Psychopharmacology for dental students - PART 1_JAN2023

Importance of Psychopharmacology for Dental Students

• Oral Health Discrepancy

  • People with severe mental illness exhibit much poorer oral health compared to the general population.

  • They are nearly three times more likely to have lost all their teeth.

  • Higher rates of dental decay and tooth loss are observed in individuals with anxiety and depression.

Lecture Overview

• Topics Covered:

  • Antipsychotics: Treatment regimes for schizophrenia and psychotic conditions.

  • Mood Stabilizers: Utilization in bipolar disorder.

Antipsychotic Medications

• Definition and Use:

  • Primarily utilized to manage schizophrenia and other psychotic disorders.

Schizophrenia and the Dopamine Hypothesis

• Clinical Implications of Antipsychotics:

  • Dopamine pathways are critical to understanding schizophrenia symptoms.

Dopamine Hypothesis

• Dopamine pathway linked to schizophrenia symptoms

  • Overactivity in the mesolimbic pathway is associated with positive symptoms (e.g., hallucinations).

  • → normal ppl - dopamine mediates attention, reward

  • however in overactivity in mesolimbic pathway - dopamine abherrent salience - brain misattributing importance to irrelevent stimuli

  • see chatgpt for red light example

  • Dysfunction in the mesocortical pathway relates to negative and cognitive symptoms.

Symptoms of Schizophrenia

• Chronic Nature:

  • Onset typically occurs in early adulthood (20s) and has a prevalence of 1%.

• Symptom Classification:

  • Positive Symptoms: delusions, hallucinations, distressing — respond well to antipsychotics.

  • Negative Symptoms: Emotional blunting, social withdrawal, apathy — can be disabling and require long-term support.

  • Cognitive Impairment: a drop in IQ. difficulties in thinking, memory, attention, and problem-solving that affect daily life

Types of Antipsychotics

• First Generation (Typical):

  • Includes Chlorpromazine, Trifluoperazine, Fluphenazine, Haloperidol, etc.

• Second Generation (Atypical):

  • Includes Olanzapine, Quetiapine, Risperidone, Aripiprazole, Clozapine.

Characteristics of Antipsychotics

• 1st vs 2nd Generation:

  • Atypicals - fewer extra pyramidal side effects (EPSE) (movement disorder), But may cause metabolic side effects. (weight gain)

  • typical - blocks dopamine receptors

  • atypical - blocks dopamine and serotonin receptors

Mechanism of Action of Antipsychotics

• Target Interaction:

  • Acts as antagonists at dopamine D2 receptors which reduces positive psychotic symptoms but does not affect negative symptoms.

Adverse Effects of Antipsychotics

• Common Mediated Effects:

  1. EPSE arise in the nigrostriatal tract.

  • Common EPSE:

    • Acute Dystonia, Parkinsonism, Akathisia, Tardive Dyskinesia

    2. prolactin elevation in tuberoinfundibular system

    3. Other side effects may arise from actions on

       serotonin antagonism - sexual dysfunction

       histamine antagonism - sedation

       muscarinic receptors ant - dry mouth, constipation

       alpha adrenergic - postural hypotension

Metabolic Side Effects

• Predominantly Associated with Atypicals:

  • Common in medications such as Quetiapine and Olanzapine and clozapine

  • Include weight gain, dyslipidemia, and risk of Type 2 diabetes

Clozapine

atypical

dopamine antagonist

resistant schizophrenia treatment

2 trials, munimum 6 weeks

side effect - sedation, weight gain, constipation, hypersalivation, nutropenia (not enough neutrophil)

Aripiprazole

atypical

partial agonist at dopamine D2 receptor - modulates dopamine level

acts as antagonist when increase dopamine in mesolimbic area

agonist in mesocortical area

side effect - weight gain, sedation, akathisia, agitaiton NO EPSE

Therapeutic Use of Antipsychotics

• Indications:

  • Effective in conditions like schizophrenia, severe depression with psychotic features, delusional disorders, and maintenance therapy in bipolar disorder.

Mood Stabilizers for Bipolar Disorder

• Definition:

  • Mood stabilizers are medications that prevent recurrence of manic and depressive episodes without exacerbating the other pole of mood.

Overview of Bipolar Disorder

• Prevalence: Affects approximately 2% of the population.

• Symptomatic Patterns:

  • Periods of depression and mania with normal mood (euthymia).

  • Potential for mixed episodes, combining features of both mania and depression.

Symptoms of Bipolar Disorder

• Depression Core Symptoms:

  • Persistent feelings of sadness, fatigue, lack of interest…

• Mania/Hypomania Symptoms:

  • Characterized by elevated mood, overactivity , grandiosity,

Neurobiology Behind Bipolar Disorder

• Manic Episodes:

  • Enhanced dopamine and glutamate transmission with reduced GABA levels may promote manic episodes.

• Depressive Episodes:

  • Dysregulation of dopamine may contribute to bipolar depression.

Treatment Strategies for Bipolar Disorder

• Treatments:

  • Focus on managing episodes and preventing relapses.

  • Caution advised against typical antidepressants due to potential risk of inducing manic episodes.

Mood Stabilizing Pharmacology

• Agents:

  • Lithium, Sodium valproate, and Lamotrigine.

Lithium

• Mechanism of Action:

  • Modulates excitatory and inhibitory neurotransmission, influencing broad neurochemical systems to stabilize mood.

• Pharmacokinetics:

  • Complete absorption within 6-8 hours; excreted unchanged in urine; with no protein binding.

• Side Effects:

  • Can lead to renal and thyroid issues, with potential for severe toxicity if not monitored.

Other Mood Stabilizers

• Sodium Valproate: Enhances GABA neurotransmission; contraindicated in women of childbearing age.

• Lamotrigine: Used primarily for maintenance; requires careful titration to mitigate risks.

• Carbamazepine: 3rd line treatment; notable for its effects on Na+ channels and impact on hepatic enzyme systems.