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Dopaminergic Agents Flashcards

1
Q

List the 5 dopamine pathways.

A

Nigrostriatal, Mesolimbic, Mesocortical, Tuberoinfundibular, Thalamic (?)

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2
Q

Nigrostriatal pathway?

A

Controls movement – Projects from SN to BG of striatum as part of the extrapyramidal nervous system.

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3
Q

Mesolimbic pathway?

A

Controls reward and perception – Projects from the midbrain ventral tegmental area to the nucleus acccumbens as part of the limbiv system.

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4
Q

Mesocortical pathway?

A

Controls executive function – Projects from the midbrain ventral tegmental area to the prefrontal cortex (DLPFC - cognition & VMPFC - affect)

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5
Q

Tuberoinfundibular pathway?

A

Controls pituitary prolactin function – Projects from the hypothalamus to the anterior pituitary gland and controls prolactin secretion.

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6
Q

Hyper/o/functioning mesolimbic?

A

Addiction/hallucinations vs. Amotivation/apathy

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7
Q

Hyper/o/functioning mesocortical?

A

Hypervigilance vs. Inattention

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8
Q

Hyper/o/functioning nigrostriatal?

A

Dyskinetic movement vs. Parkinsonism

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9
Q

Hyper/o/functioning tuberoinfundibular?

A

Hypoprolactinemia vs. Hyperprolactinemia

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10
Q

Levodopa mxn and for?

A

Precursor to DA, crosses BBB, converted to DA proper in the CNS, improve nigrostriatal functioning, promote better movement in Parkinson’s syndrome

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11
Q

Levodopa side effects?

A

At too high doses, creates dyskinetic movements and hallucinations, mania, psychosis. On average: hypotension, syncope, nausea, anxiety/agitation, fatigue.

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12
Q

Cardiodopa mxn?

A

Inhibits peripheral conversion of L-DOPA to DA (does not cross BBB) – Prevents peripheral DA effects and lowers side effects (fatigue, dizziness, nausea)

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13
Q

What happens after many years of use with levodopa?

A

After many years, wears off (as such, it is first line treatment unless the patient is very young).

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14
Q

If depression is a low dopaminergic state due to inadequate 1 C cycling, what could be given?

A

L-methylfolate or S-adenosyl methionine (Both allow 1 C cycle to run and increase DA production)

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15
Q

Side effects of L-methylfolate or S-adenosyl methionine (“1 C neutriceuticals”) ?

A

Essentially none, possible GI upset

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16
Q

Bupropion mxn?

A

NE-DA reuptake inhibitor: Blocks dopamine transporter (DAT)

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17
Q

Bupropion for?

A

Depression

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18
Q

Bupropion side effects?

A

Insominia, jitteriness/hypervigilance, seizures, sympathetic stimulation (insominia, anxiety, agitation, nausea, dry mouth, sweating, palpitations, increased BP), NOT addicitve

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19
Q

Amphetamines mxn?

A

Block DAT, reverse DAT, increase vesicular monoamine transport (VMAT2) ejection of DA

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20
Q

Amphetamines for?

A

ADHD

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21
Q

List the most aggressive amphetamines.

A

Dextroamphetamine, mixed amphetamine salts, lisdexamfetamine.

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22
Q

What is unique about lisdexamfetamine?

A

Prodrug

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23
Q

Are amphetamines addictive?

A

Yes

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24
Q

What about methylphenidate?

