16-Drugs for Psychoses and Degenerative Diseases of the CNS Flashcards

1
Q

Dopaminergic system’s neurotransmitter.

A

Dopamine. Both an excitatory and inhibitory neurotransmitter. Dopamine is the precursor of norepinephrine.

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2
Q

The four tracts of the dopaminergic system and where they travel.

A
  1. nigrostriatal tract (substantia nigra to striatum)
  2. mesolimbic tract (VTA to limbic system)
  3. mesocortical tract (VTA to prefrontal cortex)
  4. tuberoinfundibular tract (hypothalamus to pituitary)
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3
Q

Which dopaminergic pathway is significant in the pathophysiology of Parkinson’s and why?

A

The nigrostriatal tract. It is implicated in motion and motor control.

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4
Q

Increased activity in which dopaminergic pathway is associated with positive symptoms of schizophrenia?

A

The mesolimbic tract.

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5
Q

Which dopaminergic pathway is implicated in the negative symptoms of schizophrenia?

A

The mesocortical tract.

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6
Q

What are the two types of dopamine receptor classes and which G proteins are associated with each?

A
  1. D1-like dopamine receptors (D1,D5 - Gs protein associated)
  2. D2-like dopamine receptors (D2, D3, D4 - Gi protein associated)
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7
Q

True or False: Increase in dopaminergic activity is associated with psychosis.

A

True

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8
Q

True or False: Increase in dopaminergic activity is associated with neurodegenerative diseases.

A

False.

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9
Q

Schizophrenia: onset & symptoms

A
  • Onset typically occurs during late adolescence
  • Positive symptoms: delusion, disorganized behaviour, agitation, disorganized speech & thinking, hallucinations, paranoia, illusions
  • Negative symptoms: anhedonia, lack of motivation, blunted affect, social withdrawal, poverty of speech, poor social skills & hygiene
  • Cognitive symptoms: deficits in long-term memory, inability to focus attention, diminished “working memory”, difficulty following instructions, difficulty following the thread of a conversation, difficulty identifying the steps needed to complete a task and placing in sequence
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10
Q

What drug class can induce psychotic symptoms?

A

Dopamine agonists. Therefore dopamine antagonists have anti-psychotic activity.

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11
Q

What change in dopamine activity is associated with schizophrenia? At which receptors

A

An increased dopaminergic activity at dopamine D2 receptors (associated with the mesolimbic tract).

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12
Q

What is an alternate name for an antipsychotic drug?

A

neuroleptic drug

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13
Q

All antipsychotic drugs are _____________ receptor antagonists?

A

dopamine D2 receptor antagonists.

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14
Q

Does the use of antipsychotic drugs in schizophrenia manage both the positive and the negative symptoms?

A

Antipsychotic drugs reduce positive symptoms by decreasing dopaminergic activity. However, some do also exhibit an affinity for serotonin receptors to bring up lows of the depression. These are atypical antipsychotics.

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15
Q

What is an example of one of the more common typical (conventional) antipsychotics? When is it used?

A

Haloperidol (Haldol), a non-phenothiazine drug. Used for acute psychosis to calm someone down or in the case of dementia and delirium.

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16
Q

Are typical antipsychotic drugs used for the treatment of schizophrenia? Why or why not.

A

Not anymore. There are negligible effects on the negative symptoms. There are also Extrapyramidal effects (EPS) of acute dystonia, pseudo-parkinsonism, akathisia and tardive dyskinesia.

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17
Q

What is the mechanism of action of conventional antipsychotics? What is the therapeutic effect?

A
  • effect mediated via the blockade of dopamine D2 receptors in the mesolimbic and mesocortical tracts
  • effective in treating the positive symptoms of schizophrenia (hallucinations & delusion diminish within days; other symptoms may take 7-8 weeks to improve)
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18
Q

Why do the EPS of conventional antipsychotics result in pseudo-parkinsonism?

A

These drugs are associated with blockade of dopamine D2 receptors in the nigrostriatal tract which induces motor deficits as in Parkinson’s.

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19
Q

True or False: Only non-phenothiazine typical neuroleptic drugs can cause extrapyramidal signs.

A

False. Both phenothiazine and non-phenothiazine typical neuroleptic drugs can cause extrapyramidal signs.

