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Psychiatric Pharmacology > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

Schizophrenia is a _____ disease with Onset in _____________________. It is Highly disabling to social & vocational functioning. It can be well controlled to avoid showing symptoms.

A
  1. Chronic

2. late adolescence / early adulthood

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2
Q

Life time incidence of schizophrenia is estimated at about ______ of people will develop disease at some point in their life.
Prevalence of schizophrenia is estimated at about ______ of people suffer from schizophrenia at any one time.

A
  1. 1 in 100 i.e. 1%

2. 1 in 300 i.e. 0.3 %

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3
Q

There are 5 symptoms domains of schizophrenia. Anxiety/depression, aggressive and cognitive symptoms are ________ to Schizophrenia. Positive and negative symptoms are _______ to Schizophrenia.

A
  1. not exclusive

2. exclusive

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4
Q

Positive symptoms of Schizophrenia refers to _____________ while Negative symptoms of Schizophrenia refers to ______________.

A
  1. abnormal behaviours added

2. normal behaviours subtracted

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5
Q

Schizophrenia presents itself in periods of acute presentation with positive symptoms are _______ with periods during which the negative symptoms predominate. As the disease progresses, the _________ symptoms generally become more dominant.

A
  1. interspersed

2. negative

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6
Q

Usually it is the presentation of _______ symptoms that is most disturbing to others and leads to first referral to a psychiatrist and detection of schizophrenia.

A

positive

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7
Q

Positive symptoms of Schizophrenia can include;
– _______ (often paranoid).
– ___________ (e.g. exhortatory voices).
– Thought disorder including feeling that thoughts are ____________________.
– Abnormal behaviours (e.g. stereotypical or aggressive behaviours).

A
  1. Delusions
  2. Hallucinations
  3. controlled by an outside agency
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8
Q

Negative symptoms of Schizophrenia includes __________ from social contacts and ________ of emotional responses.

A
  1. Withdrawal

2. Flattening

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9
Q

For the individual with schizophrenia the ________ symptoms are often the most distressing. In contrast, the positive phases are characterized by ________ (self-awareness of abnormal behaviour).

A
  1. negative

2. lack of insight

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10
Q

Schizophrenia is also frequently associated with ________, resulting in suicide in about 10 % of cases. ________thoughts form on realization of negative symptoms due to loss of normal behaviour.

A
  1. Depression

2. Depressing

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11
Q

There are many causes for negative symptoms in Schizophrenia. It can due to a ______ deficit of the illness or ______ to depression/extrapyramidal symptoms/environmental deprivation/positive symptoms.

A
  1. primary

2. secondary

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12
Q

In Schizophrenia, ____________ relates to whether the patient can return to work/society and has a _______ bearing on prognosis compared to positive symptoms. It is a persistent core feature of Schizophrenia, characterized by Impairment of _________ and __________.

A
  1. Cognitive dysfunction
  2. better
  3. selective attention
  4. working memory
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13
Q

Schizophrenia has ________ hereditary tendency and _______ schizophrenics share the same mutations of susceptibility genes. Environmental factors associations are not conclusive.

A
  1. incomplete

2. not all

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14
Q

Schizophrenia onset in late adolescence / early adulthood is consistent with neurodevelopmental abnormality involving _________ of cortico-cortical pathways. There is evidence of enlarged ventricles, abnormalities in __________ of cortical cells. Possibly a neurodevelopmental disorder?

A
  1. myelination

2. laminar organization

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15
Q

There are 3 neurochemical theories regarding Schizophrenia. They include _______, _______ and _________. Neurochemical theories proposed are primarily theories of the ______ symptoms.

A
  1. Dopamine
  2. Serotonin
  3. Glutamate
  4. positive
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16
Q

The dopamine theory was based on the fact that Amphetamine (known dopaminergic compound) produces symptoms similar to acute schizophrenia. This provided a basis for pharmacotherapy in that all antipsychotic drugs are __________.

