Flashcards in Pharm U3 L1. Deck (57):
What is dopamine made from?
transports neurotransmitters (esp dopamine, NE, serotonin, histamine) from cellular cytosol into synaptic vesicles
dopamine transporter - recycles dopamine from synaptic cleft back into neuron
MAO A or B
inside of presynaptic membrane destroying dopamine
in synaptic cleft destroying dopamine
What is the main dopamine factory
reward and perception
pituitary prolactin function
Hyperfunctioning of mesolimbic = ?
Hyperfunctioning of mesocortical = ?
Hyperfunctioning of nigrostriatal = ?
Hypofunctioning of mesolimibic = ?
Hypofunctioning of mesocortical = ?
Hypofunctioning of nigrostriatal = ?
diskinetic movement, parkinsonism
Hypofunctioning of tuberoinfundibulnar = ?
What are the dopamine enhancing drugs?
levodopa and carbidopa
precursor to DA that crosses BBB - promotes better movement by improving nigrostriatal functioning
often combined with levodopa - prevents peripheral dopamine activity and lowers fatigue, dizziness, nausea (treats side effects)
Side effects of levodopa
too much DA - psychosis, mania, dyskinesia (involuntary movements) - usually hypotension, syncope, nausea, anxiety, fatigue
What is a treatment for depression?
increase folate in order to get more dopamine (some cycle where they are connected)
blocks dopamine transporter (DAT) - dopamine reuptake inhibition, leaving more DA in the synapse - increases DA activity in the mesocortical pathway
Side effects of increased dopamine drugs (levodopa, bupropion)
think increase in norepinephrine = sympathetic stimulation = insomnia, anxiety, angitation, nausea, dry mouth, sweating, palpitations, mild increase BP
block DAT like bupropion and also increases VMAT2 which ejects more DA from nerve terminals - more aggressive
stimulants, less addictive than amphetamines - used to treat narcolepsy, apnea, NOT ADHD
modafinil/armodafinil side effect
may increase p450-3A4 enzymes - lowering birth control effectiveness; still addictive; psychosis at high doses; weight loss
increase histamine activity in tubermammilary nucleus - activating alertness in frontal cortex
MAO-B inhibitors and treatment
selegiline and rasagiline - treat parkinson’s
MAO A+B inhibition and treatment
isocarboxazid, phenelzine, tranylcypromine, selegiline - treat depression
MAOi side effects
hypotension, dizziness, insomnia, weight gain - can also interfere with breakdown of serotonin and NE (drug-drug interactions that can be life threatening)
irreversibly inhibit MAO-A/B allowing build up of DA because it cannot be broken down
What results in a hypertensive crisis?
any drug that raises NE + food source containing tyramine (fava beans, aged cheese, tofu) (causes immediate release of NE stores) - MAO-A used to breakdown tyramine
Toxic levels of serotonin causes
tremor, muscle spasm, inc/dec vitals, hyperthermia, delirium, coma, death
inhibition of COMTi - enzyme in the synapse that degrades monoamines as well - elevates DA or NE
D2 receptor agonism - MOA and drugs
increases DA activity for treatment of parkinson’s and restless leg syndrome: bromocriptine, pramipexole, ropinerole, apomorphine injections
Side effects of bromocriptine, pramipexole, ropinerole, apomorphine injections
nausea, fatigue, dizziness, mania
What is the first line treatment for Parkinson’s
D2 receptor agonism (bromocriptine, pramipexole, ropinerole, apomorphine injections because dopa only works for a few years
partial agonist at D3 - promotes more alertness and energy, also partial agonist at D2 - antipsychotic for schizophrenia
treats parkinson’s and influenza - release DA from terminal vesicles, block DAT and stimulate D2 receptors - not really used anymore
When would we want to decrease DA activity?
schizophrenia - decrease DA in mesolimbic to lower hallucinations and delusions
dopamine synapse depleters - blocks VMAT
What was reserpine originally intended to treat?
hypertension (less NE = less BP)
D2 receptor antagonism
non selective - occurs in all DA pathways; high potency - blocking in mesolimbic alleviates psychosis, in nigrostriatal causes EPS
extrapyramidal syndromes - when DA activity is forced too low. 1. akathisia (restlessness) 2. dystonia (muscle spasm) 3. parkinsonism (reversible) 4. neuroleptic malignant syndrome (hyperthermia, muscle rigidity, vital sign instability, rabdomyolysis)
What are the FGAs and SGA
first generation antipsychotics and second generation
Which drugs are very effective in parkinsonism EPS caused by FGA/SGA?
anticholinergic drugs (cholinergic muscarinic receptor antagonists) - inhibits cholinergic tone in basal ganglia, improving dopaminergic flow/tone in nigrostriatal pathway
What are the anticholinergics? What are their side effects?
benztropine, trihexyphenadyl, diphenhydramine. SE = dry mouth, blurred vision, tachycardia, constipation, confusion, delirium, hallucinations
chronic D2 receptor antagonism = abnormal movements
What are the two types of FGAs?
low potency vs high potency - low potency manipulate other receptors associated with side effects
What are the high potency FGA drugs?
haloperidol, fluphenzine, thiothixine
What are the low potency FGA drugs?
What is the SGA mechanism of action?
D2 receptor antagonism AND serotonin 2a(5HT2a) antagonism which lessens EPS risks - don’t need the anticholinergics and makes this the standard of care
What are the SGA drugs?
dones (D2 blockade - more EPS); pines (more sedating and metabolic); ‘rips (aripiprazole) - partial agonist at D2 and D3
What are the FDA precautions/boxed warnings for SGA?
suicide risk ages
used in refractory schizophrenia (SGA pine) - ALSO antagonizes D1 and D4, giving it multiple mechanisms to manipulate dopamine