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3RD YEAR SYSTEMS: Psychiatry > Anti-psychotic drugs > Flashcards

Anti-psychotic drugs Flashcards

1
Q

Which mental disorders are anti-psychotics used to treat? (5)

A
  • Schizophrenia
  • Schizoaffective disorder
  • Bipolar disorder – for mood stabilisation and/or when psychotic features are present
  • Psychotic depression
  • Augmenting agent in treatment of resistant depression or anxiety disorders
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2
Q

How do anti-psychotics work?

A
  • Anti-psychotics affect dopamine.
  • They are D2 receptor antagonists, so they reduce the amount of dopamine in the dopaminergic pathways within the brain.
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3
Q

What are the 4 major dopamine pathways in the brian?

A
  • Mesocortical
  • Mesolimbic
  • Nigrostriatal
  • Tuberoinfundibular
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4
Q

How does Nicotine affect dopamine in the mesocortical pathways?

A

It releases dopamine which alleviates the negative symptoms associated wth hypoactivity of dopamine (self-medication hypothesis)

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5
Q

Describe the Mesocortical pathway

A
  • This pathway projects from the ventral tegmentum (in the brain stem) to the cerebral cortex.
  • It is considered to be where the negative symptoms (lack of motivation, lethargy, anhedonia etc – more chronic illness) and cognitive disorders (lack of executive function, depressive symptoms) arise.
  • The problem here in psychotic patients, is there is too little dopamine.
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6
Q

Describe the Mesolimbic pathway

A
  • The Mesolimbic pathway projects from the dopaminergic cell bodies in the ventral tegmentum (brainstem) to the limbic system.
  • Hyperactivity of dopamine in this pathway mediates positive psychotic symptoms (hallucinations, delusions, and thought disorders i.e broadcast, insertion, echo) and it may mediate aggression.
  • Problem here in a psychotic patient is that there is too much dopamine – use anti-psychotic to reduce the dopamine by blocking D2 receptors.
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7
Q

Describe the Nigrostriatal dopamine pathway

A
  • Projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia.
  • This pathway is involved in motor movement regulation.
  • Dopamine hypoactivity in this pathway causes:-
    • Parkinsonian movements i.e. rigidity, bradykinesia, tremors)
    • Akathisia (restless legs, feeling uncomfortable in skin)
    • Dystonia.
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8
Q

Describe the Tuberoinfundibular pathway

A
  • Projects from the hypothalamus to the anterior pituitary.
  • Remember that dopamine release inhibits/regulates prolactin release.
  • Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia which clinically manifests as:-
    • Gynecomastia/galactorrhea
    • Sexual dysfunction i.e decreased libido/menstrual dysfunction
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9
Q

Pathophysiology of normal dopamine production and metabolism

A
  • Dopamine is synthesised from the amino acid tyrosine
  • Tyrosine is converted into DOPA by the enzyme tyrosine hydroxylase
  • DOPA is converted into Dopamine by the enzyme DOPA decarboxylase
  • This dopamine is packed and stored in vesicles until its release into the synapse
  • When it is released during neurotransmission, it acts on 5 types of post-synaptic dopamine receptors (D1-D5)
  • A negative feedback mechanism exists through a pre-synaptic D2 receptor which regulates the release of dopamine from the pre-synaptic neuron
  • Any excess dopamine is also ‘mopped up’ from the synapse by Dopamine transporter (DAT)
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10
Q

Typical anti-psychotics

  1. What are the high potency typical anti-pyschotics?
  2. What are the low potency typical anti-pyschotics?
A
  1. High potency = Fluphenazine, Pimozide and Haloperidol - these bind more strongly to the D2 receptor (higher affinity) and therefore have a higher risk of side effects
  2. Low potency = Chloropromazine - lower affinity for D2 receptors but do tend to interact with non-dopaminergic receptors resulting in more cardiotoxic (Sedation, hypotension side effects) and anti-cholinergic adverse effects such as blurred vision and dry mouth
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11
Q

Which group of side effects are more commonly associated with typical anti-psychotics?

A

Extrapyramidal side effects such as Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia (restless legs, feeling uncomfortable in skin) and dystonia (continuous spasms and muscle contractions).

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12
Q

Which group of side effects are more commonly associated with atypical anti-psychotics?

A

More likely to get metabolic side effects with atypicals:-

  • Weight gain
  • Hypercholesterolaemia
  • Hyperglycaemia
  • Hyperprolactinaemia
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13
Q

What are atypical anti-psychotics and how do they work?

A
  • These are the newer drugs on the market.
  • They are serotonin-dopamine 2 antagonists (SDAs) and are considered ‘atypical’ because they affect serotonin and dopamine neurotransmission in the 4 main pathways.
  • They have a slightly different side effect profile.
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14
Q

Is there any difference in efficacy between typicals and atypicals?

