Bipolar

2,260 views

Published on

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
2,260
On SlideShare
0
From Embeds
0
Number of Embeds
20
Actions
Shares
0
Downloads
42
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Bipolar

  1. 1. BIPOLARDISORDERLeana Atieh, Saira Nawaz, & JessicaPisano
  2. 2. BIPOLAR II DISORDER:  Previously known as manic-depressive disorder.  Experience mood swings, poor impulse control, impairments of verbal memory, and attention deficiency.  Alternates between two poles - depression and mania.  Depression is a feeling a worthlessness, lack of motivation, energy, sleep and pleasure in activities.  Mania is the opposite of depression, where one expresses over activity, excitement, rambling speech and excessive laughter.*Kapczinski, Machado-Vieira, Soares."Perspectives for the Development of Animal Models of Bipolar Disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry 28 (2004): 209-24. Print.
  3. 3. *Date, Dave, Gandhi, Parekh, Mistry. "Bipolar Disorder." Web. <http://grade8health.asb- wiki.wikispaces.net/Bipolar+Disorder>.
  4. 4. DSM IV CRITERIA: Bipolar II Disorder: includes milder manic phases known as hypomania.  Mania is an intense high where the person feels euphoric, almost indestructible in areas such as personal finances, business dealings, or relationships. They may have an elevated self-esteem, be more talkative than usual, have flight of ideas, a reduced need for sleep, and be easily distracted. The high, although it may sound appealing, will often lead to severe difficulties in these areas, such as spending much more money than intended, making extremely rash business and personal decisions, involvement in dangerous sexual behavior, and/or the use of drugs or alcohol. Depression is often experienced as the high quickly fades and as the consequences of their activities becomes apparent, the depressive episode can be exacerbated.  Bipolar II Disorder is hypo manic, rather than manic. In other words, they have similar symptoms to Bipolar l Disorder but they are not severe enough to cause marked impairment in social or occupational functioning and typically do not require hospitalization in order to assure the safety of the person.*"Bipolar Disorder in Mood Disorders at ALLPSYCH Online." Psychology Classroom at AllPsych Online. Web. 02 May 2012. <http://allpsych.com/disorders/mood/bipolar.html>.
  5. 5. CLINICAL CRITERIA FOR BIPOLAR II DISORDER: Mania Depression Mood Elevated, open, irritable Sad, miserable, dysphoric Speech Fast, flight of thoughts Slow, monotonous Energy Excessive, increased Lacking, apathetic psychomotor activity, distractible Ideation Grandiose, self confident Guilt, unworthiness, suicidal Physical Insomnia, noticeable weight Fatigue, loss of libido loss Behavior Disinhibition, hypersexuality, Retardation or agitation, poverty excessive spending of movements or expression*Kapczinski, Machado-Vieira, Soares."Perspectives for the Development of Animal Models of Bipolar Disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry 28 (2004): 209-24. Print.
  6. 6. *"Health Information Web." Bipolar Disorder. 09 Feb. 2009. Web. 02 May 2012. <http://www.caecilian.org/bipolar-disorder/>.
  7. 7. ETIOLOGY:  Research has shown a strong biological component (genetics) for this disorder, with environmental factors- which can include stress, lifestyle issues, life changing events, alcohol or drug abuse- playing a role in intensifying the symptoms. EPIDEMIOLOGY :  Lifetime prevalence of approximately 1.2%.  The U.S. has the highest prevalence rate at 4.4%, while India has the lowest at 0.1%.*Kapczinski, Machado-Vieira, Soares."Perspectives for the Development of Animal Models of Bipolar Disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry 28 (2004): 209-24. Print.*"Bipolar Disorder in Mood Disorders at ALLPSYCH Online." Psychology Classroom at AllPsych Online. Web. 02 May 2012. <http://allpsych.com/disorders/mood/bipolar.html>.
  8. 8. What is the significance of ourtreatment? Target population:  adults 18 to 40 that have been clinically diagnosed with major depression or Bipolar Disorder. Patient cannot have any other psychological disorder or be on any other medication. Our drug is Aripiam which is a combination of Abilify with a benzodiazepine called Clonazapam. Current treatment methods don’t seem to alleviate symptoms of Bipolar Disorder such as agitation, anxiety, and irritability in patients. Abilify is considered a partial agonist, this implies that the drug targets certain symptoms of the disorder; but it may not completely diminish or target all of them to the maximum response.
  9. 9. What is our rationale for creating a new drug?Our drug will be administered by depot injection so it will have a time released component which will reduce the chance of abuse potential and it will have a longer lasting effect.There is also a higher compliance rate since it will be administered and monitored by a doctor.
