atypical antipsychotic pharmacology
Download
Skip this Video
Download Presentation
Atypical Antipsychotic Pharmacology

Loading in 2 Seconds...

play fullscreen
1 / 76

Atypical Antipsychotic Pharmacology - PowerPoint PPT Presentation


  • 453 Views
  • Uploaded on

Atypical Antipsychotic Pharmacology. Stephanie Nichols, Pharm.D., BCPS, BCPP Associate Professor of Pharmacy Practice [email protected] Using Receptor Binding Profiles to Predict Adverse Effects. Objectives. Recognize atypical antipsychotics by brand and generic name

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Atypical Antipsychotic Pharmacology' - illias


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
atypical antipsychotic pharmacology

Atypical Antipsychotic Pharmacology

Stephanie Nichols, Pharm.D., BCPS, BCPP

Associate Professor of Pharmacy Practice

[email protected]

Using Receptor Binding Profiles to Predict Adverse Effects

objectives
Objectives
  • Recognize atypical antipsychotics by brand and generic name
  • Understand how key pharmacological properties of antipsychotics translate into side effects
  • Compare and contrast the pharmacology of the atypical antipsychotics
  • Predict which antipsychotics may be more, or less, desirable in various patient scenarios
slide3

1950

1960

1970

1980

1990

2000

2010

FDA Approval of Antipsychotics

Thioridazine

Perphenazine

Aripiprazole

Trifluoperazine

Risperidone

Mesoridazine

Iloperidone

Chlorpromazine

Pimozide

Clozapine

Asenapine

Quetiapine

Haloperidol

Droperidol

Ziprasidone

Prochlorperazine

Lurasidone

Fluphenazine

Paliperidone

Loxapine

Olanzapine

Thiothixene

Stephanie Nichols, PharmD BCPS BCPP

2014

what defines an antipsychotic
What defines an Antipsychotic?
  • Dopamine2 post synaptic antagonism
  • Reduce DA in the mesolimbic tract
    • Nucleus accumbens
  • Positive Symptoms
  • EPS
slide5

Antagonism

Partial Agonism

slide7

Mesolimbic

– VTA to NA, HC, amygdala

Mesocortical

– VTA to PFC

Nigrostriatal

– SN to BG

Tuberoinfundibular

– Hypothalamus to Pituitary Gland

http://psychopharmacologyinstitute.com/antipsychotics-videos/dopamine-pathways-antipsychotics-pharmacology/

what defines an atypical antipsychotic
What defines an Atypical Antipsychotic?
  • Serotonin2a post-synaptic antagonism
  • 5HT2a puts the brakes on DA in PFC
    • Disinhibiting the inhibitor – increased mesocortical DA
  • ? Improved negative and cognitive symptoms
  • Reduced EPS – at what cost?
atypical antipsychotics in the us
Atypical Antipsychotics in the US

Generic Availability

Brand Name Only

Aripiprazole (Abilify)

Paliperidone (Invega)

Iloperidone (Fanapt)

Asenapine (Saphris)

Lurasidone (Latuda)

  • Clozapine (Clozaril)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Risperidone (Risperdal)
  • Ziprasidone (Geodon)
understand how key pharmacological properties of antipsychotics translate into side effects
Understand how key pharmacological properties of antipsychotics translate into side effects
slide23

NIMH Psychoactive Drug Screening Program (PDSP) Ki Database: http://pdsp.med.unc.edu/pdsp.php

what do you think
What do you think?
  • Based upon Quetiapine’s binding profile, which of the following adverse effects is most likely to occur?
    • Parkinsonism
    • Antimuscarinic Effects
    • Sedation
metabolic changes

5HT2c

and H1

Metabolic Changes
  • Dyslipidemia and hypertriglyceridemia
    • pancreatitis
  • Hyperglycemia and insulin resistance
    • diabetic ketoacidosis
  • Increased body weight
  • Increased adiposity
quetiapine metabolic effects
Quetiapine Metabolic Effects
  • Even low dose (<200mg/day) quetiapine causes significant weight gain and increase in BMI after 52 weeks

Cates ME et al. Metabolic Consequences of Using Low Dose Quetiapine for Insomnia in Psychiatric Patients. Community Ment Health J. 2009;45:251-4.

olanzapine in healthy volunteers
Olanzapine in Healthy Volunteers
  • 10mg nightly x3 days

Albaugh VL, Singareddy R, Mauger D, Lynch CJ (2011) A Double Blind, Placebo-Controlled, Randomized Crossover Study of the Acute Metabolic Effects of Olanzapine in Healthy Volunteers. PLoS ONE 6(8): e22662.

slide40

15 healthy subjects given 10mg po olanzapine or placebo (self-control)

  • Results:
    • decrease in glucose effectiveness, free fatty acids, and serum cortisol
    • increase in fasting glucose and prolactin

After a

single

dose!!

