PPM1Psychotropic Drugs

Objectives:  

Shortcuts:

Sedative-Hypnotic and Anxiolytic Drugs

Antipsychotic Drugs

Antidepressant Drugs and Lithium

I.          Sedative-Hypnotic and Anxiolytic Drugs          (Top of Document)   

1.         Define the following terms:

                        sedative

                        hypnotic

                        sedative-hypnotic

                        anxiolytic

Anonymous

Sedative:  a drug that reduces a person’s response to external stimuli and causes drowsiness.

Hypnotic:  a drug that induces sleep

Sedative-hypnotic:  a sedative that induces sleep when administered in high doses.

Anxiolytic: an agent that reduces anxiety and is also called an antianxiety drug.

Anonymous  Brenner, p. 187

• sedative- drug that reduces a person’s response to external stimuli and causes drowsiness;

• hypnotic- drug that induces sleep.

• sedative-hypnotic- sedative that induces sleep when administered in high doses.

• anxiolytic- agent that reduces anxiety and is also called an antianxiety drug.

Ky Brenner p187

Sedative:  reduces a person’s response to external stimuli and causes drowsiness

Hypnotic:  induces sleep

Sedative-Hypnotic:  sedative that induces sleep when administered in high doses.

Anxiolytic:  reduces anxiety and is also called an anti-anxiety drug

Anonymous Brenner 187

Sedative- A drug that reduces a person’s response to external stimuli and causes drowsiness.

Hypnotic- A drug that induces sleep.

Sedative-hypnotic- A sedative that induces sleep when administered in high doses.

Anxiolytic- An agent that reduces anxiety and is also called an antianxiety drug.

2.         Review the classification and management of anxiety disorders in Brenner, p. 188, and state the recommended drug treatment for each.

Anonymous

Acute Anxiety Disorders

A benzodiazepine may provide short term relief from more severe acute anxiety.  Propranolol is useful in the prevention of stage fright, or acute situational or performance anxiety.

Panic Disorder

Patients with panic disorder often respond to a combination of psychotherapy and drug therapy with a benzodiazepine (esp. alprazolam and clonazepam)  or an antidepressant drug, such as an SSRI.  

Phobic Disorder

Treated like the panic disorder, benzos and/or antidepressants.

Obsessive-Compulsive Disorder

Treated with an antidepressant and psychotherapy.

Generalized Anxiety Disorder

Short-term therapy with a benzodiazepine may relieve acute symptoms and provide a useful bridge to psychotherapy.

Anonymous Brenner, p. 188

            Acute Anxiety Disorders- i.e. adjustment disorder, may result from illness, separation, or the anticipation of stressful events.  They are often self-limiting.  Drug treatment includes the use of benzodiazepine for short term relief of acute anxiety conditions, and Propanolol for stage fright, acute situational or performance anxiety.

            Panic disorder- Characterized by acute episodes of sever anxiety with marked psychologic and physiologic symptoms.  Panic disorder patients often respond to combination of psychotherapy and drug therapy with benzodiazepine or an antidepressant drug (i.e. selective serotonin reuptake inhibitor (SSRI)).  Benzodiazepines provide short-term relief while the antidepressant drug works more long-term.

            Phobic Disorders- condition in which an individual is overly fearful about a particular condition, such as flying.  Phobic disorders are treated with benzodiazepine or an antidepressant drug.  Benzodiazepines provide short-term relief while the antidepressant drug works long-term.

            Obsessive-Compulsive Disorder- Similar features to anxiety and mood disorders.  Obsessions are characterized by recurring or persistent thoughts and impulses, while compulsions are repetitive behaviors in response to obsessions.  They are effectively treated with an antidepressant drug and psychotherapy.

Ky Brenner p188

Anonymous

Acute Anxiety Disorder- An example is an adjustment disorder which may result from illness, separation, or anticipation of stressful events.  Acute anxiety is often self limiting, and may resolve in a few weeks to a few months without drug treatment.

Drug treatment- Benzodiazepine may provide short term relief from more severe acute anxiety conditions.

Propranolol is useful in the prevention of stage fright, or acute situational or performance anxiety.

Panic Disorders- Characterized by acute episodes of severe anxiety with marked psychologic and physiologic symptoms.  During a panic attack, an individual may feel an  impending sense of doom that is often accompanied by sweating, tachycardia, tremor, and other visceral symptoms.

Drug treatment- People with panic disorder often respond to a combination of psychotherapy and drug therapy with a benzodiazepine or an antidepressant drug, such as a selective serotonin reuptake inhibitor (SSRI).   Examples of benzodiazepines are alprazolam and clonazepam.  They provide immediate relief during the early phase of therapy.  The SSRI’s are most effective for long term prevention and treatment.

Phobic Disorders- Phobias are conditions in which an individual is overly fearful about a particular condition, such as traveling in an airplane.  Agoraphobia, which often coexists with panic disorder, is the fear of being in open or public places from which an escape might be difficult.

Drug treatment- Patients with phobic disorders often respond to a combination of psycotherapy and drug therapy.  Like panic disorder, phobic disorders are treated with a benzodiazepine or an antidepressant drug.  Benzodiazepines provide acute relief, whereas antidepressants are usually the most effective long-term drug therapy.

Obsessive-Compulsive Disorder- Has features similar to anxiety and mood disorders.  It is characterized by obsessions (recurring or persistent thoughts and impulses) and compulsions (repetitive behaviors in response to obsessions).

Drug treatment- OCD can be treated effectively with an antidepressant drug.

Generalized-Anxiety Disorder- A persistent state of fear and apprehension concerning future events.

Drug treatment- Short term therapy with benzodiazepines to relieve acute symptoms and provide a useful bridge to psychotherapy.  Buspirone provides a useful alternative to benzodiazepines for treatment of chronic anxiety, because it produces little sedation, and is not associated with tolerance or independence.

3.         Describe the pharmacologic effects and indications for benzodiazepines  (representative drug:  diazepam).

Anonymous Brenner pg. 194

Produces a dose-dependent but limited depression of CNS.  Low doses have a sedative and anxiolytic effect, higher doses produce hypnosis (sleep) and anesthesia.  In addition, benzodiazepines are able to produce anterograde amnesia (means an individual will not remember what happens from the time that the drug is administered to the time that the drug effects dissipate).  This is used when pts. undergo stressful procedures-endoscopy and surgery.  These drugs also have an anticonvulsant effect and can be used in treatment of seizure disorders. They are also occasionally used in treatment of muscle spasm and spasticity.

These drugs should only be used short term. If long term use is indicated-provider must monitor closely.

Anonymous Brenner, p. 194-95

Benzodiazepines produce a dose-dependent but limited depression of the CNS.  Lower doses have a sedative and anxiolytic effect, whereas higher doses produce hypnosis (sleep) and anesthesia.  They do not produce respiratory depression, coma or death unless they are administered with another CNS depressant, such as alcohol.

• Indications for benzodiazepines include treatment of anxiety disorders, insomnia, muscle spasm, seizure disorders and spasticity.  They should be limited to short-term treatment.  If long-term treatment is indicated the drug usage should be carefully monitored to prevent dosage escalation.

