Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CNS lectures (Bal) > Module 1.5.1 (Antipsychotics) > Flashcards

Module 1.5.1 (Antipsychotics) Flashcards

1
Q

What does increase activity in mesolimbic pathway cause?

A

–Delusions – Hallucinations – Other +ve Sx of schizophrenia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does decrease activity in the mesocortical pathway cause?

A

– Apathy – Withdrawal – Lack of motivation & pleasure – Other –ve Sx of schizophrenia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does inhibition of the nigrostriatal pathway cause?

A

Causes extrapyramidal SE of antipsychotic drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does inhibiton of the tuberoinfundibular pthway cause?

A

Elevated serum prolactin levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do most antipyschotic drugs work?

A

Most antipsychotic drugs block dopamine receptors

  • clinical dose is proportional to D2 receptor blockade

> Single positive electron tomography ligand scans show an increase in D2 receptors in nucleus accumbens of schizophrenia patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Psychotic symptoms can be induced by drugs that increase dopaminergic activity. What drugs does this?

A

anti-parkinsonian agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Drug-indcued parkinsonism is a common adverse effects of FGAs, it usually develops after weeks or months of treatment. What are these symptoms?

A
  • Stooped posture
  • Drooling
  • Back rigidity
  • Flexed elbows and wrists
  • Tremors in the legs
  • Slight flexed hip and knees
  • Shuffling gait
  • Reduced arm swing
  • Hand tremor

Bradykinesia (slow movements)

Akinesia (immobility) has also been reported

> Usually develops after weeks or months of treatment.

> Usually reversible with anticholinergics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What drugs mimic positive symptoms?

A
  • Amphetamine, methamphetamine (release dopamine & inhibit its reuptake) –> mimic positive symptoms
  • Psilocybin, LSD (5-HT2A agonists) mimic positive symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What drugs mimic positive, negative and cognitive symptoms?

A

Phencyclidine, ketamine (glutamate NMDA receptor antagonists)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are atypical antispychotics?

A

(Second Generation Antipsychotics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are positive symptoms of schizophrenia? Why does this happpen?

A

Agitation Delusions Disorganised speech Disorganised thinking Hallucination Insomnia

  • Due to excessive neuronal activity in mesolimbic neuronal pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are negative symptoms of schizophrenia? Why does this happpen?

A

Apathy (avolition) Withdrawal Lack of motivation Lack of pleasure (anhedonia) Limited speech (alogia)

  • due to insufficient activity in mesocortical neuronal pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What MOA + drug is used to treat negative and cognitive symptoms that results from deficient cortical dopamine activity?

A

Respond to 5HT2A receptor antagonism produced by SGAs –> increase dopamine release

mesocortical pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What MOA + drug is used to treat positive symptoms that results from excessive subcortical dopamine activity?

A

Respond well to D2 receptor antagonism produced by FGAs & SGAs

mesolimbic pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

5HT2A antagonists increase dopamine release in the mesocortical pathways but what effects do they have on D2 antagonists?

A

5HT2A antagonist enhance / complements action of D2 antagonist to reduce positive symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What do neagative and cognitive symyptoms respond to?

A

respond to 5-HT2A receptor antagonism produced by SGAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What do positive symptoms respond to?

A

Positive symptoms respond well to D2 receptor antagonism produced by FGAs & SGAs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Antipsychotics require 1-3 weeks to stabilise the positive symptoms of schizophrenia. What are the three-time dependent changes in dpamine neurotransmission?

A
  1. Immediate effects: An increase in dopamine synthesis, release, and metabolism but NO therapeutic effect
  2. 2Prolonged effects (1-3 weeks): Depolarization blockade –> reduced dopamine release from mesolimbic and nigrostriatal neurons –>alleviate the positive symptoms of schizophrenia while causing EPSE
  3. Extended prolong effects: Dopamine receptor up-regulation and supersensitivity to dopamine agonists –> may contribute to the development of a delayed type of EPS called tardive dyskinesia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are examples of first gen antipsychotics (typical)?

clue: CDFHPZ

A
  • Chlorpromazine
  • Droperidol
  • Flupentixol
  • Haloperidol
  • Periciazine
  • Zuclopenthixol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are examples of second gen antipsychotics (typical)?