Hahn MK. et al. J Clin Psychopharmacol 2013; 33(6):740-6.

newer agents metabolic profiles
Newer Agents: Metabolic Profiles

CNS Drugs 2012. 26(9):733-59.

slide42

*

Partial 5HT2cAgonist

Data from: Nguyen CT et al. Prim Care Comp CNS Disord 2012;12(5).

metabolic changes1
Metabolic Changes
  • iloperidone
  • quetiapine
  • risperidone
slide44

Weight Gain /

Metabolic Effects

extra pyramidal symptoms eps
Extra Pyramidal Symptoms (EPS)
  • Dystonia
  • Parkinsonism
  • Tardive Dyskinesia

_______________________________________________

  • Akathisia
akathisia
Akathisia
  • ziprasidone
  • lurasidone
  • asenapine
  • aripiprazole

Poyurovsky M. BJP 2010;196:89-91.

hyperprolactinemia

D2

Hyperprolactinemia
  • Gynecomastia
  • Amenorrhea
  • Breast tenderness
  • Sexual dysfunction
  • Galactorrhea
hyperprolactinemia1
Hyperprolactinemia

Peuskens J et al. CNS Drugs 2014. PMID 24677189

slide51

EPS and

Hyperprolactinemia

sedation

H1 and

alpha1

Sedation
  • iloperidone
  • risperidone
  • paliperidone
  • lurasidone
what do you think1
What do you think?
  • Based upon receptor binding, which agent may be expected to be associated with constipation, urinary retention, and blurred vision?
    • Clozapine
    • Asenapine
    • Ziprasidone
    • Iloperidone
anticholinergic effects
Anticholinergic Effects

M1

  • Blind as a bat
  • Dry as a bone
  • Red as a beet
  • Mad as a hatter
  • Urinary retention
  • Constipation
  • Tachycardia
  • Blurred vision
  • Dry mucous membranes
  • Flushing
  • Confusion and delirium
anticholinergic effects1
Anticholinergic Effects
  • risperidone
  • paliperidone
  • asenapine
  • lurasidone
  • iloperidone
  • ziprasidone
  • aripiprazole
orthostasis and dizziness

alpha1

Orthostasis and Dizziness
  • Reduces sympathetic tone and decreases peripheral vascular resistance
  • Especially in elderly patients and those on diuretics
qtc prolongation

All antipsychotics

can cause this

to varying degrees

QTc Prolongation

Torsades de Pointes

slide62

monotherapy

w/ paroxetine

w/ parox & keto

Potkin et al. J Clin Psychopharmacol2013;33: 3Y10

slide63

Paliperidone?

Watanabe et al. J Clin Psychopharmacol2012;32: 18Y22

slide64

P>0.05

r=0.361;

p=0.004

qtc prolongation1
QTc Prolongation
  • asenapine
  • clozapine
  • olanzapine
  • lurasidone
  • quetiapine
  • risperidone
diabetes obesity or metabolic syndrome
Diabetes, Obesity or Metabolic Syndrome

Usually Weight Neutral

Most Weight Gain

Clozapine

Olanzapine

Quetiapine

  • Aripiprazole

(except with 5HT antidepressants)

  • Lurasidone
  • Ziprasidone

5HT2c

H1

parkinson s disease or history of extra pyramidal symptoms eps
Parkinson’s Disease or History of Extra Pyramidal Symptoms (EPS)

Less likely to cause EPS

More EPS

Parkinsonism and Dystonia

Risperidone

Paliperidone

Akathisia

Aripiprazole

Lurasidone

Asenapine

Ziprasidone

  • Clozapine
  • Quetiapine

D2

orthostatic hypotension dizziness or recurrent falls
Orthostatic Hypotension, Dizziness, or Recurrent Falls

Highest Risk

Lower Risk

Aripiprazole

Lurasidone

Ziprasidone

  • Clozapine
  • Risperidone
  • Iloperidone
  • Quetiapine

α1

Titrate

insomnia
Insomnia

More Sedating

Less Sedating

Aripiprazole

Ziprasidone

  • Quetiapine
  • Clozapine

H1

5HT2a

α1

history of hyperprolactinemia or concerns about it s occurrence
History of Hyperprolactinemia or Concerns About it’s Occurrence

More Hyperprolactinemia

Less Hyperprolactinemia

Clozapine

Aripiprazole

Iloperidone

Asenapine

Quetiapine

  • Risperidone
  • Paliperidone

D2

history of ventricular a rrhythmias
History of Ventricular Arrhythmias

More likely to prolong QTc

Less likely to prolong QTc

Aripiprazole

?Lurasidone

  • Ziprasidone
  • Iloperidone

K+ channel blockade

will adjusting the dose fix the problem
Will adjusting the dose fix the problem?

Dose related effects

Non-dose related effects

Weight gain

Metabolic changes

  • EPS
  • Sedation
  • Amenorrhea
  • Agitation
  • Activation

Aripiprazole – somnolence at higher doses

Ziprasidone – activating at lower doses (5HT2c)

Quetiapine – less sedating at higher doses

take home points
Take Home Points
  • D2 antagonism = ↓ positive symptoms
    • EPS (ex. parkinsonism, dystonia) = high D2 antagonism
      • Risperidone, paliperidone
  • 5HT2a antagonism = ↓ EPS
    • may help with (or not exacerbate) negative and cognitive symptoms
  • Histamine1, alpha1, and muscarinic antagonism = side effects
    • Quetiapine, clozapine, and olanzapine
  • 5HT2c + H1 antagonism = metabolic dysregulation & weight gain
    • Olanzapine, clozapine
  • Effects of binding 5HT1a, 5HT7, alpha2a, and alpha2c are still not fully understood but felt to contribute to efficacy
ad