As azole antifungals all act at the same point in the sterol pathway, resistant isolates are normally cross-resistant to all members of the azole family. Antihormonal activity
As an antiandrogen, ketoconazole operates through at least two mechanisms of action. First, and most notably, high oral doses of ketoconazole (e.g. 40 mg three times per day) block both testicular and adrenal androgen biosynthesis, leading to a reduction in circulating testosterone levels. It produces this effect through inhibition of 17α-hydroxylase and 17,20-lyase, which are involved in the synthesis and degradation of steroids, including the precursors of testosterone. Due to its efficacy at reducing systemic androgen levels, ketoconazole has been used with some success as a treatment for androgen-dependent prostate cancer. Second, ketoconazole is an androgen receptor antagonist, competing with androgens such as testosterone and dihydrotestosterone (DHT) for binding to the androgen receptor. This effect is thought to be quite weak however, even with high oral doses of ketoconazole.Ketoconazole, along with miconazole, has been found to act as an antagonist of the glucocorticoid receptor.Ketoconazole is a racemic mixture consisting of cis-(2S,4R)-(−) and cis-(2R,4S)-(+) enantiomers. The cis-(2S,4R) isomer was more potent in inhibiting progesterone 17α,20-lyase than its enantiomer (IC50 values of 0.05 and 2.38 μM, respectively) and in inhibiting 11β-hydroxylase (IC50 values of 0.152 and 0.608 μM, respectively). Both isomers were relatively weak inhibitors of human placental aromatase.Oral ketoconazole has been used clinically as a steroidogenesis inhibitor in men, women, and children at dosages of 200 to 1,200 mg/day.
Antacids and simple analgesics do not usually relieve the pain. If chest discomfort (of whatever site) is precipitated by exertion, relieved by rest, and relieved by glyceryl trinitrate, the likelihood of angina is increased.In angina patients momentarily not feeling any chest pain, an electrocardiogram (ECG) is typically normal unless there have been other cardiac problems in the past. During periods of pain, depression, or elevation of the ST segment may be observed. To elicit these changes, an exercise ECG test ("treadmill test") may be performed, during which the patient exercises to his/her maximum ability before fatigue, breathlessness, or pain intervenes; if characteristic ECG changes are documented (typically more than 1 mm of flat or downsloping ST depression), the test is considered diagnostic for angina. Even constant monitoring of the blood pressure and the pulse rate can lead to some conclusions regarding angina. The exercise test is also useful in looking for other markers of myocardial ischemia: blood pressure response (or lack thereof, in particular, a drop in systolic blood pressure), dysrhythmia, and chronotropic response. Other alternatives to a standard exercise test include a thallium scintigram or sestamibi scintigram (in patients unable to exercise enough for the treadmill tests, e.g., due to asthma or arthritis or in whom the ECG is too abnormal at rest) or stress echocardiography.