A

D2 antagonists

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17
Q

The affinity of antipsychotic drugs for D2 receptor was also found to correlate with mean clinically efficacious dose. (higher affinity = lower dose)
Typical Antipsychotics in order of efficacy: F____________> H___________ > T____________> Clozapine > C___________

A
  1. Fluphenazine
  2. Haloperidol
  3. Trifluoperazine
  4. Chlorpromazine
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18
Q

The Nigrostriatal dopamine Pathway (__________ to dorsal striatum) is Involved in voluntary movement. (part of extrapyramidal motor system)

A

Substantia nigra

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19
Q

Mesocortical/Mesolimbic dopamine Pathways start from the Ventral tegmental area (VTA) to prefrontal cortex and _____ (emotional) brain.) is involved in emotion, cognition, and attention.

Mesolimbic - reward and emotion
Mesocortical - cognition and attention

A

limbic

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20
Q

Over activation of dopamine D2 receptors in the _________ and __________ pathways leads to issues with cognition, emotion seen in schizophrenia. In contrast in PD, the ___________ neurones are degenerated in PD causing loss of dopamine innervation and voluntary movement. Therefore, D2 antagonists help alleviate over-activation.

*hint: what are the pathways involved?

A
  1. Nigrostriatal
  2. Mesocortical/Mesolimbic
  3. substantia nigra
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21
Q

The tuberoinfundibular dopamine pathway starts from hypothalamus to anterior pituitary and regulates ______ secretion into the blood circulation. (can lead to unwanted off-target effects)

A

prolactin

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22
Q

The 5-HT (Serotonin) Theory came about due to Lysergic acid diethylamide (LSD), primarily as a _____ agonist, produces symptoms similar to acute schizophrenia. Many of the newer atypical antipsychotics have ______ antagonism which may explain the improved efficacy of newer antipsychotic drugs vs old.

A

5-HT2

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23
Q

The Glutamate Theory came about due to the fact that: Drugs which block the ____ receptor channel, e.g. phencyclidine (PCP) and ketamine, produce symptoms similar to acute schizophrenia. Gaining popularity in schizophrenia research again but still has not produced any clinically useful drugs.

A

NMDA

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24
Q

Typical Antipsychotics control ______ symptoms of schizophrenia and produce _______ side-effects. C___________ was the first antipsychotic drug derived from anti-histamine drugs.

A
  1. positive
  2. extrapyramidal (EPS)
  3. Chlorpromazine
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25
Q

Atypical Antipsychotics control _______ symptoms of schizophrenia and produced less _______________ side-effects (main difference vs typical antipsychotics).

A
  1. positive

2. extrapyramidal

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26
Q

Haloperidol ( ______ antipsychotic) remains one of the most widely used antipsychotic drugs. (cheaper than newer drugs and useful alternative for allergic reactions)

A

Typical

27
Q

Examples of Atypical antipsychotics include: A________, C________, O_________ and R_________.

A
  1. amisulpride
  2. clozapine
  3. olanzapine
  4. risperidone
28
Q

Typical Antipsychotics bind to and antagonize off target receptors such as M1 (causing _______, constipation, blurred vision), H1 (sedation, ________) and α1 (____________ , dizziness).

A
  1. dry mouth
  2. weight gain
  3. postural hypotension
29
Q

Haloperidol is better compared to Chlorpromazine as Haloperidol has improved _______ , loses _______ binding (fewer side effects). However, Haloperidol still binds to ___ .

A
  1. selectivity
  2. M1 & H1
  3. α1
30
Q

The pyramidal motor pathway is the output from the primary motor cortex via the pyramids of the medulla oblongata to the spinal cord. The extrapyramidal pathway involves the b___ g____, including the s______ and s_____ n___ .

A
  1. basal ganglia
  2. striatum
  3. substantia nigra
31
Q

Extrapyramidal side effects include Acute ______, Tardive ______ and A_____ (subjective sensation of restlessness). Motor side-effects due to actions on the extrapyramidal motor pathways.

A
  1. Dystonias
  2. Dyskinesia
  3. Akathisia
32
Q

Acute Dystonias show a Parkinsonism-like syndrome e.g. cogwheel rigidity and tremor at rest. It occurs within first few weeks of treatment. and is ______ when drug is stopped. They appear to be caused by D2 antagonism in the _______ pathway.

A
  1. reversible

2. nigrostriatal

33
Q

Tardive Dyskinesia develops slowly (tardive) over months or years of treatment. Repetitive and stereotyped involuntary movements of face, tongue, and limbs (dyskinesia).
Akathisia refers to Involuntary movements and compulsion to act associated with restlessness, anxiety and agitation. Only ______ correlates directly with duration on medication.

A

Akathisia

34
Q

Tardive Dyskinesia and Akathisia occurs in ______% of patients on ______ antipsychotics and is often _______. (Most probably due to upregulation or super sensitivity of dopamine receptors in the nigrostriatal system, similar to levodopa.)

A
  1. 20 to 40
  2. typical
  3. irreversible
35
Q

Atypical antipsychotics are antipsychotics that produce ____ severe extrapyramidal side effects compared to typical antipsychotics. (only definition of atypicality)

A

less

36
Q

Many atypical antipsychotics have:

  • ______ affinity at 5-HT2 receptors
  • ______ affinity at D4 receptors
  • _____ antagonism at α-adrenoceptors, H1 histamine receptors, muscarinic acetylcholine receptors, and 5-HT2 receptors.
A
  1. Greater
  2. Greater
  3. Mixed
37
Q

The ______________ (SDA) is the “core” of most atypical antipsychotics but the atypical antipsychotics have complex mixtures of actions (‘dirtier drug’).

A

Serotonin-dopamine antagonism (5-HT2A and D2)

38
Q

A common atypical antipsychotic is Clozapine that also binds the same off target receptors as typical antipsychotics, which include M1 (causing dry _____,
constipation, blurred vision), H1 (sedation,
_____ gain) and α1 (postural _______ , dizziness).

A
  1. mouth
  2. weight
  3. hypotension
39
Q

Clinical use of clozapine is limited by __________ (develops in only approx. 1 % of patients, potentially fatal) _______________ are required to monitor patients. This led to development of similar compounds without this adverse effect e.g. _________.

A
  1. agranulocytosis (lack of granulocyte type white blood cells)
  2. Regular blood counts
  3. olanzapine
40
Q

Side effects due to

  1. off-target Muscarinic receptor antagonism (causing Dry mouth, constipation, blurred vision) and
  2. off-target histamine H1 receptor antagonism (causing weight gain and sedation) are especially evident for _______ and ________.
A
  1. clozapine

2. olanzapine

41
Q

Side effects due to off-target α1-adrenoceptor antagonism (causing Postural hypotension, reflex tachycardia) are especially evident for _________.

A

Risperidone

42
Q

The atypical antipsychotics are _______ compared to typical antipsychotics in terms of M1/H1/α1 side effects.

A

not better

43
Q

The reduced Extrapyramidal side effects of atypical antipsychotics are ______ result of increased off-target receptor antagonism.

A

not the

44
Q

Amisulpride is a selective ______ antagonist (but recently also reported to have _____ antagonism). For an atypical antipsychotic, it has an atypical pattern of receptor affinities.

A
  1. D2/D3

2. 5-HT7

45
Q

Amisulpride has fewer side-effects due to selectivity for ______ receptors. (absence of α-adrenoceptor block, antihistaminergic, and anticholinergic side-effects)

A

D2 / D3

46
Q

Amisulpride has adverse effects on mammary glands and tissues and causes increased _______ secretion due to block of dopamine receptors in the ______________. This can lead to breast swelling, pain, lactation (females) and _________ (males). This is mediated via the _____________ pathway.

A
  1. prolactin
  2. anterior pituitary gland
  3. gynaecomastia
  4. tuberoinfundibular
47
Q

__________ is a partial agonist with antagonistic effects in presence of agonists (i.e. Dopamine). Considered as a newer ____ line drug. (may have lowered adverse effects)

A
  1. Aripiprazole

2. 2nd

48
Q

Atypical antipsychotics such as C______, O_______ and R_________ can induce hyperglycaemia and diabetes. Among them, _________ has the lowest rate of diabetes reversal. The MOA may involve 5-HT antagonism in pancreatic beta cells/hypothalamus. However, _________ is an exception.