A

Clozapine

Olanzapine

Quetiapine

Risperidone

Paliperidone

Amisulpride

Aripiprazole

Asenapine (Saphris wafer)

Ziprasidone (Zeldox®)

Lurasidone

Brexipiprazole (new drug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are some differences between FGAs and SGAs?

A

FGA only effective for positive symptoms

SGA can alleviate positive and negative symptoms

  • Incidence of extrapyramidal side-effects (less in the SGAs )
  • Efficacy in treatment-resistant groups of patients
  • Receptor selectivity
  • Pharmacological properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What receptors does FGA have high affinity for?

A

High affinity for D2 receptors

> chlorpromazine, haloperidol, flupentixol

23
Q

What receptors does SGA have high affinity for?

A

high affinity for 5-HT2 receptors

> clozapine, risperidone, sertindole, quetiapine, aripiprazole

24
Q

What are pharmcokinetic considerations of antipsychotics?

A

Most antipsychotics have half-lives of 15-30h ™

Given orally or IM ™

Considerable individual variation ™

Dose needs to be individualised ™

Elderly requires reduction in dose ™

Depot formulation – long-term therapy

Fluphenazine decanoate – up to 28 days

ncreased risk of EPS with depot formulation

25
Q

What is responsible for antipsychotic action?

A

D2 receptor antagonism is essential for antipsychotic action

26
Q

How does SGA alleviate both positive and negative symptoms?

A

5HT2A antagonist

Negative symptoms: Inhibits 5HT2A receptors = increases dopamine release

Positive symptoms: HT2A antagonist enhance / complements action of D2 antagonist to reduce positive symptoms

27
Q

Howe does SGA protect against EPS in SGAs?

A

preserving nigrostriatal DA activity

> Also alleviate anxiety and insomnia in schizophrenia

28
Q

what does affinity for D2 receptors cause in FGA?

A

Affinity for D2 receptors cause of EPS (extrapyramidal sideeffects)

> FGAs are quite ineffective in treating negative & cognitive symptoms and EPS may become intolerable.

29
Q

Why are SGAs better than FGAs?

A
  • Alleviation of negative & cognitive symptoms as well as positive symptoms
  • Lower incidence of EPS and generally better tolerated
  • SGAs are superior to FGAs interact with 5-HT2A and D2 receptors
  • Antagonism of D3, D4 and other receptors may also contribute to the favourable clinical profile of SGAs
30
Q

What are the adverse effects of antipsychotics?

A
  • Adverse effects on Dopaminergic pathways

Psychological effects (mesolimbic/mesocortical)

Movement disorders (nigrostriatal)

Neuroendocrine (tuberoinfundibular)

> elevated prolactin

  • Blockade of a1 receptors –> Hypotension, reflex tachycardia
  • Blockade of histamine H1-receptor –> sedation and weight gain
  • Blockade of 5-HT2C & H1 receptors –> weight gain
  • Anti-cholinergic effects –> Blurred vision, dry mouth, constipation, urinary retention
  • Adverse effects due to immune reaction –> Hypersensitivity reactions, dermatitis, rashes, photosensitivity, urticaria
  • Adverse effects due to individual drug –> Clozapine cause agranulocytosis - neutropenia, bone marrow depression
  • Idiosyncratic reaction –> neuroleptic malignant syndrome
31
Q

What are acute EPS effects?

A
  • Acute neurological effects:

acute dystonia, akathisia, parkinsonism

  • Early EPS (within days)
  • Acute dystonias involuntary muscle spasms
  • Parkinsonian-like movements -tremor, rigidity & bradykinesia
32
Q

What is used to reverse parkinsonian like symptoms? What is the MOA?

