Males with this condition are born with ambiguous genitalia and a severely underdeveloped or even absent prostate gland. In addition, at the time of puberty, such males develop normal musculature, voice deepening, and libido, but have reduced facial hair, a female pattern of body hair (i.e., largely restricted to the pubic triangle and underarms), no incidence of male pattern hair loss, and no prostate enlargement or incidence of prostate cancer. They also notably do not develop gynecomastia as a consequence of their condition. Functional selectivity
An animal study found that two different kinds of androgen response elements could differentially respond to testosterone and DHT upon activation of the AR. Whether this is involved in the differences in the ratios of anabolic-to-myotrophic effect of different AAS is unknown however. Non-genomic mechanisms
Testosterone signals not only through the nuclear AR, but also through mARs, including ZIP9 and GPRC6A. It has been proposed that differential signaling through mARs may be involved in the dissociation of the anabolic and androgenic effects of AAS. Indeed, DHT has less than 1% of the affinity of testosterone for ZIP9, and the synthetic AAS metribolone and mibolerone are ineffective competitors for the receptor similarly. This indicates that AAS do show differential interactions with the AR and mARs. However, women with complete androgen insensitivity syndrome (CAIS), who have a 46,XY ("male") genotype and testes but a defect in the AR such that it is non-functional, are a challenge to this notion.
US prescribing recommendations warn against the concurrent use of alcohol and/or other central nervous system depressants, but to date there have been no studies to assess the effects of azelastine nasal spray on the CNS in humans. More recent studies have shown similar degrees of somnolence (approx. 2%) compared with placebo treatment. The most common side effect is a bitter taste (about 20% of people). Due to this, the manufacturer has produced another formulation of azelastine with sucralose. The problem of bitter taste may also be reduced by correct application of the nasal spray (i.e. slightly tipping the head forward and not inhaling the medication too deeply), or alternatively using the azelastine/sucralose formulation.In addition, anosmia (loss in the ability to smell) can occur with nasal spray antihistamines (including both formulations of azelastine). Pharmacology
Pharmacodynamics
Azelastine has a triple mode of action:
Anti-histamine effect,
Mast-cell stabilizing effect and
Anti-inflammatory effect. Pharmacokinetics
The systemic bioavailability of azelastine is approximately 40% when administered intranasally. Maximum plasma concentrations (Cmax) are observed within 2–3 hours. The elimination half life, steady-state volume of distribution and plasma clearance are 22 h, 14.5 L/kg and 0.5 L/h/kg respectively (based on intravenous and oral administration data). Approximately 75% of an oral dose is excreted in feces. Pharmacokinetics of orally administered azelastine are not affected by age, gender or hepatic impairment. Metabolism
Azelastine is oxidatively metabolized by the cytochrome P450 family into its active metabolite, desmethylazelastine, and two inactive carboxylic acid metabolites. Chemical properties
The chemical nomenclature of azelastine is (±)-1-(2H)-phthalazinone, 4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-monohydrochloride. It is white, almost odorless with a bitter taste. References
External links
"Azelastine".