CNS Drugs: Dopaminergic Agents Flashcards
making of dopamine
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.
where is dopamine packaged?
stored in vesicles by VMAT2 (vesicular monoamine transporter). stored there until release into synapse during neurotransmisson
termination of dopamine’s action
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.
nigrostriatal pathway
controls movement
mesolimbic pathway
controls reward and perception
mesocortical pathway
controls executive function
tuberoinfundibular pathway
controls pituitary prolactin function. hyperfunctioning leads to hypoprolactinemia
thalamic pathway
function not currently well known
what is hyper and hypo active in schizophrenia
dorsolateral prefrontal cortex is hypoactive. ventromedial cortex is hyperactive
inverted U shape
theoretical construct that describes CNS homeostasis. systems need just the right amount of neurotransmitter to have proper function
what are dopamine enhancing drugs used for?
used to treat low DA states like parkinson’s disease
side effects of levodopa
at worst: psychosis, dyskinesia. normally hypotension, syncope, nausea, anxiety, fatigue
is depression a low DA state?
some depression is. increasing the 1 carbon cycle can allow DA neurons to make more DA, improving the patient’s condition
side effects of 1 carbon nutraceuticals
none really, perhaps slight GI irritation.
norepinephrine-dopamine reuptake inhibitors
block dopamine transporter (DAT). leaves more DA in the synapse. side effects are insomnia, jitteriness, seizures
side effects of increased norepinephrine activity?
sympathetic stimulation. insomnia, anxiety, agitation, nausea, dry mouth, sweating, palpitations, mild increases in blood pressure
stimulants for ADHD mechanism
Amphetamines block DAT, may even reverse it and increase vesicular monoamine transport ejecting more DA from nerve terminals. methylphenidate products block DA transporter
modafinil/armodafinil
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
modafinil/armodafinil mechanism
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
stimulant side effects
psychosis at very high doses. moderate doses: appetite and weight loss can occur. at any dose, patients may get norepi and dopamine side effects
MAOi
irreversibly inhibit MAO A/B generally within the neuron allowing a buildup of DA because it cannot be broken down
MAOi side effects
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
hypertensive crisis
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
serotonin syndrome
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.