A

Just blocks the DAT

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25
"Pseudostimulants?"
Modafinil/Armodafinil
26
What class are pseudostimulants?
Class IV addictive drugs ("less" addictive)
27
Modafinil/Armodafinil for?
Fatigue (due to narcolepsy, apnea, shiftwork) -- NOT ADHD
28
Modafinil/Armodafinil side effects?
Less severe but similar to other stimulants. Increase p450-3A4 and lower BC effectiveness
29
Modafinil/Armodafinil mxn?
Increase Histamine in the tuberomammilary nucleus (TMN) and activate alertness in the frontal cortex. Increase orexin. Manipulate noradrenergic receptor post-synaptically.
30
Modafinil/Armodafinil effectiveness requires?
An operating DAT system
31
In general, stimulant side effects?
Because of involvement of mesolimbic pathway: Addiction. "Super high" doses: Psychosis. "Moderate" doses: Appetite and weight loss. Any dose: NE or DA side effects.
32
Selegiline mxn?
MAO-BI at low doses, MAOA+BI at high doses
33
Selegiline for?
Parkinson's (B), Depression (A + B)
34
Rasagiline mxn?
MAOBI
35
Rasagiline for?
Parkinson's
36
Is MAOA or B more relevant for DA?
B
37
MAOA & B Inhibitors? For what?
For depression: Isocarboxazid, Phenelzine, Tranylcypromine, Selegiline
38
MAOI side effects?
Hypotension, dizziness, insomnia, weight gain. Those for depression have greater effects, interfering with ability to breakdown seretonin and NE (drug-drug interactions)
39
How does a HTN crisis happen with an MAOI?
Addition of a drug that raises NE will elevate BP (not necessarily a crisis). Addition of a food source with tyramine causes immediate release of NE stores created the HTN crisis (MAOA is used to breakdown tyramine)
40
Foods with tyramine?
Smoked meets, aged cheese, tofu, fava beans, pickled herring, banana peel, spoiled meat/fish, marmite
41
Seretonin syndrome symptoms? Caused how?
Tremor, muscle spasm, inc/dec vitals, hyperthermia, delirium, coma, death. MAOIs decrease seretonin breakdown, so addition of an aggressive serotonin drug (antidepressant, narcotics, some antihistamines) creates toxic levels.
42
COMTIs?
Entacapone, Tolcapone
43
COMTIs for?
Parkinson's
44
What does COMT do?
Catechol-o-methyltransferase degrades monoamines in the synapse.
45
Entacapone side effects?
Nausea, fatige
46
Tolcapone side effects?
Liver failure
47
Is D2 tonic or phasic?
Phasic
48
Is D3 tonic or phasic?
Tonic
49
D2 receptor agonists for?
Parkinson's, Restless Legs Syndrome
50
D2 receptor agonists?
Bromocriptine, Pramipexole, Ropinerole, Apomorphine injections
51
D2 receptor agonist side effects?
Nausea, fatigue, dizziness, mania
52
D3 agonist?
Aripiprazole
53
Aripiprazole for?
Schizophrenia, Depression
54
Aripiprazole mxn?
Partial D3 agonists, Partial D2 agonist
55
Amantadine for?
Parkinson's, Flu, Malaria
56
Amantadine mxn?
Release DA from terminal vesicles, block DAT, stimulate D2
57
Amantadine side effects?
Nausea, dizziness, psychosis, insominia, seizures
58
Reserpine mxn?
Blocks VMAT so that vesicles with monoamines cannot be released
59
Reserpine for?
HTN (less NE), Theoretically, less DA, so decreased psychosis
60
Tetrabenzine mxn?
Block VMAT, vesicles with monoamines cannot be released into synapses
61
Tetrabenzine for?
Huntington's chorea
62
"Schizophrenia meds?"
D2 receptor antagonists: 1st generation antipsychotics = Typicals/FGAs & 2nd generation antipsychotics = Atypicals/SGAs
63
FGA mxn?
Non-selective D2 receptor antagonists in all DA pathways
64
FGA drug classes?
High potency/High affinity & Low potency/Low affinity
65
FGA high potency side effects?
Extrapyramidal Syndromes (EPS) when DA is too low: Akathisia (restlessness), dystonia, parkinsonism, neuroleptic malignant syndrome (hyperthermia, muscle rigidity, vital sign instability, rhabdomyolysis)
66
Why do anticholinergics help Parkinson's?
Inhibiting cholinergic tone in the BG improves DA flow in the nigrostriatal pathway
67
Anticholinergics for?
Early Parkinson's, but most effective in treating EPS caused by FGAs/SGAs
68
Anticholintergics used?
Benztropine, diphenhydramine, trihexyphenadyl
69
Side effects of anticholinergics?
Dry mouth, blurred vision, tachy, constipation, confusion, delirium, hallucinations
70
What is tardive dyskinesia? When does it happen?
Permanent movement disorder with choreic movements &/or athetotic movements, caused by chronic D2 receptor antagonism
71
FGA low potency side effects?
EPS, H1 receptor antagonism (fatigue, increased appetite/weight), anticholinergic muscarinic antagonism (dry mouth...), NE a1 antagonism (orthostasis), LOWER risk for TD
72
FGA high potency drugs?
Haloperidol, Fluphenazine, Thiothixine
73
FGA low potency drugs?
Chlorpromazine, Thioridazine
74
SGA mxn? Significance of added effect?
D2 receptor antagonism AND Serotonin 2a (5HT2a) antagonism. This loweres EPS risk. All in all, greater blocking of DA in the mesolimbic system and better transmission in all other DA pathways
75
SGAs may help what besides schizophrenia?
Depression, anxiety, autism, mania in bipolar
76
SGA 'dones?
Risperidone, paliperidone, ziprasidone, iloperidone, lurasidone
77
SGA 'pines?
Olanzapine, quetiapine, asenapine, clozapine (antagonizes D4 and D1 too)
78
SGA 'rips/'pips?
Aripiprazole (partial agonist @ D2 and D3)
79
Side effects of 'dones?
More EPS
80
Side effects of 'pines?
More sedating (antihistamine effect), More metabolic syndrome
81
SGA boxed warnings?
Suicide < 25, Metabolic syndrome, TD/EPS, stroke in dementia patients
82
Clozapine mxn?
D2, 5HT2a antagonist, D1, D4 antagonist
83
Clozapine for?
Refractory schizophrenia
84
Clozapine risk?
agranulocytosis: requires WBC and ANC monitoring, most metabolic risk of any agent, but little to no EPS/TD risk
85
What is the most effective antipsychotic?
Clozapine

Pharmacology (46 decks)

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