7.3: Antipsychology Drugs (Lithium) Flashcards
What are the two types of drugs for psychoses and bipolar disorders?
- Antipsychotics
- Bipolar drugs
The antipsychotic drugs have two types, what are those?
- Classic drugs (D2 receptor affinity)
- Newer agents (5HT2 receptor affinity)
What are the main class of first generation antipsychotic drugs (D2 receptor affinity)?
- Chlorpromazine
- Haloperidol
- Fluphenazine
- Thioridazine
- Trifluoperazine
CHeaF TT
What are the main class of second generation antipsychotic drugs (5HT2 receptor affinity)?
- Clozapine
- Risperidone
- Olanzapine
- Quetiapine
- Ziprasidone
CROQ Z
Identify this medication:
- Used to treat schizophrenia, other psychoses and agitated states
- Protracted therapy (years)
- Severe toxicity
Neuroleptics
Enumerate the symptoms of schizophrenia:
- Disorganized speech
- Catatonic or disorganized behavior
- Hallucinations
- Delusions
- Negative symptoms
True or False:
In schizophrenia, impairment in major areas of functioning at work or interpersonal relationship or self care, schizoaffective and bipolar disorder are ruled out, and the disturbance is not due to other substance abuse.
True
What are the other associated features in Schizophrenia?
- Inappropriate laughing
- Disturbed sleep pattern
- Dysphoric mood (depression, anger, anxiety
- Anxiety and phobia
- Cognitive deficits impacting language processing, executive function or memory
- Hostility and aggression
Identify if manic or hypomanic in Bipolar Disorder:
Distinct episode of abnormally and persistently elevated expansive or irritable mood for 1 week
Manic episode
Identify if manic or hypomanic in Bipolar Disorder:
During the period of mood disturbance, three (or more) of the following have persisted (4 if mood is only irritable)
- Inflated self esteem or grandiosity
- Decrease need for sleep (3 hrs still feels rested)
- More talkative than usual or pressure to keep talking
- Insomnia or hypersomnia everyday
- Psychomotor agitation or retardation
- Flight of ideas or subjective experience that thoughts are racing
- Increase in goal-directed activity or psychomotor agitation
- Excessive involvement in pleasurable activities that have high potential for painful consequences (e.g buying sprees, sexual indiscretions, foolish)
Manic episode
Identify if manic or hypomanic in Bipolar Disorder:
- During the mood disturbance is sufficiently severe to cause impairment in occupational functioning or in usual social activities or relationships or necessitates hospitalizations
- Not due to physical substance abuse
Manic episode
Identify if manic or hypomanic in Bipolar Disorder:
- Low mood
- Lack of interest or pleasure in activities once enjoyed
- Slowed down behavior
- Fatigue or loss of energy
Hypomanic episode
Identify if manic or hypomanic in Bipolar Disorder:
- Thinking of death or suicide
- Feeling guilty
- Sleeping problems
- Problems concentrating
Hypomanic episode
What are the four major chemical subgroups of antipsychotic drugs and lithium?
- Phenothiazines
- Thioxanthenes
- Butyrophenones
- Atypical Antipsychotics
Identify this major chemical subgroup:
Aliphatic (Chlorpromazine)
Advantage: Generic, inexpensive
Disadvantage: Many adverse effects, especially autonomic
Phenothiazines
Identify this major chemical subgroup:
Piperidine (Thioridazine)
Advantage: Slight extrapyramidal syndrome, generic
Disadvantage: 800 mg/d limit; no parenteral form; cardiotoxicity
Phenothiazines
Identify this major chemical subgroups:
Piperazine (Fluphenazine)
Advantage: Depot form also available (enanthate, decanoate)
Disadvantage: Possible increased tardive dyskinesia
Phenothiazines
Identify this major chemical subgroups:
Thiothixene
Advantage: Parenteral form also available; possible decreased tardive dyskinesia
Disadvantage: Uncertain
Thioxanthenes
Identify this major chemical subgroups:
Haloperidol
Advantage: Parenteral form also available; generic
Disadvantage: Severe extrapyramidal syndrome
Butyrophenones
Identify this major chemical subgroup:
Clozapine
Advantage: May benefit treatment-resistant patients; little extrapyramidal toxicity
Disadvantage: May cause agranulocytosis in up to 2% of patients
Atypical Antipsychotic
Identify this major chemical subgroups:
Loxapine
Advantage: Possible no weight gain
Disadvantage: Uncertain
Atypical Antipsychotic
Identify this major chemical subgroup:
- More effective
- Less toxic
- More costly
- Prescribed generically
Atypical Antipsychotic
What are the pharmacokinetics of antipsychotic drugs and lithium?