  10. 10. Why Abilify?Abilify is seen on many television commercials to alleviate the symptoms of depression and when we researched the drug, we learned that it is also used to treat Bipolar Disorder. Although individuals taking Abilify can experience similar side effects as other drugs, we were curious to research how the drug would act in conjunction with a benzodiazepine.
  11. 11. WHAT’S IN A DRUG’S NAME?  Chemical: 7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}- 3,4- dihydroquinolin-2(1H)- 5-(2-chlorophenyl)-7-nitro-2,3- dihydro-1,4-benzodiazepin-2-one  Generic:  Trade:
  12. 12. CURRENT TREATMENT METHODS:  Treatment for Bipolar Disorder can be divided into three groups:  Acute treatment focuses on suppressing current symptoms and continues until remission, which occurs when the symptoms are diminished for a period of time.  Continuation treatment prevents a return of symptoms from the same manic or depressive episode.  Maintenance treatment prevents a recurrence of symptoms. The risks of long-term medication use must be weighed against the risk of getting sick again (relapse).*Prien, Robert F., and James H. Kocsis. "Long-Term Treatment of Mood Disorders." Home. 2000. Web. 02 May 2012. <http://www.acnp.org/g4/GN401000104/CH102.html>
  13. 13. CURRENT MEDICATIONS FOR BIPOLAR DISORDER: Lithium (most commonly used) Depakote Sprinkle Risperdal Consta Abilify*Segal, Robert. "Treatment for Bipolar Disorder." Helpguide.com. 2012. Web. <•http://www.helpguide.org/mental/bipolar_disorder_diagnosis_treatment.htm>.*Abraham, Raya. "Medications for Bipolar Disorder." Www.webmd.com. 2010. Web. <• http://www.wedmd.com/bipolar- disorder/bipolar-disorder-medications>.
  14. 14. EFFECTIVE TREATMENT METHODS:  Medication is not enough!  Cognitive Behavioral Therapy (CBT)  Support System  Educating yourself and your family about the disorder*Haggerty, Jim. "Combination Therapy for Bipolar." Psychcentral.com. 2006. Web. http://psychcentral.com/lib/2006/combination-therapy-for-bipolar-disorder/.*Tracy, Natasha. "Cognitive Behavioral Therapy Effective for Bipolar Disorder." Pdresources.wordpress.com. Web. 2012. <http://pdresources.wordpress.com/2012/03/15/cognitive-behavioral-therapy-effective-for-bipolar-disorder/>.
  15. 15. PHARMACOKINETICS
  16. 16. PHARMACOKINETICS:  Aripiam activity is primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma.  The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydro-aripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties.  Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady state, the pharmacokinetics of aripiprazole are dose-proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4.*Bristol Myers Squibb Company. "Abilify." (2005): 1-39. Web. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf.
  17. 17. ROUTE OF ADMINISTRATION AND ABSORPTION:  The process of a substance entering the blood circulation.  Aripiam will be admininstered through an intramuscular injection with peak plasma concentrations at one and three hours.  A 5 mg intramuscular injection of Aripiam had an absolute bioavailability of 100%.*Bristol Myers Squibb Company. "Abilify." (2005): 1-39. Web. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf.
  18. 18. DISTRIBUTION:  The spreading of substances throughout the fluids and tissues of the body.  The steady-state volume of distribution of Aripiam following intravenous administration is high (404 L or 4.9 L/kg), indicating extensive extravascular distribution. At therapeutic concentrations, Aripiam and its major metabolite are greater than 99% bound to serum proteins, primarily to albumin.*Bristol Myers Squibb Company. "Abilify." (2005): 1-39. Web. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf.
  19. 19. METABOLISM:  The irreversible transformation of parent compounds into daughter metabolites.  Aripiam is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4. Aripiprazole is the predominant drug moiety in the systemic circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma.  Clonazepam is metabolized through cytochrome P450, including CYP3A. Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative. This derivative can be acetylated, hydroxylated, and glucuronidated.*Bristol Myers Squibb Company. "Abilify." (2005): 1-39. Web. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf.*GENONE ALBERTA AND GENOME CANADA. "DrugBank: Clonazepam (DB01068)." DrugBank. 2005. Web. 02 May 2012. http://www.drugbank.ca/drugs/DB01068.
