Download 16- Antideptessant Drugs and Neuroleptic Drugs

Antideptessant Drugs and Neuroleptic Drugs
Schizophrenia (thinking disorder)
Mania (mood disorder)
Psychiatic Disorders
Depression (mood disorder)
Anxiety
【Classfications】
1.Antipsychotic agents:e.g.phenothiazines(chlorpromazine)
2.Antimanic and antidepressive agents:e.g.Lithium carbonate.
3.Antianxiety agents:e.g.benzodiazepines.
Section 1 Antipsychotic Agents
Schizophrenia is characterized by Personality change and behavior disorders with
environmentPositive symptoms: thinking disorder,hallucination,delusion.
Negative symptoms: disturbance of feeling,discommunication.
The illness probably reflects some fundamental biochemical abnormality,possibly an
overactivity of the mesolimbic dopaminergic neurons.
Chlorpromazine（Wintermine）
History
Originally developed as an antihypertensive agent.
In 1952 chlorpromazine was used to treat schizophrenia in France.
【Pharmacologic effects】
1.Effets on CNS
1)Behavioral and psychological effects
a.for animals:docile and friendly.
b.for normal person:sedation, induce to sleep.
C.for schizophrenia patients
Antipsychotic effect (neuroleptic effect):calming effect and peaceful;make them feel
indifferent,then induce sleep;6 wks-6ms to Emax.
Mechanism:Block D2 receptor in the mesolimbic and mesocortical pathways of brain.
2)Antiemetic effects:The agents block D2 receptors in medullary CTZ(chemoreceptor trigger
zone)to inhibit vomiting.In high doses,the agents may directly depress the medu1lazy vomiting
center.
3)Effects on temperature-regulating
a.The temperature changed dependent with environment temperature.
cold environment ,T↓
hot environment,T↑
1
b.Hypothermia is not only in fever patients, but also in normal individuals.
[Mechanisms]
a.↓temperature-regulating center in hypothalamus;
b.α blocking, vessel dilatation;
c.inhibit basic metabolism.4)Potentiate the effects of CNS
depressants(analgesics,sedative-hypnotics).5)Altering endocrine:Tuberoinfundibular DA pathway
blockade.
a.↓prolactin release-inhibiting factor.
b.↓gonadotropin-release hormone.
c.↓corticotropin and growth hormone.
6)Extrapyramidal effects:Block DA receptors on Nigrosubstantia-striatal DA system
2.Autonomic nervous system
(1)Block α-R result in orthostatic hypotension.
(2)Block M-R induce atropine-like effects:blurred vision,constipation,dry mouth,decreased
sweating and urinary retention.
The Main Pathways of DA and Functions in Brain1.Nigrosubstantia-striatal DA system
From A9 of meso-nigrosubstantia to caudate nucleus, putamen.
Extrapyramidal function
Decrease-PD
Augmentation-Chorea(irregular,involuntary mucle jerks that occurs in different parts of the
body and impair voluntary activity).
2.Meso-cortical DA system
Regulate Cognition,thinking and consciousness。
3.Meso-limbic DA system
The center of Emotion and feelingSystem 2 and 3 augmentation-schizophrenia
4.Tubero-infundibular DA system
Regulate pituitary hormone release.
5.Area postrema of medulla DAergic stimulating
Central vomiting
[The Subtypes of DA Receptor]
According to protein structure, transmembrane signaling mechanisms, effect properties and
sites of receptors, DA receptor classified to D1 and D2 subtypes.
So far,five types of dopamine receptors have been identified.
D1-like receptors(D1 and D5) and D2-like receptors in Nigro-striatal system.
2
D2-like receptors and D4 in Meso-cortical and mesolimbic system.D2 in Tubero-infundibular
system.
【Therapeutic uses】
1.Treatment of schizophrenia
2.Prevention of severe nausea and vomiting
Useful in the treatment of nausea and vomiting induced by certain diseases and some
drugs.But,ineffective for vomiting induced by stimulating vestibules of ears(kinetia or sickness).
3.Artificial hibernation.
Lyticcocktail(chlorpromazine plus dolantin plus promethazine)and physical reduction of body
temperture can reduce the body temperature below normal level.
