Activity No. 5: Pharmacology of Central Nervous System Mood Disorders PDF

ACTIVITY NO. 5 PHARMACOLOGY OF CENTRAL NERVOUS SYSTEM: MOOD DISORDERS  Ion Channels and Neurotransmitter Receptors Voltage-gated channels - respond to changes in membrane potential. They are found in high concentration on the axons of nerve cells and include the...

ACTIVITY NO. 5 PHARMACOLOGY OF CENTRAL NERVOUS SYSTEM: MOOD DISORDERS  Ion Channels and Neurotransmitter Receptors Voltage-gated channels - respond to changes in membrane potential. They are found in high concentration on the axons of nerve cells and include the sodium channels responsible for action potential propagation.  Ligand-gated ion Also called ionotropic receptors, respond to chemical channel neurotransmitters that bind to receptor subunits present in their macromolecular structure.  Metabotropic receptoralso bind to G-protein-coupled receptors Neurotransmitters (metabotropic receptors) that can modulate voltage-gated ion channels. Neurotransmitter-coupled ion channels are found on cell bodies and on both the presynaptic and postsynaptic sides of synapses.  Synaptic Potentials Synaptic potentials mediated by ionotropic receptors are the fundamental means by which information is transmitted rapidly between neurons. Transmitters cause channels to open in an all-or-none fashion, and the currents through these individual channels summate to produce the macroscopic postsynaptic potential  Mood disorders. Mood disorders, also known as affective disorders, are characterized by significant disturbances in emotions. These conditions are prevalent psychiatric disorders that are associated with heightened rates of morbidity and mortality. According to the Diagnostic and Statistical Manual of Mental Disorders, mood disorders have been broadly categorized as; Bipolar disorders Major depressive disorder Bipolar I & Bipolar II disorder Persistent depressive disorder (PDD) Cyclothymia Disruptive mood dysregulation disorder (DMDD) Hypomania Premestrual dysphoric disorder  Bipolar Disorder Bipolar I disorder Characterized by a week-long occurrence of mania symptoms or hospitalization. If mood is irritable, at least four symptoms are required for a manic episode criteria. Bipolar II Consists disorder of current or past major depressive episodes interspersed with current or past hypomanic periods of at least four days duration.  Cyclothy mia A milder form of bipolar disorder characterized by periods of low-grade depression and mild hypomania lasting at least 2 years in adults or 1 year in children or adolescents. Hypoman ia severe form of mania lasting at least four days without significant social or Less occupational impairment. Major depressive disorder Having less interest in normal activities, feeling sad or hopeless, and other symptoms for at least 2 weeks may mean depression Persistent depressive disorder (PDD) A chronic formor dysthymia of depression that must last at least two years in adults and one year in children and adolescents  Disruptive mood dysregulation Seen in children disorder (DMDD) and adolescents with frequent anger outbursts and irritability out of proportion to the situation. Premenstrual dysphoric disorder Characterized (PMDD) by irritability, anxiety, depression, and emotional lability occurring in a week before the onset of menses followed by resolution of the symptoms after onset  Treatment / Selective serotonin reuptake inhibitors (SSRIs) Management First-line treatment option for depressive disorder, as they are tolerated better with lesser side effects. They normally take 4 to 5 weeks to display full effects. Adverse effects includes nausea, vomiting, diarrhea, dizziness, loss of appetite, reduced sexual desire, anxiety, and insomnia. Serotonin-norepinephrine reuptake Next in line(SNRI) inhibitors medication for the treatment of depression after SSRIs. This category of the medication has a dual-action and found to be beneficial in cases with comorbid pain. Side effects include nausea, dry mouth, hypertension, fatigue, loss of appetite, insomnia, sweating, and anxiety. Monoamine oxidase Marketed(MAOIs) inhibitors as antidepressants in the United States (eg, phenelzine, tranylcypromine, isocarboxazid) are irreversible and nonselective (inhibiting MAO-A and MAO-B). Another MAOI (selegiline), which inhibits only MAO-B at lower doses. Adverse effects include erectile dysfunction, anxiety, nausea, dizziness, insomnia, pedal edema, and weight gain. Mood stabilizers Mood stabilizers, like lithium and anticonvulsants, help regulate mood swings in disorders like bipolar disorder by reducing abnormal brain activity. They may be prescribed alongside antidepressants. QUESTION S  1.What characteristics of drug molecules affort access Lipid solubilityto is anthe CNS? important characteristic of most CNS drugs in terms of their ability to cross the blood-brain barrier. Access to the CNS of water-soluble (polar) molecules is limited to those of low molecular weight such as lithium ion and ethanol 2. Any important concerns regarding CNS drug use in Use pregnant the during early pregnancy women?may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. 