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20
Q

What is the difference between the adverse effects associated with phenothiazine drugs vs. non-phenothiazine drugs.

A

Non-phenothiazine drugs are associated with extra pyramidal signs such as acute dystonia, akathisia, pseudo-parkinsonism and tardive dyskinesia. Phenothiazine drugs are associated with greater anticholinergic effects (dry mouth, tachycardia and blurred vision) and increased sedation.

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21
Q

Other than EPS, anticholinergic effects and sedation, what are some other adverse effects of conventional antipsychotic drugs?

A

Hypotension, sexual dysfunction and neuroleptic malignant syndrome (high fever, confusion, muscle rigidity, and high serum creatine kinase - can be fatal)

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22
Q

What is the first line therapy for both the positive and the negative symptoms of schizophrenia?

A

Atypical antipsychotic drugs.

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23
Q

Atypical antipsychotic drugs:

  1. onset
  2. mechanism of action
  3. adverse effects
A
  1. 1-2 weeks
  2. blockade of D2-like receptors reduces hallucinations and delusion; blockade of serotoninergic 5HT2A and alpha adrenergic receptors AND stimulation of 5HT1A receptors reduces blunted affect anhedonia, etc….
  3. vary with each drug, but all produce fewer movement disorders (EPS) than typical neuroleptics; all are associated with obesity and its risk factors
24
Q

Why are atypical neuroleptics associated with fewer EPS?

A

They bind weakly to D2-like receptors.

25
Q

Which atypical neuroleptics are not associated with obesity and its risk factors?

A

Aripiprazole & Brexpiprazole

26
Q

Why does a client with schizophrenia have a reduced life expectancy?

A

Because of the medication they are taking and their adverse effects.

27
Q

Aripiprazole is known as a “dopamine system _____________ “

A

stabilizer

28
Q

Aripiprazole (atypical neuroleptic) has what actions on the following receptors?

  1. Dopamine D2 & D3
  2. Serotonin 5HT1A
  3. Serotonin 5HT2A
A
  1. partial agonist
  2. partial agonist
  3. antagonist
29
Q

Why is aripiprazole a preferred treatment for schizophrenia?

A
  • improves both the positive and negative symptoms and improves cognition
  • minimal risk of EPS, with little to no weight gain, absence of anticholinergic effects
30
Q

What about the mechanism of action of aripiprazole and other atypical antipsychotics decreases the risk of EPS.

A
  • Since the drug produces only a partial effects of the agonist it modulates dopamine activity so that the movement isn’t affected in the same way
31
Q

What adverse effects are associated with aripiprazole (atypical antipsychotic)?

A

drowsiness, indomnia, agitation, changes in BP, anxiety, headache

32
Q

What other conditions might atypical antipsychotics be prescribed for?

A

Bipolar and MDD

33
Q

Drug interactions of antipsychotic drugs.

A
  • clients should avoid CNS depressants such as alcohol, antihistamines, sedative-hypnotics or opioid analgesics
  • caution if co-prescribed medications that affect CYP-450 activity
  • use caution with herbal supplements
34
Q

Clozapine, Seroquel and Olanzapine bind to muscarinic Ach receptors. What adverse effects can this result in?

A

Blurred vision, dry mouth, constipation, urinary retention

35
Q

Clozapine binds to alpha-adrenergic receptors potentiating which adverse effects?

A

Orthostatic hypotension & light-headedness.

36
Q

Drug binding to which receptors potentiates EPS?

A

D2 dopaminergic receptor.

37
Q

Seroquel, Clozapine and Olanzapine bind to which receptor to cause sedation?

A

Histamine receptor.

38
Q

Explain the pathophysiology of Parkinson’s Disease.

A
  • characterized by a loss of dopaminergic neurons in the nigrostriatal pathway
  • loss of dopaminergic neurons produces an imbalance between DA and Ach in the basal ganglia
  • inhibitory effect of dopamine on movement is lost and excitatory effect of Ach on movement is unopposed
  • tremor, muscular rigidity, bradykinesia and postural instability result
39
Q

What symptoms, other than motor symptoms are associated with Parkinson’s Disease?

A

Anxiety, depression, sleep disturbances, ANS dysfunction

40
Q

High doses of what type of drug can induce parkinsonism?

