Pharm Cards

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Antipsychotics Absorbtion

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o Rapid but incomplete absorption

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Antidepressants absorbtion

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o Generally completely absorbed

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Antidepressants high lipophilicity

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• Removing drug from tissues such as

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Antipsychotics and Antidepressants High plasma protein binding

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• ­’d levels of free (unbound, active) drug

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Antipsychotics Absorbtion

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o Rapid but incomplete absorption

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Antidepressants absorbtion

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o Generally completely absorbed

Front 7

Antidepressants high lipophilicity

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• Removing drug from tissues such as

Front 8

Antipsychotics and Antidepressants High plasma protein binding

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• ­’d levels of free (unbound, active) drug

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Antipsychotics and Antidepressants active metabolites

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• Long half-life active metabolites

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Antipsychotics and Antidepressants halflife

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• Most have t 1/2 ~24h

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antipsychotics theraputic index

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o High therapeutic index

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Histamine H1 - blockade SE's

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sedation, decreased bp, weight gain

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Muscarinic Ach receptor blockade SE's

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dry mouth, increased HR, blurred vision, decreased memory, Worsening of narrow angle glaucoma, constipation, urinary retention

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alpha adrenergic blockade SE's

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sexual dysfunction, decreased BP, increased HR, sedation

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antipsychotic agents

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• Schizophrenia and schizoaffective disorder

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antipsychotic agents

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Not indicated for anxiety or insomnia

Front 17

Antipsychotics

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typical and atypical types

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typical atisphychotics

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Low potency Phenothiazines

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Atypical Antipsychotics

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clozapine, olanzapine, risperidone, paliperidone, aripiprazole, ziprasidone, quetiapine

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Regardless of diagnosis, all antipsychotics treat “positive” psychotic symptoms (i.e. the presence of a symptom that isn’t ordinarily experienced)

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Therapeutic Effects of Antipsychotics

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Atypical antipsychotics may also treat (or be less likely to worsen) negative symptoms of schizophrenia (i.e., the absence of an ordinarily experienced feeling or behavior)

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The Dopamine Hypothesis

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Is D2 receptor blockade needed for antipsychotic action?

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Probably not - likely does not contribute to antipsychotic action

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Newer antipsychotics

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have much less binding at D2 receptors and greater variation in clinical and adverse effect profiles

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Other receptor sites may also be relevant to antipsychotic actions

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• Serotonin (5-HT) receptors

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5-HT Receptor Binding Properties of Atypical Antipsychotics

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• Highly variable across atypical agents

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Extrapyramidal Side Effects (EPS) due to D2 Blockade

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• Dystonic reactions: • Parkinsonism

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Neuroanatomy of the Dopamine System suggests an Approach to Treating EPS

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• In the nigrostriatal pathway, there are complex interconnections between dopamine and acetylcholine neurons.

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Anticholinergic medications can be used to treat EPS

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• Examples of anticholinergic medications used to treat EPS are:

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Anticholinergic medications can be used to treat EPS - SIDE EFFECTS IMPORTATNT

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Dystonic reactions may be life-threatening

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Side effects from D2 receptor blockade do not always respond to anticholinergic medications

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• Akathisia

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Extrapyramidal Side Effects (EPS) due to D2 Blockade

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• Akathisia

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Neuroleptic Malignant Syndrome (NMS)

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• Can be fatal

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Neuroleptic Malignant Syndrome

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• Early recognition is essential

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Tardive dyskinesia

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• Late onset side effect of antipsychotics

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Tardive dyskinesia mechanism

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• Seems due to hypersensitivity of D2 receptors with long-term D2 blockade

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Effects of Hyperprolactinemia with D2 Receptor Blockade

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• Gynecomastia

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Other Receptor Binding Properties of Atypical Antipsychotics

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• Hyperglycemia

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Cardiac Effects of Antipsychotics

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• Dermatological effects – hypersensitivity, photosensitivity

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Specific side effects relevant to clozapine treatment

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• Seizures

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Drug Interactions with Antipsychotics

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• Enhanced sedation with alcohol, anesthetics, antihistamines, hypnotics, opiates

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Side Effects with Sudden Antipsychotic Cessation

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• Withdrawal dyskinesias

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Factors influencing choice of an antipsychotic

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• Data from the CATIE trial suggest:

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Factors influencing choice of an atypical antipsychotic

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Greater risk of EPS, esp. in high doses; less sedation than some; once daily dosing

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- Factors influencing choice of an atypical antipsychotic

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Sedating; weight gain is often sig.

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Sedating; weight gain common; sz risk with rapid dose ’s; risk of myocarditis; risk of agranulocytosis requires WBC ’s; beneficial in treatment resistant pts. & those at high risk of suicide

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Moderately sedating esp. at therapeutic doses; theoretical  risk of cataracts; generally requires BID dosing; low EPS

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More activating; weight neutral; ? Risk of  QTc interval; low EPS; generally requires BID dosing

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Unique properties as D2 partial agonist; long half-life; active metab.; minimal antichol. effect; low EPS

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Goals of treatment of bipolar disorder

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• Treat acute symptoms during an episode of mania or depression

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Specific Treatments for Bipolar Disorder – Acute Mania

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• Medications with FDA indications for treatment of acute mania include:

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Specific Treatments for Bipolar Disorder – Episode Prophylaxis

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• Medications with “Mood stabilizing properties” to minimize or prevent further episodes

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Lithium

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• Best evidence of “mood stabilizing” effect

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Mechanisms of Lithium Action

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• Exact mechanism of action is unclear

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Pharmacology of Lithium

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• Exact mechanism of action is unclear

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Lithium Pharmacokinetics

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• Differs from most other psychotropics

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Lithium Elimination

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• Because of renal excretion, dosage must be adjusted for:

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lithium theraputic range

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Acute Treatment 1.0 - 1.2 mEq/L

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Chronic Lithium Treatment

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• Renal changes

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Other Adverse Effects of Lithium Treatment

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• Thyroid abnormalities

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Lithium Use during Pregnancy

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• Pregnancy is a relative, but not absolute, contraindication to this treatment

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(Divalproex Sodium)

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• Originally developed as an anticonvulsant

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Serum levels of Valproic Acid in Treatment of Bipolar Disorder

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• Best clinical response in mood disorders occurs with serum levels > 45 mg/mL.

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Adverse Effects of Valproic Acid

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• Sedation

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Drug Interactions with Valproic Acid

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• May increase levels of antipsychotics and antidepressants

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Lamotrigine

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• Originally developed as an anticonvulsant