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House Pharmacology > Antipsychotic Agents > Flashcards

Antipsychotic Agents Flashcards

1
Q

Four major categories of psychiatric disorders:
__________ (__________)

__________

__________

__________

A

Psychosis (Schizophrenia)
Anxiety
Depression
Mania

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2
Q

Schizophrenia is a form of ___________ ; a (short or long?) -term mental disorder of a type involving a breakdown in the relation between ___________, ___________, and ___________,

A

psychosis

long

thought
emotion
behaviour

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3
Q

Schizophrenia

it incorporates a broad range of symptoms that can include bizarre __________ , __________, __________ of thought processes, inappropriate affect, and grossly __________ __________

A

delusions ; hallucinations

incoherence

disorganized movements.

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4
Q

Schizophrenic symptoms

Positive: ___________ , ___________ thougth disorder, incoherent ___________, ___________, ___________ movements,

Negative: indicate a _______________________ , such as poverty of ___________ or ___________ affect.

A

hallucinations ; delusions

Speech ; agitation

stereotyped

loss or decrease in function

speech ; blunted

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5
Q

Schizophrenic symptoms

(Positive or Negative?) signs are more chronic and persistent and less responsive to treatment.

A

Negative

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6
Q

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:

A

The dopamine (DA)

Excessive DA-ergic activity

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7
Q

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;

A

post- synaptic D2; mesolimbic-frontal

levodopa; amphetamines; apomorphine

aggravate; psychosis de novo

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8
Q

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.

A

DA receptor density

Positron Emission Tomography

both treated and untreated schizophrenics ; nonschizophrenic

homo- vanillic acid (HVA)

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9
Q

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.

A

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

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10
Q

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.

A

DA; D4

5-HT2A; serotonin

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11
Q

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.

A

neuroleptic syndrome

indifference ; paucity ; slowing

emotional ;initiative.

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12
Q

Pharmacological actions of anti-psychotics
(1) CNS.
The __________ effect is produced immediately while the __________ effect takes ______ to develop.

Tolerance develops only to the _________________ effect.

A

psychosedative

antipsychotic

a week

psychosedative effect.

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13
Q

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 _________

A

rigidity ; immobility

catalepsy; thermoregulatory

poikilothermic ; falls

cold ; medullary

respiratory ; coma

CTZ ; thioridazine

motor sickness.

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14
Q

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.

A

alpha- adrenergic ; hypotension

postural ; hypotensive

parenteral ; Anticholinergic

H1-antihistaminic ; anti-5-HT

sedative ; H1-antihistaminic

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15
Q

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

A

prolactin release

inhibitory ; DA

pituitary

galactorrhea ; gynecomastia.

reduce

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16
Q

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

A

Neuroleptics

Major Tranquilizers

dopamine

motor activity

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17
Q

Antipsychotics

Typical – _________ , _________, _________, _________ etc

Atypical – _________, _________, _________ _________, _________

A

Typical – Chlorpromazine, haloperidol, fluphenazine, thioridazine etc

Atypical – risperidone, clozapine, olanzepine Sertindole, aripiprazole

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18
Q

Antipsychotics

Act on a number of receptors :

List them

A

NA, DA, 5HT

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19
Q

Classification of Anti-psychotics
I.Typical antipsychotics ((with or lack?) extrapyramidal motor symptoms)

II. Atypical antipsychotics ((with or lack?) of extrapyramidal motor symptoms)

A

with

lack

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20
Q

Classification

Typical antipsychotics

•___________
• ____________
• ________________, etc.

A

• Phenothiazines
• Thioxanthenes
• Butyrophenone

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21
Q

Typical Neuroleptics (____-blockers) Phenothiazines

Type 1 (_______ side chain)
Type 2 (_________ side chain)
Type 3 (____________ side chain)

A

D2-blockers

aliphatic

piperidine

piperazine

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22
Q

Typical Neuroleptics

Phenothiazines
Type 1 : list 4

Type 2 : list 1

Type 3 : list 3

A

Chlorpromazine, Promazine, Levomepromazine, Promethazine

Thioridazine

Trifluoperazine, Prochlorperazine, Fluphenazine

23
Q

Thioxanthenes

This is a _____-ring compound structurally related to ________ but having the nitrogen atom at position ____ replaced by a _____ atom with a _______ bond.

A

three; phenothiazine

10 ; carbon

double

24
Q

Thioxanthenes have nearly equivalent potency with phenothiazines.

