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► Med Misc 10 > Pharmacology - CNS Drugs - Dopaminergic Agents > Flashcards

Pharmacology - CNS Drugs - Dopaminergic Agents Flashcards

1
Q

Hyperfunctioning (dopamine) in the mesolimbic pathway causes:

A

Addiction, hallucination

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2
Q

Hyperfunctioning (dopamine) in the mesocortical pathway causes:

A

Hypervigilance

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3
Q

Hyperfunctioning (dopamine) in the tuberoinfundibular pathway causes:

A

Hypoprolactinemia

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4
Q

Parkinsonism is hypodopamine in what brain area?

A

Nigrastriatal system

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5
Q

What is the main theory behind high or low dopamine functioning?

A

If you inherit an abnormal gene (val substitution), then you have aggressive COMT (catechol-O-methyltransferase) and break down too much dopamine and develop symptoms

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6
Q

What is Levodopa?

A
  • Precursor to DA
  • Crosses BBB (and is converted to DA; improves nigrostriatal functioning)
  • 1st line tx for Parkinson’s unless pt young (want to delay as long as possible)
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7
Q

What drug is often used in combination with Levodopa, and why?

A
  • Carbidopa
  • b/c it prevents peripheral dopamine activity and lowers fatigue, dizziness, and nausea SEs
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8
Q

Give the side effects: Levodopa

A
  • If too much dopamine –> psychosis, mania, dyskinesias (abnormal, involuntary movements)
  • Hypotension, syncope, nausea, anxiety/agitation, fatigue
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9
Q

People with the T-allele for folate metabolism have less of what chemical that may contribute to depression?

A
  • less dopamine
  • T allele = faulty methylhydrofolate reductase enzyme (MTHFR) –> less DA
  • “you don’t want to have T (allele for MTHFR) with Val (substitution –> abn, aggressive COMT)”
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10
Q

What is the mechanism of action of Norepinephrine Dopamine Reuptake Inhibitors (NDRIs)?

A
  • NDRIs block the dopamine transporter (aka dopamine reuptake inhibition)
  • Leaves more DA in the synapse to increase to increase DA in the mesocortical pathway
  • Can lower depression symptoms
  • Buproprion is an example
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11
Q

Give the side effects of NDRIs.

A

Insomnia, jitteriness, hypervigilance, seizures, anxiety, dry mouth, palpitations, mild increases in BP, sweating think sympathetic stimulation (NE)

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12
Q

Give the class: dextroamphetamine lisdexamfetamine mixed amphetamine salts

A

Stimulants

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13
Q

Give the indication: dextroamphetamine lisdexamfetamine mixed amphetamine salts

A

ADHD

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14
Q

What is the mechanism of action of the stimulant class?

A

Stimulants block the DAT like buproprion, and may even reverse it, and increase vesicular monoamine transport (VMAT2) , ejecting more DA from nerve terminals

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15
Q

What is the mechanism of action of methylphenidate?

A

block DA transporter less effective than the stimulants

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16
Q

Give the class: Modafinil; Armodafinil

A

Stimulants Different MOA than amphetamine

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17
Q

Give the indications: Modafinil; Armodafinil

A

Narcolepsy, Apnea, Shiftwork disorder NOT ADHD approved Less severe side effects

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18
Q

What are unique side effects of Modafinil; Armodafinil?

A

May lower birth control effectiveness bc may increase p450-3A4 enzymes

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19
Q

Give the mechanism of action: Modafinil, Armodafinil

A

Increases histamine activity in the tuberomammilary nucleus; may block DAT May increase orexin activity

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20
Q

What are side effects of stimulants?

A

Psychosis at high doses Addiction Weight loss DA and NE side effects at any dose

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21
Q

Monoamine Oxidase Enzymes A and B are responsible for breaking down:

A

Dopamine and other monoamines like NE and serotonin

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22
Q

Give the mechanism of action: MAOi

A

Block the breakdown of DA

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23
Q

Give the indication for Selegiline.

A

Parkinson’s Depression MAO-B inhibitor at low dose, full MAO-A and B at higher dose (patch)

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24
Q

Give the indication for Rasagiline.

A

Parkinson’s MAO-B inhibitor

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25
Q

Give the mechanism of action: Tranylcypromine (Parnate); Isocarboxazid (Marplan); Phenelzine (Nardil)

A

Irreversibly inhibit both MAO-A and MAO-B

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26
Q

Give the side effects: MAOi

A

Hypotension, dizziness, insomnia, weight gain Hypertensive crisis (with tyramine-rich foods); serotonin syndrome (MAOI + SSRI)

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27
Q

What things in combination with MAOi use can precipitate a hypertensive crisis?