3. How are most CNS drugs usually eliminated from the body? Excretion is the process by which the drug is eliminated from the body. The kidneys most commonly conduct excretion, but for certain drugs, it may be via the lungs, skin, or gastrointestinal tract. 4. Antipsychotic drugs to varying degrees act as antagonists at several receptor types, including those for acetylcholine, dopamine, norepinephrine, and serotonin. What are the second-messenger systems for each of the following receptor subtypes that are blocked by antipsychotic drugs? Here are the second-messenger systems for the receptor subtypes blocked by antipsychotic drugs: A. D2 (Dopamine D2 receptor): The D2 receptor is coupled to the Gi protein, which inhibits adenylyl cyclase, leading to a decrease in cAMP levels. This also activates potassium channels and inhibits calcium channels. B. M3 (Muscarinic acetylcholine receptor M3): The M3 receptor is coupled to the Gq protein, which activates phospholipase C (PLC). PLC hydrolyzes phosphatidylinositol 4,5- bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 releases calcium from intracellular stores. C. Alpha1 (Alpha-1 adrenergic receptor): The alpha-1 receptor is coupled to the Gq protein, similar to the M3 receptor. This activates PLC, leading to the production of DAG and IP3, which in turn activate PKC and release calcium. D. 5-HT2A (Serotonin 5-HT2A receptor): The 5-HT2A receptor is coupled to the Gq protein, similar to the M3 and alpha-1 receptors. This pathway also activates PLC, leading to the production of DAG and IP3, which activate PKC and release calcium. Case Study 1 FS, a 35-year-old woman, is receiving risperidone, 3 mg b.i.d., to control a psychotic disorder. She has taken the drug for 6 months but has recently become agitated and is complaining of insomnia. 1.What is the relation between FS’s drug dose and her FS's agitation and insomnia complaints? Explaincould be related your to her risperidone dose. While risperidone is generally answer. well-tolerated, it can cause akathisia, a restless feeling that can manifest as agitation and insomnia. This side effect is more common at higher doses. 2. What further assessment should be made concerning FS and the drug regime? A thorough assessment should be made to determine the cause of FS's symptoms. This should include: Reviewing her medical history and current medications: Are there any other medications that could contribute to her agitation or insomnia? Evaluating her mental status: Is there any evidence of worsening psychosis or other psychiatric symptoms? Assessing her physical health: Are there any underlying medical conditions that could explain her symptoms? Examining her sleep patterns: A sleep diary can help identify potential sleep disturbances. 3. How does risperidone compare with other antipsychotics such as chlorpromazin, fluphenazine, olanzapine, and haloperidol regarding actions and adverse Risperidone, effects? chlorpromazine, fluphenazine, olanzapine, and haloperidol are all antipsychotic medications that work by blocking dopamine receptors in the brain. However, they differ in their potency, side effect profiles, and other characteristics: Risperidone: A second-generation antipsychotic (SGA) with a relatively low risk of extrapyramidal symptoms (EPS) like tremors and muscle stiffness. It can cause metabolic side effects like weight gain and increased blood sugar. Chlorpromazine: A first-generation antipsychotic (FGA) with a high risk of EPS. It is also associated with sedation and anticholinergic effects. Fluphenazine: An FGA with a high potency and a higher risk of EPS compared to chlorpromazine. Olanzapine: An SGA with a high risk of metabolic side effects. It is generally well-tolerated but can cause sedation and weight gain. Haloperidol: An FGA with a high potency and a high risk of EPS. It is also associated with prolactin elevation, which can cause breast enlargement and menstrual irregularities. REFERENCE/ Mood disorders: What they are, symptoms & treatment. (n.d.). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/17843-mood-disorders S Medications for treatment of depression - Medications for treatment of depression - MSD manual professional edition. (2023, October 2). MSD Manual Professional Edition. Sekhon, S., & Gupta, V. (2023, May 8). Mood disorder. StatPearls - NCBI Bookshelf. Pajouhesh, H., & Lenz, G. R. (2005). Medicinal chemical properties of successful central nervous system drugs. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics, 2(4), 541–553. https://doi.org/10.1602/neurorx.2.4.541 Källén, B., Borg, N., & Reis, M. (2013). The use of central nervous system active drugs during pregnancy. Pharmaceuticals (Basel, Switzerland), 6(10), 1221–1286. https://doi.org/10.3390/ph6101221 Siafis, S., Tzachanis, D., Samara, M., & Papazisis, G. (2018). Antipsychotic Drugs: From Receptor-binding Profiles to Metabolic Side Effects. Current neuropharmacology, 16(, 1210–1223. https://doi.org/10.2174/1570159X15666170630163616 Stahl, S. M. (2014). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications. Cambridge University Press. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Publishing.