Ky Brenner p191

Classification: sedative hypnotic.  Metabolized in liver.  Gut absorption and lipid soluble.

Pharm effects:  sedation.  Dose dependent CNS depression.  Low dose = sedative & anxiolytic.  Higher doses= hypnosis & anesthesia.  Anxiolytic effects at low dose with little sedation.  Anterograde amnesia—impairs formation of new memories.

Indications:  anxiety and insomnia.  Alcohol detoxification. Seizure disorders (anticonvulsant effects). Spasticity.  Undergoing stressful procedures like endoscopy or surgery.

Anonymous Brenner 194

The benzodiazepines produce a dose-dependent but limited depression of the CNS.  Lower doses have a sedative and anxiolytic effect, whereas higher doses produce hypnosis (sleep) and anesthesia.  When benzodiazepines are given orally, their depressant effect on neurotransmission inhibits the further release of GABA before severe CNS depression occurs.  

Benzodiazepines are indicated for the treatment of anxiety disorders, insomnia, muscle spasm, seizure disorders and spasticity.

4.         Describe the adverse effects of benzodiazepines.

Anonymous  Brenner pg. 195

 The adverse effects are largely due to CNS depression.  Cause motor incoordination, dizziness, and excessive drowsiness.  They interfere with driving and other psychomotor skills.  If drug is given intravenous administration may cause respiratory depression.  These drugs also have a mild euphoric effect and may reduce behavioral inhibitions similarly to the effects of alcohol.  I think the most important one to remember is after several months of continued use, most pts will develop some degree of physical dependence.  If medication is abruptly discontinued, the pt will experience a withdrawal syndrome, characterized by rebound anxiety, insomnia, headache, irritability and muscle twitches.  These drugs have also been assoc. with hypotension, arrhythmias (tachycardia and bradycardia) and are contraindicated in pregnancy.

Anonymous  Brenner pg195

            Are largely due to CNS depression.

            Cause motor incoordination, dizziness, and excessive drowsiness.  They impair cognitive processing and may affect concentration, judgment, and planning.  They may also interfere with driving and psychomotor skills.   May cause respiratory depression in large amounts.  

            Long-term use may produce physical dependence and withdrawals when d/c.

Ky Brenner p195

Adverse effects:  largely due to CNS depression and include:  motor incoordination (driving problems); dizziness; excessive drowsiness; impairs cognitive processing and concentration, judgment and planning.  Longer acting benzos may cause hangover.

Considerations:  CNS depression—IV > oral.  Therefore IV may cause respiratory depression.  Benzos also provide an euphoric effect that ↓ behavioral inhibitions.  Behavioral component & euphoria may contributes to their recreational misuse.  Long term usage produces physical dependence and pts will have withdrawal symptoms when discontinued like rebound anxiety, insomnia, headaches, irritability and muscle twitches.  Withdrawal usually mild and not life-threatening.  Taper dosage.  Pharmacodynamic tolerance also occurs during long-term use.  Category X even though incidence of fetal malformations is very low.

Anonymous Brenner 195

The adverse effects of benzodiazepines are largely due to CNS depression.  The drugs frequently cause motor incoordination, dizziness, and excessive drowsiness.  They impair cognitive processing and may affect concentration, judgement, and planning.  Benzodiazepines have a mild euphoric effect, and may reduce behavioral inhibitions in a manner similar to the disinhibitory effect of alcohol.  Long-term usage may produce physical independence.  

5.         Recognize the potentiating effects of alcohol and other CNS depressants on benzodiazepines.

Anonymous Brenner pg.   192

 Alcohol and other CNS depressants potentiate effects of benzodiazepines.

Anonymous  Brenner pg 194

            May cause respiratory depression, coma, or death.

Ky Brenner p194

Oral benzos do not produce respiratory depression, coma or death unless administered with another CNS depressant like alcohol.

Anonymous Brenner 194

When benzodiazepines are administered with alcohol or other CNS depressants they may produce respiratory depression, coma, or death.

6.         State advantages and disadvantages of buspirone compared to     benzodiazepines in the treatment of chronic anxiety.

Anonymous Brenner pg. 193-5

Buspirone: This drug is used in the treatment of chronic anxiety and produces an anxiolytic effect without causing marked sedation, amnesia, tolerance dependence or muscle relaxation.  It may cause headache, dizziness and nervousness-but side effects are usually mild and temporary. Onset of action is very slow but duration of action is usually >12 hours.  This is a great drug for chronic anxiety when the patient would need to be on medication for a long time. There are no known common drug interactions with this drug.

Benzodiazepines: Onset of action is fast- anywhere from 15-59 minutes.  The duration of action can last anywhere between 7-12 hrs. depending on the drug.  This drug is great for insomnia, situational anxiety, anesthesia and sedation. Not great for long term use due to the potential of addiction and withdrawal symptoms.

Anonymous  Brenner pg 198

• Advantages:  produces a long acting anxiolytic effect without causing marked sedation, amnesia, tolerance, dependence, or muscle relaxation.  

• Disadvantages:  Have dizziness, and nervousness, but are mild and temporary.

Ky Brenner p198

Buspirone is a nonsedating anxiolytic.  Causes up-regulation of postsynaptic serotonin receptors.  Takes 3-4 weeks to get the effect.  Does not cause marked sedation, amnesia, tolerance, dependence or muscle relaxation.  May temporarily cause mild: headaches dizziness, nervousness.

D Higbee.  Brenner pg. 188

Buspirone provides a useful alternative to Benzodiazepines for the treatment of chronic anxiety states because it provides little sedation and is not associated with tolerance or dependence.  However, it must be taken for 3 or 4 weeks before its anxiolytic effects are felt.

Anonymous Brenner 198

Advantages- Buspirone is used in the treatment of chronic anxiety and produces an anxiolytic effect without causing marked sedation, amnesia, tolerance, dependence, or muscle relaxation.

Disadvantages- In some patients it may cause headaches, dizziness, and nervousness, but they are usually mild and temporary.  The anxyiolytic effect may also take 3-4 weeks to develop.

II.        Antipsychotic Drugs          (Top of Document)   

1.         List or recognize “positive symptoms” vs. “negative symptoms” in schizophrenia.

Anonymous

Positive symptoms—delusions, hallucinations, probably result form excessive neuronal activity in mesolimbic neuronal pathways. These symptoms are usually the primary manifestations of acute psychotic episodes.

Negative symptoms – apathy, withdrawal, and lack of motivation and pleasure, probably result from insufficient activity in mesocorotical neuronal pathways.  The negative symptoms are generally more difficult to treat, often persist after positive symptoms resolve, and are associated with a poor prognosis.

Anonymous

Janelisa, Brenner 223

v     Positive sx: agitation, delusions, disorganized speech/thinking, hallucinations, insomnia

v     Negative sx: apathy, affective flattening, lack of motivation/pleasure, poverty of speech, social isolation

Sung K, CMDT2003 p.1026

Anonymous Brenner 222

Positive symptoms- Include delusions and hallucinations, probably resulting from excessive neuronal activity in mesolimbic neuronal pathways.  These symptoms are usually the primary manifestations of acute psychotic episodes.