4.Intractable hiccup
【Adverse effects】
1.Common adverse reactions
Excessive sedation, nasal stuffiness, orthostatic hypotension, dry mouth, cardiac depression, M
block effects and endocrine effects
2.Extrapyramidal effects
parkinsonian syndrome :rigidity and tremor at rest
akathisia
acute dystonic reaction:facial grimacing and torticollis
tardive dyskinesia:sucking and macking of the lips and other involuntary facial movements.
The symptoms occur most often with chronic administration because of blocking DA receptors
in the nigrostriatum.They can be treated by using an anticholinergic antiparkinsonian drugs such
artane.
3.psychiatric disorders.
4.Allergic reactions
5.Seizure:lower its threshold.
ThioxanthenesChloprothixene(tardan)
1.Stronger sedative action.
2.Weak anti-depressant effect.
treatment in schizophrenia accompanied by anxiety or depression.Butyrophenones
Haloperidol
1.More effects in antipsychotic,to treat the schizophrenia and the mania.
2.The extrapyramidal reaction is very severe.
3.Strong antiemetic activity.
3
Droperidol
Combined with a potent narcotic analgesic,such as fentanyl,to produce neuroleptanalgesia(trade
name Innovar) used in small surgery.
Other Antipsychotic DrugsPenfluridol
1.Long acting antipsychotic agent.
2.Used for chronic schizophrenia.
Sulpiride
1.Stronger antipsychotic and antiemetic activity.
2.Having antidepressant efficacy.
3.The extrapyramidal reaction is light.
Clozapine
It is an atypical antipsychotic agent.
1.Low affinity for D2, high affinity for D4 and 5-HT.
2.More effective for positive and negative symptoms of schizophrenia
3.Onset rapidly: a week.
4.Lacking in extrapyramidal adverse effects.
5.Major adverse effect is agranulocytosis.
Risperidone1.Effective against negative as well as positive symptoms.
2.Improve the cognition disturbance.
3.Few adverse reactions.
New theory of psychosis
D1function↓,D2function↑.
New drugs
l-stepholidine (l-SPD):Stimuli D1,block D2
Section 2 Mood-Altering Drugs
(Antimanic and Antidepressive Agents)
[Definations]
The symptoms of depression are intense feeling of sadness,hopelessness,despir and inability to
experience pleasure in usual activities.
Mania is the opposite behaivor:rapid thought,extreme self-confidence etc.
[Etiology]
4
Biochemical bases:
amine theory
Mania
5-HT↓
NE(norepinephrine)↑
Depression
5-HT↓
NE↓
Antimanic
Drugs
Lithium carbonate
.[Pharmacological effects and mechanism]
1.“Mood-stabilizing”agent
2.Effects on neurotransmitters and their release.
↓NA and DA release from synapse in the brain,↑those reuptake
.[Clinical Uses]
1.mania
2.psychosis.
[Adverse reactions]
Lithium toxicity due to overdose:nausea,vomit,abdominal pain,diarrhea,and ataxia.
more severe:mental confusion,tremor,convulsion.
Use Nacl2 by intravenous to treat.
Antidepressant Agents
[Classification]
1.Non-selective monoamine reuptake inhibitors
Imipramine
Doxepin
2.Norepinepherine reuptake inhibitors
Desipramine
3.Serotonine reuptake inhibitors
Amitriptyline
Imipramine
[Pharmacological effects and mechanism]
1.CNS effects
Elevating the mood that is depressed and increasing physical activity.
It blocks the reuptake
of NA or 5-HT.2.Autonomic nervous system:Anticholinergic activity
3.Cardiovascular system:postual hypotentson,tachycardia,and arrhythmias.
[Clinical Uses]
Endogenous depression characterized by regression and inactivity.[Adverse reactions]
5
1.Atropine-like action
2.Cardiovascular reaction:arrhymias and hypotension.
Drd.New developed antidepressantsMaprotilinereduce reuptake of NA.Fluoxetine
1.Selectively inhibits reuptake of 5-HT
2.Less adverse reactions.
Section 3 Antianxiety Drugs[Defination]
Anxiety symptom:a neurosis with the characterstics of the repeated acute anxiety accompanied
by dysfunction of autanomic nerves such as tension,apprehension,or fear.
BuspironeUses:relief of anxiety
Mechanism:
A partial agonist of 5-HT1A-R at brain.
Advantages:
no sedative-hypnotic effects
no psychomotor impairment
no tolerance and dependence
6