Antipsychotic Drugs Flashcards
Antipsychotic drugs are also called
Antischizophrenic drugs
Major tranquillisers
Neuroleptics
What are the features of antipsychotic drugs
Not curative.
Requires several weeks to control symptoms
90%of patients require a maintenance dose
There’s usually a relapse
70%of patients experience a relapse when the drug is stopped
There’s a level of tolerance and physical dependence
What is psychosis
Psychosis is simply a disconnection from reality
What is schizophrenia
A mental disorder characterized by psychosis
The prevalence of schizophrenia is equal in males and females T/F
True
The prognosis of schizophrenia is poor T/F
True
What receptor is mainly responsible for the action of antipsychotic drugs
D2 - inhibitory
The dopamine receptor selective for sulpiride is
D2 like Receptor
D1B receptor is ……..
D5 receptor
D2 receptors inhibit ……..
cAMP and
GIRK
GIRK keeps the neurons in the hyperpolarized state, its inhibition by D2-like receptors results in …….
It allows the neurons to remain depolarized making them unable to initiate another signal
D1 receptor is selective for ……
SCH2339
The dopaminergic Pathways include
Mesocortical pathway
Mesolimbic
Nigrostriatal
Tuberoinfudibular pathway
A loss of integrity of the dopaminergic Pathways manifests as …… in the respective pathways
Mesolimbic - positive symptoms
Mesocortical- negative symptoms
Nigrostriatal pathway- extrapyramidal symptoms
Tuberoinfudibular - hyperprolactinaemia
The 5 functions of dopamine and the system or Pathways involved
Motivation, reward, cognition-mesolimbic
Hyperfunction in schizophrenia
Mesocortical- emotions and cognition hypofunction I schizophrenia
Motor control- nigrostriatal pathway
Extrapyramidal side effects
Endocrine control -Tuberoinfidibular
Hyperprolactinemiain treatment
Emetic effects CTZ in medulla
The major neurotransmitters involved in the pathogenesis of schizophrenia is
Dopamine
Glutamate
Serotonin
Briefly describe the effects of drugs on schizophrenia
Drugs like amphetamine. Cocaine and levodopa which results in Increased release of dopamine or in the quantity aggravates the positive sympathetic associated with schizophrenia
D2 receptor agonist like Apomorphine and bromocriptine also produce behavioural abnormalities in animals
D2 receptor antagonist are then effective in controlling the positive features of schizophrenia
Some evidence show that there is variation in D4 receptor which might make it a potent receptor for antipsychotic drugs
Role of glutamate in schizophrenia
Reduced glutamate conc and densities have been reported in postmortem brains of schizophrenics
Glutamate NMDA receptor antagonists like ketamine and phencyclidine have been reported to produce thought disorders, Hallucinations in humans
What is the role of serotonin in schizophrenia
Serotonin has a modulator effect on dopamine i.e it sort of counter the effect of dopamine..
Drugs like LSD with mixed agonist and antagonist effects have been found to produce behavioral abnormalities
Some antipsychotic drugs also work on serotonin receptors (antagonists)
The MOA of typical antipsychotics include
D2 antagonism
Some work on D4 receptor toi
Serotonin blockade ( may improve negative symptom)
Histamine blockade( drowsiness)
Alpha adrenoceptor blockade( postural hypertension)
Typical antipsychotics have a limited spectrum of efficacy, explain
They target the control of positive symptoms
The atypical antipsychotics have
Significantly reduced side effect
Improved efficacy profile
Group 1 phenothiazenes aka aliphatic anti psychotic are
Chlorpromazine
Promazine
Triflupromazine
Group 2 phenothiazenes include aka piperidine size chain
Thioridazine
Mesoridazine
Piperazine derivatives group 3 include
Prochlorperazine
Trifluperazine
Thioethylperazine
Butaperazine
Perpenazine
Fluphenazine
Acetophenazine
Carphenazine
Substitution on ……. position alters the efficacy ( activity) of phenothiazenes
R2
Position 2
Substitution at ………. alters potency and adverse effects
Nitrogen at position 10
Phenothiazenes differ in their potency but not their efficacy T/F
True
Phenothiazenes are antagonist at ..
……. receptors
D1
D2
Adrenergic alpha 1
Muscarinic
Serotonin receptor( less)
Allantipsychotics work majorly at …….
D2
And sometimes D4 receptor
The main side effects of phenothiazenes are
Extrapyramidal side effects
Akathisia( hours)
Dystonias( hours to days)
Parkinsonism ( weeks to months)
Rigidity, tremor, and loss of mobility
Tardive dyskinesia (months to years)
Acute dystopia side effect in antipsychotic medication
MOA: dopamine receptor blockade
Treatment Diphenhydramine and beztropine
Akathisia side effects of phenothiazenes
MOA: unknown. Extreme motor restlessness
Treatment: reduced dose
Switch to low-potency
Atypical antipsychotics
Propranolol
Benzodiazepine
Amantadine
Sometimes resistant to Anticholinergic antiparkinson agent
Muscarinic receptor blockade result in
Dry mouth, blurred vision
Urinary retention in males with prostatism aggravation of glaucoma
Phenothiazenes cardiac effect os
Depressed T Wave and prolonged Q-T interval.
It is reversible after discontinuing the drug
The endocrine effect of phenothiazines are
Increase prolactin secretion produces lactation in fees and gynecomastia in males.
Menstruation and ovulation disturbances.
Decreased secretion of gonadotropin, growth hormone and ACTH
Phenothiazenes causes humans to become poikilothermic by …..
Depression of temperature regulating and vasomotor mechanism
Why are phenothiazenes used as pre-anesthetic agent
To facilitate hypothermia for certain types of surgery
Alpha 1 adrenergic antagonism have ……. side effects
Orthostatic hypertension
Reflex tachycardia
Sexual dysfunction
Antihistaminergic side effevt of phenothiazines are
Sedation
Confusion
Disturbed concentration
Weight gain
Why can’t clozapine be discontinued abruptly
Exacerbation, worsening of pre existing tardiness dyskinesia.
Prominent involuntary lingual movement and somatic symptoms relapse
Depot preparations are administered through …….. for an interval of ……
Deep IM
1-4 weeks
Contraindications of depot preparations
Not to be used in children
Confusional state
Parkinsonism
Coma due to CNS depression
Intolerance to antipsychotic
Depot preparations are available as
Oily injections of decanoate derivatives or incorporation into carbohydrate microspheres
Fluphenazine
Risperidone
Haloperidol
Flupenthixol
Zuclopenthixol
