P H R M A C O L O G Y - NOTE 10 - Anti-Psychotic Drugs

ANTI-PSYCHOTIC DRUGS

Typical Atypical

Phenothiazines Thioxanthines others Risperidone

Flupenthixol Haloperidol Quetiapine

Group 1 Group 2 Group 3

Chlorpromazine Pericyazine Fluphenazine Zuclopenthixol Pimozide Olanzapine

•Schizophrenia
•Brain damage Trifluperazine Sulpiride Clozapine
Psychoses are: •Mania
•Toxic delirium
•Agitated depression
Aripiprazole
•manifest disorders of
•perception
Schizophrenic •thinking
•speech
patients •emotion •+ve •delusions •Social/occupational
•physical activity

Negative symptoms of
symptoms •hallucinations dysfunction

Positive symptoms of
•Neuroleptics •disorganized •lack of self care
•-ve
Schizophrenia has

•due tp neurological effects e.g.

speech
Antipsychotic Parkinsonism symptoms

Schizophrenia
Schizophrenia
•Minor tranquilizersas •catatonia
drugs are called •du to calm or ‘tranquilize’ psychotic
symptoms without loss of
•agitation
consciousness
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P H R M A C O L O G Y - NOTE 10 - Anti-Psychotic Drugs

 Typical Anti-Psychotics
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
G1 Chlorpromazine  Taken Orally.  Mainly antagonize D2 receptors. • Dopamine hypothesis for  ANS
 Some of them may also antagonize 5-HT2
Phenothiazines

schizophrenia: Anti-muscarinic
G2 Pericyazine receptors • Increased dopamine  blurred vision, IOP.
 More effective in the control of positive receptor density in  dry mouth,HR, confusion.
symptoms mesolimbic-frontol area  constipation, urine retention
G3 Fluphenazine  Given I.M. Inj. /3-4 wks
 Cause more extrapyramidal side effects in schizophrenics α – blocking
• Most antipsychotic drugs  ejaculation & impotence.
Trifluperazine  Taken Orally. block Dopamine D2  HR & orthostatic BP.
receptors in brain  CNS
Flupenthixol  Given I.M. Inj. /3-4 wks • Successful treatment of D R blocker
schizophrenia reduces  Parkinsonism.
Thioxanthines

homo-vanilic acid (HVA),  Akathesia.

a metabolite of  Dystonia
dopamine in CSF
Zuclopenthixol  Taken Orally. Super sensitivity of D R
• Drugs that increase  Tradive dyskinesia.
dopamine activity like  Sedation.
levodopa, cocaine,  Toxic confusional state.
apomorphine &  Neuroleptic malignant
Haloperidol  Given I.M. Inj. /3-4 wks amphetasmines syndrome.
aggravate schizophrenia  Endocrine(due to DR block &
or produce psychosis prolactin)
• There is possible
Pimozide  Taken Orally. Female
involvement of other  Amnorrhra & galactorrhea.
neurotransmitters also Male
others

like glutamate,  Gynecomastia & impotence.

Sulpiride serotonin, histamine, etc
e.g. Glutamate receptor  Weight gain (appetite).
(NMDA-receptor) antagonist  Hyperglycemia.
(phencyclidine) can produce
 Cholestatic jaundice.
schizophrenia like state
 Cataract.
& atypical anti-
 Risk of teratogenecity.
psychotics also inhibit 5-HT2 & D4
receptors

DRUGS sedation anti-muscarinic extra-pyramidal PATHO-PHYSIOLOGY OF SCHIZOPHRENIA

side effects side effects
G1 Marked Moderate Moderate   dopamine receptor density in mesolimbic-frontol area in schizophrenics.
G2 Moderate Marked Less   dopamine activity by drugs (like levodopa, cocaine, apomorphine & amphetasmines) that
G3 Less Less Marked aggravate schizophrenia or produce psychosis. 31
Thioxa.  NT (like glutamate, serotonin, histamine) that agonist 5-HT & D receptors.
others  Successful treatment of schizophrenia reduces homo-vanilic acid (HVA) in CSF.

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P H R M A C O L O G Y - NOTE 10 - Anti-Psychotic Drugs
 Atypical Anti-Psychotics
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT
 Given I.M. Inj. /3-4 wks  Block both D2 & 5-HT2 receptors.  Schizophrenia (1 line
st

 less extra-pyramidal &

Risperidone Anti-muscarinic & prolactin related se

prolactin related side

 Relive both + &- symptoms. drug) Less extra-pyramidal se.
Weight gain.
 Relatively low affinity for May cause:
dopamine receptors  Anxiety.
 Also or receptors  Insomnia.

effects
 Dizziness.
 BP
Quetiapine  They metabolized by P-450 in the liver.  Anti-muscarinic & prolactin related se

 More effective in the control

 Drug interactions occur with enzyme inducers  Less extra-pyramidal se.
& inhibitors.  Weight gain.
Olanzapine

of negative symptoms
 May cause:
 Drowsiness.
 Headache.
 Hyperglycemia (by olanzapine)
 Resistant Schizophrenia  Agranulocytosis (1 3 m).
st
Clozapine
nd
(2 line drug) So, monitor WBC count:
 before start.
 every 2 wk for 6 m
Aripiprazole  partial agonist at D2 receptors.  α – blocking

& 5-HT2 receptors

 Antagonist at 5-HT2 receptors.  orthostatic BP.

 antagonize D2, D4
 D2 R blocker
 Tradive dyskinesia.
 Neuroleptic malignant
syndrome
 Weight gain.
 Hyperglycemia.
PHARMACOKINETIC ACTION OF DOPAMINE RECEPTORS MECHANISIM OF ACTION of anti-psychotic drugs
Administration Metabolism
 Taken Orally.  It occur in liver & subject to 1
st
R Action Adenyl- cAMP SITE OF D2 RECEPTORS EFFECT
 The bioavailability is good pass effect. via cyclase
 Some are taken I.M inj. D1 Gs Activated  Mesolimbic-Mesocortical anti-psychotic
Drug interactions D5 pathway
Distribution  activity of anti-Parkinsonism drugs
 High lipid solubility. that are DA agonists (levodopa,
D2 Gi Inhibited  Nigro-Striatal pathway Extra-pyramidal
D3
 Taken 1-2/d due to long T1/2. amantadine, bromocriptine),
 due to blocking of D2R D4 Tubero-Infundibular ↑ prolactin secretion
 Potentiate sedative effects of pathway Galactorrhea
benzodiazepines & antihistamines Medullary-Periventricular  appetite
 May interact with liver enzyme pathway
inducers & inhibitors. CTZ Anti-emetic
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