T/F

A

T

Thioxanthenes have nearly equivalent potency with phenothiazines.

25
Q

Thioxanthenes

•________________

•_____________

•_________________

A

•Chlorprothixene

•Flupenthixol

•Zuclopenthixol

26
Q

Butyrophenones

•__________
•____________
•_____________

A

•Droperidol
•Benperidol
•Haloperidol

27
Q

The butyrophenones are structurally similar to ________.

They offer (lesser or greater?) potency
and (fewer or more ?) autonomic side effects.

A

GABA

Greater

Fewer

28
Q

Atypical Neuroleptics

They block mainly ______ and _______ receptors

A

5-HT2- and D4

29
Q

Atypical Neuroleptics

They cause (little or plenty?) extrapyramidal toxicity.

_________ is representative of many of the newer agents in having a better side effect profile.

A

little

Risperidone

30
Q

Atypical neuroleptics

Clozapine •Olanzapine •Quetiapine •Risperidone •Ziprasidone •Amisulpiride •Zotepine •Sertindole

Pimozide Molindone Loxapine Reserpine.

A

Lol, not me

31
Q

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.

A

lipophilic ; avidly

highly

incomplete ; erratic

more

32
Q

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.

A

body fat ; brain myelin.

long ; single

33
Q

An esterified derivate of ________ requires dosing only once every few weeks

A

fluphenazine

34
Q

Psychiatric indications of neuroleptics

__________ is the primary
indication for neuroleptics.

Unfortunately, many patients show little response.💔

A

Schizophrenia

35
Q

Antipsychotics are also indicated for ___________ disorders, which share characteristics of both __________ and _________ disorders.

A

schizoaffective

schizophrenia

affective

36
Q

Schizoaffective disorders

The psychotic aspects of the illness require treatment with ____________ drugs, which may be used with other drugs such as _________,__________ or __________

A

antipsychotic

antidepressants, lithium, or valproates.

37
Q

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 _________.

A

positive ; hallucinations

delusions ; negative

apathy ; flattening

alogia.

38
Q

Evidence suggests that clozapine and the newer atypicals have a significant advantage over typical drugs against _________ symptoms.

A

negative

39
Q

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.

A

manic ; lithium ; valproic acid

high; benzodiazepines

40
Q

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.

A

monotherapy ; atypical

acute ; 4 weeks

olanzapine

41
Q

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.

A

benzodiazepines

Alzheimer’s disease

antidepressants

42
Q

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.

A

withdrawal syndromes ; opioid withdrawal.

wrongly; anxiety

emotional ; anxiolytic

43
Q

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).

A

thioridazine ; antiemetic

D2-receptor ; chemoreceptor trigger zone

the medulla ; stomach

prochlorperazine ; H1-receptor-

pruritus ; preoperative sedatives.

an opioid ; fentanyl

44
Q

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.

A

unpleasant

giving small doses during the day and the major portion at bedtime.

“pseudodepression”

higher ; decreasing

Toxic-confusional states

45
Q

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 ___________.

A

Parkinson’s syndrome

akathisia ; restlessness

dystonic ; spastic retrocollis ; torticollis

antiparkinsonian ; antimuscarinic

amantadine ; self-limiting

3–4 months.

46
Q

Neurologic effects:

Akathisia and dystonic reactions also respond to such treatment but many prefer to use a _______ ________ with ___________ properties, e.g. ______________.

A

sedative antihistamine

anticholinergic

diphenhydramine.

47
Q

Tardive dyskinesia
- persistent involuntary movements of ______,_______ or _________

A

mouth, tongue or face.

48
Q

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.

A

Atropine

Retention; dry

Orthostatic hypo

49
Q

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 _________ ————-.

A

anterior

cornea and lens

aging ; retinal deposits

retinitis pigmentosa.

50
Q

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.

A

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.

51
Q

Toxic or allergic reactions
________cytosis, ________ jaundice, and skin _________ occur (often or rarely?) with the high-potency antipsychotic drugs currently used.

A

Agranulocytosis

cholestatic jaundice

skin eruptions

rarely

52
Q

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.

A

extrapyramidal ; muscle rigidity

sweating ; leukocytosis

an infectious process. ; blood pressure
and pulse rate

Creatine kinase

53
Q

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.

A

postsynaptic DA receptors

extrapyramidal syndrome

antiparkinsonian ; diazepam

dantrolene ; bromocriptine,

physical

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