Drugs for Mania and Schizophrenia Flashcards
Alternating between periods of EXTREMELY low mood and euphoric/irritable mood
Strong familial component, genetically determined
Manic-Depressive Disease
Elevated, expansive or irritable mood accompanied by
hyperactivity, pressure of speech, flight of ideas,
grandiosity, hyposomnia, and distractibility.
Mania
MOA of Lithium Carbonate
Inhibits recycling of phosphoinositide leading to decreased levels of IP3 and DAG
Pharmacokinetics of Lithium Carbonate
Not metabolized in the liver
Sodium competes with Lithium for renal tubular
reabsorption and thereby can increase the
excretion of Lithium
Adverse effects of Lithium Carbonate
Fine tremors at therapeutic doses (one of the most
common adverse effect
Polyuria (interferes with the action of ADH)
Limitation of Lithium Carbonate
Not effective in the management of RAPID CYCLING
→is a term used when a person with bipolar disorder experiences four or
more mood swings (episodes) within a 12-month period.
An episode may consist of depression, mania, or a condition known as mixed-state
in which depression and mania are co-occurring
Drug better than lithium in the management of rapid cycling
Valproic Acid
Drug used in the management and prophylaxis of mania
Alternative for patients who did not respond to lithium therapy
Carbamazepine
Examples of Antipsychotics
Aripiprazole
Risperidone
Ziprasidone
Olanzapine
Quetiapine
Causes of Schizophrenia
Genetic & Ecological
Dopamine & Serotonin Hypothesis
Evidences of Dopamine Hypothesis
Abnormalities in DA neurotransmission.
Most antipsychotic drugs block D2 receptors.
Drugs that act by increasing neuronal release of DA or by
blocking the neuronal reuptake of DA can induce psychotic
behavior that resembles the behavior of schizophrenic
patients.
Post-mortem studies have reported increase in dopamine
receptor density in brain of schizophrenics who were not
treated with antipsychotic drugs.
Description of Serotonin Hypothesis
5HT2A and 5HT2C stimulation leads to inhibition of cortical
and limbic DA release.
Positive Psychotic Symptoms (D,H,C,A)
Delusions
Hallucinations
Catatonia
Agitation
Disorganized Psychotic Symptoms (CT, DS, DB,DP)
Confused thinking
Disorganized speech
Disorganized behavior
Disorganized perceptions
NEGATIVE-deficit Symptoms (EF, Al, Av, An)
Emotional flattening
Alogia – limited speech
Avolition – lack of motivation
Anhedonia – lack of interest and pleasure
Cognitive Symptoms (DA, IM, DAF)
Decreased attention
Impaired memory
Decreased abstractive functions
Mood Symptoms (D,S,H)
Dysphoria
Suicidality
Hopelessness
Three Schizophrenia Phases
Prodromal
Psychotic (acute)
Residual (chronic)
Prodromal Phase (D,S,H,I,PC)
Dysphoria
Suicidality
Hopelessness
Decline in functioning
that precedes 1st
psychotic episode
Socially withdrawn
Irritable
Physical complaints
Psychotic (acute) Phase (DHCA,PD,D,DT)
Positive symptoms
Perceptual disturbance
Delusions
Disorganized thought
Residual (chronic) Phase
Occurs between episodes of psychosis
Marked by negative symptoms
Increased activity in this pathway may
cause delusions, hallucinations, and
other positive symptoms.
Mesolimbic Pathway
Decreased activity in this pathway can
cause apathy, withdrawal, lack of
motivation and pleasure, and other
negative symptoms.
Mesocortical Pathway
Inhibition of this pathway causes
extrapyramidal side effects of
antipsychotic drugs.
Nigrostriatal Pathway
Inhibition of this pathway leads to
elevated serum prolactin levels.