A

Tyramine-rich foods such as cheeses, fava beans or fermented things; Nasal decongestants NE-based antidepressants

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28
Q

Give two examples of COMT inhibitors.

A

Entacapone (nausea and fatigue) Tolcapone (not used anymore bc of liver failure) Catechol-O-methyltransferanse inhibitors COMT is an enzyme that degrades monoamines. Inhibit this enzyme to increase DA or NE Used to help treat Parkinson’s

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29
Q

D2 receptor agonism increases DA activity mainly in the nigrastriatal pathway. In this way, it is therapeutically indicated for what diagnosed?

A

Parkinson’s Restless Leg Syndrome

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30
Q

Give the class: Bromocriptine

A

Ergot D2 receptor agonist

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31
Q

Give the class: Pramipexole (Mirapex); Ropinerole

A

Selective D2 receptor agonist

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32
Q

Give the class: Apomorphine

A

D2 receptor agonist

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33
Q

Give the class: Aripiprazole (Abilify)

A

D2 & D3 receptor (partial) agonist

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34
Q

Give the class: Amantadine

A

Antiviral

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35
Q

Bromocriptine, Pramipexole, Ropinerole and Apomorphine are all used to treat mild Parkinson’s and RLS. What other diagnosis is indicated specifically for Bromocriptine?

A

Hyperprolactinemia

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36
Q

Give the indication: Aripiprazole

A

Schizophrenia and depression Antipsychotic

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37
Q

Give the indication: Amantadine

A

Mild Parkinson’s (2nd-line); influenza

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38
Q

Give the side effects: Amantadine

A

Nausea, dizziness, psychosis, insomnia, seizures

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39
Q

Give the side effects: Bromocriptine, Pramipexole, Ropinerole and Apomorphine

A

Mania, nausea, dizziness, fatigue

40
Q

The goal in therapy for narcolepsy, RLS and ADHD is to ____ DA activity

A

increase same with Parkinson’s and Depression

41
Q

Give the class: Reserpine Tetrabenazine

A

Synapse depleters

42
Q

Give the indication: Reserpine

A

HTN can be used for schizophrenia

43
Q

Give the indication: Tetrabenazine

A

Huntington’s Chorea

44
Q

Give the mechanism of action: Reserpine Tetrabenazine

A

Blocks VMAT (no release of monoamines into synapses) Synapse depleters

45
Q

Give the notable side effect: Reserpine Tetrabenazine

A

Depression

46
Q

What is the mechanism of action of the first generation antipsychotic (FGA)?

A

D2 receptor antagonism Non-selective, occurs in all DA pathways can lead to induced Parkinsonism

47
Q

Give the side effects of FGAs such as: Chlorpromazine (Thorazine); Thioridazine

A

EPS - extrapyramidal syndromes - when DA is too low akathisia (restlessness) from D2 blockade, dystonia (muscle spasm), Parkinsonism, NMS (neuroleptic malignant syndrome)

48
Q

What is Neuroleptic Malignant Syndrome (NMS)?

A

Hyperthermia Muscle rigidity Vital sign instability Rhabdomyolisis (kidney failure) SE of FGAs such as Chlopromazine, Thioridazine, Fluphenazine, Thioxixine, Haloperidol

49
Q

Give the side effects: Fluphenazine, Thioxixine, Haloperidol

50
Q

Why were anticholinergics such as Benztropine, Trihexyphenadyl and diphenhydramine used for Parkinson’s disease?

A

Inhibiting cholinergic tone in the basal ganglia improves dopaminergic flow/tone in the nigrostriatal pathway, thus lowering Parkinson’s symptoms

51
Q

Give the side effects: Benztropine, Trihexyphenadyl and diphenhydramine (anticholinergics)

A

Dry mouth Blurred vision Tachycardia Constipation Confusion Delirium Hallicinations

52
Q

Chronic D2 receptor antagonism may cause what permanent disorder?

A

Tardive Dyskinesia (longer effects than EPS side effect)

53
Q

Name the high affinity FGAs.

A

Haloperidol Fluphenazine Thiothixine

54
Q

Name the low potency FGAs.

A

Chlorpromazine Thioridazine

55
Q

Serotonin 2a (5HT2a) antagonism has more or less risks for EPS than FGAs?