Negative symptoms- Include apathy, withdrawal and lack of motivation and pleasure.  Probably result from insufficient activity in mesocortical neuronal pathways.  These symptoms are generally more difficult to treat, often persist after positive symptoms resolve, and are associated with poor prognosis.

2.         Describe the dopamine hypothesis for schizophrenia, and how this relates to the primary mode of action of most antipsychotic drugs.

Anonymous

According to the dopamine, hypothesis schizophrenia results from abnormalities in dopamine neurotamsmission in mesolimbic and mesocrotical neuronal pathways (Box22-1).  Because much of the evidence supporting this hypothesis is based on the effects of drugs that alter dopamine neurotransmission, the hypothesis has been called a pharmacocentric hypothesis.   First most antipsychotic drugs block dopamine D2 receptors, and there is an excellent correlation between the clinical potency of these drugs and their into vitro affinity for these receptor. Second, drugs that act by increasing the neuronal dopamine (drugs such as amphetamines and cocaine can induce psychotic behavior that resembles the behavior of schizophrenic patients.

Anonymous Brenner p. 223

            According to the dopamine hypothesis, schizophrenia results from abnormalities in dopamine neurotransmission in mesolimbic and mesocortical neuronal pathways.  Because much of the evidence supporting this hypothesis is based on the effects of drugs that alter dopamine neurotransmission, they hypothesis has been called a pharmacocentric hypothesis.

            Several observations support the dopamine hypothesis.

First, most antipsycotic drugs block dopamine D2 receptors, and there is an excellent correlation between the clinical potency of these drugs and their in vitro affinity for these receptors.        

Second, drugs that act by increasing the neuronal release of dopamine or by blocking the reuptake of dopamine ( drugs such as amphetamines and cocaine) can induce psychotic behavior that resembles the behavior of schizophrenic patients.  

            Dopamine turnover in the brain, which reflects the neuronal release of dopamine, can be studied by measuring the concentration of the principal metabolite of dopamine, homovanillic acid, in the CSF.  While elevated levels of homovanillic acid are not found in-patients with chronic schizophrenia, they are found in some schizophrenic patients undergoing acute psychotic episodes.  There is also evidence for a dopamine receptor defect in schizophrenic patients.  Positive emission topography scanning (PET) using D2 receptor ligands has revealed that schizophrenic patients have decreased D2 receptor densities in the prefrontal lobe cortex (but increased D2 receptor densities in the caudate nucleus).  These findings lend support to the dopamine hypothesis and to another hypothesis called the hypo frontally hypothesis.

Janelisa, Brenner 223-4

v     Schizophrenia results from abnormalities in dopamine neurotransmission in mesolimbic and mesocortical neuronal pathways (see Box22-1 on p. 224).

v     Most antipsychotic drugs block dopamine D₂ receptors. There is excellent correlation between the clinical potency of these drugs and their in vitro affinity for these receptors.

v     Drugs that act by increasing the neuronal release of dopamine or by blocking the reuptake of dopamine (amphetamines and cocaine) can induce psychotic behavior that resembles schizophrenia

v     Higher levels of dopamine’s metabolite, homovanillic acid, are found in some schizophrenic patients during an acute psychotic episode.

v     These patients also have a dopamine receptor defect

Sung K, Melmon: Clinical Pharmacology p.490

            The dopaminergic hypothesis postulates that for one reason or another dopaminergic activity is increased in the mesolimbic system of the brain. Thus, this hypothesis is the foundation of drug therapy. All effective antipsychotic drugs seem to act by blocking postsynaptic dopamine D2 receptors; schizophrenia may be aggravated by dopamine precursors (e.g. levodopa), by dopamine releasers (e.g. amphetamines), and by dopamine-receptor agonists (e.g. apomorphine). 

Anonymous Brenner 223

According to this hypothesis schizophrenia results from abnormalities in dopamine neurotransmission in mesolimbic and mesocortical neuronal pathways.  Supporting data suggests most antipsychotic drugs block dopamine D2 receptors, and there is an excellent correlation between the clinical potency of these drugs and their in vitro affinity for these receptors.  Second, drugs that act by increasing the neuronal release of dopamine or by blocking the reuptake of dopamine (drugs such as amphetamines and cocaine) can induce psychotic behavior that resembles the behavior of schizophrenic patients.  

3.         Distinguish between the older ("typical") antipsychotic drugs (e.g. chlorpromazine, thioridazine, haloperidol) and the newer ("atypical") antipsychotic drugs (e.g., olanzapine, risperidone).

Anonymous

Typical antipsychotic drugs have an equal or greater affinity for D2 receptors than for 5HT2 receptors.

Atypical antipsychotic drugs, have a greater affinity for 5-HT2 receptors than for D2 receptors and some atypical drugs have increased affinity for D3 or D4 receptors.

Anonymous  Brenner p. 225, 229, See table 22-3 on 226

            Anti psychotic  drugs are usually classified on the basis of their chemical structure, but they can also be classified according to whether they display typical or atypical pharmacologic properties.  The typical anti  psychotic drugs include phenothiazines, the thioxanthenes, the butyrophenones, and some azepines (such as loxapine).  Phenothiazines are primarily used to treat schizophrenia and other forms of psychosis, including drug induced psychosis and psychosis associated with the manic phase of bipolar disorder.  They are also used to treat severely agitated patients, including those with dementia and severe mental retardation.  Because the phenothiazamines have antiemetic activity, some of them are used in the management of nausea and vomiting.  These drugs have extensive side effects, such as, sedation, extra pyramidal effects, antichollenergic effects, orthostatic hypotension, as well as elevated serum prolactin levels, poikilothermy, cardiac arrythmia, elevated serum prolactin levels, and retinopathy.

            Atypical anti psychotic drugs include, olanzapine, and risperidone, which is are derivatives of the azepines ,  these drugs have fewer extra pyramidal side effects, less sedation, fewer anticholenergic effects and less incidence of orthostatic hypotension.  However these drugs affect cardiac arrhythmias, and weight gain.

Janelisa, Brenner 225

v     Typical antipsychotics have an equal or greater affinity for D₂ receptors than for 5-HT₂ (serotonin) receptors. Blockade of  D₂ receptors in the basal ganglia is believed to be responsible for the parkinsonian and other extrapyramidal side effects that can occur

v     Atypical antipsychotics have a greater affinity for 5-HT₂ receptors than D₂ receptors

Sung K, Koda-Kimble p.76.10

            Typical antipsychotics: increased incidence of EPS, prolactin elevation, mainly treat positive symptoms (no effect for negative symptoms), and less efficacious for refractory schizophrenia

            Atypical antipsychotics: decreased incidence of EPS, lack of effect on serum prolactin, greater efficacy for refractory schizophrenia, and expanded spectrum of activity against negative symptoms. 

Anonymous Brenner 225, 230, 241

Typical antipsychotic drugs are believed to act by blocking dopamine D2 receptors in mesolimbic pathways.  Atypical antipsychotic drugs act by blocking serotonin 5-HT2 and D2 receptors.  Both classes of drugs alleviate the positive symptoms of schizophrenia, but the typical drugs cause a higher incidence of extrapyramidal side effects (akathisa, pseudoparkinsonism, dystonia, and tardive dyskinesia) and are less effective against the negative symptoms of schizophrenia.