A
  1. Clozapine
  2. Olanzapine
  3. Risperidone
  4. Risperidone
  5. Amisulpride
49
Q

Some atypical antipsychotics induce weight gain, especially ______, _______ and _________. This has led to experimental use of __________ in the treatment of anorexia nervousa.

A
  1. Clozapine
  2. Olanzapine
  3. Risperidone
  4. Olanzapine
50
Q

It is thought that ___ antagonism causes sedation, leading to a sedentary lifestyle while _____ and _______ receptor antagonism affects hypothalamus and feeding behaviour, all of which may contribute to ___________. However, this effect is not seen in C___________.

A
  1. H1
  2. α-adrenoceptor
  3. 5-HT2
  4. drug induced weight gain
  5. Chlorpromazine
51
Q

The reason atypical antipsychotics produce less EPS side effects is possibly due to ______ affinity for ____ and __ receptors, with __having the greatest impact on causing EPS symptoms.

A
  1. lowered
  2. D2
  3. D1
  4. D1
52
Q

Clozapine and Olanzapine may cause less EPS side effects as they have Potent ______ receptor antagonism vs. weak ____ antagonism. They also have higher efficacy against ______ symptoms

A
  1. 5-HT2A
  2. D2
  3. negative
53
Q

_______ has a High D3 to D2 antagonism ratio which favours actions on the __________ (preferred target with more D3) over the ______ (contains less D3 and causes EPS).

A
  1. Amisulpride
  2. nucleus accumbens
  3. striatum
54
Q

Similar to Amisulpride, _______ has a High D4 to D2 antagonism ratio which favours actions on the __________ (preferred target with more D4) over the ______ (contains less D4 and causes EPS).

A
  1. Clozapine
  2. prefrontal cortex
  3. striatum
55
Q

For drugs like A__________ and R________, a high __ to __antagonism ratio reduces impact of antagonism in the striatum.

A
  1. Amisulpride
  2. Risperidone
  3. D2
  4. D1
56
Q

Pre-synapses function as auto-receptors have a ___________ function, meaning that blockage of pre-synaptic dopamine receptors will induce _________ , resulting in a less complete blockade.

A
  1. negative feedback loop

2. more dopamine release

57
Q

D2 receptors are located on ______________ synapses while D1 receptors are found on __________ synapses. Therefore, A higher D2 to D1 antagonism ratio should confer ____________ of dopaminergic function in the striatum as D2 (pre-synaptic) antagonism will ____________.

A
  1. both pre- and post
  2. the post
  3. less complete blockade
  4. increase dopamine release
58
Q

Some atypical antipsychotics such as (______, _______ and _________) are more effective against _________ symptoms of schizophrenia than typical antipsychotics.

A
  1. clozapine
  2. olanzapine
  3. risperidone
  4. negative
59
Q

Some atypical antipsychotics such as (________ and _________) may ameliorate ____________ in schizophrenia better than typical antipsychotics.

A
  1. clozapine
  2. risperidone
  3. cognitive dysfunction
60
Q

Some atypical antipsychotics such as (______, _______ and _________) may be better at _____________ than typical antipsychotics.

A
  1. clozapine
  2. olanzapine
  3. risperidone
  4. mood stabilization
61
Q

Despite the numerous additional benefits of atypical antipsychotics, their effect on _______ symptoms, ______ and stability of _____ are weak.

A
  1. negative
  2. cognition
  3. mood
62
Q

Effects of atypical antipsychotics on _______ symptoms are weak and incomplete, and hence are only relevant for patients who start out with _______ symptoms.

A
  1. negative

2. more severe negative

63
Q

______ % of schizophrenics remain treatment resistant and do not respond to any antipsychotics.
______ % of schizophrenics respond to antipsychotic therapy but remain severely disabled in social and occupational function.
______ % of schizophrenics recover to near pre-illness levels of function.
Very few schizophrenics (< 1%) are able to come off medication and retain near pre-illness levels of function.
Overall, there is still an unmet need for improved antipsychotic drugs.

A
  1. 15-20
  2. 60-75
  3. 10-20

Psychiatric Pharmacology (8 decks)

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