chapter 13- Dopaminergic neurotransmission

Question 1

what is the precursor of all catecholamines

Answer 1

tyrosine

Question 2

what enzyme has the key function to terminate the action of catecholamines in the brain and periphery

Answer 2

MAO

Question 3

where is MAO-A expressed

Answer 3

brain and periphery

Question 4

where is MAO-B expressed

Answer 4

CNS

Question 5

what do D1 and D5 dopamine receptors lead to

Answer 5

increased cAMP

Question 6

what do D2, D3, and D4 dopamine receptors lead to

Answer 6

inhibits cAMP generation

Question 7

where are D1 and D2 expressed at high levels

Answer 7

striation as well as nucleus accumbens and olfactory tubercle

Question 8

what dopamine receptor is expressed highly in anterior pituitary gland

Answer 8

D2

Question 9

where is D3 expressed at high levels

Answer 9

limbic system

Question 10

where is D4 localized

Answer 10

frontal cortex, diencephalon, brainstem

Question 11

where is D5 mainly located

Answer 11

hippocampus, olfactory tubercle and hypothalamus

Question 12

what is the clinical application of levodopa

Answer 12

parkinson disease

Question 13

what stages of parkinson disease is levodopa particularly effective

Answer 13

early stages

Question 14

what are some common side effects of levodopa

Answer 14

dyskinesia, orthostatic hypotension, loss of appetite

Question 15

what side effect with basically be for sure to happen with levodopa within 5 years of use

Answer 15

dyskinesia

Question 16

what are some contraindications for levodopa use

Answer 16

history of melanoma; narrow angle glaucoma; concomitant use of MAO-inhibitor

Question 17

what are some contraindications for rasagiline and selegiline

Answer 17

concomitant use of cyclobenzaprine, mirtazapine, st johns wort; concomitant use of dextromethorphan

Question 18

what is levodopa almost always administered with

Answer 18

carbidopa

Question 19

what is the mechanism of action of carbidopa

Answer 19

inhibitor of DOPA decarboxylase

Question 20

what is the clinical application of pramipexole and ropinirole

Answer 20

parkinson disease

Question 21

what is another clinical application of ropinirole besides parkinson

Answer 21

restless leg syndrome

Question 22

what are some adverse effects seen with pramipexole and ropinirole

Answer 22

orthostatic hypotension, extrapyramidal movements, hallucinations

Question 23

what are some cognitive effects seen with pramipexole and ropinirole

Answer 23

excessive sedation, vivid dreams and hallucinations

Question 24

what does rasagiline and selegiline inhibit

Answer 24

MAO-B

Question 25

what are some adverse effects seen with rasagiline and selegiline

Answer 25

bundle branch block, GI hemorrhage insomnia (selegiline), confusion (selegiline)

Question 26

what is the mechanism of action of tolcapone

Answer 26

inhibit COMT and inhibit breakdown of levodopa by COMT in periphery

Question 27

what is the clinical application of tolcapone and entacapone

Answer 27

parkinson disease

Question 28

what parkinson drug can cause orthostatic hypotension, hyperpyrexia, fulminant hepatic failure and rhabdomyolysis

Answer 28

tolcapone

Question 29

what is the main difference between tolcapone and entacapone

Answer 29

tolcapone is highly lipid-soluble agent that can cross the BBB, while entacapone distributes only to periphery

Question 30

what rare toxicity has been reported with tolcapone use

Answer 30

fatal hepatic toxicity

Question 31

what is the mechanism of action of amantadine in respect to parkinson disease

Answer 31

antagonism of excitatory NMDA receptors

Question 32

what is the mechanism of action of trihexyphenidyl

Answer 32

muscarinic receptor antagonist that reduces cholinergic tone in the CNS by modifying the actions of striatal cholinergic interneurons

Question 33

what is the mechanism of action of benztropine

Answer 33

muscarinic receptor antagonist that reduces cholinergic tone in the CNS by modifying the actions of striatal cholinergic interneurons