4.         Describe the major side effects of the typical agents, especially tardive dyskinesia.

Anonymous While akathisia, pseudoparkinsonism, and dystonias are acute extrapyrmidal side effects that often occur early in the course of treatment with antipsychotic drugs TD is a disorder that usually develops after months or years of treatment.  Abnormal oral and facial movement, such as tongue protrusion and leap smacking characterizes the disorder.  In later stages abnormal limb and truncal movements may also be observed

Anonymous Brenner p. 229

            While akathisia, psydoparkinsonism, and dystonias are acute extrapydramidal side effects that often occur early in the course of treatment with anti psychotic drugs, tardive dyskinesia is a disorder that usually develops after months or years of treatment.  The disorder is characterized by abnormal oral and facial movements, such as tongue protrusion and lip smacking.  In later states, abnormal limb and truncal movements may also be observed.  Investigators believe that TD results from super sensitivity to dopamine, which develops during long-term dopamine receptor blockage.  This hypothesis is supported by the fact that the symptoms of TD temporarily subside if dopamine receptor blockade is increased by giving larger doses of an ant psychotic drug.  However, this approach eventually leads to further receptor super sensitivity and worsening of the manifestations of TD.

Janelisa, Brenner 229 Akathisia, pseudoparkinsonism, and dystonia often occur early in the course of treatment. Tardive dyskinesia usually develops after months or years of treatment.

v     Akathisia: motor restlessness shown by compulsion to pace, shuffle feet, or shift positions. Unable to sit quietly.

v     Pseudoparkinsonism: characterized by rigidity, bradykinesia, and tremor

v     Dystonia: state of abnormal muscle tension that often affects the neck and facial muscles, including the tongue, pharynx, larynx, and eyes. Severe reactions include oculogyric crisis, where the eyeballs become fixed in one position, glossospasm, tongue protrusion, and torticollis, a twisting of the neck and an unnatural position of the head.

v     Tardive dyskinesia: characterized by abnormal oral and facial movements, such as tongue protrusion and lip smacking. In later stages, may see abnormal limb and truncal movements. Believed to occur from supersensitivity to dopamine which develops during long-term dopamine receptor blockade

Sung K, CMDT2003 p.1031-1033

a)   Anticholinergic effects – dry mouth, blurred near vision, urinary retention, delayed gastric emptying, esophageal reflux, ileus, delirium, and precipitation of acute glaucoma in patients with narrow anterior chamber angles.

b)   cardiac effects – orthostatic hypotension from alpha-1-adrenergic blockade, QTc prolongation, T-wave flattening, and QRS widening

c)   Sedation

d)   Extrapyramidal symptoms – broad term to describe several types of acute and chronic drug-induced movement disorders including acute dystonia, pseudoparkinsonism, and akathisia, which tend to occur early in treatment, and tardive dyskinesia which has a late onset.

      Tardive dyskinesia

Anonymous Brenner 229

Akathisia- “motor restlessness.”  These patients shuffle their feet, or shift positions, and are unable to sit quietly.

Pseudoparkinsonism- resembles idiopathic Parkinson’s disease and is characterized by rigidity, bradykinesia, and tremor.

Dystonia- a state of abnormal muscle tension that often affects the neck and facial muscles, including the tongue, pharynx, larynx, and eyes.

*Tardive dyskinesia(TD)- a disorder that usually develops after months or years of treatment.  This disorder is characterized by abnormal oral and facial movements, such as tongue protrusion and lip smacking.  In later stages, abnormal limb and truncal movements may also be observed.  It is believed that TD results from supersensitivity to dopamine, which develops during long term dopamine receptor blockade.  

5.         Describe the neuroleptic malignant syndrome.

Anonymous Pharmacology pg 229 Neuroleptic malignant syndrome is a severe form of drug toxicity that occurs in 0.5 to1% of patients treated with antipsychotic drugs.  It is a life-threatening condition characterized by muscle rigidity, elevated temperature >38oC, altered consciousness, and autonomic dysfunction (tachycardia, diaphoresis, tachypnea, and urinary and fecal incontinence).  

Anonymous  Brenner p. 229

            Neuroleptic malignant syndrome is a severe form of drug toxicity that occurs in 0.5-1% of patients treated with ant psychotic drugs.  It is a life threatening conditions characterized by muscle rigidity, elevated temperature (>38.0C), altered consciousness, and autonomic dysfunction (tachycardia, diaphoresis, tachypnea, and urinary and fecal incontinence).  The syndrome resembles malignant hyper thermia.  

Janelisa, Brenner 229 This is a life-threatening condition characterized by muscle rigidity, elevated temperature >38^oC, altered consciousness, and autonomic dysfunction (tachycardia, diaphoresis, tachypnea, and urinary and fecal incontinence). It occurs in 0.5-1% of patients treated with antipsychotic drugs

Sung K, CMDT2003 p.1031

      It is a catatonia-like state manifested by extrapyramidal signs, blood pressure changes, altered consciousness, and hyperpyrexia; it is uncommon but serious complication of neuroleptic treatment. Muscle rigidity, involuntary movements, confusion, dysarthria, and dysphagia are accompanied by pallor, cardiovascular instability, fever, pulmonary congestion, and diaphoresis and may result in stupor, coma, and death. The cause may be related to a number of factors, including poor dosage control of neuroleptic medication, affective illness, decreased serum iron, dehydration, and increased sensitivity of dopamine receptor sites. Lithium in combination with a neuroleptic drug may increase vulnerability which is already increased in patients with an affective disorder. In most cases the symptoms develop within the first 2 weeks of antipsychotic drug treatment. The syndrome may occur with small doses of the drugs. IM administration is a risk factor. Eleveated creatine kinase and leukocytosis with a shift to the left are present early in half of cases.

      Summary

      Neuroleptic malignant syndrome (NMS)

Anonymous Brenner 229

This is a severe form of drug toxicity that occurs in 0.5-1% of patients treated with antipsychotic drugs.  It is a life-threatening condition characterized by muscle rigidity, elevated temperature, altered consciousness, and autonomic dysfunction (tachycardia, diaphoresis, tachypnea, and urinary and fecal incontinence).  The syndrome resembles malignant hypertension.

6.         Describe the indications for using atypical antipsychotics instead of typical agents.  

Anonymous Pharmacology pg 229-231 The atypical antipsychotic drugs represent an appealing choice for the treatment of schizophrenia, and some authorities believe they will become the drugs of choice for treating most forms of psychosis.  They do this by alleviating the negative symptoms of schizophrenia and decreasing the incidence of extrapyramidial side effects (side effects caused by drugs that block dopamine receptor sites in the extrapyramidial system – i.e. part of the Nervous system / basal ganglia/substantia nigra/ subthalamic nucleas/part of the midbrain/and motor neurons of the spine)            

Anonymous  Brenner 230

            In comparison with the typical drugs, the atypical anti-psychotics produce lower incident e of extra pyramidal side effects and appear to be more effective against the negative symptoms of schizophrenia.  Most common side effects are anxiety and insomnia. Atypical anti-psychotic drugs include azepines (such as clozapine and olanzapine) and a benzisoaxazole drug called risperdone.

