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Sir James Black (1924-2010): The Father Of Analytical Pharmacology

Sir James Black - David Levenson Rex Features.jpgHave you ever taken an over-the-counter heartburn relief remedy such as Tagamet, Zantac, or Pepcid? How about the beta-blocker atenolol (Tenormin) or metoprolol (Lopressor) for antihypertensive therapy, or the original less-selective beta-blocker propranolol (Inderal) for migraines, presentation anxiety, or stage fright?

If you answered “yes” to either question, you owe a debt of gratitude to Sir James Black, the Scottish physician who left us earlier this week at age 85. The best obituary I have seen memorializing Sir James comes from the UK Telegraph.

Black was called the father of analytical pharmacology and was said to have relieved more human suffering than thousands of doctors could have done in careers spent at the bedside. Certainly, no man on earth earned more for the international pharmaceutical industry. Read more »

*This blog post was originally published at Terra Sigillata*

Blood Pressure Medicine Cures Facial Deformity

There is an article (see reference below) in the June 12, 2008 issue of the New England Journal of Medicine (h/t Medpage Today) that shows some amazing regression of hemagiomas using propranolol.

Hemangiomas of infancy are the most common tumor of infancy. They typically appear within a few weeks after birth and peak within three months. Hemagiomas are more common in girls than boys, more common in white than other races, and more common in preemies. Most of these lesions are innocuous and regress without treatment. Up to 75% shrink to insignificance by the time the child reaches school age. However, 5-10% of the lesions that will ulcerate during the rapid growth phase in the first 6 months of life. Ulceration is the most common reason for referral to specialists, and may be associated with pain, bleeding, infection, disfigurement, and scarring.

This one series of photos shows the results:

Panel A shows the patient at 9 weeks of age, before treatment with propranolol, after 4 weeks of receiving systemic corticosteroids (at a dose of 3 mg per kilogram of body weight per day for 2 weeks and at a dose of 5 mg per kilogram per day for 2 weeks).

Panel B shows the patient at 10 weeks of age, 7 days after the initiation of propranolol treatment at a dose of 2 mg per kilogram per day while prednisolone treatment was tapered to 3 mg per kilogram per day. Spontaneous opening of the eye was possible because of a reduction in the size of the subcutaneous component of the hemangioma.

Panel C shows the patient at 6 months of age, while he was still receiving 2 mg of propranolol per kilogram per day. Systemic corticosteroids had been discontinued at 2 months of age. No subcutaneous component of the hemangioma was noted, and the cutaneous component had considerably faded. The child had no visual impairment.

Panel D shows the child at 9 months of age. The hemangioma had continued to improve, and the propranolol treatment was discontinued.

Christine Léauté-Labrèze, M.D., of Bordeaux Children’s Hospital, and colleagues used the drug to treat two infants with heart disease (one with cardiomyopathy, the another with increased cardiac output) who just happened to also have hemangiomas. Unexpectedly, the lesions began to fade. They then used propranolol on nine other children with hemangiomas with similar success.

Johns Hopkins researchers have developed a protocol for the beta-blocker as a first-line treatment for the skin disorder. Propranolol could replace or supplement steroids such as prednisone which are often used currently. The children receive 1 mg/kg of propranolol on the first day, divided over three doses, and 2 mg/kg — also divided in thirds — after that.

Prednisone use carries the side effects of growth retardation, elevated blood sugars, and reduced resistance to infection.

Propranolol has side effects that include hypotension and hypoglycemia, but these are short-lived.

So far, Dr. Cohen and Katherine Puttgen, M.D., also at Johns Hopkins, say they have treated 20 patients with propranolol. Working with cardiologists, they decided to hospitalize the infants for the first two days of treatment to monitor for possible side effects such as hypotension or hypoglycemia. (They have seen none so far.)

Dr. Léauté-Labrèze, and colleagues reported that they are applying for a patent for the use of beta-­blockers in infantile capillary hemangiomas.


Propranolol for severe hemangiomas of infancy; New Engl J Med 2008; 358: 2649-2651; Léauté-Labrèze, C et al

Ulcerated Hemangiomas of Infancy: Risk Factors and Management Strategies; eLiterature Review (John Hopkins Medicine) , Oct 2007, Vol 1, No 4; Bernard A. Cohen, MD, Susan Matra Rabizadeh, MD, MBA, Mark Lebwohl, MD, and Elizabeth Sloand, PhD, CRNP

Related Blog Posts

Vascular Birthmarks (July 15, 2007)

Early Surgical Intervention for Proliferating Hemagiomas of the Scalp — An Article Review (Sept 1, 2008)

**This post was originally published at the Suture For A Living blog**

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