  20. 20. EXCRETION:  The elimination of the substances from the body.  The elimination of Aripiam is approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces, respectively.  Clonazepam is highly metabolized, with less than 2% unchanged Clonazepam being excreted in the urine. Metabolites of Clonazepam are excreted by the kidneys.*Bristol Myers Squibb Company. "Abilify." (2005): 1-39. Web. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf.*GENONE ALBERTA AND GENOME CANADA. "DrugBank: Clonazepam (DB01068)." DrugBank. 2005. Web. 02 May 2012. http://www.drugbank.ca/drugs/DB01068.
  21. 21. PHARMACODYNAMICS
  22. 22. ARIPIAM  Abilify, as already stated, is a partial agonist. It is able to regulate dopamine levels by behaving as an agonist when there is too little dopamine, and behaving as an antagonist when there is too much dopamine present. Animal studies suggest that when levels of dopamine in the brain are low, Abilify may enhance the dopamine effect by stimulating the D2 receptor.  Clorazepam is a benzodiazepine and works on the GABA receptor to reduce the chemical activity of the brain.  Irritability, agitation and anxiety result from high levels of dopamine which result from the administration of Abilify.  Aripiam is a combination of Abilify (which is used to treat Bipolar Disorder) and Clorazepam (a benzodiazepine).*"Coming Off Psychiatric Medication - Atypical." Coming Off Psychiatric Medication. Web. 02 May 2012. <http://www.comingoff.com/index.php?Itemid=36>.
  23. 23. RECEPTOR ACTIVITY Abilif Clonazepam y*Paulev-Zubieta. "Chapter 2." New Human Physiology. 2nd ed. Copenhagen, Denmark. New Human Physiology Ch 2. Web. 01 May 2012. <http://www.zuniv.net/physiology/book/chapter2.html>.
  24. 24. MECHANISM *Key: D2 Receptor Glutamate Receptor Abilify Metabolite (Stimulator) Dopamine Clonazepam Metabolite (Inhibitor) Chloride Ion (Polarize)*This will take place in the substantianigra,
  25. 25. PHARMACODYNAMIC TOLERANCE  Pharmacodynamics tolerance to anti-anxiety effects of benzodiazepines develops with chronic use. This occurs because of a decrease of benzodiazepine binding sites.  Dosage of Aripiam administered will be titrated.*Longo & Johnson. "Tolerance." Mark Nawrot, NDSU Department of Psychology. Web. 15 Apr. 2012. http://nawrot.psych.ndsu.nodak.edu/courses/465Projects06/Benzo/Tolerance.htm.
  26. 26. ANIMAL MODELS
  27. 27. ANIMAL MODELS:  Behavioral changes in animal models of mania can present two basic and distinct dimensions, the subjective and objective aspects.  Subjective changes include modulation of emotions, such as fear, aggressiveness, irritability, social behavior, and dysphoria (i.e. an emotional state marked by anxiety, depression, and restlessness).  Objective changes include aspects related to locomotor activity and circadian rhythm.*Kapczinski, Machado-Vieira, Soares."Perspectives for the Development of Animal Models of Bipolar Disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry 28 (2004): 209-24. Print.
  28. 28. Continuation… Each group consisted of 20 rats for a total of 60 rats. Our experiment was based on the Genetics model in which the rats’ genes were altered prior to shipment enabling them to display symptoms of Bipolar Disorder (we were not required to alter the rats in any way to induce Bipolar Disorder). Each group was given the same dosage of either saline, Abilify, or Aripiam at the same time daily for three weeks. We monitored the rats’ behavior for the first two weeks. At the start of the third week, we videotaped our rats and special encoders watched the video to encode behavioral changes in our subjects.
  29. 29. ANIMAL MODEL Control • Give saline  shows no change in behavior over time Abilfy • Relieves behavior while maintaining anxiety, irritability & agitation Aripiam • Relieves the expected side effects except for anxiety, which is reduced
  30. 30. DOSE RESPONSE CURVE Dose-Response Curves Aripiam 100 ED50 =150mg TD50=500mg 75 LD50=1500mg Response 50 25 Margin of safety/ TI= 1500/150 = 10 0 0 20 40 60 80 100 150 200 250 300 500 1500 2000 Dose mg Effective Toxic/Side Effects Lethal*Kapczinski, Machado-Vieira, Soares."Perspectives for the Development of Animal Models of Bipolar Disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry 28 (2004): 209-24. Print.
  31. 31. IN HUMANS… MARGIN OF SAFETY: 500/150= 3.33 This is a very low TI, but that’s OKAY because humans will be administered a depot injection rather than pill form. This injection can only be given by the doctor and is unavailable at the pharmacy or by prescription. The dosage may be titrated.