Brent Brenner 229-30

They produce fewer extrapyramidal side effects (akathisia, pseudoparkinsonism, and dystonias).  They also exhibit a greater activity against negative symptoms.

Janelisa, Brenner 231 All of the typical antipsychotics have equal efficacy in treating schizophrenia. Because the atypical antipsychotics produce a lower incidence of extrapyramidal side effects and appear to be more effective against the negative symptoms of schizophrenia, many believe they will become the drug of choice. The long-term effectiveness of these atypical drugs  in patients with chronic schizophrenia has not been adequately studied.

v     Olanzapine: is as effective as haloperidol in alleviating the positive symptoms of schoizophrenia, superior to haloperidol in alleviating the negative symptoms, and has fewer side effects. The most common adverse reactions are sedation and weight gain.

v     Risperidone: in comparison to olanzapine, causes less sedation, more orthostatic HTN, and higher incidence of extrapyramidal side effects. In some patients, risperidone elevates serum prolactin and lengthens the QT interval predisposing patients to cardiac arrhythmias.

Anonymous Brenner 231

The atypical antipsychotic drugs represent an appealing choice for the treatment of schizophrenia.  In comparison with the typical drugs, the atypical drugs produce a lower incidence of extrapyridimal side effects and appear to be more effective against the negative symptoms of schizophrenia.  

III.       Antidepressant Drugs and Lithium          (Top of Document)   

1.         List or recognize the indications and adverse effects of tricyclic antidepressants (TCAs).   (representative drug:  amitriptyline)

Anonymous Pharmacology pg 232

Indications – TCAs have been used to treat all forms of depression and to treat several other conditions, such as panic disorder, phobic disorders, and obsessive-compulsive disorder.  They are beneficial in management of certain sleep disorders, including somnambulism, night terrors, and enuresis by repressing abnormal REM sleep and dreaming, which are conditions that contribute to somnambulism and night terrors.  It also increases the awareness of the need to urinate and thus facilitates waking up for this purpose. They also help in Chronic Pain Syndrome because of their mood elevating effect and analgesic activity.

Adverse Effects – Like many of the antipsychotic drugs, the TCAs produce autonomic side effects by blocking muscarinic and α-adrenergic receptors.  Some of the TCAs also produce marked sedation.  The TCAs lower the seizure threshold and may induce seizures at therapeutic as well as toxic serum concentrations.  An overdose of TCA can cause life-threatening cardiac arrhythmia, marked autonomic effects, including hypotension and sinus tachycardia.

Anonymous Brenner 232-234

            TCAs block the neuronal reuptake of norepinephrine and serotonin which produces and antidepressant effect that becomes apparent about 2-4 weeks after initial therapy.

            Indications:  All forms of depression, anxiety disorders (panic phobic and obsessive compulsive disorders), sleep disorders (including somnambulism, night terrors, and enuresis), and chronic pain syndrome.

            Adverse Effects:  TCAs produce autonomic side effects by blocking muscarinic and alpha adrenergic receptors, including marked sedation, orthostatic hypotension, cardiac conduction disturbances, and anti-cholernigic effects.

            Treatment of Adverse Effects:  overdose can be treated by IV sodium bicarbonate.

Greg Brenner p. 232

Indications- Anxiety, depression, sleep disorders and chronic pain.

Adverse effects- produces automonic side effects by blocking muscarinic and alpha andrenergic receptors.  Produce marked sedation, sz, orthostatic hypotension and cardiac conduction disturbances (sinus tach, wide QRS > 0.12 sec.).

Paul, Brenner pg 232-233

Indications:  

• TCAs have been used to treat all forms of depression

• TCAs are effective in treating certain anxiety disorders such as:

• Panic disorder

• Phobic disorders

• Obsessive-compulsive disorder

• TCAs are beneficial in the management of certain sleep disorders including:

• Somnambulism

• Night terrors:  TCAs repress abnormal Rapid eye movement sleep and dreaming which are conditions that contribute to somnambulism and night terrors

• Enuresis:  TCAs appear to increase the awareness of the need to urinate and facilitate waking up for this purpose

• TCAs have a role in the treatment of chronic pain syndromes because of their mood elevating effect and analgesic activity

Adverse effects:

• Like many other antipsychotic drugs, the TCAs produce autonomic side effects by blocking muscarinic and alpha-adrenergic receptors.

• Some produce marked sedation.  In fact, TCAs are often administered at bedtime, when their sedative effects may have the added benefit of promoting sleep

• Lower the seizure threshold and may induce seizures at therapeutic as well as toxic serum concentrations

• Overdose of a TCA may cause life-threatening cardiac arrhythmia (wide QRS complex tachycardia), marked autonomic effects including hypotension and sinus tachycardia; excessive sedation; and seizures

Anonymous Brenner 232

Indications- TCA’s have been used to treat all forms of depression and to treat several other conditions.  They are effective in the treatment of certain anxiety disorders, such as panic disorder, phobic disorders, and obsessive compulsive disorder.  TCA’s are also beneficial in the management of certain sleep disorders, including somnambulism, night terrors, and enuresis.  TCA’s also have a role in the treatment of chronic pain disorders.

Adverse effects- The TCA’s produce autonomic side effects by blocking muscarinic and alpha-adrenergic receptors.  Some also produce marked sedation.  TCA’s also lower the seizure threshold and may induce seizures at therapeutic as well as toxic serum concentrations.  Taking an overdose of TCA may cause life-threatening cardiac arrhythmia; marked autonomic effects, including hypotension and sinus tachycardia; excessive sedation; and seizures.  

2.         List or recognize the indications, adverse effects, and interactions of and selective serotonin reuptake inhibitors (SSRIs).

            (representative drugs:  fluoxetine, sertraline)

Anonymous Indications – SSRIs are used to treat depression; to treat eating disorders, such as bulimia nervosa and anorexia nervosa; and to treat anxiety disorders, such as panic disorder, phobic disorders, and obsessive-compulsive disorder.  SSRIs may also be effective in management of other conditions such as fibromyalgia, autism, and premenstrual syndrome.

Adverse Effects – SSRIs produce fewer sedative, autonomic, and cardiovascular side effects than do the TCA’s.  SSRIs are usually administered in the morning because they tend to increase alertness in patients and there most common adverse effects are nervousness, dizziness, and insomnia.  They occasionally cause male sexual dysfunction in the forms of priapism and impotence.  SSRIs need to be used cautiously in patients with seizure disorders, hepatic disorders, diabetes, or bipolar disorder.

