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Pharmacology > DRUGS FOR SCHIZOPHRENIA & DEGENERATIVE DISEASES OF THE CNS > Flashcards

DRUGS FOR SCHIZOPHRENIA & DEGENERATIVE DISEASES OF THE CNS Flashcards

1
Q

dopaminergic system

A

dopamine (DA) is both an excitatory neurotransmitter an a inhibitory neurotransmitter
- precursor of norepinephrine (made of dopamine)

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2
Q

important brain areas

A

nigrostriatal tract (substantia nigra - striatum)
mesolimbic tract (VTA - limbic system)
mesocortical tract (VTA - prefrontal cortex)
tuberoinfundibulnar tract (hypothalamus - pituitary)

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3
Q

out of the important brain areas, which does not have any implications for schizophrenia/Parkinson’s?

A

tuberoinfundibulnar tract

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4
Q

what are the two major types of dopamine receptors?

A
  • D1 like dopamine receptors (D1, D5 all Gs protein associated)
  • D2 like dopamine receptors (D2, D3, D4 all Gi protein associated)
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5
Q

what does an increase in dopaminergic energy indicate?

A

psychosis (eg. schizophrenia)

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6
Q

what does a decrease in dopaminergic energy indicate?

A

neurodegenerative diseases (eg. Parkinson’s)

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7
Q

what are the 2 dopamine receptors involved in?

A

motor control, reward an motivation

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8
Q

which 3 symptoms (at least 1 of them) must be present during a significant portion of time through a 1 month period to determine if you have schizophrenia?

A
  1. delusions
  2. hallucinations
  3. disorganized speech
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9
Q

what are positive symptoms of schizophrenia?

A

hallucinations, delusions, illusions, paranoia, agitation, anxiety, disorganized thoughts an speech, aggressiveness, combativeness

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10
Q

what are negative symptoms of schizophrenia?

A

apathy, withdrawal from persons and the social environment, lack of ability to perform activities of daily living, diminished or missing affect, poor judgement, lack of awareness or insight, little or no functional speech

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11
Q

what are cognitive symptoms of schizophrenia?

A

deficits in long term memory, inability to focus attention, diminished “working memory” - inability to remember recently learned info and use it right away, difficulty following instructions, difficulty following the thread of a conversation, difficulty in identifying the steps needed to complete a task and placing them in a proper sequence

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12
Q

most antipsychotic drugs are which antagonists?

A

dopamine D2 receptor antagonists

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13
Q

what is haloperidol?

A
  • typical antipsychotic drug
  • non phenothiazine antipsychotic drug
  • effective in treating the positive symptoms of schizophrenia; delusions an hallucinations diminish within days
    -effect mediated via antagonist action on D2 receptors in the mesolimbic and mesocortical tracts
  • negligible effect on negative symptoms of schizophrenia
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14
Q

extrapyramidal effects (EPS)

A

acute dystonia, pseudo-parkinsonism, akathisia, tar dive dyskinesia
- associated with antagonist action on D2 receptors in nigrostriatal tract

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15
Q

chlorpromazine an other phenothiazine drugs are associated with what effects?

A

greater anticholinergic effects
- hypertension, sedation
compared to non phenothiazine antipsychotic drugs such as haloperidol

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16
Q

what is there a risk of for typical antipsychotic drugs?

A

EPS an weight gain

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17
Q

what are elderly pt with dementia related psychosis at an increased risk for when taking typical antipsychotic drugs?

A

death

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18
Q

atypical antipsychotic drugs

A
  • effective in treating both positive and negative symptoms of schizophrenia
  • antagonist activity at D2 receptors reduces hallucinations and delusions
  • antagonist activity at (postsynaptic) 5HT2A and alpha2 adrenergic receptors and agonist activity at (presynaptic) 5HT1A receptors reduces negative symptoms of schizophrenia
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19
Q

all adverse effects of atypical antipsychotic drugs are associated with what?

A

obesity

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20
Q

what are the “3rd Generation” antipsychotic drugs (dopamine system stabilizers)?

A

aripiprazole, brexpiprazole

21
Q

what are aripiprazole, brexpiprazole?

A
  • partial agonists at dopamine D2 an D3 receptors
  • partial agonist at (presynaptic) serotonin 5HT1a receptors; antagonist at (postsynaptic) serotonin 5HT2a receptors
  • improves both the positive and negative symptoms of schizophrenia an has some beneficial effects on cognition
  • minimal risk of EPS, low incidence of serious side effects compared to other antipsychotic drug therapy, little to no weight gain, absence of anticholinergic effects
22
Q

adverse effects of dopamine system stabilizers?

