August
11, 2003
Question:
I’m reading a book of yours. In it, you say that narcotics could
increase heart rate and prevent patients from reaching their therapeutic
dose of thyroid medication. Is this true for Ultram, which I take daily?
I also take 2.5 grains (90 mg) of Armour and feel that I should increase
it further. I don’t because my heart rate is 90-to-105 in the mornings.
Could the Ultram and Armour be interacting to cause the rapid heart rate?
I’m frustrated, depressed, and feel hopeless because I haven’t had
any improvement yet. I have Hashimoto's thyroiditis and fibromyalgia and
haven’t been able to work for six years. All other possible health
problems have been ruled out. I’ve eaten a good diet and taken tons of
supplements for years, although I can’t exercise much. Thanks for
answering my questions.
Dr. Lowe:
Yes, Ultram can increase one’s heart rate. It may also interact with
thyroid hormone to cause a rapid heart rate so that the patient isn’t able
to reach an effective dose of the hormone.
Ultram is an opioid like morphine, but it is 5-to-10 times less effective
than morphine in reducing pain.[8]
It is less effective than morphine probably because it binds less readily to
opiate receptors than does morphine. Ultram’s advantage over morphine is
that it doesn’t cause life-risking respiratory depression.[1]
Ultram has few adverse effects. The most common ones I’ve seen listed
in the research literature are dizziness, vomiting, nausea, and dry mouth.[2][4]
Some patients have had seizures and convulsions, especially those who also
take tricyclic antidepressants, other tricyclic compounds, and selective
serotonin reuptake inhibitors.[10]
The pharmacy websites I’ve looked at list rapid heart rate among the
potential "serious side effects" of Ultram.[11][12][13][14]
But for reasons I give below, I’m surprised that rapid heart rate isn't
more prominent among adverse effects reported in the research literature.
Effects of Ultram on the heart.
Interestingly, reports of the effects of Ultram on the heart rate are mixed. In anesthesized rabbits,
small doses of Ultram slightly increased the heart rate.[4]
In one study, when doctors gave children Ultram for pain following surgery,
their heart rates didn’t change.[1]
In contrast, when patients took Ultram following major orthopedic surgery,
their heart rates increased by a maximum of 17%.[5]
In another study, though, Ultram slowed the heart rates of rats.[3]
There is little point in citing other studies. My quick review in PubMed
suggests that other studies are consistent with the ones I just cited; they
are mixed, with some reporting no change in heart rate, others reporting an
increase, and others reporting a decrease.
Ultram increases the norepinephrine level.
As I said
above, the mixed results of studies of Ultram’s effect on heart rate
surprise me. I say this because of the way Ultram works to relieve pain.
The chemical structure of Ultram is similar to that of antidepressants
that increase the levels of serotonin[7]
(such as Proazc) and norepinephrine (such as desipramine).[3][6][9][7]
By increasing the levels of these nerve-transmitting chemicals, Ultram
enhances mood. Some researchers speculate that Ultram reduces pain mainly
through this mood enhancing effect which decreases the emotional component
of pain.
It is the increase in the norepinephrine level that’s of most concern
regarding patients’ heart rates. I would expect an increase in
norepinephrine to raise the heart rate. Researchers report that Ultram
increases the force of contraction of the heart muscle,[4]
but I haven’t found studies reporting that the increased norepinephrine
level increases the Ultram-user’s heart rate.
On principal, however, the patient taking Ultram should be cautious when
she also takes thyroid hormone. Thyroid hormone increases gene transcription
for the proteins (called beta-adrenergic receptors) that norepinephrine
binds to on cell membranes. When norepinephrine binds to the receptors,
metabolic processes accelerate. The acceleration sets off excitatory
physiological reactions, such as increased heart rate. When a patient
increases the number of these receptors by taking thyroid hormone, and she
increases her norepinephrine level by using Ultram, she may get a combined
effect—an increase in the force and rate of contraction of the heart.
Mood effect of Ultram.
That Ultram works partly by improving mood raises another issue that I’m
concerned about with you. You wrote that you’re depressed and feel
hopeless. Despite these feelings, you may be getting some antidepressant
effect from Ultram. If that’s true, and you reduce your dosage of Ultram
too quickly, or if you stop it abruptly, your depression may temporarily
worsen. We call this "rebound" depression.
To avoid rebound depression, it will be prudent for you to reduce your
dosage or stop Ultram only under two conditions: first, that you’re guided
by a physician who knows how Ultram works and is experienced in its use; and
second, you have immediate access to a mental health professional
experienced at helping patients get through severe episodes of depression.
Summary.
Ultram may have increased your norepinephrine level, and Armour has probably
increased the density of beta-adrenergic receptors on your cell membranes.
These two effects of the medications may be interacting to cause your rapid
heart rate. Increasing your Armour dosage may speed your heart rate even
more by further increase the density of beta-adrenergic receptors on your
cell membranes. If you intend to increase your Armour dosage, it’s
important that you first talk with your doctor about possibly decreasing
your Ultram dosage or stopping it altogether. But I can’t overemphasize
the importance of you doing this only with the guidance and support
of your doctor and possibly a mental health professional.
References
[1] Schaffer J, et al.: Nalbuphine
and tramadol for the control of postoperative pain in children. Anaesthesist,
35(7):408-413, 1986.
[2] Fu YP, et al.: Epidural tramadol
for postoperative pain relief. Ma Zui Xue Za Zhi, 29(3):648-652,
1991.
[3] Nagaoka E, et al.: Tramadol has
no effect on cortical renal blood flow--despite increased serum
catecholamine levels--in anesthetized rats: implications for analgesia in
renal insufficiency. Anesth. Analg., 2002 Mar;94(3):619-625, 2002.
[4] Muller, B. and Wilsmann, K.:
Cardiac and hemodynamic effects of the centrally acting analgesics tramadol
and pentazocine in anaesthetized rabbits and isolated guinea-pig atria and
papillary muscles. Arzneimittelforschung, 34(4):430-433, 1984.
[5] Hopkins D, et al.: Comparison of
tramadol and morphine via subcutaneous PCA following major orthopaedic
surgery. Can J Anaesth., 45(5 Pt 1):435-442, 1998.
[6] Rojas-Corrales MO, et al.:
Antidepressant-like effects of tramadol and other central analgesics with
activity on monoamines reuptake, in helpless rats. Life Sci.,
72(2):143-152, 2002.
[7] Hopwood, S.E., et al.: Effects of
chronic tramadol on pre- and post-synaptic measures of monoamine function.
J.
Psychopharmacol., 15(3):147-153, 2001.
[8] Franceschini, D, et al.: Effect
of acute and chronic tramadol on [3H]-norepinephrine-uptake in rat cortical
synaptosomes. Prog. Neuropsychopharmacol. Biol. Psychiatry,
23(3):485-496, 1999.
[9] Reimann, W. and Hennies, H.H.:
Inhibition of spinal noradrenaline uptake in rats by the centrally acting
analgesic tramadol. Biochem. Pharmacol., 47(12):2289-2293, 1994.
[10]
Gibson, T.: Executive Director, Ortho-McNeil Pharmaceutical.
http://www.fda.gov/medwatch/safety/ultram.htm.
[11]
http://ultram.phentermine-rx.net/
Question:
Are you aware of the fibromyalgia drug called