A

Typical antipsychotics.

41
Q

What type of drugs can improve symptoms of Parkinson’s Disease?

A

Dopamine agonists and Acetylcholine antagonists.

42
Q

What is pharmacological therapy aimed at in the treatment of Parkinson’s Disease?

A
  • restoring dopamine levels in the basal ganglia
  • inhibiting the excitatory effect of cholinergic neurons
  • enabling the client to perform normal daily activities
43
Q

Types of dopaminergic drugs used for Parkinson’s Disease. Types of cholinergic drugs used for Parkinson’s Disease

A

Dopaminergic:

  • levodopa & carbidopa
  • dopamine agonists
  • MAOIs and COMT inhibitors

Cholinergic:
- muscarinic cholinergic antagonists

44
Q

Why does pharmacological therapy for Parkinson’s Disease only work for a defined period of time?

A

Because the neurons continue to disintegrate in which case the drug will not be useful.

45
Q

What is the gold standard treatment for parkinson’s disease? How does it work?

A

Levodopa. L-Dopa is converted to dopamine by dopamine decarboxylase.

46
Q

Why is L-Dopa, the precursor to dopamine, given instead of just dopamine.

A

L-Dopa is small so that it can cross the blood-brain barrier. You don’t give dopamine because it has difficulty crossing the blood-brain barrier, binds to the periphery and will have adverse effects.

47
Q

What is L-Dopa therapy dependent on? What are its adverse effects and why?

A
  • Therapy is dependent on a sufficient number of dopamine neurons converting L-Dopa to dopamine.
  • Peripheral dopamine results in nausea, vomiting, cardiac arrhythmias and orthostatic hypotension.
  • A significant fraction of L-dopa is converted to dopamine before penetrating the CNS and therefore you get these symptoms.
48
Q

What drug is co-prescribed with L-Dopa and why?

A

Carbidopa. This prevents the L-dopa being broken down in the blood stream, so L-dopa in the CNS is still converted. This reduces the L-dopa dose by 70%.

49
Q

What pharmacological treatment can you continue for Parkinson’s Disease once you can no longer give dopaminergics? What is its mechanism of action.

A

Anticholinergic drugs can be given. Benztropine (Cogentin) preferentially binds to muscarinic cholinergic receptors in the CNS. This inhibits Ach, reducing motor symptoms.

50
Q

What adverse effects are seen in anticholinergic therapy for treatment of Parkinson’s Disease?

A

Adverse effects are associated with inhibition of the parasympathetic division. These include dry mouth, blurred vision, tachycardia, urinary retention and constipation.

51
Q

When are anticholinergic drugs prescribed in Parkinsons?

A

They are prescribed early on in Parkinson’s Disease or when a patient can’t tolerate L-dopa therapy. They can also be used to reverse the EPS of antipsychotic drugs.

52
Q

Alzheimer’s disease:

  1. what it is: at what age does it occur?
  2. causes
  3. pathophysiology
  4. symptoms
A
  1. progressive, neurodegenerative disorder affecting individuals over 65
  2. family history, brain atrophy attributed to environmental, immunological and nutritional factors
  3. structural damage: amyloid plaques & neurofibrillary tangles; and chronic inflammation, oxidative cellular(neuron) damage
  4. impaired memory, confusion, inability to recognize family and friends, aggressive behaviour, depression, psychoses, anxiety
53
Q

What is the goal of therapy for Alzheimer’s Disease? What pharmacological drug class is used?

A

The goal is to improve activities of daily living, behaviour and cognition. Acetylcholinesterase inhibitors (Donezepil) are prescribed.

54
Q

Acetylcholinesterase inhibitors:

  1. mechanism of action
  2. use
  3. adverse effects
  4. onset
A
  1. increase Ach levels at the hippocampus by inhibiting Ach metabolism
  2. used in early stages of Alzheimer’s Disease when Ach neurons are still present & functioning in the cerebral cortex
  3. parasympathomimetic effects (especially GI)
  4. moderate benefit, effects seen after 1-4 weeks
55
Q

Other than acetylcholinesterase inhibitors, what other drug therapy may be prescribed for a patient with Alzheimer’s Disease?

A

antipsychotic, antidepressant and antianxiety drugs.