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Types of psychoses
1. Schizophrenia (split mind)
2. Affective disorders (Depression / Mania)
3. Anxiety
Schizophrenia
A clinical syndrome characterized by profound
disruption in cognition and emotion, affecting the most
fundamental attributes: language, thought, perception,
affect and sense of self
Positive Symptoms
Delusions
Hallucinations
Erratic/extreme emotions
Thought disorder
Negative Symptoms
Evidences:
1.Drugs (L-dopa and amphetamine) that increase DOPA
can aggravate the symptom of schizophrenia
2.Dopamine receptor density in schizos
3.Anti-psychotic drugs block postsynaptic D2 receptor in
CNS
There is some evidence for involvement of 5-HT, and
possibly other mediators, such as glutamate
Typical antipsychotics
Phenothiazines (chlorpromazine, perphenazine,
fluphenazine, thioridazine et al)
Thioxanthenes (flupenthixol, clopenthixol)
Butyrophenones (haloperidol, droperidol)
Atypical antipsychotics
(e.g. clozapine, risperidone, sulpiride, olanzapine)
Chlorpromazine: wintermine
Pharmacologic effects :
(1) CNS: a. neuroleptic effect
1. In animals: suppress spontaneous movements and
complex behaviors, but spinal reflexes remain intact
2. In normal humans: reduce initiative and interest,
produce drowsiness and slowness in response to
external stimuli
3.In psychotic patients: soon become less agitated,
aggressive and impulsive behavior diminishes.
Gradually, psychotic symptoms of hallucinations,
delusions, and disorganized thinking ameliorate.
Chlorpromazine
Pharmacologic effects :
(1)CNS:
Chlorpromazine
Pharmacologic effects:
(2) autonomic nervous system: block adrenergic and M-Cholinergic receptors and
result in hypotension, dry mouth, constipation
and blurred vision.
Dopamine receptors
Five subtypes of Dopamine receptors:
D1, D2, D3, D4, D5
D1 and D5 are named as D1 like receptor
Increase cAMP
D2, D3 and D4 are named as D2 like receptor
Decrease cAMP
D2 like receptor is highly related to schizophrenia
Mechanism of chlorpromazine
a nonspecific dopamine receptor blocker
Block
Block
Mesolimbic
Mesocortical
D2
Antipsychotic effects
Nigrostriatal
Tuberoinfundibular
D2
Adverse effects
Therapeutic uses
(1) treatment of psychotic disorders:
schizophrenia, mania, alcoholic hallucinosis.
(2) treatment of nausea and vomiting of certain
causes (digitalis, uremia, cancer)
(3) anesthesia in hypothermia and artificial
hibernation (used with pethidine and
promethazine)
Adverse Effects
1. Ordinary side effects
(1)Anticholinergic (antimuscarinic) side effects:
Dry mouth, blurred vision, urinary retention
(2)Antiadrenergic (Alpha-1) side effects:
Orthostatic hypotension w/ reflex tachycardia
(3)Antihistamine effect:
sedation, weight gain
Adverse Effects
2. Extrapyramidal side effects (EPS)
(1) Acute dystonisa :
spasm of muscles of tongue, face, neck, back, may
mimic seizures, during the first 1 -5 days of Rx
(2) Akathisia: motor restlessness
(3) Parkinson-like symptoms:
bradykinesia, rigidity, tremor, mask facies
Mechanism: nigrostriatal dopaminergic function
weakened, while cholinergic function strengthened
Treatment: anticholinergic :benzhexol
Atypical neuroleptics
Clozapine:
(1) be effective in treating some patients with psychosis
unresponsive to standard neuroleptic drug,effective
against negative symptoms
(2) blocks D4 receptor and have low affinity for D1 and
D2 dopamine receptors.
(3) lacks extrapyramidal side effects.
(4) must monitor the granulocyte counts weekly.
Risperidone:
(1)Highly effective against positive and negative symptoms
be used for first episode and chronic schizophrenia
(2)Dopamine-2 and Serotonin-2 receptor blockade
(3)EPS incidence is dose-related
Weight gain, prolactin elevation
Clinical Efficacy of
Antipsychotic Drugs
Anti-Manic Agents
Mania-- State of elevated mood and
psychomotor acceleration, with excess
catecholamines activity and decrease 5-HT
activity
Treatment: lithium carbonate
LITHIUM
PHARMACOKINETICS
ABSORPTION : virtually complete within 6 -8
hrs; peak plasma levels in 30 min to 2 hrs
DISTRIBUTION: in total body water; slow
entry into intracellular compartment. No
protein binding
METABOLISM: None
EXCRETION: virtually entirely in urine;
plasma half life is about 20 hours
lithium carbonate
Mechanism
Substitute for sodium in generating action potentials
Decrease norepinephrine & dopamine turnover
Block dopamine receptor supersensitivity
Enhance effects of serotonin
lithium carbonate
Adverse effects:
Nausea, vomiting and diarrhea.
Tremor.
Renal effect: polyuria (with resulting thirst)
Various neurological effects, progressing from
confusion and motor impairment , to coma,
convulsion and death.
narrow therapeutic limit for the plasma means
the monitoring is essential
Antidepressant
Depression Syndrome: depression, anxiety, tension,
bodily complaints, guilt (> 60%)
imipramine
amitriptyline
Fluoxetine,pa
roxetine,
sertraline
Imipramine
mechanism of action
to block NA and 5-HT reuptakes into the
presynaptic neurons to increase NA and 5HT level in the synaptic cleft in CNS.
Monoamine receptor densities in the brain
may change over 2 to 4 week with drug use
and may be important in the onset of activity.
Imipramine
Pharmacologic effects:
(1) CNS: a normal person experiences
sleeping. In the depressed patient, an
elevation of mood occurs 2-3 weeks after
administration begins.
(2) autonomic nervous system: anticholinergic
effects.
(3) cardiovascular effects: orthostatic
hypotension and arrhythmias.
Therapeutic uses
(1) Treatment of severe endogenous
depression (characterized by regression
and inactivity).
(2) Treatment of enuresis.
(3) Treatment of obsessive-compulsive
neurosis accompanied by depression, and
phobic-anxiety syndromes, chronic pain
and neuralgia.
Adverse effects: anticholinergic effects
Fluoxetine
Mechanism of action:
(1) is a selective inhibitor of serotonin uptake in the
CNS.
(2) has little effect on central norepinephrine and
dopamine function.
(3) has less adverse effects because of minimal
binding to cholinergic, histaminic, and adrenergic receptors.
Therapeutic uses:
(1) is used for treatment of mild to
moderate endogenous depression.
(2) be useful in treating obsessivecompulsive disorder, obesity.
Adverse effects:
(1) cause anorexia.
(2) precipitate mania or hypomania.
(3) result in nausea, nervousness,
headache, and insomnia.
(4) cause 5-HT syndromes
(hyperpyrexia, convulsions, and coma)
when combinated with and MAO
inhibitor.