Ziprasidone and Quetiapine

[TheSeanieB]

Could someone explain to me the pharmacokinetics of ziprasidone. Specifically, I am confused about the amount of time it take to reach peak plasma concentration, 6-8 hours. A simular drug, quetiapine, only take 1.5 hours to reach peak plasma concentration.

Does the plasma concentration correlate with the side effects of sediation. This is a topic that is confusing to me. Clonazepam (long acting benzo) also causes sediation, but has an extremely long half life. The sedation cannot completely correlate with the plasma concentration, but why? Are receptors down regulated on a daily basis when a patient takes clonazepam?

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[tompharm]

I dont know but I know that you must take ziprasidone with meals or it will not be absorbed.

 

[naseuy]

Effects of sedation are due to the receptor affinities of the particular AP. Here's a table from medscape, because I effing love tables!

More sedation is seen with quetiapine because of its higher affinity for histaminergic receptors, as compared to ziprasidone.

 

[1800callsaul]

Does the plasma concentration correlate with the side effects of sediation. This is a topic that is confusing to me. Clonazepam (long acting benzo) also causes sediation, but has an extremely long half life. The sedation cannot completely correlate with the plasma concentration, but why? Are receptors down regulated on a daily basis when a patient takes clonazepam?

"Sedation is the most common effect of the benzodiazepines and its intensity and duration depend on the dose and concentration of drug in plasma and brain"

That comes right from my pharmacology book.

With benzos you need to consider: metabolites (whether they are active or inactive), the rate of absorption from GI (if it's an oral dose), and how well you can distribute into the brain (depends on lipophilicity). All of these drugs have huge volumes of distribution, so they really aren't "sitting" in the plasma compartment. In order to have any sort of CNS effect they need to distribute OUT of the blood & into the CNS. But of course, if you give a larger dose, you get more drug into the blood, allowing more to distribute into the CNS & tissues.

With regards to the receptors being down regulated... I'm not exactly sure. I can't find it anywhere in my text references. It would make sense though: you can't abruptly stop these drugs and patients develop tolerance necessitating higher doses over time. Ask any pharmacist that deals with patients chronically on ativan/ xanax/ k-pins: these patients are "too soon" for refills a large majority of the time.

Best of luck.

 

[TheSeanieB]

Effects of sedation are due to the receptor affinities of the particular AP. Here's a table from medscape, because I effing love tables!

More sedation is seen with quetiapine because of its higher affinity for histaminergic receptors, as compared to ziprasidone.

I effing love tables too. I know that trying to understanding dopamine is almost impossible. Please correct my thought process though. I thought that bc amphetamine causes stimulation via excessive dopamine release, drugs like quetiapine and ziprasadone would cause sediation by doing the opposite, blocking the dopamine receptors. Wouldn't either of these medications induce amphetamine withdrawl in a paient with ADHD?