Interactions – SSRIs inhibit (cytochrome P450 isozymes).   inhibition  of CYP2D can increase the serum levels of antipsychotic drugs, TCAs, and dextromethorphan.  Inhibition of CYP2C and CYP3A can increase serum levels of alprazolam, diazepam, carbamazepine, phenytoin, and other drugs.  SSRIs may also increase the hypoprothrombinemic effect of warfarin  SSRIs should not be used concurrently with momomine oxidase (MAO) Inhibitors, because both types of drugs increase the seratonin levels in the brain and their concurrent use may precipitate the serotonin syndrome (agitation, restlessness, confusion, insomnia, seizures, severe hypertension, and gastrointestinal symptoms)

Anonymous Brenner 234-237

            Indications: SSRIs are used to treat depression, eating disorders (bulimia nervosa and anorexia nervosa) and anxiety disorders (panic, phobic and obsessive compulsive disorders). They may also be effective in the management of fibromyalgia, autism and premenstrual syndrome.

            Adverse Effects: Nervousness, dizziness, insomnia, occasionally cause male sexual dysfunctions (priapism & impotence), should be used with caution in pts with seizure disorders, hepatic disorders, diabetes or bipolar disorder.

            Interactions: SSRIs, especially fluoxetine, increase serum levels of many other drugs, including:

•        Β-adrenergic receptor antagonists

•        alprasolam

•        Antiepileptic drugs

•        Antipsychotic drugs

•        Carbamazepine

•        Dextromethorphan

•        Diazepam

•        Methadone

•        Phenytoin

•        TCAs

•        Theophylline

Concurrent use of an SSRI with an anticoagulant, lithium or MAO inhibitor may result in increased pharmacologic effects or toxicity. SSRIs inhibit CYP2D which can increase the serum levels of antipsychotic rugs, and they inhibit CYP2C and CYP3A, which can increase levels of alprasolam, diazepam etc, and (see above). SSRIs may also increase the hypo-pro-thrombinemic effect of warfin.  SSRIs in conjunction with MAOs can precipitate the serotonin syndrome: characterized by agitation, restlessness, confusion, and GI symptoms.

            Fluoxetine: the first drug approved for the treatment of bulimia and may be effective in treating anorexia nervosa as well. Well absorbed orally, and converted to active metabolite, norfluoxetine. Causes more drug interactions than other SSRIs, can impair the regulation of blood glucose levels in diabetic pts, and can also cause a syndrome of inappropriate antidiuretic hormone secretion (SIADH), characterized by persistent hyponatremia and elevated urine osmolality.

            Sertraline:  undergoes 1^st pass elimination and has relatively little effect on P450 isozymes and causes fewer drug interactions than Fluoxetine, and is preferred in elderly pts because its elimination isn’t affected by aging.

Greg Brenner p. 236

Indications- depression, anxiety disorders such as panic disorder and OCD

Adverse effects- less sedation, less autonomic and less cardiac than TCA’s, nervousness, they increase alertness, dizziness and some sexual disfunction but these side effects decrease with continued use.

Interactions- Inhibit P450 isoenzyme so they will have significant effects with many drugs.  Will ^ serum levels of antiepileptic, antipsychotics, carbmazepine, dextromethorphan, diazepam, methadone, phenytoin, TCA’s, theophylline.

Paul, Brenner pg 234-237

Indications:

• Depression

• Eating disorders such as bulimia nervosa and anorexia nervosa

• Anxiety disorders such as panic disorders, phobic disorders, and obsessive – compulsive disorder

• May be effective in the management of:

• Fibromyalgia

• Autism

• Premenstrual syndrome

Adverse Reactions:

• Unlike TCAs, SSRIs are usually administered in the morning as they increase the patients alertness

• Most common adverse reactions:

• Nervousness

• Dizziness

• Insomnia

• Occasionally cause male sexual dysfunction such as priapism and impotence

• Many side effects subside with continued use

• SSRIs should be used with caution in patients with seizure disorders, hepatic disorders, diabetes, or bipolar disorder

Interactions:

• Because of their ability to inhibit cytochrome P450 isozymes, SSRIs have significant interactions with a variety of drugs.

• SSRIs, especially fluoxetine, increase serum levels of many other drugs, including beta-adrenergic receptor antagonists, alprazolam, antiepileptic drugs, antipsychotic drugs, carbamazepine, dextromethorphan, diazepam, methadone, phenytoin, TCAs and theophylline

• Concurrent use of an SSRI with an anticoagulant, lithium, or MAO inhibitor may result in increased pharmacologic effects or toxicity.

• SSRIs and MAO Inhibitors should not be used concurrently as both drugs increase the serotonin levels in the brain and may precipitate the serotonin syndrome which is characterized by:

• Agitation

• Restlessness

• Confusion

• Insomnia

• Seizures

• Severe hypertension

• GI symptoms

• At least 2 weeks should elapse between use of MAO inhibitor or SSRI and at least 5 weeks between MAO inhibitor and fluoxetine

Fluoxetine is the first drug approved for the treatment of bulimia and may be effective in the management of anorexia.  Causes more drug interactions that other SSRIs do. It may impair the regulation of blood glucose levels in diabetic patients.  Can also cause a syndrome of inappropriate antidiuretic hormone secretion (SIADH), characterized by persistent hyponatremia and elevated urine osmolality

Sertraline has relatively little effect on P450 isozymes and causes fewer drug interactions tan does fluoxetine.  May be preferred in elderly patients because its elimination is not affected substantially by aging.  

Anonymous Brenner 234

Indications- SSRI’s are used to treat depression; to treat eating disorders such as bulimia nervosa and anorexia nervosa; and to treat anxiety disorders, such as panic disorder, phobic disorders, and obsessive-compulsive disorder.  They may also be effective in the management of other conditions such as fibromyalgia, autism, and premenstrual syndrome.

Adverse effects- The SSRI’s produce fewer sedative, autonomic, and cardiovascular side effects than do TCA’s.  The most common adverse effects are nervousness, dizziness, and insomnia.  They occasionally cause male sexual dysfunction in the forms of priapism and impotence.

Interactions- Because of their ability to inhibit cytochrome P450 isozymes, the SSRI’s have significant interactions with a variety of drugs.  Among the SSRI’s, fluoxetine had the greatest effect on the CYP2D isozyme and sertraline had the least effect.  Inhibition of CYP2D can increase the serum levels of antipsychotic drugs, TCA’s, and dextromethorphan.  Inhibition of CYP2C and CYP3A can increase serum levels of alprazolam, diazepam, carbamezipine, phenytoin, and other drugs.  SSRI’s may also increase the hypoprothrombinemic effect of warfarin.  SSRI’s should also not be used with Monoamine oxidase (MAO) inhibitors, because both types of drugs increase serotonin levels in the brain and their concurrent use may precipitate the serotonin syndrome.

3.         Compare the tricyclic antidepressants (TCAs) and selective serotonin  reuptake inhibitors (SSRIs), specifically advantages and disadvantages of each.

Anonymous – Brenner, pp 232-237

TCAs Advantages: highly effective, sedation is useful when taken q.h.s.           

Disadvantages: high association w/ adverse effects.  (E.g., ANS probs, sedation) severe

toxicity when taken in high doses (easily overdosed w/ toxic/fatal result including cardiac arrhythmia, seizure)

SSRIs Advantages: As effective as TCAs, fewer ANS probs, less sedation.  Safer than

TCAs following overdose.

