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Pharmacology > Dopaminergic Agents > Flashcards

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
Q

“Pseudostimulants?”

A

Modafinil/Armodafinil

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26
Q

What class are pseudostimulants?

A

Class IV addictive drugs (“less” addictive)

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27
Q

Modafinil/Armodafinil for?

A

Fatigue (due to narcolepsy, apnea, shiftwork) – NOT ADHD

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28
Q

Modafinil/Armodafinil side effects?

A

Less severe but similar to other stimulants. Increase p450-3A4 and lower BC effectiveness

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29
Q

Modafinil/Armodafinil mxn?

A

Increase Histamine in the tuberomammilary nucleus (TMN) and activate alertness in the frontal cortex. Increase orexin. Manipulate noradrenergic receptor post-synaptically.

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30
Q

Modafinil/Armodafinil effectiveness requires?

A

An operating DAT system

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31
Q

In general, stimulant side effects?

A

Because of involvement of mesolimbic pathway: Addiction. “Super high” doses: Psychosis. “Moderate” doses: Appetite and weight loss. Any dose: NE or DA side effects.

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32
Q

Selegiline mxn?

A

MAO-BI at low doses, MAOA+BI at high doses

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33
Q

Selegiline for?

A

Parkinson’s (B), Depression (A + B)

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34
Q

Rasagiline mxn?

A

MAOBI

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35
Q

Rasagiline for?

A

Parkinson’s

36
Q

Is MAOA or B more relevant for DA?

A

B

37
Q

MAOA & B Inhibitors? For what?

A

For depression: Isocarboxazid, Phenelzine, Tranylcypromine, Selegiline

38
Q

MAOI side effects?

A

Hypotension, dizziness, insomnia, weight gain. Those for depression have greater effects, interfering with ability to breakdown seretonin and NE (drug-drug interactions)

39
Q

How does a HTN crisis happen with an MAOI?

A

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
Q

Foods with tyramine?

A

Smoked meets, aged cheese, tofu, fava beans, pickled herring, banana peel, spoiled meat/fish, marmite

41
Q

Seretonin syndrome symptoms? Caused how?

A

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
Q

COMTIs?

A

Entacapone, Tolcapone

43
Q

COMTIs for?

A

Parkinson’s

44
Q

What does COMT do?

A

Catechol-o-methyltransferase degrades monoamines in the synapse.

45
Q

Entacapone side effects?

A

Nausea, fatige

46
Q

Tolcapone side effects?

A

Liver failure

47
Q

Is D2 tonic or phasic?

A

Phasic

48
Q

Is D3 tonic or phasic?

A

Tonic

49
Q

D2 receptor agonists for?

A

Parkinson’s, Restless Legs Syndrome

50
Q

D2 receptor agonists?

A

Bromocriptine, Pramipexole, Ropinerole, Apomorphine injections

51
Q

D2 receptor agonist side effects?

A

Nausea, fatigue, dizziness, mania

52
Q

D3 agonist?

A

Aripiprazole

53
Q

Aripiprazole for?

A

Schizophrenia, Depression

54
Q

Aripiprazole mxn?

A

Partial D3 agonists, Partial D2 agonist

55
Q

Amantadine for?

A

Parkinson’s, Flu, Malaria

56
Q

Amantadine mxn?

A

Release DA from terminal vesicles, block DAT, stimulate D2

57
Q

Amantadine side effects?

A

Nausea, dizziness, psychosis, insominia, seizures

58
Q

Reserpine mxn?

A

Blocks VMAT so that vesicles with monoamines cannot be released

59
Q

Reserpine for?

A

HTN (less NE), Theoretically, less DA, so decreased psychosis

60
Q

Tetrabenzine mxn?

A

Block VMAT, vesicles with monoamines cannot be released into synapses

61
Q

Tetrabenzine for?

A

Huntington’s chorea

62
Q

“Schizophrenia meds?”

A

D2 receptor antagonists: 1st generation antipsychotics = Typicals/FGAs & 2nd generation antipsychotics = Atypicals/SGAs

63
Q

FGA mxn?

A

Non-selective D2 receptor antagonists in all DA pathways

64
Q

FGA drug classes?

A

High potency/High affinity & Low potency/Low affinity

65
Q

FGA high potency side effects?

A

Extrapyramidal Syndromes (EPS) when DA is too low: Akathisia (restlessness), dystonia, parkinsonism, neuroleptic malignant syndrome (hyperthermia, muscle rigidity, vital sign instability, rhabdomyolysis)

66
Q

Why do anticholinergics help Parkinson’s?

A

Inhibiting cholinergic tone in the BG improves DA flow in the nigrostriatal pathway

67
Q

Anticholinergics for?

A

Early Parkinson’s, but most effective in treating EPS caused by FGAs/SGAs

68
Q

Anticholintergics used?

A

Benztropine, diphenhydramine, trihexyphenadyl

69
Q

Side effects of anticholinergics?

A

Dry mouth, blurred vision, tachy, constipation, confusion, delirium, hallucinations

70
Q

What is tardive dyskinesia? When does it happen?

A

Permanent movement disorder with choreic movements &/or athetotic movements, caused by chronic D2 receptor antagonism

71
Q

FGA low potency side effects?

A

EPS, H1 receptor antagonism (fatigue, increased appetite/weight), anticholinergic muscarinic antagonism (dry mouth…), NE a1 antagonism (orthostasis), LOWER risk for TD

72
Q

FGA high potency drugs?

A

Haloperidol, Fluphenazine, Thiothixine

73
Q

FGA low potency drugs?

A

Chlorpromazine, Thioridazine

74
Q

SGA mxn? Significance of added effect?

A

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
Q

SGAs may help what besides schizophrenia?

A

Depression, anxiety, autism, mania in bipolar

76
Q

SGA ‘dones?

A

Risperidone, paliperidone, ziprasidone, iloperidone, lurasidone

77
Q

SGA ‘pines?

A

Olanzapine, quetiapine, asenapine, clozapine (antagonizes D4 and D1 too)

78
Q

SGA ‘rips/’pips?

A

Aripiprazole (partial agonist @ D2 and D3)

79
Q

Side effects of ‘dones?

A

More EPS

80
Q

Side effects of ‘pines?

A

More sedating (antihistamine effect), More metabolic syndrome

81
Q

SGA boxed warnings?

A

Suicide < 25, Metabolic syndrome, TD/EPS, stroke in dementia patients

82
Q

Clozapine mxn?

A

D2, 5HT2a antagonist, D1, D4 antagonist

83
Q

Clozapine for?

A

Refractory schizophrenia

84
Q

Clozapine risk?

A

agranulocytosis: requires WBC and ANC monitoring, most metabolic risk of any agent, but little to no EPS/TD risk

85
Q

What is the most effective antipsychotic?

A

Clozapine

Pharmacology (46 decks)

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