Page 1156 - Basic _ Clinical Pharmacology ( PDFDrive )

1142 SECTION X Special Topics

by 3.7% when used short term (2–28 weeks). It is unclear whether Dosage
improvements in ejection fraction are applicable to all patients with
heart failure, including those receiving the current standard of care As a dietary supplement, 30 mg/d of coenzyme Q10 is adequate
for heart failure management. More research is required to assess to replace low endogenous levels. For cardiac effects, typical dos-
the role of coenzyme Q10 in heart failure and its impact on disease ages are 100–600 mg/d given in two or three divided doses. These
severity, particularly with concomitant prescription medications. doses increase endogenous levels to 2–3 mcg/mL (normal for
healthy adults, 0.7–1 mcg/mL).
3. Ischemic heart disease—The effects of coenzyme Q10 on
coronary artery disease and chronic stable angina are modest but GLUCOSAMINE
appear promising. A theoretical basis for such benefit could be meta-
bolic protection of the ischemic myocardium by reducing proinflam- Glucosamine is found in human tissue, is a substrate for the pro-
matory markers (including interleukin-6 and C-reactive protein) duction of articular cartilage, and serves as a cartilage nutrient.
that contribute to oxidative stress. Double-blind, placebo-controlled Glucosamine is commercially derived from crabs and other crusta-
trials have suggested that coenzyme Q10 supplementation improved ceans. As a dietary supplement, glucosamine is primarily used for
a number of clinical measures in patients with a history of acute pain associated with knee osteoarthritis. Sulfate and hydrochloride
myocardial infarction (AMI). Improvements have been observed in forms are available, but recent research has shown the hydrochlo-
lipoprotein (a), high-density lipoprotein cholesterol, exercise toler- ride form to be ineffective.
ance, and time to development of ischemic changes on the electro-
cardiogram during stress tests. In addition, very small reductions in Pharmacologic Effects & Clinical Uses
cardiac deaths and rate of reinfarction in patients with previous AMI
have been reported (absolute risk reduction 1.5%). Endogenous glucosamine is used for the production of glycosami-
noglycans and other proteoglycans in articular cartilage. In osteo-
4. Prevention of statin-induced myopathy—Statins reduce arthritis, the rate of production of new cartilage is exceeded by
cholesterol by inhibiting the HMG-CoA reductase enzyme (see the rate of degradation of existing cartilage. Supplementation with
Chapter 35). This enzyme is also required for synthesis of coen- glucosamine is thought to increase the supply of the necessary
zyme Q10. Initiating statin therapy has been shown to reduce glycosaminoglycan building blocks, leading to better maintenance
endogenous coenzyme Q10 levels, which may block steps in and strengthening of existing cartilage.
muscle cell energy generation, possibly leading to statin-related Many clinical trials have been conducted on the effects of both
myopathy. It is unknown whether a reduction in intramuscular oral and intra-articular administration of glucosamine. Early stud-
coenzyme Q10 levels leads to statin myopathy or if the myopathy ies reported significant improvements in overall mobility, range of
causes cellular damage that reduces intramuscular coenzyme Q10 motion, and strength in patients with osteoarthritis. More recent
levels. A meta-analysis evaluating the effect of coenzyme Q10 on studies have reported mixed results, with both positive and nega-
statin-induced myopathy as measured by muscle pain and plasma tive outcomes. One of the largest and best-designed clinical trials,
creatine kinase activity found that coenzyme Q10 supplementa- which compared glucosamine, chondroitin sulfate, the combina-
tion (30 days to 3 months) did not demonstrate any benefit in tion, celecoxib, and placebo, found no benefit for glucosamine
reducing myopathy. More information is needed to determine therapy in mild to moderate disease. Unfortunately the investiga-
which patients, if any, with statin-related myopathy might benefit tors studied the glucosamine hydrochloride formulation, which
from coenzyme Q10 supplementation, especially as it relates to has been shown to be inferior to the sulfate formulation. The
the specific statin, the dose, and the duration of therapy. formulation of glucosamine appears to play a critical role with
regard to efficacy, and this may be a factor contributing to the
Adverse Effects variability observed across published studies. Research suggests
that use of a crystalline formulation of glucosamine sulfate leads
Coenzyme Q10 is well tolerated, rarely leading to any adverse to less pain, functional improvements in knee osteoarthritis, and
effects at doses as high as 3000 mg/d. In clinical trials, gastrointes- an improvement in joint space narrowing at 3 years. Currently,
tinal upset, including diarrhea, nausea, heartburn, and anorexia, national orthopedic and rheumatic societies do not recommend
has been reported with an incidence of less than 1%. Cases of glucosamine for knee osteoarthritis primarily because of formula-
maculopapular rash and thrombocytopenia have very rarely been tion variability and study heterogeneity. More research is needed
observed. Other rare adverse effects include irritability, dizziness, to better define the ideal glucosamine formulation and patient
and headache. populations that stand to benefit from glucosamine sulfate.

Drug Interactions Adverse Effects
Coenzyme Q10 shares a structural similarity with vitamin K, and Oral glucosamine sulfate is very well tolerated. In clinical trials,
an interaction has been observed between coenzyme Q10 and mild diarrhea, abdominal cramping, and nausea were occasionally
warfarin. Coenzyme Q10 supplements may decrease the effects reported. Cross-allergenicity in people with shellfish allergies is a
of warfarin therapy. This combination should be avoided or very potential concern; however, this is unlikely if the formulation has
carefully monitored. been properly manufactured and purified.