A

No difference in efficacy between atypical and typical anti-psychotics so the decision r.e treatment is based on choice and side effect profile or the preparation (i.e short acting / long acting IM etc).

General rule of thumb is that 1/3 will have good response to first line anti-psychotic, 1/3 will have some response and a 1/3 will have a poor response.

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15
Q

What are the 4 main atypical anti-psychotics used as 1st line treatment for Schizophrenia etc?

A
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Aripiprazole
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16
Q

Respiridone:

  1. What is its associated side effect profile?
  2. Preparation?
  3. Who can be given it?
A
  1. HYPERPROLACTINAEMIA (may present as galactorrhoea), weight gain and sexual dysfunction
  2. Available in regular tablets, IM depot injection (monthly injection) or rapidly dissolving tablet
  3. Used for manic and mixed patients
17
Q

Olanzapine:

  1. What is its associated side effect profile?
  2. Preparation?
A
  1. WEIGHT GAIN (can be intense) may cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain) and may cause hyperprolactinemia (but < risperidone)
  2. Regular tablet, immediate release IM formulation, rapidly dissolving tab, depot injection (monthly as slow releasing)
18
Q

Quetiapine:

  1. What is its associated side effect profile?
  2. Preparation?
A
  1. Quite sedative (used regularly as adjunctive treatment for depression especially if patient is suffering from sleep disturbance), may cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain), however less than olanzapine. May cause abnormal LFT’s (6% of all patients). May be associated with weight gain, though less than seen with olanzapine. Most likely to cause orthostatic hypotension.
  2. Only available in regular tablet form
19
Q

Aripiprazole:

  • What is its associated side effect profile?
  • Preparation?
A
  1. Main side effect is AKATHISIA (restless legs/feeling uncomfortable) / activation (disinhibition, impulsivity, insomnia, restlessness, hyperactivity, and irritability) and this makes people stop taking it. It is the most weight neutral medication so good choice for a first episode. Unique mechanism of action as a D2 partial agonist – causes a balancing of levels so lower level of extra-pyramidal side effects, much less sedation and no heart problems i.e QT prolongation
  2. Available in regular tablets, immediate release IM formulation and depot injection
20
Q

Why is it important to treat symptoms such as Akathisia when they come up?

A

Because it is associated with an increased suicide risk

21
Q

When do psychiatrists define someone as ‘treatment resistant’?

A

If a patient has had a trial (8 weeks) of:-

  • 1 atypical anti-psychotic
  • Then swapped to a 2nd atypical anti-psychotic or an atypical added on for another 8 weeks

And still sees no effect then that is classed as treatment resistant.

22
Q

Which drug is given to anti-psychotic treatment resistant patients?

A

Clozapine

23
Q

Clozapine:

  1. Side effect profile
  2. Preparation
A
  1. AGRANULOCYTOSIS - (requires weekly blood tests for 6 months). More severe side effects. It is associated with the most sedation, weight gain and abnormal LFT’s. Increased risk of seizures. Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including non-ketotic hyperosmolar coma and death with and/or without weight gain – can cause heart attacks / myocarditis because of hypercholesterolaemia.
  2. Available in 1 form - a regular tablet
24
Q

What is Tardive dyskinesia?

A

An adverse anti-psychotic effect involving involuntary muscle movements that may not resolve with drug discontinuation

25
Q

What is Neuroleptic malignant syndrome (NMS)?

A

An adverse anti-psychotic drug effect characterised by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC – potentially fatal

26
Q

Prophylaxis in schizophrenia

A

Life-long relapse of psychosis such as in schizophrenia is inevitable. Tend to use the same medication that got them better as prophylaxis treatment.

  • Relapse is most commonly due to non-compliance with medication - only 30% of patients take medication as prescribed.
  • The commonest psychotic symptom is lack of insight so they don’t have that understanding that they are ill and that they need medication.
  • After 1st episode of schizophrenia patients tend to go back to normal level of functioning and after a 2nd episode, they go back to about 90% functioning. After a third episode of schizophrenia there is a clear link to reduced functioning, lower IQ and negative symptoms.
27
Q

How might you get around the problem of non-compliance with Schizophrenic patients?

A

Consider using long acting intra-muscular injection/depot preparation for better compliance!!

28
Q

How are extra-pyramidal side effects treated/managed?

A

Reduce dose if possible then…

  • Anti-cholinergic i.e benztropine
  • Beta blocker i.e Propanolol
  • Dopamine facilitators i.e amantadine
29
Q

Which of the following parameters is not monitored annually after the patient is on an established dose of clozapine?

A. Weight

B. Blood lipids

C. FBC

D. Fasting blood glucose

E. Prolactin

A

C. FBC

3RD YEAR SYSTEMS: Psychiatry (15 decks)

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