  32. 32. ASSESSMENT OF ABUSE POTENTIAL/ LIABILITY Conditioned Place Preference
  33. 33. • Animals will spend 33.3% Abilify of their time in this chamber Test day- animals • Animals will get no Saline spend 33.3% treatment, they will be placed in this injection of their time in chamber and this chamber decide where to go. • Animals will spend 33.3% Nothing of their time in this chamber**This shows that Abilify has no abuse potential because the animalsspend equal amount of their time in each chamber.
  34. 34. • Animals will Clonazopa spend 99% of m their time in this chamber Test day- animals • Animals will get no treatment, they will Saline spend less than be placed in this injection 1% of their time chamber and in this chamber decide where to go. • Animals will spend less than Nothing 1% of their time in this chamber**Based on this model, clonazopam has a very high abuse potential.
  35. 35. • Animals will spend 40% of Aripiam their time in this chamber Test day- animals • Animals will get no treatment, they will Saline spend 30% of be placed in this injection their time in this chamber and chamber decide where to go. • Animals will spend 30% of Nothing their time in this chamber**Based on this model, Aripiam has very little abusepotential because although the animals spend more time in the Aripiamchamber, the percentage isn’t much greater.
  36. 36. In the future…Based on our findings, future studies should test for the lethal dose (LD50) and the toxic dose (TD50) because they are currently undefined for Bipolar Disorder.Future studies should also eliminate the separation between depression and mania in animal models/studies.
  37. 37. AcknowledgmentsWe would like to thank Professor Kristine Stigi Bonacchi for all her wonderful support and advice throughout the semester.We would also like to thank all the psychology studies done in an effort to further advance and treat Bipolar Disorder.Of course we would not have been able to test our drug without the help of the National Rat Lab (NRL) and all their rodents.And where would we be without the marvelous wonders of google.
  38. 38. References*Kapczinski, Machado-Vieira, Soares."Perspectives for the Development of Animal Models of Bipolar Disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry 28 (2004): 209-24. Print.*Date, Dave, Gandhi, Parekh, Mistry. "Bipolar Disorder." Web. <http://grade8health.asb- wiki.wikispaces.net/Bipolar+Disorder>.*"Bipolar Disorder in Mood Disorders at ALLPSYCH Online." Psychology Classroom at AllPsych Online. Web. 02 May 2012. <http://allpsych.com/disorders/mood/bipolar.html>.*"Health Information Web." Bipolar Disorder. 09 Feb. 2009. Web. 02 May 2012. <http://www.caecilian.org/bipolar-disorder/>.*Prien, Robert F., and James H. Kocsis. "Long-Term Treatment of Mood Disorders." Home. 2000. Web. 02 May 2012. <http://www.acnp.org/g4/GN401000104/CH102.html>*Segal, Robert. "Treatment for Bipolar Disorder." Helpguide.com. 2012. Web. <•http://www.helpguide.org/mental/bipolar_disorder_diagnosis_treatment.htm>.*Abraham, Raya. "Medications for Bipolar Disorder." Www.webmd.com. 2010. Web. <• http://www.wedmd.com/bipolar- disorder/bipolar-disorder-medications>.*Haggerty, Jim. "Combination Therapy for Bipolar." Psychcentral.com. 2006. Web. http://psychcentral.com/lib/2006/combination-therapy-for-bipolar-disorder/.*Tracy, Natasha. "Cognitive Behavioral Therapy Effective for Bipolar Disorder." Pdresources.wordpress.com. Web. 2012. <http://pdresources.wordpress.com/2012/03/15/cognitive-behavioral-therapy-effective-for-bipolar-disorder/>.*Bristol Myers Squibb Company. "Abilify." (2005): 1-39. Web. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021713s004,021436s007lbl.pdf.*"Coming Off Psychiatric Medication - Atypical." Coming Off Psychiatric Medication. Web. 02 May 2012. <http://www.comingoff.com/index.php?Itemid=36>.*Paulev-Zubieta. "Chapter 2." New Human Physiology. 2nd ed. Copenhagen, Denmark. New Human Physiology Ch 2. Web. 01 May 2012. <http://www.zuniv.net/physiology/book/chapter2.html>.*Longo & Johnson. "Tolerance." Mark Nawrot, NDSU Department of Psychology. Web. 15 Apr. 2012. http://nawrot.psych.ndsu.nodak.edu/courses/465Projects06/Benzo/Tolerance.htm.*GENONE ALBERTA AND GENOME CANADA. "DrugBank: Clonazepam (DB01068)." DrugBank. 2005. Web. 02 May 2012. http://www.drugbank.ca/drugs/DB01068.

×