- Well absorbed when given orally
- Lipid soluble
- Bound extensively to plasma proteins
- Require metabolism by liver enzymes before elimination
- Long plasma half-lives
- IV forms
Whats the IV forms in pharmacokinetics of Antipsychotic Drugs and Lithium?
- Rapid initiation
- Depot treatment
Identify this mechanism of action:
Relative excess of functional activity of dopamine
The Dopamine Hypothesis
Identify this mechanism of action:
- Not fully satisfactory
- Antipsychotic drugs are only partly effective in most patients
- Many effective drugs have a much higher affinity for other receptors than D2 receptors
The Dopamine Hypothesis
Identify this mechanism of action:
Many antipsychotic drugs block brain dopamine receptors (especially D2 receptors)
The Dopamine Hypothesis
What are the dopamine-agonist drugs that exacerbate schizophrenia?
- Amphetamine
- Levodopa
Identify this mechanism of action:
Increased density of dopamine receptors has been detected in certain brain regions of untreated schizophrenia.
Dopamine hypothesis
Identify this mechanism of action:
- Has 5 different dopamine receptors
- Therapeutic efficacy of most older antipsychotic drugs correlate with relative affinity to D2 receptors
Dopamine Receptors
Identify this mechanism of action:
Correlation between blocking of D2 receptors and extrapyramidal dysfunction
Dopamine Receptors
Identify this mechanism of action:
Newer atypical antipsychotic agents
have higher affinities for other
receptors than for the D2 receptor
Other receptors
Identify this mechanism of action:
Table on relative receptor blocking
actions of neuroleptic drugs (Katzung)
Other receptors
Identify this mechanism of action:
Alpha adrenoceptor blockade- antipsychotic effect of most drugs
Other receptors
Enumerate the receptor based on this mechanism of actions:
- Newer atypical drugs
- High affinity for 5-HT2A
- May also interact with D2 and other receptors
- Olanzapine
- Quetiapine
- Risperidone
Enumerate the receptor based on this mechanism of actions:
- Significant D4 and 5-HT2 receptor blocking actions
- Low affinity for D2 receptors
Clozapine
Identify this mechanism of action:
Causes less extrapyramidal dysfunction than standard drugs
OTHER RECEPTORS
All antipsychotic drugs have H1 receptor blockade to some degree, except:
Haloperidol
True or False:
In Dopaminergic receptor blockade, it has major effect for older antipsychotics.
True
What are the Dopaminergic tracts in the brain?
- Mesocortical-mesolimbic
- Nigrostriatal tract
- Tuberoinfundibular pathways
- Chemoreceptor trigger zone
Mintis (MNTC)
Identify what Dopaminergic tracts:
Menstruation and mood
Mesocortical-mesolimbic pathway
Identify what Dopaminergic tracts:
Extrapyramidal function
Nigrostriatal tract
Identify what Dopaminergic tracts:
Prolactin release
Tuberoinfundibular pathways
Identify what Dopaminergic tracts:
Emesis
Chemoreceptor trigger zone
Identify what blockade:
Blockade of Antipsychotic effect of the drug
Blockade #1
Identify what blockade:
Blockade of Antiemetic properties
Blockade of #4
Identify what blockade:
Blockade of Adverse effects like extrapyramidal dysfunction and hyperprolactinemia respectively
Blockade #2 and#3
Treatment of schizophrenia includes reducing some of the positive symptoms, what are these positive symptoms?
- Hyperactivity
- Bizarre ideation
- Hallucinations and delusions
Facilitate functioning in both out and inpatient environments
Treatment of schizophrenia
Negative symptoms of Treatment of schizophrenia
- Older drugs do not have much effect
- Newer atypical drugs improve some
1. Emotional blunting
2. Social withdrawal
Other psychiatric and neurologic indications:
Mania
Used together with lithium.
Drug that is sole agent in the manic phase
Olanzapine
Drug that is mood stabilizer in bipolar disorders
Olanzapine
What is the drug treated for Tourette’s syndrome?
Molindone
What is the treatment for Alzheimer’s and Parkinsonism?
Newer drugs
What are the effects of nonpsychiatric indications?
- Antiemetic action
- Antipruritics
Identify this nonpsychiatric indication:
H1 receptor blockade basis for use.
Antipruritics
Identify this nonpsychiatric indication:
- Phenothiazines except thioridazine
- Prochlorperazine
Antiemetic action
Parkinson-like syndrome
- Rigidity
- Akinesia
- Flat facies
- Tremor
Identify this toxicity:
Dose dependent extrapyramidal effects
Reversible neurologic effects
Identify this toxicity:
Decrease in dose and antagonized with
muscarinic blocking agents
Reversible neurologic effects
What are the drugs that occurs most frequently in reversible neurologic effects?