Disadvantages: most common adverse effects = nervousness, dizziness, insomnia. Occasionally cause priapism or impotence.  Though the text only mentions adverse sexual effects in the male, these meds are commonly known to cause decreased sexual response and/or anorgasmia in enough women that doctors mention it as a side effect to watch for.  Use w/ caution in pts. w/ seizure disorders, hepatic disorders, diabetes, bipolar disorder.       

Anonymous  Brenner 234

            SSRIs are as effective as TCAs, but cause fewer autonomic side effects and less sedation. They are also much safer than the TCAs following an overdose, in that the SSRIs seldom cause cardiac arrhythmia and less likely to induce seizures.

Table 22-7 Adverse Effects of Antidepressant Drugs p236

Greg Brenner p. 239

Paul, Brenner pg 241

• TCAs block serotonin and norepinephrine reuptake.  They effectively treat depression, but they have significant autonomic and cardiovascular side effects.  When taken in an overdose, they may cause seizures and cardiac arrhythmia

• SSRIs are antidepressants that have fewer autonomic and cardiovascular side effects and cause less sedation than do the TCAs.  Fluoxetine has a longer half-life and causes more drug interactions.  Sertraline causes fewer drug interactions.

Anonymous Brenner 239

TCA’s

Advantages- Lower cost than most SSRIs, and are not known to cause as many drug interactions.

Disadvantages- Produce more adverse effects (marked sedation), and are not as safe in overdose than SSRI’s.

SSRIs

Advantages- Produce fewer adverse effects, are better tolerated, and are safer in overdose than TCA’s.

Disadvantages- Most are higher in cost, and have an increased tendency to cause drug interactions.

4.         List or recognize other antidepressant drugs, such as MAO inhibitors, bupropion, hypericum (St. John’s wort), nefazodone, and venlafaxine.

Anonymous Brenner pp 238-239

Monoamine Oxidase Inhibitors have many interactions w/ drugs & food.  Not drug of choice for depression since we have so many others.  Used only when other options fail.

Bupropion is Wellbutrin and Zyban.  Weak inhibitor of reuptake of dopamine, norepinephrine, and serotonin.  Mechanism of action not well understood.  Though not documented here, I have also seen higher doses of this med used for OCD.

Hypericum is St. John’s Wort, used extensively in Europe and recently in US.  Not much is known here, though I have heard (from a doc) of a study in Europe that shows it works when taken consistently, 3 times daily for several months, and doesn’t work when taken occasionally or not on the proper regimen.

Nefazodone (Serzone), related to trazodone though they occupy their own separate classes under the category “other”.  Usu. tried when SSRIs fail, fewer associated side effects than TCAs.  May cause sedation, dizziness, nausea, visual changes. No sexual side affects.  People seem to like this.  J                 

Venlafaxine – structurally unique.  Strongly blocks reuptake of dopamine and serotonin.  Side effects similar to SSRIs.

Anonymous

There are two types of MAO inhibitors:  type A preferentially oxidizes serotonin but will also metabolize NE and dopamine.  Type B preferentially metabolizes dopamine. Type A is believed to be responsible for the antidepressant effects of the MAO inhibitors.  

Bupropion- an aminoketone whose mechanism of action is not well understood.  A relatively weak inhibitor of the neuronal reuptake of dopamine, NE, and serotonin.  It produces few anticholinergic SE, little sedation, rarely CV SE or sexual dysfunction.

Hypericum- extracts of the plant called St. John’s wort have been found to exhibit antidepressant activity, and can be found in health food stores.

Mirtazapine- new tetracylic piperazinoazine drug that is structurally different from other antidepressants and has both antidepressant and antianxiety effects.  It is better tolerated and has fewer adverse reactions than do the TCA’s.

Nefazodone and Trazodone- both triazolopyridine drugs.  Trazodone selectively inhibits the neuronal reuptake of serotonin.

Venlafaxine- a structurally unique antidepressant that strongly blocks the reuptake of both NE and serotonin.  

Greg Brenner p. 238

Bupropion- weak inhibitor of reuptake of dopamine, norepi and serotonin. Few anticholinergic side effects, very little sedation, rarely causes CV effects or sexual disfunx, may cause agitation, insomnia, nausea, weight loss

Hypericum- inhibits MAO or block reuptake of serotinin, fewer side effects of TCA’s, being studied to test safety and effectivness.

Nefazodone- inhibits 5-HT2 receptors, little or no antichol, antiadren, or antihistamine activity.  May cause sedation, dizziness, nausea, and visual changes, but no sexual stuff.

Venlafaxine- strongly blocks reuptake of norepi and serotonin.  Side effects like SSRI’s, few autonomic sedative or CV effects.

Paul, Brenner pg 238-239

MAO inhibitors:  classified according to their selectivity for the two main types of MAO.  Type A (MAO-A) oxidizes serotonin but will also metabolize norephinephrine and dopamine.  Type B (MAO-B) metabolizes dopamine.  MAO-A is found in higher concentrations in the gut and other peripheral tissues, and the inhibition of MAO-A is believed to be responsible for the antidepressant effects of MAO inhibitors.  

• First generation:  phenelzine and tranylcypromine

• Second generation:  meclobemide

• Selegiline represents a third type of MAO inhibitor

Bupropion:  relatively weak inhibitor of the neuronal reuptake of dopamine, norepinephrine, and serotonin.  Produces few anticholinergic side effects, causes very little sedation, and rarely produces cardiovascular effects or sexual dysfunction.  May cuase agitation, insomnia, nausea, and weight loss.

Hypericum (St John’s wort):  found to exhibit antidepressant activity.  Extract contains hypericin and several flavones, which inhibit reuptake of serotonin.  Appears to cause fewere adverse effects than TCAs.  Clinical studies being done to evaluate efficacy and safety

Mirtazapine:  newer tetracyclic piperazinoazepine drug that has both antidepressant and antianxiety effects.  Blocks presynaptic alpha2-adrenergic autoreceptors and heteroreceptors which increase the neuronal release of norepinephrine and serotonin

Nefazodone and trazodone:  triazolopyridine drugs.  Nefazodone acts primarily by inhibiting 5-HT2 receptors.  It has little or no anticholinergic, antiadrenergic, or antihistamine activity.  May cause sedation, dizziness, nausea, and visual changes.  Trazodone selectively inhibits the neuronal reuptake of serotonin.  Causes considerable sedation and othostatic hypotension, without anticholinergic side effects or cardiac conduction effects

Venlafaxine:  structurally unique antidepressant that strongly blocks the reuptake of both norepinephrine and serotonin.  Side effects similar to SSRIs.  It does not inhibit muscarinic, adrenergic, or histamine receptors, and it produces few autonomic, sedative, or cardiovascular side effects

Anonymous Brenner 238

MAO inhibitors- They are classified into two main types.  Type A (MAO-A) preferentially oxidizes serotonin but will also metabolize norepinephrine and dopamine.  Type B (MAO-B) preferentially metabolizes dopamine.  MAO-A is believed to be responsible for the antidepressant effects of MAO inhibitors.  First generation MAO inhibitors for treating depression include phenelzine and tranylcypromine.  Second generation MAO inhibitors include meclobemide, which are not yet available in the USA.

