Pharmacokinetics 2 Flashcards
Pharmacokinetics of Risperidone?
First-pass hepatic metabolism to 9-hydroxyrisperidone.
What enzyme forms active metabolite of Risperidone?
CYP 2D6 catalyzes hydroxylation
Protein binding of Risperidone?
90%
Protein binding of Risperidone metabolite?
77%
What is the major metabolite of Risperidone?
Paliperidone
Receptor effects of Paliperidone?
5HT2 receptor blocker
Partially blocks D2 receptors
Absorption of Paliperidone?
Gradual water absorption delivers drug molecules slowly
Half life of Quetiapine?
6-12 hours
Dosing of Quetiapine?
Multiple daily dosing is required, but with longer duration once daily dosing is sufficient.
Active metabolite of Aripriprazole?
Dihydroaripiprazole
Half-life of Aripriprazole?
75 hours
Half-life of Dihydroaripiprazole?
94 hours
When is steady state conc of Aripriprazole reached?
14 days
What metabolizes Aripriprazole?
CYP 3A4
CYP 2D6
Protein binding of Aripripraozle?
99%
Which atypical antipsychotics can be given as depots?
Aripiprazole
Palpiperidone
Risperidone microspheres
Olanzapine
Oral dose tapering needed for Aripiprazole depot?
2 weeks oral dose tapering
Oral tapering needed for Paliperidone depot?
Does not need oral tapering
How often is Paliperidone depot given?
Once a month
How is paliperidone depot excreted?
Renal
How does Risperidone microsphere depot work?
Releases active drug at therapeutic levels 3 weeks after injection
How should long-acting risperidone depot be supplemented?
With oral risperidone for 3 weeks
What is olanzapine depot composed of?
Olanzapine and pamoic acid
Half-life of olanzapine depot?
30 days
When is steady state of olanzapine depot reached?
12 weeks
Oral supplementation of olanzapine depot?
None required
Which depots need to be refridgerated?
Risperidone microspheres - granular
Why is oral antipsychotic medication required with some depots?
As the depots show delayed as well as prolonged release.
Name some anti-dementia drugs
Tacrina Donepezil Rivastigmine Galantamine Memantine
What metabolizes Tacrine?
CYP 1A2 hepatic enzymes
Half life of Tacrine?
Short
Poor absorption
Oral bioavailability of Donepezil?
100%
Linear pharmakokinetics
How long does it take for Donepezil to reach steady state?
2 weeks
Half life of Donepezil?
70 hours
Plasma protein binding of Donepezil?
Extensively plasma protein bound
What metabolizes Donepezil?
CYP 2D6 and 3A4 hepatic enzymes
What is oral bioavailability of Rivastigmine?
40% up to dose of 3mg after which this increases non-linearly.
Half life of Rivastigmine?
1.5 hours
Metabolism of Rivastigmine?
Hydrolysis by cholinesterase
Minimal hepatic involvement
Excretion of Rivastigmine?
Urine as sulfate of decarbamylated metabolite
Oral bioavailability of galantamine?
90%
Plasma protein binding of Galantamine?
Low - 18%
Metabolism of Galantamine?
CYP2D6
CYP3A4
Excretion of Galantamine?
One-third is excreted unchanged in urine
Plasma protein binding of Memantine?
45%
Half life of Memantine?
60-80 hours
Excretion of Memantine?
Half excreted unchanged in urine
Half undergoes hepatic conversion to inactive metabolites
What reduces clearance of mematine?
Drugs that alkalinize urine such as carbonic anhydrase inhibitors
Absorption of Methylphenidate?
Absorbed well orally
When does Methylphenidate reach peak plasma levels?
1-2 hours
Half-life of Methylphenidate?
2-3 hours
When does Modafinil reach peak plasma?
2-4 hours
Half life of Modafinil?
15 hours
Half life of Atomoxetine?
5 hours
What metabolizes Atomoxetine?
CYP 2D6
Impact of SSRIs on Atomoxetine?
SSRIs may raise Atomoxetine levels
Which benzos are long-acting?
Diazepam
Chlordiazepoxide
Clonazepam
Flurazepam
When can toxicity of long-acting benzos be evident?
1-2 weeks
Which benzos are intermediate or short-acting?
Lorazepam
Oxazepam
Temazepam
Alprazolam
Clinical effect of intermediate/short-acting benzos?
Severe withdrawl phenomenon but lesser risk of daytime imapirment and daytime sedation.
Rebound insomnia and anterograde amnesia more often seen in shorter half-life.
Half-life of Lorazepam?
15 hours
Half-life of Temazepam?
10 hours
Whch benzo has a very short duration of action?
Triazolam
What is Triazolam often used in?
Anaesthesia
Oral bioavailability of Diazepam?
Nearly 100%
When is peak plasma conc of diazepam reached?
15-90 minutes after oral administration
Second peak 6-12 hours due to enterohepatic recirculation
How is diazepam distributed
Widely as highly lipophilic (CSF conc equals plasma conc)
How much of diazepam is plasma binding?
95-99%
Elimination half life of Diazepam?
30 hours
How long does it take diazepam to reach steady state?
5-6 days
Metabolism of Diazepam?
In liver with 3 active metabolites.
What are the three active metabolites of diazepam?
Nordiazepam/desmethyldiazepam
Oxazepam
Temazepam
What is the principal metabolite of Diazepam?
Desmethyldiazepam - could accumulate due to long half-life
Which z-hypnotics are quickly absorbed when given orally?
Zolpidem
Zaleplon
Eszopiclone
Impact of food on quickly-absorped z-hypnotics?
Food can delay absorption for up to an hour
Accummulation of quickly-absorbed z-hypnotics?
None - no active metabolites
Give e.g. of z-hypnotics?
Zopcilone/Eszopiclone
Zaleplon
Zolpidem
Onset of Zopiclone?
45 mins
Half-life of Zopiclone?
4-5 hours
How does zopcilone work?
Benzo receptor selective for alpha 1 subunit
What is eszopiclone?
Enantiaomer - only z-hypnotic indicated for sleep maintenance therapy
Onset of Zaleplon?
Within 30 mins
Half-life of Zaleplon?
1-2 hours
Effect of Zaleplon?
Shorter half life and quick onset makes it suitable for sleep initation problems.
Onset of Zolpidem?
Within 30 mins
Half life of Zolpidem?
1-4 hours
Effect of Zolpidem?
Short half-lif and onset mades it suitable for sleep initation problems.
Less hangover effect.
