29 - H. Other drugs

H. Other drugs:

© SPMM Course be supplemented with oral risperidone for 3 weeks. Requires refrigeration as it is granular, not ester-based. o Olanzapine depot is a crystalline salt composed of olanzapine and pamoic acid with a half-life of 30 days and steady state reached at 12 weeks. Oral supplementation of olanzapine is not required.

G. Antidementia drugs:  Tacrine is poorly absorbed with short t1/2. It is metabolized by CYP 1A2 hepatic enzymes.  Donepezil has an oral bioavailability around 100%, with linear pharmacokinetics. The drug reaches steady state in about two weeks. Its t1/2 is long - 70 hours, enabling once-daily dosing. Donepezil is extensively bound to plasma proteins, and while a part is excreted unchanged the other is extensively metabolized by CYP 2D6 and 3A4 hepatic enzymes to active and inactive metabolites.  The oral bioavailability of rivastigmine is about 40% up to a dose of 3 mg, after which this increases non-linearly. The t1/2 of rivastigmine is just 1.5 hours. The drug undergoes hydrolysis by cholinesterase itself, with minimal hepatic involvement. It is excreted almost entirely in the urine as the sulfate of the decarbamylated metabolite.  The oral bioavailability of galantamine is about 90%; it has low protein binding (18%). It undergoes metabolism by CYP2D6 and CYP3A4 enzymes while one-third is excreted unchanged in the urine.  Memantine has low protein binding (45%) and a long half-life of 60–80 hours. Approximately half the dose of memantine is excreted unchanged in the urine; the remainder undergoes hepatic conversion to inactive metabolites. Drugs that alkalinize the urine (e.g., carbonic anhydrase inhibitors) reduce the clearance of memantine.

H. Other drugs:  Methylphenidate is absorbed well orally and achieves peak plasma levels in 1-2hrs with t1/2 2-3 hrs necessitating multiple daily dosing. This is obviated by sustained release preparation that can be given once daily.  Modafinil reaches peak plasma concentrations in 2 to 4 hours and has a half-life of 15 hours.  Atomoxetine has a t1/2 5 hours and is metabolized by the CYP 2D6 pathway. SSRIs may raise atomoxetine levels.