A

Benztropine – anticholinergic – block muscarinic receptors that mediate striatal cholinergic excitation – reduce the excessive cholinergic activity due to D2 blockade by FGAs

33
Q

What is acute dystonia? What does it include?

A

Muscle spasm of face, tongue, neck, jaw and/ or hands

Hyperextension of neck & trunk & arching of back.

Can interfere with walking, talking or swallowing

Inlcudes

  • Torticollis
  • Carpopedal spasm
  • Trismus (lock-jaw)
  • Perioral spasm
  • Oculogyric crisis
34
Q

What is akathisia (acute eps)? When does it happen?

A
  • Motor restlessness ™
  • Person unable to sit or stand still, feels urgent need to move, pace, rock or tap foot ™
  • Can also present as apprehension, irritability & general uneasiness ™
  • Often confused with worsening agitation* ™
  • More common in females

Usually occurs 2-3 days (up to several weeks) after starting Tx & may subside spontaneously.

35
Q

What are some chronic EPS effects?

A

Chronic neurological effects: Tardive dyskinesia, Tardive dystonia

Tardive dyskinesia

  • Characterised by abnormal involuntary movements of the mouth, face, tongue and sometimes head, neck, trunk or limbs
  • Best approach is prevention / Use SGAs rather than FGAs
36
Q

Why does Tardive dyskinesia occur? How long does it take to occur?

A

May be due to a delayed adaptive proliferation of nigrostriatal D2 receptors or neurodegeneration resulting from excessive glutamate release due to chronic antagonism of inhibitory D2 receptors

  • usually after 6-24 months of chronic FGA treatment
37
Q

What are symptoms of neuroleptic malignant snydrome? Which patients does it occur in?

> caused by antipsychotics

A
  • Symptoms include fever, extrapyramidal motor disturbances, muscle rigidity and COMA

Rare but potentially fatal adverse event occurring in patients extremely sensitive to EPS (muscle rigidity & hyperthermia)

38
Q

what treatment for neuroleptic malignant snydrome?

A

URGENT treatment required –dantrolene (direct-acting skeletal muscle relaxant) and bromocriptine (dopamine agonist)

39
Q

What is mnemnic for neuroleptic malginant syndrome features?

A

FEVER

F - Fever • E - Encephalopathy • V - Vitals unstable • E - Elevated enzymes (elevated CPK) • R - Rigidity of muscles

40
Q

What are the major drug interactions for the following FGA:

A) Chlorpromazine

B) Fluphenazine

C) Haloperidol

A

A)

  • Additive effects with antiadrenergic, anticholinergic, and CNS depressants.
  • Decreases serum levels of lithium
  • Concurrent use of a β-adrenergic receptor antagonist or an antidepressant may increase serum levels of both drugs

B)

  • Additive effects with anticholinergic and CNS depressants
  • Concurrent use of a β-adrenergic receptor antagonist (beta blocker) or an antidepressant may increase serum levels of both drugs

C)

  • Barbiturates and carbamazepine decrease serum levels
  • Quinidine increases serum levels
41
Q

What are the major drug interactions for the SGA:

A) clozapine

B) olanzapine

C) risperidone

A

A)

Not established; possible interaction with drugs that induce or inhibit cytochrome P450 isozyme CYP1A2.

B)

same as clozapine

C)

Not established; possible interaction with drugs that induce or inhibit cytochrome P450 isozyme CYP2D6.

42
Q

What are precautions for antispyhcotic drugs?

A

Parkinson’s disease •

Epilepsy •

Respiratory failure •

Hyperthyroidism •

Shock •

Risk factors for prolonged QT interval •

GI obstruction, urinary retention, myasthenia gravis –> anticholinergic effects exacerbate this

Low WCC or previous blood dyscrasia •

Diabetes –> olanzapine, clozapine, quietapine increases BSL

Elderly –> Associated with increased risk of stroke & death

43
Q

D2 receptors blockade lead to increased prolactin release, what are the effects of this?

