PSYCHOTROPICS

dr. Agung Wiwiek Indrayani, M.Kes

Department of Pharmacology Faculty of Medicine Udayana University

PSYCHOTROPICS

- Antipsychotics - Antineurotics
- Antidepressants - Psychotomimetics

Organic : CNS infections, intoxication, tumor etc.

Psychosis
Schizophrenia Paranoid Psychosis affective

Psychogenic

Psychosomatics Psychoneurosis Psychopath

Psychiatric disorders

Personality disorders Sociopath Sex-deviation Addiction

Mental deficiency

Others

ANTIPSYCHOTICS

ANTIPSYCHOTICS

Effective in controlling many manifestations of psychotic illness

*thought disorder *emotional withdrawal *hallucinations, delusions

CLASSIFICATION

Pharmacokinetics
- Lipophylic, and bound to the protein
tends to be accumulated in the SNC

- Gastrointestinal absorption often irratics

much better result if be given by i.m. injection

- Long half life

the dose once a day (flufenazine : once every 2 weeks)

MECHANISM OF ACTION
Neurochemical theory
1. Dopaminergic receptor theory
proposed by Carlsson (awarded a Nobel Prize 2000)

amphetamine cause dopamine release in the brain

can produce a syndrome resemble to schizophrenia.

in animal dopamine releasing drugs may cause a stereotypic repetitive behaviour resemble to a schizophrenia

D-receptor theory psychosis

1. Most antipsychotics block r-D2 mesolymbic 2. Drugs which are * levodopa the dopaminergic activity : precusor of dopamine

* amphetamine : dopamine release * apomorphine : r-D2 agonist

trigger a schizophrenia attack

elicit symptoms of schizophrenia

D-receptor theory
3. Postmortem study
* r-D2 population in schizophrenia patient who received antipsychotics than those who did not

received the drugs up regulation

4. Using PET (positron emission tomography)

schizophrenic patients (under therapy or not)
r-D2 population (density) more than normal

D-receptor theory
5. Homovalynic acid (dopamine metabolite) concentration in the cerebrospinal fluid, blood and urine of schizophrenic patients who is improved by a drug therapy higher than those before therapy homeostatic mechanism in the dopaminergic nerve activity

PSYCHOSIS
Neurochemical theory
2. Glutamate theory
proposed by Goff and Coyle (2001)

glutamate NMDA (N-methyl-D-asparate) receptor antagonist such as phencyclidine, ketamine and dizocilpine produce psychotic symptoms postmortem studies in schizophrenic patients showed that glutamate concentration and glutamate receptors less than those of non schizophrenia

D-receptor theory
r-D2 plays an important role in the pathophysiological of schizophrenia
(conventional antipsychotics showed strong affinity to r-D2)

but
* antipsychotics which is not r-D2 selective showed a very effective for schizophrenia there are must be other mechanism

glutamate theory, theory involves r-5HT2 ?

PSYCHOSIS
Block the r-D2 (dopaminergic-2 receptors) r-D subtyping :
- r-D1 postsynaptic - r-D2 pre and postsynaptic - r-D3 (homolog D2) - r-D4 (homolog D1) - r-D5 (homolog D1)
Limbic D5 ventral striatum D3 cortex frontal D4 amigdala D4 hypocampus D4

D1, D2, D4

1. Transmitter synthesis 2. Transmitter release 3. Postsynaptic receptor

G : guanine nucleotide protein Dto G-GTP and G-GDP :G-protein which is bound 4 GTP (guanosinetriphosphate) or GDP (guanosine diphosphate)

PSYCHOSIS
* Block r-D
- in mesolombics antipsychotic effects - in basal ganglia parkinsonism, chorea

* Block peripheral r-M

- dry mouth etc.

* Block r-a
- hypotension

Drug therapy of psychosis

Causative for organic psychosis
* Treat the intoxication * Antibiotics and chemotherapeutics

* Surgery

Drug therapy of psychosis - Most psychosis

* the causes is not known ignota

Antipsychotics

Side effects of

PSYCHOSIS
Type A

Parkinsonism, chorea athetoid

(caused by blockade of r-D in basal ganglia)

dry mouth cycloplegia constipation

hypotension, tachycardia

r-M blockage r-a blockage

Side effects of PSYCHOSIS

Type B
- bone marrow depression - hepatic malfunction * jaundice

* steatosis
- renal malfunction

Side effects of some antipsycotics

Drugs Classical 1. Chlorpromazine 2. Thioridazine 3. Haloperidol 4. Flupenthixol Atypical 1. Sulpiride 2. Clozapine 3. Risperidone 4. Sertindole 5. Quetiapine ++ +++ ++ ++ ++ + ++ ++ ++ +++ ++ ++ ++ ++ + +++ +++ +++ + + + + ++ ++ ++ + + ++ ++ ++ + + ++ +++ ++ +++ +++ +++ +++ ++ ++ ++ + ++ ++ ++ + ++ ++ + +++ ++ + +++ ++ ++ ++ _ + ++ ++ ++ + D1 Receptor affinity D2 H1 M a
5-HT

Side effects ESP Sed Hypot

Toxicity

Reversible neurologic effects Tardive dyskinesias Autonomic effects Endocrine and metabolic effects Neuroleptic malignant syndrome Sedation Overdosage toxicity

Lithium & Other Drugs Used in Bipolar Disorder

Pharmakokinetics

Lithium absorbed rapidly & completely Half life 20 hours Therapeutic plasma concentration 0.6-1.4 meq/L Plasma levels of drug altered by changes body water dehydration/diureticstoxic levels Theophylline increase renal clearence

Mechanism of Action

Not well defined Inhibits the recycling of neuronal membrane phosphoinositides involved in the generation inositol triphosphate (IP3) and diacylglycerol (DAG)
Decrease Ca2+ intraceluler Decrease hyperactivity

Clinical Use
Bipolar

Affective Disorder (manic depresive

disease)
Alternative

drugs

carbamazepine, clonazepam, gabapentin, valproic acid

Toxicity

Tremor Sedation Ataxia Aphaxia Thyroid enlargement Reversible nephrogenic diabetes insipidus Edema Pregnancy: congenital cardiac anomalies Contraindicated in nursing mothers