound
healing. The patient was instructed to cover the wound twice
In the treatment of a diabetic foot ulcer another problem
daily with approximately 0.2 mL of this preparation. The sec-
must be considered: circulation. Over time, circulation is re-
ond preparation was nifedipine 10% in a Pluronic lecithin
duced in the patient with diabetes due to the hardening and
organogel (PLO) gel 20%. The patient was instructed to apply
International Journal of
Pharmaceutical Compounding 265
W O U N D C A R E
Week 10 – Obvious closing of skin around
Week 14 – Obvious narrowing of wound.
Week 17 – Skin completely closed and
0.6 mL twice daily around the wound and callous and up the
foot to increase circulation to the wound area. The patient wasinstructed to continue saline rinses as before. After rinsing
Wounds in patients with diabetes can be difficult to control.
with saline, the patient applied nifedipine gel to the foot. It
Treatment of foot ulcers tends to follow a three-step process:
was applied around the callous of the wound and up the foot to
(1) removal of the callous, (2) eradication of any infection and
the ankle using a ﬁnger cot, glove or sterile swab. Each appli-
(3) reduction of weight-bearing forces. This speciﬁc treatment
cation consisted of 0.6 to 1 mL of the nifedipine gel. Next,
plan was to shrink the callous, since the wound had no appar-
the phenytoin/misoprostol mixture was applied directly to the
ent infection at the time. It was discovered with this patient
wound. Finally, the wound was covered with sterile gauze.
that as the callous shrank the wound size almost seemed to get
This process was repeated twice daily.
larger. This was most likely due to the physician cutting away
After two weeks of application, noticeable progress was seen.
at the dead skin and revealing more wound underneath the cal-
The callous began to shrink and the wound appeared shallow-
lous. Cutting of the wound may interfere with granulation. As
er. The entire foot appeared healthier, with better color and
seen with this patient and other case reports,16 healing is opti-
good venous return. Progress continued, and after 8 weeks the
mized when minimal cutting is done. The increase of blood
healing began to increase dramatically. During the next 4
ﬂow to the wound appeared to play a large part in the success
weeks the ﬁnal closure of the wound occurred. Total time of
of this patient’s therapy. The patient had failed on former
healing of the wound was 17 weeks. Photos included with this
treatments, possibly because circulation was not addressed.
article were taken on week 10, week 14 and week 17 of the
Once circulation was returned to the foot and the callous was
under control, the wound began to heal rapidly.
The only adverse effects reported during the course of
therapy were a slight headache and an increase in peripheral
Case Reports: Their Impact
Lisa D. Ashworth, RPh
■ Transdermal Methimazole for the Treatment of Feline
International Journal of Pharmaceutical Compounding
■ Flavoring Solves Compliance Problem in Pediatric
One case report may not have significant impact, but when
■ Compounded PLO Successful in Early Treatment of
you compile reports for 7 years, you’ve got significant data doc-
umenting the validity of individualized therapy.
■ Oral Amphotericin B for the Treatment of Intestinal
The International Journal of Pharmaceutical Compounding
) has compiled and centralized its case reports. These
■ Natural Progesterone Treats Infertility
valuable resources of compounded therapy are now available
■ Ketoprofen 5% and Gabapentin 5% Gel for Neuropathy
on IJPC’s Website (www.ijpc.com/casereports). There are more
■ Cimetidine and 2-deoxy-d-Glucose for Treatment of
than 140 human case reports and 20 animal case reports.
Below is a short list presenting some of the topics and case
Thank you to all the pharmacists and physicians who have
reports you can find on IJPC’s Website.
worked with IJPC
over the years to publish this valuable data.
■ Ketoconazole 2% and Ibuprofen 2% in Dimethyl
If you would like assistance with publishing case reports,
Sulfoxide, USP, Topical Nail Solution for Onychomycosis
please contact Lisa D. Ashworth, RPh, 972-471-2805. E-mail:firstname.lastname@example.org
W O U N D C A R E
neuropathy. The headache was later determined to be possibly
8. Glasnapp A. Basics of compounding for Raynaud’s disease. IJPC
aggravated or caused altogether by a change in the patient’s
9. Meece J. Five compounds for treating diabetes-related conditions. IJPC
lanoxin dose; the increased neuropathy is harder to explain.
The neuropathy may have increased because the increased
10. Kincaid MR. Options in wound care. IJPC
2002; 6(2): 92-95.
blood ﬂow in the leg had awakened the nerves, allowing the
11. Todd G, Todd L. Case report: Nifedipine in Pluronic lecithin organogel
pain to be felt. However, no literature can be found to substan-
improves circulation in the feet of a diabetic patient. RxTriad
12. Blais LR, Blais B, Sundel RP. Case report: Nifedipine oral solution for the
Due to the effectiveness of wound gels in healing diabetic
treatment of compromised peripheral vascular circulation in a pediatric
foot ulcers, it has become a promising therapeutic alternative
July 2001: 1.
that we recommend to patients with refractory foot ulcers.
13. Yarzab R, Graham D. Case report: Nifedipine in PLO 40 mg/mL for
gangrene of the foot. RxTriad
October 2000: 2.
14. Torsiello MJ, Kopacki MH. Transdermal nifedipine for wound healing:
Case reports. IJPC
2000; 4(5): 356-358.
1. Watkins PJ. ABC of diabetes. BMJ
2003; 216: 977-979.
15. Jones M. Chronic neuropathic pain: Pharmacological interventions in
2. Gibbons GW. Lower extremity bypass in patients with diabetic foot
the new millennium—a theory of efficacy. IJPC
2000; 4(1): 6-15.
ulcers. Surg Clin North Am
2003; 83(3): 659-669.
16. Israel A. Topical gel for the treatment of refractory leg ulcer. IJPC
3. Bennett SP, Griffiths BDF, Schor AM et al. Growth factors in the treat-
ment of diabetic foot ulcers. Br J Surg
2003; 90(2): 133-146.
17. Rojas AI, Phillips TJ. Patients with chronic leg ulcers show diminished
4. Kincaid MR. Options in wound care. IJPC
2002; 6(2): 92-95.
levels of vitamins A and E, carotenes, and zinc. Dermatol Surg
5. Talas G, Brown RA, McGrouther DA. Role of phenytoin in wound heal-
ing—a wound pharmacology perspective. Biochem Pharmacol
6. Anstead GM, Hart LM, Sunahara JF et al. Phenytoin in wound healing.
Address correspondence to: Tom Wynn, RPh, Tri-State
1996; 30(7-8): 768-775.
Compounding Pharmacy, 7715 Beechmont Avenue, Cincin-
7. Rhodes RS, Heyneman CA, Culbertson VL et al. Topical phenytoin
nati, OH 45255. E-mail: email@example.com
treatment of stage II decubitus ulcers in the elderly. Ann Pharmacother
2001; 35(6): 675-681.
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International Journal of
Pharmaceutical Compounding 267
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In the last chapter we considered parameter estimation andconfidence intervals. We now look at the other primary aspect ofinferential statistics, hypothesis testing. In statistics, a hypothesis is a claim or statement about aparameter of a population. Often the hypothesis will have to do with the values of parameters. Rare Event Rule for Inferential StatisticsWe make inferences using t