DRUGS FOR SCHIZOPHRENIA & DEGENERATIVE DISEASES OF THE CNS

Question 1

dopaminergic system

Answer 1

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

Question 2

important brain areas

Answer 2

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

Question 3

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

Answer 3

tuberoinfundibulnar tract

Question 4

what are the two major types of dopamine receptors?

Answer 4

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

Question 5

what does an increase in dopaminergic energy indicate?

Answer 5

psychosis (eg. schizophrenia)

Question 6

what does a decrease in dopaminergic energy indicate?

Answer 6

neurodegenerative diseases (eg. Parkinson’s)

Question 7

what are the 2 dopamine receptors involved in?

Answer 7

motor control, reward an motivation

Question 8

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?

Answer 8

1. delusions
2. hallucinations
3. disorganized speech

Question 9

what are positive symptoms of schizophrenia?

Answer 9

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

Question 10

what are negative symptoms of schizophrenia?

Answer 10

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

Question 11

what are cognitive symptoms of schizophrenia?

Answer 11

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

Question 12

most antipsychotic drugs are which antagonists?

Answer 12

dopamine D2 receptor antagonists

Question 13

what is haloperidol?

Answer 13

• 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

Question 14

extrapyramidal effects (EPS)

Answer 14

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

Question 15

chlorpromazine an other phenothiazine drugs are associated with what effects?

Answer 15

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

Question 16

what is there a risk of for typical antipsychotic drugs?

Answer 16

EPS an weight gain

Question 17

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

Answer 17

death

Question 18

atypical antipsychotic drugs

Answer 18

• 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

Question 19

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

Answer 19

obesity

Question 20

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

Answer 20

aripiprazole, brexpiprazole

Question 21

what are aripiprazole, brexpiprazole?

Answer 21

• 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

Question 22

adverse effects of dopamine system stabilizers?

Answer 22

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

Question 23

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

Answer 23

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

Question 24

atypical antipsychotic drugs bind to ___ and cause ___?

Answer 24

binds to 5HT receptor
causes: reduces negative symptoms

Question 25

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

Answer 25

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

Question 26

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

Answer 26

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

Question 27

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

Answer 27

binds to histamine receptors causes: sedation

Question 28

what is Parkinson's disease?

Answer 28

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

Question 29

what are symptoms of Parkinson's disease?

Answer 29

tremors, muscular rigidity, bradykinesia, postural instability

Question 30

how do the symptoms occur in Parkinson's disease?

Answer 30

- 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

Question 31

what induces Parkinsonism?

Answer 31

high doses of typical antipsychotics

Question 32

what improves the symptoms of Parkinson's?

Answer 32

DA agonists and Ach antagonists

Question 33

what mood disorders are associated with Parkinson's?

Answer 33

anxiety, depression and sleep disturbances

Question 34

what do pharmacological therapies do for Parkinson's?

Answer 34

- 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

Question 35

what are the dopaminergic drugs for Parkinson's?

Answer 35

levodopa & carbidopa, dopamine agonists, MAOIs an COMT inhibitors

Question 36

what are the cholinergic drugs for Parkinson's?

Answer 36

muscarinic cholinergic antagonists

Question 37

what is levodopa?

Answer 37

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

Question 38

what does increased peripheral dopamine result in?

Answer 38

nausea, vomiting, cardiac arrhythmia's an orthostatic hypotension

Question 39

what is carbidopa?

Answer 39

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

Question 40

what is Benztropine (cogentin)?

Answer 40

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

Question 41

what are side effects of Benztropine?

Answer 41

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

Question 42

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

Answer 42

benztropine

Question 43

what is Alzheimers disease?

Answer 43

progressive, neurodegenerative disorder affecting individuals >65 yrs of age

Question 44

what is dementia?

Answer 44

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

Question 45

causes of Alzheimers disease?

Answer 45

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

Question 46

what is the structural damage in Alzheimers?

Answer 46

- amyloid plaques and neurofibrillary tangles - chronic inflammation, oxidative cellular (neuron) damage

Question 47

what are symptoms of Alzheimer's disease?

Answer 47

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

Question 48

what is donezepil (aricept)?

Answer 48

-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