Antipsychotic Agents Flashcards
Four major categories of psychiatric disorders:
__________ (__________)
__________
__________
__________
Psychosis (Schizophrenia)
Anxiety
Depression
Mania
Schizophrenia is a form of ___________ ; a (short or long?) -term mental disorder of a type involving a breakdown in the relation between ___________, ___________, and ___________,
psychosis
long
thought
emotion
behaviour
Schizophrenia
it incorporates a broad range of symptoms that can include bizarre __________ , __________, __________ of thought processes, inappropriate affect, and grossly __________ __________
delusions ; hallucinations
incoherence
disorganized movements.
Schizophrenic symptoms
Positive: ___________ , ___________ thougth disorder, incoherent ___________, ___________, ___________ movements,
Negative: indicate a _______________________ , such as poverty of ___________ or ___________ affect.
hallucinations ; delusions
Speech ; agitation
stereotyped
loss or decrease in function
speech ; blunted
Schizophrenic symptoms
(Positive or Negative?) signs are more chronic and persistent and less responsive to treatment.
Negative
The __________ (_____) hypothesis for schizophrenia is the basis for rational drug therapy.
(Carlson) Several Lines of circumstantial evidence suggest that _______ __________ activity plays a role in this psychosis:
The dopamine (DA)
Excessive DA-ergic activity
The dopamine (DA) hypothesis for schizophrenia is the basis for rational drug therapy.
(1) Many antipsychotic drugs strongly block ______________-receptors in the CNS, especially in the ______________ system;
(2) Drugs that increase DA-ergic activity, such as ________ (a precursor), _________ (releasers of DA), and __________ (a direct DA-ergic agonist), either ________ schizophrenia or produce ___________________ in some patients;
post- synaptic D2; mesolimbic-frontal
levodopa; amphetamines; apomorphine
aggravate; psychosis de novo
The dopamine (DA) hypothesis for schizophrenia is the basis for rational drug therapy.
(3) ____________ has been found postmortem to be increased in the brains of schizophrenics who have not been treated with antipsychotic drugs;
(4)___________________ (PET) has shown increased DA receptor density in ________________________ when compared with such scans of ________ persons;
(5) Successful treatment of schizophrenic patients has been reported to increase the amount of ___________, a metabolite of DA, in the cerebrospinal fluid, plasma, and urine.
DA receptor density
Positron Emission Tomography
both treated and untreated schizophrenics ; nonschizophrenic
homo- vanillic acid (HVA)
Pathophysiology Several important DA-ergic systems or pathways are now recognized in the brain:
(1) The first pathway (the one most closely related to behavior) is the ___________________ ,
which projects from _________ near the
_________ to the _________ system and _________.
(2) The second system (the _________ tract) consists of neurons that project from the _________ to the _________ and _________; it is involved in the coordination of _________ _________
3) The third pathway (the _________ tract) connects _________ and _________ neurons to the _________ and _________.
DA released by these neurons physiologically inhibits ________ secretion.
mesocortical tract ; cell bodies
substantia nigra ; limbic system ; neocortex.
nigrostriatal tract; substantia nigra
caudate ; putamen;
voluntary movement.
tuberoinfundibular tract; arcuate nuclei ; periventricular
hypothalamus ; posterior pituitary
prolactin
It has not been convincingly demonstrated that antagonism of any ________ receptors (especially _____)
plays a role in the action of “atypical” antipsychotic drugs.
Most of the newer “atypical” antipsychotics and some of the traditional ones have significant affinity for the _______ receptor, suggesting
an important role for the _______ system.
Participation of glutamate, GABA, and ACh receptors in the pathophysiology of schizophrenia has also been proposed.
DA; D4
5-HT2A; serotonin
Pharmacological actions
(1) CNS.
In normal individuals antipsychotics produce _________ syndrome – _________ to surroundings, ______ of thought, psychomotor _________, _________ quietening, reduction in _________.
In psychotic patients neuroleptics reduce _________ behaviour, _________ and _________.
They control psychotic symptomatology. Disturbed thought and behaviour are gradually normalized, anxiety is relieved. Hyperactivity, hallucinations and delusions are suppressed.
neuroleptic syndrome
indifference ; paucity ; slowing
emotional ;initiative.