A

Galactorrhoea Amenorrhoea Gynaemastia Infertility

44
Q

Pharmacalogy of chlorpromazine (fga)

A

EPS can become troublesome

Prominent sedation, hypotension & antimuscarinic effects /

Can cause obstructive jaundice and photosensitivity leading to sunburn

Useful when sedation is desired

Administered orally, IV or IM

45
Q

Pharmacology of haloperidol (fga)

A

“high potency antipsychotic” /

EPS is a main problem /

Favoured when sedation, hypotension, and antimuscarinic effects are undesirable (elderly patients)

Administered orally or IM

46
Q

pharmacology of flupentixol decanoate (FGA)

A

“depot preparation” that can be administered IM every 2-4 weeks /

Minimal sedation & hypotension, but prominent EPS

47
Q

When should long acting depot antipsychotics such as Flupenthixol decanoate, haloperidol decanoate, risperidone be used?

A

Should be considered for schizophrenic patients who do not reliably take oral antipsychotic medication

48
Q

What are the clinical used of FGAs?

A

Treatment of acute and chronic psychoses ›

Treatment of acute mania ›

Management of “organic psychoses”, such as those seen in elderly patients with dementia and dementia-associated agitation (progressive failure of intellectual and cognitive function.) ›

Severe behavioural disorders on children ›

Adjunct in psychotic depression ›

Adjunct in anaesthesia ›

Adjunct in treatment of alcoholic hallucinosis ›

Treatment of Gilles de la Tourette and other choreas ›

Acute treatment of intractable nausea and vomiting (haloperidol, droperidol). ›

Treatment of intractable hiccough (chlorpromazine).

49
Q

Pharmacology of clozapine

A

Highly effective for treating the positive, negative & cognitive symptoms of schizophrenia without producing EPS

Reduces the suicide rate /

Risk of agranulocytosis (1% of patients). Regular monitoring of blood required if prescribed. /

Convulsions can occur /

Other side-effects include: prominent sedation, weight gain, impaired glucose regulation, hypotension and antimuscarinic effects

> Use clozapine in schizophrenics unresponsive to other antipsychotics

50
Q

Pharmacology of olanzapine

A

Has a similar therapeutic profile to clozapine. However, it may not be as effective as clozapine in severely impaired schizophrenics.

Does not cause agranulocytosis

Convulsions can occur

Side-effects include: sedation, weight gain, impaired glucose regulation, hypotension and antimuscarinic effects

Olanzapine is a widely prescribed antipsychotic for schizophrenia and other psychoses

51
Q

Pharmacology of risperidone

A

Effective for treating positive, negative & cognitive symptoms of schizophrenia.

Above usual therapeutic doses (!4-6 mg/day), it can produce EPS

Does not cause agranulocytosis

Antimuscarinic effects are minimal /

Side-effects include: mild sedation, mild weight gain & impaired glucose regulation, hypotension, hyperprolactinaemia

Risperidone is a widely prescribed antipsychotic for schizophrenia and other psychoses

52
Q

Pharmacology of Quetiapine

A

Can treat positive, negative & cognitive symptoms without producing EPS

Does not cause agranulocytosis

Side-effects include sedation, dry mouth, constipation, hypotension, mild weight gain & impaired glucose regulation

Quetiapine is a useful antipsychotic for treating schizophrenia

53
Q

Pharmacology of aripiprazole

A

Improve positive symptoms and reduce relapse rates after an acute episode.

Does not cause agranulocytosis

Side-effects include: sedation, weight gain, impaired glucose regulation, hypotension and antimuscarinic effects

precautions

Recent history of MI, unstable heart

Treatment with CYP3A4

Poor metaboliser - CYP2D6

Indicated for schizophrenia and bipolar disorder as monotherapy

54
Q

What are the clinical used of atypical antipsychotic drugs?

A

Treatment of acute and chronic psychoses (e.g. schizophrenia)

Acute mania (olanzapine, quetiapine, risperidone)

Organic psychoses (e.g. dementiaassociated agitation)

Severe behavioural disorders in children

CNS lectures (Bal) (29 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions