The audiogram associated with sensory presbycusis is thought to show a sharply sloping high-frequency loss extending beyond the speech frequency range, and clinical evaluation reveals a slow, symmetric, and bilateral progression of hearing loss. Diagnosis
Hearing loss is classified as mild, moderate, severe or profound. Pure-tone audiometry for air conduction thresholds at 250, 500, 1000, 2000, 4000, 6000 and 8000 Hz is traditionally used to classify the degree of hearing loss in each ear. Normal hearing thresholds are considered to be 25 dB sensitivity, though it has been proposed that this threshold is too high, and that 15 dB (about half as loud) is more typical. Mild hearing loss is thresholds of 25–45 dB; moderate hearing loss is thresholds of 45–65 dB; severe hearing loss is thresholds of 65–85 dB; and profound hearing loss thresholds are greater than 85 dB. Tinnitus occurring in only one ear should prompt the clinician to initiate further evaluation for other etiologies. In addition, the presence of a pulse-synchronous rushing sound may require additional imaging to exclude vascular disorders. Otoscopy
An examination of the external ear canal and tympanic membrane performed by a medical doctor, otolaryngologist, or audiologist using an otoscope, a visual instrument inserted into the ear. This also allows some inspection of the middle ear through the translucent tympanic membrane. Tympanometry
A test administered by a medical doctor, otolaryngologist or audiologist of the tympanic membrane and middle ear function using a tympanometer, an air-pressure/sound wave instrument inserted into the ear canal.
In an open-label, fixed-dose, 2-week trial in eight males with schizophrenia, PET scans of dorsal striatal regions (caudate nucleus and putamen) and ventral striatum (nucleus accumbens) showed maximum occupancy (‡ 90%) at a 3-mg target dose of cariprazine following 14 d of treatment [40,41]. After 14 d of cariprazine 1.5 mg/d, receptor occupancy was 69% in the caudate nucleus, 69% in the nucleus accumbens, and 75% in the putamen". Pharmacokinetics
Cariprazine has high oral bioavailability and can cross the blood brain barrier easily in humans because it is lipophilic. In rats, the oral bioavailability was 52% (with a dose of 1 mg/kg).Cariprazine is metabolized primarily by the cytochrome P450 3A4 isoenzyme (CYP3A4), with some minor metabolism by CYP2D6. Cariprazine does not induce the production of CYP3A4 or CYP1A2 in the liver, and weakly, competitively inhibits CYP2D6 and CYP3A4. Research
Cariprazine is also potentially useful as an add-on therapy in major depressive disorder. It is being developed jointly by AbbVie and Gedeon Richter Plc, with AbbVie responsible for commercialization in the U.S., Canada, Japan, Taiwan and certain Latin American countries (including Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru and Venezuela). In February 2022 AbbVie requested FDA approval for adjunctive treatment for major depressive disorder. References
External links
"Cariprazine". Drug Information Portal. U.S. National Library of Medicine.