Pharmacological actions of anti-psychotics
(1) CNS.
The __________ effect is produced immediately while the __________ effect takes ______ to develop.
Tolerance develops only to the _________________ effect.
psychosedative
antipsychotic
a week
psychosedative effect.
In animal (CNS) antipsychotic agents produce:
a state of _________ and _________ (_________).
The _________ centre is turned off,
rendering the patient ______thermic (body temperature ____ if surroundings are _____ and the contrary).
The _________, _________ and other vital centres are not affected, except of very high doses. It is very difficult to produce ______ with neuroleptics.
Antiemetic effect is exerted through the _______. Almost all neuroleptics, except _________, have this effect. However, they are ineffective in _________
rigidity ; immobility
catalepsy; thermoregulatory
poikilothermic ; falls
cold ; medullary
respiratory ; coma
CTZ ; thioridazine
motor sickness.
Pharmacological actions of Anti-psychotic
(2) ANS.
Neuroleptics have varying degrees of ______________ blocking activity and produce _____tension (primarily ________ ). The _____tensive effect is more marked after ________ administration.
____________ property of neuroleptics is weak.
The phenothiazines have weak _____________ and ____________ actions as well.
Promethazine has strong ___________, and __________ action.
alpha- adrenergic ; hypotension
postural ; hypotensive
parenteral ; Anticholinergic
H1-antihistaminic ; anti-5-HT
sedative ; H1-antihistaminic
Pharmacological actions of Anti-psychotic
(3) Endocrine system.
Neuroleptics consistently increase _____________ by blocking the _____________ action of ____ on _____________ gland.
This may result in _____________ and _____________. They (increase or reduce?) gonadotrophins, ACTH, GH and ADH secretion
prolactin release
inhibitory ; DA
pituitary
galactorrhea ; gynecomastia.
reduce
Antipsychotics
The symptoms of schizophrenia can be controlled, in varying degrees, by a large group of drugs called antipsychotics.
(_____________, _______________ )
They all attenuate the activity of ___________
Direct bearing on ______ activity
Neuroleptics
Major Tranquilizers
dopamine
motor activity
Antipsychotics
Typical – _________ , _________, _________, _________ etc
Atypical – _________, _________, _________ _________, _________
Typical – Chlorpromazine, haloperidol, fluphenazine, thioridazine etc
Atypical – risperidone, clozapine, olanzepine Sertindole, aripiprazole
Antipsychotics
Act on a number of receptors :
List them
NA, DA, 5HT
Classification of Anti-psychotics
I.Typical antipsychotics ((with or lack?) extrapyramidal motor symptoms)
II. Atypical antipsychotics ((with or lack?) of extrapyramidal motor symptoms)
with
lack
Classification
Typical antipsychotics
•___________
• ____________
• ________________, etc.
• Phenothiazines
• Thioxanthenes
• Butyrophenone
Typical Neuroleptics (____-blockers) Phenothiazines
Type 1 (_______ side chain)
Type 2 (_________ side chain)
Type 3 (____________ side chain)
D2-blockers
aliphatic
piperidine
piperazine
Typical Neuroleptics
Phenothiazines
Type 1 : list 4
Type 2 : list 1
Type 3 : list 3
Chlorpromazine, Promazine, Levomepromazine, Promethazine
Thioridazine
Trifluoperazine, Prochlorperazine, Fluphenazine
Thioxanthenes
This is a _____-ring compound structurally related to ________ but having the nitrogen atom at position ____ replaced by a _____ atom with a _______ bond.
three; phenothiazine
10 ; carbon
double
Thioxanthenes have nearly equivalent potency with phenothiazines.
T/F
T
Thioxanthenes have nearly equivalent potency with phenothiazines.
Thioxanthenes
•________________
•_____________
•_________________
•Chlorprothixene
•Flupenthixol
•Zuclopenthixol
Butyrophenones
•__________
•____________
•_____________
•Droperidol
•Benperidol
•Haloperidol
The butyrophenones are structurally similar to ________.
They offer (lesser or greater?) potency
and (fewer or more ?) autonomic side effects.
GABA
Greater
Fewer
Atypical Neuroleptics
They block mainly ______ and _______ receptors
5-HT2- and D4
Atypical Neuroleptics
They cause (little or plenty?) extrapyramidal toxicity.
_________ is representative of many of the newer agents in having a better side effect profile.
little
Risperidone
Atypical neuroleptics
Clozapine •Olanzapine •Quetiapine •Risperidone •Ziprasidone •Amisulpiride •Zotepine •Sertindole
Pimozide Molindone Loxapine Reserpine.
Lol, not me
PHARMACOKINETICS of Anti-psychotics
Most neuroleptic drugs are highly _____philic, bind (avidly or mildly?) to proteins, and tend to accumulate in (mildly or highly?) perfused tissues.
Oral absorption is often _________ and ________, whereas IM injection is (more or less?) reliable.
lipophilic ; avidly
highly
incomplete ; erratic
more
PHARMACOKINETICS of Anti-psychotics
With repeated administration, variable accumulation occurs in ________ and possibly in __________
Half-lives are generally (short or long?) , and so a _______ daily dose is effective.
body fat ; brain myelin.
long ; single
An esterified derivate of ________ requires dosing only once every few weeks
fluphenazine
Psychiatric indications of neuroleptics
__________ is the primary
indication for neuroleptics.
Unfortunately, many patients show little response.💔
Schizophrenia
Antipsychotics are also indicated for ___________ disorders, which share characteristics of both __________ and _________ disorders.
schizoaffective
schizophrenia
affective
Schizoaffective disorders
The psychotic aspects of the illness require treatment with ____________ drugs, which may be used with other drugs such as _________,__________ or __________
antipsychotic
antidepressants, lithium, or valproates.
Whilst a typical antipsychotics should
provide adequate treatment of (positive or negative ?) symptoms including __________ and __________ in at least 60% of cases, patients are often left with unresolved (positive or negative?) symptoms such as _________ , _________ of affect, and _________.
positive ; hallucinations
delusions ; negative
apathy ; flattening
alogia.
Evidence suggests that clozapine and the newer atypicals have a significant advantage over typical drugs against _________ symptoms.
negative
The _______ phase in bipolar affective disorder often requires treatment with neuroleptics , though _________ or __________ supplemented with (low or high?) -potency _________ (e.g. lorazepam or clonazepam) may suffice
in milder cases.
manic ; lithium ; valproic acid
high; benzodiazepines
Recent controlled trials support the efficacy of _____therapy with (typical or atypical?) antipsychotics in the _____ phase (up to ________) of mania, and __________ has been approved for this indication.
monotherapy ; atypical
acute ; 4 weeks
olanzapine
Nonmanic excited states may also be managed by antipsychotics, often in combination with _____________.
Other indications for the use of antipsychotics include disturbed behavior in patients with __________ disease, and, with ___________, psychotic depression.
benzodiazepines
Alzheimer’s disease
antidepressants
Antipsychotics are not indicated for the treatment of various ________ syndromes, e.g. ____________.
In small doses antipsychotics have been promoted (_________!) for the relief of _______ associated with minor _________ disorders, but the __________ agents are preferred.
withdrawal syndromes ; opioid withdrawal.
wrongly; anxiety
emotional ; anxiolytic
Nonpsychiatric indications
Most older antipsychotics, with the exception of _________, have a strong ________ effect.
This action is due to _____-receptor blockade, both centrally (in the _________________ of the _______) and peripherally (on receptors in the ________).
Some drugs, such as _______ are promoted only as antiemetics.
Phenothiazines with shorter side chains have considerable _____-receptor-blocking action and used for relief of _______ or, in the case of promethazine,
as _____________.
The butyrophenone droperidol is used in combination with an _______, ___________, in neurolept-anaesthesia (-analgesia).
thioridazine ; antiemetic
D2-receptor ; chemoreceptor trigger zone
the medulla ; stomach
prochlorperazine ; H1-receptor-
pruritus ; preoperative sedatives.
an opioid ; fentanyl
Adverse reactions – behavioral effects:
The older typical antipsychotic drugs are (pleasant or unpleasant?) to take. Many patients stop taking these drugs because of the adverse effects, which may be mitigated by ____________________________________________________________________.
