Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine (in descending order of inhibition) due to their effects on the CYP3A4 enzyme.Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations. Mechanism of action
Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and T-type calcium channels, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity). It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant topiramate). It is also known to modulate GABAergic and glutamatergic neurotransmission. Pharmacokinetics
Absorption
Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Bioavailability is close to 100% and food has no effect on the bioavailability of zonisamide but may affect the rate of absorption. Metabolism
Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5, to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring. History
Zonisamide was discovered by Uno and colleagues in 1972 and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran in Japan. It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai Co., Ltd. in 2004.
Crackles are much more common during the inspiratory than the expiratory phase of breathing, but they may be heard during the expiratory phase. Crackles are often associated with inflammation or infection of the small bronchi, bronchioles, and alveoli. Crackles that do not clear after a cough may indicate pulmonary edema or fluid in the alveoli due to heart failure, pulmonary fibrosis, or acute respiratory distress syndrome. Crackles that partially clear or change after coughing may indicate bronchiectasis. Crackles are often described as fine, medium, and coarse. They can also be characterized as to their timing: fine crackles are usually late-inspiratory, whereas coarse crackles are early inspiratory. Fine crackles are soft, high-pitched, and very brief. This sound can be simulated by rolling a strand of hair between ones fingers near the ears, or by moistening ones thumb and index finger and separating them near the ears. Their presence usually indicates an interstitial process, such as pulmonary fibrosis or congestive heart failure. The sounds from interstitial pulmonary fibrosis have been described as sounding like opening a Velcro fastener. Coarse crackles are somewhat louder, lower in pitch, and last longer than fine crackles. Their presence usually indicates an airway disease, such as bronchiectasis.They can also be described as unilateral or bilateral, as well as dry or moist/wet. See also
Bronchophony
Egophony
Consumption
Whooping cough
Croup
Pertussis toxin
Allergic asthma
Respiratory sounds

References
External links

Audio Breath Sounds - Multiple case studies with audio files of lung sounds. R.A.L.E. Repository - sound files of breath sounds