A

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

23
Q

typical/atypical antipsychotic drugs bind to ___ and cause ___?

A

binds to D2 dopamine receptor
causes reduction of positive symptoms, typical neuroleptics: EPS, anti-emetic effects

24
Q

atypical antipsychotic drugs bind to ___ and cause ___?

A

binds to 5HT receptor
causes: reduces negative symptoms

25
Q

atypical antipsychotic drugs (clozapine, Seroquel, olanzapine) bind to ___ and cause ___?

A

binds to muscarinic receptors
causes: blurred vision, dry mouth, constipation, urinary retention

26
Q

atypical antipsychotic drugs (clozapine) bind to ___ and cause ___?

A

binds to a1 adrenergic receptors
causes: orthostatic hypotension, light headaches

27
Q

atypical antipsychotic drugs (Seroquel, clozapine, olanzapine) bind to ___ and cause ___?

A

binds to histamine receptors
causes: sedation

28
Q

what is Parkinson’s disease?

A

neurogenerative disorder affecting the individuals >50 years of age
- characterized by a loss of dopaminergic neurons in the nigrostriatal pathway

29
Q

what are symptoms of Parkinson’s disease?

A

tremors, muscular rigidity, bradykinesia, postural instability

30
Q

how do the symptoms occur in Parkinson’s disease?

A
  • loss of dopaminergic neurons in this region produces an imbalance between DA and Ach in the basal ganglia
  • inhibitory effect of dopamine on movement is lost (this is why tremor occurs)
  • excitatory effect of acetylcholine on movement is unopposed
31
Q

what induces Parkinsonism?

A

high doses of typical antipsychotics

32
Q

what improves the symptoms of Parkinson’s?

A

DA agonists and Ach antagonists

33
Q

what mood disorders are associated with Parkinson’s?

A

anxiety, depression and sleep disturbances

34
Q

what do pharmacological therapies do for Parkinson’s?

A
  • symptomatic treatment to enable activities of normal daily living
  • restore dopamine levels in the basal ganglia and inhibiting the excitatory effect of cholinergic neurons on movement
35
Q

what are the dopaminergic drugs for Parkinson’s?

A

levodopa & carbidopa, dopamine agonists, MAOIs an COMT inhibitors

36
Q

what are the cholinergic drugs for Parkinson’s?

A

muscarinic cholinergic antagonists

37
Q

what is levodopa?

A

(L-dopa) converted to dopamine by the enzyme dopamine decarboxylase
- significant fraction of L-dopa converted to dopamine before it penetrates the CNS

38
Q

what does increased peripheral dopamine result in?

A

nausea, vomiting, cardiac arrhythmia’s an orthostatic hypotension

39
Q

what is carbidopa?

A

prevents the conversion of L-dopa into DA, but does not penetrate the blood brain barrier; reduces L-dopa dose 70%

40
Q

what is Benztropine (cogentin)?

A

-used to treat EPS associated with antipsychotic therapy
-binds to muscarinic cholinergic receptors in the CNS
- not as effective as L-dopa

41
Q

what are side effects of Benztropine?

A

dry mouth, blurred vision, tachycardia, urinary retention an constipation

42
Q

what drug should be used if L dopa is not an option?

A

benztropine

43
Q

what is Alzheimers disease?

A

progressive, neurodegenerative disorder affecting individuals >65 yrs of age

44
Q

what is dementia?

A

is degenerative disorder; progressive memory loss, confusion, inability to think or communicate effectively

45
Q

causes of Alzheimers disease?

A

genetics, brain atrophy attributed to environmental, immunological and nutritional factors

46
Q

what is the structural damage in Alzheimers?

A
  • amyloid plaques and neurofibrillary tangles
  • chronic inflammation, oxidative cellular (neuron) damage
47
Q

what are symptoms of Alzheimer’s disease?

A

impaired memory, confusion, inability to recognize family an friends, aggressive behaviour, depression, psychoses, anxiety

48
Q

what is donezepil (aricept)?

A

-acetylcholinesterase inhibitor
- used in early stages of Alzheimers when Ach neurons are still present and functioning in the cerebral cortex
- parasympathomimetic effects (especially GI)
- moderate benefit, effect seen after 1-4 weeks

Pharmacology (20 decks)

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