A “__________” that may be due to drug-induced akinesia usually responds to treatment with antiparkinsonian drugs.
Other pseudodepressions may be due to _______ doses; the ____easing the dose may relieve the symptoms.
________-_________ states may occur with very high doses of drugs that have prominent antimuscarinic actions.
unpleasant
giving small doses during the day and the major portion at bedtime.
“pseudodepression”
higher ; decreasing
Toxic-confusional states
Neurologic effects:
Extrapyramidal reactions occurring early during treatment with older agents include typical _______ syndrome, _________ (uncontrollable restlessness), and acute ______ reactions
(________ _____ or ______).
Parkinsonism can be treated, with conventional _________ drugs of the ______ type or, in rare cases, with ________.
Parkinsonism may be __________,so that an attempt to withdraw antiparkinsonian drugs should be made every ___________.
Parkinson’s syndrome
akathisia ; restlessness
dystonic ; spastic retrocollis ; torticollis
antiparkinsonian ; antimuscarinic
amantadine ; self-limiting
3–4 months.
Neurologic effects:
Akathisia and dystonic reactions also respond to such treatment but many prefer to use a _______ ________ with ___________ properties, e.g. ______________.
sedative antihistamine
anticholinergic
diphenhydramine.
Tardive dyskinesia
- persistent involuntary movements of ______,_______ or _________
mouth, tongue or face.
Autonomic nervous system effects
Antimuscarinic (______-like) adverse effects: urinary _______, _____ mouth, midriasis.
Alpha-blockade: ________tension or impaired __________ should be managed by switching to drugs with less marked adrenoceptor-blocking actions.
Atropine
Retention; dry
Orthostatic hypo
Ocular complications
Deposits in the (anterior or posterior?) portions of the eye (_______ and _____) are a common complication of Chlorpromazine therapy.
They may accentuate the normal processes of ______ of the lens.
Thioridazine is the only antipsychotic
drug that causes ———————— ,
which in advanced cases may resemble _________ ————-.
anterior
cornea and lens
aging ; retinal deposits
retinitis pigmentosa.
Metabolic and endocrine side effects
Weight _____ is very common, especially with ________ and ________, and requires monitoring of food intake, especially ________. ________glycemia may develop.
Hyperprolactinemia in women results in the ________ – ________ syndrome and ________; in men ,___________, ________, and ________ may result.
gain ; clozapine and olanzapine
carbohydrates ; Hyperglycemia
amenorrhea – galactorrhea
infertility; loss of libido
impotence ; infertility
may result.
Toxic or allergic reactions
Agranulocytosis, cholestatic jaundice, and skin eruptions occur rarely with the high-potency antipsychotic drugs currently used.
Toxic or allergic reactions
________cytosis, ________ jaundice, and skin _________ occur (often or rarely?) with the high-potency antipsychotic drugs currently used.
Agranulocytosis
cholestatic jaundice
skin eruptions
rarely
Neuroleptic malignant syndrome
This life-threatening ADR occurs in patients who are extremely sensitive to the ___________ effects of antipsychotics.
The initial symptom is marked __________. If _________ is impaired, as it often is during treatment with anticholinergic drugs, fever may ensue, often reaching dangerous levels.
The stress _________ and high fever associated with this syndrome suggest _______________ process.
Autonomic instability, with altered __________ and ________ , is often present.
___________ isoenzymes are usually elevated, reflecting muscle damage.
extrapyramidal ; muscle rigidity
sweating ; leukocytosis
an infectious process. ; blood pressure
and pulse rate
Creatine kinase
Neuroleptic malignant syndrome
This syndrome is believed to result from an excessively rapid blockade of ___________ receptors.
A severe form of _____________________________ follows.
Early in the course, vigorous treatment of the extrapyramidal syndrome with _________ drugs is worthwhile.
Muscle relaxants, particularly __________, are often useful. Other muscle relaxants, such as _________, or DA agonists, such as __________, have been reported to be helpful.
If fever is present, cooling by ________ measures should be tried.
postsynaptic DA receptors
extrapyramidal syndrome
antiparkinsonian ; diazepam
dantrolene ; bromocriptine,
physical
