chapter 13- Dopaminergic neurotransmission Flashcards
what is the precursor of all catecholamines
tyrosine
what enzyme has the key function to terminate the action of catecholamines in the brain and periphery
MAO
where is MAO-A expressed
brain and periphery
where is MAO-B expressed
CNS
what do D1 and D5 dopamine receptors lead to
increased cAMP
what do D2, D3, and D4 dopamine receptors lead to
inhibits cAMP generation
where are D1 and D2 expressed at high levels
striation as well as nucleus accumbens and olfactory tubercle
what dopamine receptor is expressed highly in anterior pituitary gland
D2
where is D3 expressed at high levels
limbic system
where is D4 localized
frontal cortex, diencephalon, brainstem
where is D5 mainly located
hippocampus, olfactory tubercle and hypothalamus
what is the clinical application of levodopa
parkinson disease
what stages of parkinson disease is levodopa particularly effective
early stages
what are some common side effects of levodopa
dyskinesia, orthostatic hypotension, loss of appetite
what side effect with basically be for sure to happen with levodopa within 5 years of use
dyskinesia
what are some contraindications for levodopa use
history of melanoma; narrow angle glaucoma; concomitant use of MAO-inhibitor
what are some contraindications for rasagiline and selegiline
concomitant use of cyclobenzaprine, mirtazapine, st johns wort; concomitant use of dextromethorphan
what is levodopa almost always administered with
carbidopa
what is the mechanism of action of carbidopa
inhibitor of DOPA decarboxylase
what is the clinical application of pramipexole and ropinirole
parkinson disease
what is another clinical application of ropinirole besides parkinson
restless leg syndrome
what are some adverse effects seen with pramipexole and ropinirole
orthostatic hypotension, extrapyramidal movements, hallucinations
what are some cognitive effects seen with pramipexole and ropinirole
excessive sedation, vivid dreams and hallucinations
what does rasagiline and selegiline inhibit
MAO-B
what are some adverse effects seen with rasagiline and selegiline
bundle branch block, GI hemorrhage insomnia (selegiline), confusion (selegiline)
what is the mechanism of action of tolcapone
inhibit COMT and inhibit breakdown of levodopa by COMT in periphery
what is the clinical application of tolcapone and entacapone
parkinson disease
what parkinson drug can cause orthostatic hypotension, hyperpyrexia, fulminant hepatic failure and rhabdomyolysis
tolcapone
what is the main difference between tolcapone and entacapone
tolcapone is highly lipid-soluble agent that can cross the BBB, while entacapone distributes only to periphery
what rare toxicity has been reported with tolcapone use
fatal hepatic toxicity
what is the mechanism of action of amantadine in respect to parkinson disease
antagonism of excitatory NMDA receptors
what is the mechanism of action of trihexyphenidyl
muscarinic receptor antagonist that reduces cholinergic tone in the CNS by modifying the actions of striatal cholinergic interneurons
what is the mechanism of action of benztropine
muscarinic receptor antagonist that reduces cholinergic tone in the CNS by modifying the actions of striatal cholinergic interneurons
what are some adverse rxns seen with trihexphenidyl and benztropine use
angle-closure glaucoma, increased intraocular pressure, psychosis, xerostomia
what are some contraindications for trihexyphenidyl and benztropine use
narrow angle glaucoma; younger than 3 years; tragic dyskinesias (for trihexyphenidyl)
what is the clinical application of phenothiazines and derivatives
psychotic disorder
what is the additional clinical application of chlorpromazine and perphenazine specifically
nausea and vomiting
what is the mechanism of action of phenothiazines and derivatives
antagonize mesolimbic and possibly mesocortical D2 receptors
how is fluphenazine administered
intramuscularly every 3-4 weeks
what are the butyrophenones
haloperidol and droperidol
what is the clinical application of haloperidol
psychoses and tourettes syndrome
what is the clinical application of droperidol
nausea and vomiting; anesthesia adjunct
what is the most widely used butyrophenone
haloperidol
what is the clinical application of pimozide
psychotic disorders; tourettes syndrome
what does molindone exert its antipsychotic effects on
ascending reticular activating system in the absence of muscle relaxation and incoordination effects
what atypical antipsychotics are effective at antagonizing dopamine D2 and serotonin 5-HT2 receptors but also dopamine D4 receptor antagonist
clozapine and olanzapine
what is the clinical application of risperidone
psychotic disorders; bipolar disorder
what is the clinical application of clozapine
schizophrenia refractory to other antipsychotics
what is the clinical application of olanzapine
psychotic disorders; bipolar disorder
what is the clinical application of quetiapine
psychotic disorders; bipolar disorder
what is the clinical application of ziprasidone
psychotic disorders; bipolar disorder
what are some adverse reactions seen with clozapine
mild extrapyramidal symptoms; agranulocytosis; anticholinergic symptoms
what are some contraindications for clozapine use
history of clozapine-induced agranulocytosis or severe granulocytopenia; myeloproliferative disorders
what receptors does clozapine bind to
D1-5, 5-HT2, alpha1, H1, muscarinic receptors
what receptors does olanzapine bind to
D1-4, 5-HT2, alpha1, H1, M1-M5 receptors
what does aripiprazole bind to
D2 and 5-HT1A partial agonist and 5-HT2a antagonist
what is the clinical application of paliperidone
schizophrenia; schizoaffective disorder
what are some adverse reactions seen with paliperidone
agranulocytosis, tachyarrhymthmia, ischemia, death; hyperprolactinemia, akathisia, extrapyramidal disease, somnolence
what is the active metabolite of risperidone
paliperidone
what receptors does paliperidone effect
D2 and 5-HT2a antagonist and alpha1 adrenergic, alpha2 adrenergic, and H1 histaminergic antagonist to lesser degree
what is the clinical application of Iloperidone
schizophrenia
what are some adverse reactions seen with Iloperidone
stroke, TIA, prolonged QT interval, suicidal intent, dizziness
what receptors does iloperidone effect
D2 and 5HT2a antagonist, with higher affinity for 5-HT2a than D2