- Haloperidol
- Fluphenazine
- Trifluoperazine
Identify this toxicity:
Less frequent with clozapine
Less common with the newer drug
Reversible neurologic effects
Identify this toxicity:
Other neurologic dysfunction in Reversible neurologic effects
- Akathisia
- Dystonia
- Respond to diphenhydramine and muscarinic blocking agents
Identify this toxicity:
Choreoathetoid movements of the muscle of the lips and buccal cavity
Tardive dyskinesia
Identify this toxicity:
- Tend to develop after years of therapy
- May appear as early as 6 months
- Maybe irreversible
Tardive dyskinesia
Identify this toxicity:
Antimuscarinic drugs that improve extrapyramidal effects increase the severity of symptoms.
Tardive dyskinesia
Identify this disorder:
- No effective drug for treatment
- Switching to clozapine does not exacerbate the condition
Tardive dyskinesia
Identify this toxicity:
- Improved temporarily by increasing neuroleptic dosage
- Maybe caused by dopamine receptor sensitization
Tardive dyskinesia
Identify this toxicity:
Result from blockade of peripheral muscarinic receptors and alpha adrenoceptors
Autonomic effects
Drug:
Strongest autonomic effects
Thioridazine
Drug:
Weakest autonomic effects
Haloperidol
Toxicity:
Intermediate autonomic effects
Clozapine and most atypical antipyschotics
Toxicity:
Atropine-like effects
- Dry mouth
- Constipation
- Urinary retention
- Visual problems
- Not with ziprasidone and aripiprazol
Toxicity:
Alpha receptor blockade
- Postural hypotension
- All atypical drugs
Drug:
Failure to ejaculate
Phenothiazines
Endocrine and metabolic effects:
Dopamine D2 receptor blockade in the pituitary
- Hyperprolactinemia
- Gynecomastia
- Amenorrhea-galactorrhea syndrome
- Infertility
Endocrine and metabolic effects
- Dopamine D2 receptor blockade in the pituitary
- Weight gain and hyperglycemia
Drug:
Weight gain and hyperglycemia
- Clozapine
- Olanzapine
Toxicity:
Neuroleptic malignant syndrome (NMS) signs and symptoms
- Muscle rigidity
- Impairment of sweating
- Hyperpyrexia
- Autonomic instability
Toxicity:
- Patients who are sensitive to the extrapyramidal effects are prone to develop NMS
- Life threatening
Neuroleptic malignant syndrome
What are the treatment used for Neuroleptic malignant syndrome (NMS)?
- Dantrolene
- Dopamine agonist
Sedation (toxicity):
More marked sedation
Phenothiazines (chlorpromazine)
Sedation (toxicity):
Less sedating among the older drugs
Fluphenazine and haloperidol
Sedation (toxicity):
Least sedating among newer drugs
Aripiprazole
Miscellaneous (toxicity):
Visual impairment due to retinal deposits
Thioridazine
Miscellaneous (toxicity):
At high doses, fatal ventricular arrhythmias
Thioridazine
Miscellaneous (toxicity):
Arrhythmias
Ziprasidone
Miscellaneous (toxicity):
Agranulocytosis, seizure at high doses
Clozapine
Miscellaneous toxicities
- Arrhythmias
- Agranulocytosis, seizure at high doses
- At high doses, fatal ventricular arrhythmias
- Visual impairment due to retinal deposits
Overdosage toxicity:
Drug for seizures:
- Diazepam
- Phenytoin
This is absorbed rapidly and completely from the gut and distributed throughout the body water.
Lithium
Lithium is cleared by the kidney at a rate of __ of creatinine.
1/5
Half-life of Lithium:
20 hours
What week of therapy for Lithium:
- Plasma levels monitored
- Effective and safe dosage regimen
1st week of therapy
Lithium may increase to toxic levels by:
- Dehydration
- Treatment with thiazide diuretics
Drug that increases renal clearance in lithium:
Theophylline
MOA of lithium
- Recycling of neuronal membrane phosphoinosotides (IP3 & DAG - neurotransmission)
Alternative drugs for lithium:
- Olanzapine
- Valproic acid
- Carbamazepine
- Clonazepam
- Gabapentin
- Lamotrigine
Toxicity of Lithium:
Increase congentical cardiac anomalies
Ebstein’s anomaly
T or F:
The toxicity of Lithium has containdicated in nursing mothers.
True