Question 34

what are some adverse rxns seen with trihexphenidyl and benztropine use

Answer 34

angle-closure glaucoma, increased intraocular pressure, psychosis, xerostomia

Question 35

what are some contraindications for trihexyphenidyl and benztropine use

Answer 35

narrow angle glaucoma; younger than 3 years; tragic dyskinesias (for trihexyphenidyl)

Question 36

what is the clinical application of phenothiazines and derivatives

Answer 36

psychotic disorder

Question 37

what is the additional clinical application of chlorpromazine and perphenazine specifically

Answer 37

nausea and vomiting

Question 38

what is the mechanism of action of phenothiazines and derivatives

Answer 38

antagonize mesolimbic and possibly mesocortical D2 receptors

Question 39

how is fluphenazine administered

Answer 39

intramuscularly every 3-4 weeks

Question 40

what are the butyrophenones

Answer 40

haloperidol and droperidol

Question 41

what is the clinical application of haloperidol

Answer 41

psychoses and tourettes syndrome

Question 42

what is the clinical application of droperidol

Answer 42

nausea and vomiting; anesthesia adjunct

Question 43

what is the most widely used butyrophenone

Answer 43

haloperidol

Question 44

what is the clinical application of pimozide

Answer 44

psychotic disorders; tourettes syndrome

Question 45

what does molindone exert its antipsychotic effects on

Answer 45

ascending reticular activating system in the absence of muscle relaxation and incoordination effects

Question 46

what atypical antipsychotics are effective at antagonizing dopamine D2 and serotonin 5-HT2 receptors but also dopamine D4 receptor antagonist

Answer 46

clozapine and olanzapine

Question 47

what is the clinical application of risperidone

Answer 47

psychotic disorders; bipolar disorder

Question 48

what is the clinical application of clozapine

Answer 48

schizophrenia refractory to other antipsychotics

Question 49

what is the clinical application of olanzapine

Answer 49

psychotic disorders; bipolar disorder

Question 50

what is the clinical application of quetiapine

Answer 50

psychotic disorders; bipolar disorder

Question 51

what is the clinical application of ziprasidone

Answer 51

psychotic disorders; bipolar disorder

Question 52

what are some adverse reactions seen with clozapine

Answer 52

mild extrapyramidal symptoms; agranulocytosis; anticholinergic symptoms

Question 53

what are some contraindications for clozapine use

Answer 53

history of clozapine-induced agranulocytosis or severe granulocytopenia; myeloproliferative disorders

Question 54

what receptors does clozapine bind to

Answer 54

D1-5, 5-HT2, alpha1, H1, muscarinic receptors

Question 55

what receptors does olanzapine bind to

Answer 55

D1-4, 5-HT2, alpha1, H1, M1-M5 receptors

Question 56

what does aripiprazole bind to

Answer 56

D2 and 5-HT1A partial agonist and 5-HT2a antagonist

Question 57

what is the clinical application of paliperidone

Answer 57

schizophrenia; schizoaffective disorder

Question 58

what are some adverse reactions seen with paliperidone

Answer 58

agranulocytosis, tachyarrhymthmia, ischemia, death; hyperprolactinemia, akathisia, extrapyramidal disease, somnolence

Question 59

what is the active metabolite of risperidone

Answer 59

paliperidone

Question 60

what receptors does paliperidone effect

Answer 60

D2 and 5-HT2a antagonist and alpha1 adrenergic, alpha2 adrenergic, and H1 histaminergic antagonist to lesser degree

Question 61

what is the clinical application of Iloperidone

Answer 61

schizophrenia

Question 62

what are some adverse reactions seen with Iloperidone

Answer 62

stroke, TIA, prolonged QT interval, suicidal intent, dizziness

Question 63

what receptors does iloperidone effect

Answer 63

D2 and 5HT2a antagonist, with higher affinity for 5-HT2a than D2