Tuberofundibular Pathway
MOA of Typical/1st Generation Antipsychotics
Antipsychotics AKA “Neuroleptics/ Major tranquilizers” usually take several weeks for their effects to fully develop
Blockade of Dopamine
Target: Mesolimbic neurons, Nigrostriatal neurons, Tuberofundibular neurons
Effect: Alleviate Positive symptoms, Extrapyramidal side effects, Hyperprolactinemia
MOA of Typical/2nd Generation Antipsychotics
Blockade of Serotonin
Target: Mesocortical neurons
Effect : Alleviate Negative symptoms
Examples of First generation Phenothiazines (“ZINE”)
CHLORPROMAZINE
PROMAZINE
TRIFLUPROMAZINE
FLUPHENAZINE
PERPHENAZINE
ACETOPHENAZINE
TRIFLUOPERAZINE
PROCHLORPERAZINE
THIORIDAZINE
MESORIDAZINE
*PIMOZIDE
PIPERACETAZINE
Examples of First generation Butyrophenone (“PERIDOL”)
- HALOPERIDOL
DROPERIDOL
Examples of First generation Thioxanthines (“XENE” | “XOL”)
THIOTHIXENE
CHLORPROTHIXENE
FLUPENTIXOL
Nervous system disorder that involves
repetitive movement or unwanted sounds (tics)
that can’t be controlled, caprolalia, and
echolalia.
Tourette Syndrome
Examples of Second Generation (“PINE” | “ONE” | “OLE” | “PRIDE”)
OLANZAPINE - As effective as Haloperidol in alleviating positive symptoms
CLOZAPINE
- First atypical neuroleptic; lowers the risk of suicide and tardive dyskinesia
- Use us limited because of adverse effects
QUETIAPINE - Indicated for mania and adjunctive therapy for MDD
ARIPRIPRAZOLE - Indicated for Tourette Syndrome
LOXAPINE
RISPERIDONE
PRALIPERIDONE
ZIPRASIDONE
SERTINDOLE
AMILSUPRIDE
Adverse effects of clozapine
Seizures
Agranulocytosis - requires
monitoring of leukocyte during the
first 6 months of therapy.
Adverse effects of risperidone
QT prolongation
Adverse effects of Thioridazine
Pigmentary retinopathy
Cardiac toxicity
Adverse effects of Chlorpromazine
Corneal Deposits
General adverse effects of Antipsychotics
Alpha-1 adrenoceptor blockade
Muscarinic receptor blockade
Histamine receptor blockade (CNS)
Neuroleptic Malignant Syndrome
A severe form of drug toxicity that occurs in 0.5% to 1% of patients treated with antipsychotics
A life-threatening condition characterized by
muscle rigidity, hyperthermia, and autonomic dysfunction (tachycardia, diaphoresis, tachypnea, and urinary and
fecal incontinence)
Neuroleptic Malignant Syndrome
Management of Neuroleptic Malignant Syndrome
Discontinue antipsychotic drug
Administer DANTROLENE
Provide supportive care
Adverse effects of dopamine blockade: inhibition of the dopamine receptors in the striatal pathway
Extrapyramidal Syndrome
Tardive Dyskinesia
Adverse effects of dopamine blockade: inhibition of the dopamine receptors in the tuberofundibular pathway
Hyperprolactinemia
General management of Extrapyramidal Syndrome
Decrease the dose of the antipsychotic drug
Change into atypical antipsychotic
Administration of drug that can counteract it
Extrapyramidal Syndrome Manifestations
Akathisia
Pseudo parkinsonism
Dystonia
motor restlessness; most difficult to treat
compelled to pace, shuffle their feet, shift positions, unable to sit quietly
Akathisia
Management of Akathisia
Administration of BZD (Benzodiazepines)
tremors, rigidity, and bradykinesia
Pseudo parkinsonism
Management of Pseudo Parkinsonism
Administration of anticholinergic agents
abnormal muscle tension of the neck and face (oculogyric crisis, gloss spasm, tongue protrusion, torticollis)
difficulty to move
Dystonia
Management of Dystonia
Diphenhydramine, anticholinergic agents
Abnormal involuntary movements occurring with CHRONIC antipsychotic therapy (months to years).
Abnormal movements of the face and tongue with widespread choreoathetosis.
“superdensity phenomenon”
Tardive Dyskinesia
Management of Tardive Dyskinesia
Lower the dose or discontinue and give atypical agents
Prevention of Tardive Dyskinesia
Lowest dose for the shortest period of time required to control symptoms of schizophrenia. The drug should be discontinued periodically to assess the need for continued treatment and possibly to reduce dopamine super sensitivity.
Manifestations of Hyperprolactinemia
Galactorrhea - milk production from the breast unrelated to pregnancy or lactation
Amenorrhea - the absence of menstruation
Gynecomastia in men
