BUPROPION ANTIDEPRESSANT

Dr keli F med III lectures

Case Study - Jane Doe (JD)

female 25 year old symptoms:

o o o o o o o o o

change in sleeping habits (sleep too much/too little) change in eating habits (weight gain/loss) lethargic sad & irritable mood socially withdrawn loss of interest feelings of hopelessness/worthlessness difficulty concentrating suicidal thoughts

JD diagnosed with Depression

Case Study - JD Cont'd.

How does depression occur? normally o Norepinephrine and/or Dopamine o Message sent down the nerve o Axon terminal releases norepinephrine or dopamine o Crosses synaptic gap o Gets into receptor o Message continues o Reuptake from first cell depression o imbalance of norepinephrine and/or dopamine (or serotonin) o perhaps message not being sent through

Case Study- JD
JD diagnosed with depression and she is treated with Bupropion.

What is Bupropion?

Class of antidepressant medication Inhibits neurotransmitters (norepinephrine and dopamine) reuptake Results in neurotransmitters transmitting signals to nerves
o

Used to treat depression (Jane Doe's Case) Used for smoking cessation Brand Name Medication: Zyban,Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin
o

Structure of Bupropion
IUPAC: 2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one Molecular Formula: C13H18ClNO

Side Effects
Some Minor Side Effects: drowsiness dry mouth headache vomiting weight loss Some Major Side Effects: seizures confusion hallucinating fever itching

Off-label uses for bupropion

Bipolar disorder Attention-deficit/hyperactivity disorder (ADHD) Restless Leg Syndrome (RLS) Weight Loss Periodic Limb Movement Disorder (PLMD)

Bupropion & Depression

classified as NDRI- Norepinephrine Dopamine Reuptake Inhibitor affects dopamine (DA) and norepinephrine (NE) levels o -inhibits sodium-dependent dopamine transporter and sodium-dependent norepinephrine transporter no appreciable effect on serotonin

Metabolism

3 active metabolites produced by Cytochrome P450 enzymes relative contributions to beneficial and adverse effects unknown

Bupropion & Neurotransmitters

dopamine

bupropion

Therapeutics

doesn't bind to neurotransmitter receptors or have serotonergic effects -unique to classical antidepressants -limited common side effects i.e. sexual dysfunction and weight gain comparable efficacy with other drug classes (ex. TCAs) Relatively low affinity for transporters means high concentrations needed in plasma to be effective -therefore low therapeutic index

Bupropion & Smoking Cessation

decreases cravings and withdrawal symptoms o increase in NE may attenuate withdrawal symptoms o increase in DA may reduce nicotine cravings and the urge to smoke works just as well as nicotine replacement therapies o clinical trials show abstinence rates approximately double when compared with placebo or nicotine patch

Bupropion & Nicotine

Nicotine

BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors inhibits DA reuptake and nicotine receptor binding BP binds AchR, reducing probability of ion channel opening

Bupropion vs other drugs

Doctors may prescribe bupropion over other antidepressant drugs as it has less side effects such as weight gain and sexual dysfunction

SUMMARY- Bupropion(BP)

Antidepressant drug- inhibits NT( norepinephrine and dopamine) reuptake

Norepinephrine- resp. alertness,concentration,energy, attention, mood, cognitive function Dopamine- attention, mood, cognitive function, pleasure, motivation, appetite,

Used to treat depression (imbalance of norepinephrine and/or dopamine) Off label uses: Bipolar disorder, Attention-deficit/hyperactivity disorder(ADHD), restless Leg Syndrome (RLS), weight loss, periodic limb movement disorder (PLMD) BP metabolized into three other active metabolites- (their relative and beneficial effects are unclear) BP a unique antidepressant drug since it shows less side effects than other antidepressant drugs- no weight gain and sexual dysfunction. o BP Mechanism- inhibits sodium-dependent dopamine transporter and sodium-dependent norepinephrine transporter. Therefore, dopamine and norepinephrine can remain in the synapse longer. o BP and smoking cessation- increase in NE may attenuate withdrawal symptoms, and increase in DA may reduce nicotine cravings and the urge to smoke. BP is a non-competive inhibitor of nicotinic acetylcholine receptors.

References

Arias, H. R., Santamaria, A., & Santamaria, A. (2009). Pharmacological and neurotoxicological actions mediated by bupropion and diethylpropion. Int Rev Neurobiol., 2009(88), 223-55. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19897080 Bupropion molecule. [Web Photo]. Retrieved from http://www.ganfyd.org/images/thumb/6/6d/BupropionMolecule.png/180pxBupropionMolecule.png Bupropion(wellbutrin andzyban). (2012). [Print Photo]. Retrieved from http://nursingmnemonics.blogspot.ca/2012/07/bupropionwellbutrin-and-zyban.html Causey , L. (Photographer). (2012). headache. [Print Photo]. Retrieved from http://www.aperfectworld.org/healthcare.html Clayton, A. (Artist). (2003). Figure 4. [Print Photo]. Retrieved from http://www.primarypsychiatry.com/userdocs/articleimages/119/Clayton_BigFIg_4.jpg Datasheet- o-nicotine. (n.d.). Retrieved from http://www.scbt.com/datasheet-212458-o-nicotine.html Image 1. (2012). [Print Photo]. Retrieved from http://journals.prous.com/journals/dot/20064210/html/dt420671/images/image01.jpg Medlineplus. (2012, September 27). Retrieved from http://www.nlm.nih.gov/medlineplus/druginfo/meds/a695033.html Mitrouska, I., Bouloukaki, I., & Siafakas, N. M. (2007). Pharmacological approaches to smoking cessation. Pulmonary Pharmacology & Therapeutics, 20(3), 220-232. Retrieved from http://www.sciencedirect.com/science/article/pii/S1094553905001355 Modern theory of depression. (n.d.). Retrieved from http://www.emsamhcp.com/depression.aspx Monson, K. (2011, December 22). Medtv. Retrieved from http://mental-health.emedtv.com/bupropion/what-is-bupropion-usedfor.html Novick, A. (2011, September 3). Chemically correct: Bupropion Mind and Muscle, Retrieved from http://www.mindandmuscle.net/articles/chemically-correct-bupropion-by-andrew-novick/ Nutt, D. (2006). The role of dopamine and norepinephrine in depression and anitdepresant treatment. J Clin Psychiatry, 67([supp 6]), 3-8. Preskorn, S. H. (2000). Bupropion: What mechanism of action?. Journal of Practical Psychiatry and Behavioral Health, 272-276. Stahl, S. M, et al. (2004). A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry, 6(4), 159-166. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514842/ Wilkes, S. (2006). Bupropion. Drugs of Today, 42(10), 671. Retrieved from http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=4&p_RefId=1025701&p_IsPs=N Zimmerman, M., et al.(2005). Why isn't bupropion the most frequently prescribed antidepressant?. PubMed, 65(5), 603-610. Retrieved from Why isn't bupropion the most frequently prescribed antidepressant?