Bupropion- this is an aminoketone whose mechanism of action is not well understood.  It is a relatively weak inhibitor of the neuronal uptake of dopamine, norepinephrine, and serotonin.  A formulation has been developed as adjunct therapy for patients who are attempting to quit smoking.

Hypericum- Extracts from a plant called St. John’s Wort have been found to exhibit antidepressant activity.  These products are found in health food stores.  The extracts contain a substance called hypericin and several flavones.  Some of these compounds inhibit MAO, while others appear to block the neuronal reuptake of serotonin.

Nefazodone- This is a triazolopyridine drug.  It acts primarily by inhibiting 5-HT2 receptors.  It has little or no anticholinergic, antiadrenergic, or antihistamine activity.  It may cause sedation, dizziness, nausea, and visual changes.

Venlafaxine- A structurally unique antidepressant that strongly blocks the reuptake of both norepinephrine and serotonin.  It has side effects similar to SSRIs.  It produces few autonomic, sedative, or cardiovascular effects.

5.         Identify the primary use for lithium.

Anonymous -Brenner 239

Mood stabilizer w/ stronger impact on mania than depression.  Used in bipolar disorder to control/prevent hypomanic and manic episodes.  Need lithium or other mood stabilizer on board before giving anti-depressant to bipolar pt. to avoid iatrogenic mania.

Anonymous   Brenner, p.239

Lithium has been called a mood stabilizer because it reduces both manic and depressive symptoms and thereby tends to normalize the mood in patients with bipolar disorder (mainly the manic phase).

Greg Brenner p. 239

Primarily used to treat the manic phase of bipolar disorder.  Has been called the mood stabilizer.

Paul, Brenner pg 239

Lithium has been called a “mood stabilizer”.  It is primarily used to treat or prevent the manic phase of bipolar disorder

Anonymous Brenner 239

Lithium has been called a mood stabilizer because it reduces both manic and depressive symptoms and thereby tends to normalize the mood in patients with bipolar disorder.  It has greater activity against manic symptoms than it does depression.  It is primarily used to treat or prevent the manic phase of bipolar disorder.

6.         Describe adverse effects and interactions of lithium.

Anonymous-Brenner 237-240

Low margin of safety.  Elevated lith levels may cause neurotoxicity, cardiac toxicity w/ arrhythmia.  Nausea w/ vomiting early sign of OD.  Important to distinguish these signs of toxicity from adverse effects of associated w/ normal dosing:  drowsiness, weight gain, fine hand tremor, polyuria, sometimes hypothyroidism.  Interactions:  NSAIDS diuretics decrease lith clearance by ~25%, thereby increasing lith levels.  Antipsychotic drugs may increase neurotoxicity.  NaCl increases excretion of lith, decreasing serum levels.                       

EChing, Brenner, P237 Table 22-8, P240

Adverse effects

Elevated lithium levels may cause neurotoxicity and cardiac toxicity leading to arrhythmia.  Nausea with vomiting may be one of the earliest signs of lithium overdose.

Common side effects of lithium include drowiness, weight gain, a fine hand tremor, and polyuria.  In some pts, lithium causes hypothyroidism by blocking thyroid hormone synthesis and release.

Interactions:

• Diuretics and NSAIDs (except sulindac) decrease the clerance of lithium by about 25%, increase the serum levels of lithium, and may cause lithium toxicity.

• Antipsychotic drugs increase the neurotoxicity of lithium.

• Sodium chloride increases the excretion of lithium and decreases the serum levels of lithium.

Anonymous Brenner, p.237 & 240

Elevated lithium levels may cause neurotoxicity leading to arrhythmia.  Nausea with vomiting may be one of the earliest signs of lithium overdose.  Common SE:  drowsiness, weight gain, a fine hand tremor, and polyuria.  In some patients, lithium causes hypothyroidism by blocking the thyroid hormone synthesis and release.

Interactions:  NSAIDS and diuretics decrease lithium clearance by 25% and increase lithium levels.  Antipsychotic drugs increase the neurotoxicity of lithium.  NaCl increases the excretion of lithium and decreases the serum levels of lithium.

Aprilt Brenner p. 240

Adverse effects- Low margin of safety, and may cause neuro and CV tox. In elevated levels. Nausea and vomiting is the earliest sign of OD.  Common side effects: drowsiness, weight gain, fine hand tremor, polyuria.  Hypothyroidism in some pt.

Interactions- NSAID’s and diuretic ^ lithium levels leading to toxicity.  Antipsychotic drugs ^ neuro tox. of lithium.  Sodium chloride dcrs lithium levels.  

Anonymous Brenner 237,240

Adverse effects- Lithium has a relatively low margin of safety.  Elevated lithium levels may cause neurotoxicity and cardiac toxicity leading to arrhythmia.  Nausea with vomiting may be one of the earliest signs of lithium overdose.  Common side effects include drowsiness, weight gain, a fine hand tremor, and polyuria.

Interactions- Non-steroidal antiinflammatories (NSAID’s) and diuretics decrease lithium clearance by about 25% and increase lithium levels.  Other drugs may increase lithium neurotoxicity such as antipsychotics.  Sodium chloride increases the excretion of lithium and decreases the serum levels of lithium.

7.         Identify anticonvulsants as alternatives to lithium therapy in the treatment of bipolar disorder.   

Anonymous

Carbamazepine and valproate (Tegritol and Depakote) are antiepileptic drugs that have mood stabilizing effects, often better tolerated than lithium (read, fewer side effects).  Brenner pp 240   Interesting note:  these were both discovered to work for mania during drug trials of seizure meds.  The subset of the study population that also had bipolar disorder was noted to have decreased mania and this sideline was pursued.  Pretty cool.

EChing, Brenner, P237 Table 22-8, P240

Carbamazepine and Valproate.

Carbamazepine exhibits antimanic, antidepressant, and prophylactic effects that are equivalent to those of lithium, and it causes fewer adverse effects in many pts.  There is also evidence that lithium and carbamazepine may be synergistic in their antimanic activity in pts with refractory bipolar disorder.

Valproate is another drug for the treatment of mania in bipolar disorder.  It is especially useful in pts with rapid cycling of manic and depressive episodes and in pts with coexisting substance abuse.

Anonymous   Brenner, p. 240

Carbamazepine:  exhibit antimanic, antidepressant, and prophylactic effects that are equivalent to those of lithium and it causes fewer SE in many patients.  About 60% of patients that don’t respond to lithium will respond to carbamazepine within the first several days of treatment.

Valproate- approved for the treatment of mania in bipolar disorder.  It appears to be especially useful in patients with rapid cycling of manic and depressive episodes and in coexisting substance abuse.

Aprilt Brenner p. 240

Alternatives- carbamazepine and valporate, are alternatives to lithium.

Anonymous Brenner 240

Two examples are carbamazepine and valproate.  Carbamazepine exhibits antimanic, antidepressant, and prophylactic effects that are similar to those of lithium, and it causes fewer adverse effects in many patients.  About 60% of patients who do not respond to lithium will respond to carbamazepine.  Valproate is useful in patients with rapid cycling of manic depressive episodes and in patients with coexisting substance abuse.