CNS Drugs: Dopaminergic Agents

Question 1

making of dopamine

Answer 1

tyrosine is taken up into dopamine nerve terminals and converted into DOPA by the enzyme tyrosine hydroxylase. DOPA is converted to dopamine by DOPA decarboxylase.

Question 2

where is dopamine packaged?

Answer 2

stored in vesicles by VMAT2 (vesicular monoamine transporter). stored there until release into synapse during neurotransmisson

Question 3

termination of dopamine’s action

Answer 3

removed from the synapse by the DAT (dopamine transporter). destroyed inside the neuron by MAO A/B (present in the mitochondria within the presynaptic neuron and glia cells). destroyed in the synapse by COMT.

Question 4

nigrostriatal pathway

Answer 4

controls movement

Question 5

mesolimbic pathway

Answer 5

controls reward and perception

Question 6

mesocortical pathway

Answer 6

controls executive function

Question 7

tuberoinfundibular pathway

Answer 7

controls pituitary prolactin function. hyperfunctioning leads to hypoprolactinemia

Question 8

thalamic pathway

Answer 8

function not currently well known

Question 9

what is hyper and hypo active in schizophrenia

Answer 9

dorsolateral prefrontal cortex is hypoactive. ventromedial cortex is hyperactive

Question 10

inverted U shape

Answer 10

theoretical construct that describes CNS homeostasis. systems need just the right amount of neurotransmitter to have proper function

Question 11

what are dopamine enhancing drugs used for?

Answer 11

used to treat low DA states like parkinson’s disease

Question 12

side effects of levodopa

Answer 12

at worst: psychosis, dyskinesia. normally hypotension, syncope, nausea, anxiety, fatigue

Question 13

is depression a low DA state?

Answer 13

some depression is. increasing the 1 carbon cycle can allow DA neurons to make more DA, improving the patient’s condition

Question 14

side effects of 1 carbon nutraceuticals

Answer 14

none really, perhaps slight GI irritation.

Question 15

norepinephrine-dopamine reuptake inhibitors

Answer 15

block dopamine transporter (DAT). leaves more DA in the synapse. side effects are insomnia, jitteriness, seizures

Question 16

side effects of increased norepinephrine activity?

Answer 16

sympathetic stimulation. insomnia, anxiety, agitation, nausea, dry mouth, sweating, palpitations, mild increases in blood pressure

Question 17

stimulants for ADHD mechanism

Answer 17

Amphetamines block DAT, may even reverse it and increase vesicular monoamine transport ejecting more DA from nerve terminals. methylphenidate products block DA transporter

Question 18

modafinil/armodafinil

Answer 18

class IV addictive drugs, approved for fatigue due to narcolepsy, apnea, shiftwork, but not ADHD. may increase p450-3A4 enzymes and lower birth control effectiveness

Question 19

modafinil/armodafinil mechanism

Answer 19

increases histamine activity in the tuberomammilary nucleus, thus activating alertness in the frontal cortex. requires an operating DAT system. may also manipulate noradrenergic receptors post synaptically

Question 20

stimulant side effects

Answer 20

psychosis at very high doses. moderate doses: appetite and weight loss can occur. at any dose, patients may get norepi and dopamine side effects

Question 21

MAOi

Answer 21

irreversibly inhibit MAO A/B generally within the neuron allowing a buildup of DA because it cannot be broken down

Question 22

MAOi side effects

Answer 22

hypotension, dizziness, insomnia, weight gain. MAOi for depression usually hit MAO A more interfering with ability to breakdown serotonin and norepinephrine. can lead to life threating drug drug interactions

Question 23

hypertensive crisis

Answer 23

adding any other drug that raises NE can additively elevte blood pressure. adding any food that contains tyramine may cause an immediate release of NE stores creating a hypertensive crisis resulting in stroke or heart attack

Question 24

serotonin syndrome

Answer 24

adding an aggressive serotonin drug while on an MAOi may create toxic levels of CNS serotonin causing tremor, muscle spasm, increased/decreased vitals, hyperthermia, delirium, coma, death.

Question 25

D2 receptor agonism

Answer 25

increases DA activity in treating parkinson’s or restless leg syndrome

Question 26

D3 receptor agonism

Answer 26

aripiprazole: antipsychotic for schizophrenia that is also used to treat depression. partial agonist against D2 and D3 receptors

Question 27

amantadine

Answer 27

used for parkinsons and influenza. theorized to release DA from terminal vesicles, block DAT, and stimulate D2. side effects are nausea, dizziness, psychosis, insomnia, seizures

Question 28

synapse depleters

Answer 28

reserpine and tetrabenzine. VMAT inhibitors, vesicles with monoamines cannot be released into synapses

Question 29

first gen antipsychotics mechanism

Answer 29

D2 receptor antagonism. non selective, occurs in all DA pathways. high potency agents.

Question 30

first gen antipsychotics side effects

Answer 30

extrapyrimidal syndromes occur when DA is too low. akathisia, dystonia, parkinsonism. neuroleptic malignant syndrome: hyperthermia, muscle rigidity, vital sign instability, rhabdomyolysis

Question 31

tardive dyskinesia

Answer 31

chronic D2 receptor antagonism may cause permanent movement disorder. fast, quirky in nature (choreic movements). athetotic movements are slow, writhing in nature

Question 32

second gen antipsychotics mechanism

Answer 32

D2 receptor antagonism. Serotonin 2a antagonism. allows greater blocking of DA in the mesolimbic system while allowing better transmission in all other DA pathways. improved selectivity from First gen drugs.

Question 33

second gen antipsychotics side effects

Answer 33

dones: more EPS (extrapyrimidal syndromes). Pines: more sedating due to more antihistamine activity, more metabolic syndrome inducing as well

Question 34

clozapine

Answer 34

original atypical antopsychotic. schizophrenia. antagonizes D2 and 5HT2a. also D1 and D4. may block NMDA glutamate receptors. risk of agranulocytosis. most metabolic risk of any agent. little to zero risk of EPS/TD