A

Less ie risperidone

56
Q

How are SGAs different from FGAs?

A

SGAs have Greater blocking of DA in the mesolimbic system, while allowing better transmission in all other DA pathways

57
Q

SGAs that agonize 5HT1a help to treat:

58
Q

SGAs that antagonize 5HT2c, 3, 7 help to treat:

A

depression

59
Q

T/F: Some SGAs have SRI and NRI properties that treat depression.

60
Q

D2 blockage lowers aggression in what diagnosis?

61
Q

D2 blockade lowers mania in what diagnosis?

A

Bipolar disorder

62
Q

Give the class: Risperidone

63
Q

Give the class: Paliperidone

64
Q

Give the class: Ziprasidone

65
Q

Give the class: Iloperidone

66
Q

Give the class: Lurasidone

67
Q

Give the mechanism of action: Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone

A

SGA D2 receptor antagonist; but various other receptor agonism/antagonism

68
Q

Give the indication: Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone

A

Psychosis, mania, aggression

69
Q

Give the side effects: Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone

A

Suicide risk in ages

70
Q

Give the class: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

71
Q

Give the mechanism of action: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

A

D2 receptor antagonist, 5HT2a receptor antagonist

72
Q

Give the indication: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

A

Psychosis, mania, aggression

73
Q

Give the class: Clozapine

74
Q

Give the mechanism of action: Clozapine

A

D2 (& D1, D4) receptor antagonist; 5HT2a receptor antagonist

75
Q

Give the indication: Clozapine

A

Refractory schizophrenia

76
Q

Give the side effects: Clozapine

A

Side effects similar to other “pines”, but also agranulocytosis (inhibits bone marrow) (NMDA receptor antagonism?) Suicide risk in ages

77
Q

Give the side effects: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

A

Suicide risk in ages

78
Q

What receptor antagonism in SGAs is responsible for weight gain?

79
Q

Of the SGAs, which has the highest risk of developing metabolic syndrome?

A

Clozapine Developing diabetes is guaranteed

80
Q

Expected side effects of a patient on high potency first generation antipsychotics:

A

EPS symptoms because DA is too low: akathisia (state of agitation, distress, and restlessness) dystonia (muscle spasm) parkansonianism

81
Q

What are parkinsonian symptoms?

A

Decrease in facial expressions. Difficulty starting and controlling movement. Loss or weakness of movement (paralysis) Soft voice. Stiffness of the trunk, arms, or legs. Tremor.

82
Q

Expected side effects of a patient on low potency first generation antipsychotics:

A

Less EPS symptoms (still more than SGAs) but also many other symptoms because interferes with other pathways Dry mouth blurred vision constipation Fatigue and increased appetite/weight Orthostasis (faint/dizzy)

83
Q

If question asks what antipsychotics cause agranular anemia and Clozapine is not listed as answer choice which antipsychotic should you choose?

A

Chose the 2nd generation antipsychotic - always more likely to inhibit bone marrow than 1st gens

84
Q

What are the D2 agonists?

A

Bromocriptine Pramipexole Ropinerole Apomorphine injections

85
Q

What is a D3 receptor agonist?

A

Aripiprazole

86
Q

What are the MAOi drugs used for depression?

A

Isocarboxazid, phenelzine, tranylcypromine, selegiline

87
Q

What is Rasagiline? What is it used for?

A

MAO-B inhibitor for Parkinson’s

88
Q

Which drugs inhibit COMT?

A

Entacapone- may cause nausea, fatigue side effects Tolcapone- liver failure too

89
Q

COMT inhibiting drugs should be used to treat parkinson’s disease or schizophrenia?

A

Parkinson’s

90
Q

Which class of drugs can cause Hyperthermia Muscle rigidity Vital sign instability Rhabdomyolysis

A

high potency first generation antipsychotics (D2 antagonists): Haloperidol Fluphenazine Thiothixine

91
Q

In addition to blocking D2 receptors, 2nd generation antipsychotics also block Serotonin 2a (5HT2a) receptors. The benefit is:

A

lessens risk of EPS symptoms (dystonia, irritability, restlessness, agitation, parkinsonianism)

92
Q

Which 2nd generation antipsychotic is actually a partial agonist at D2 and D3 receptors?

A

Aripiprazole

93
Q

Major side effect relating to 5HT2c antagonism?

A

Weight gain!

94
Q

Which drugs are synapse depleting drugs? What are they used for?

A

Reserpine - treats hypertension, it blocks VMAT so that vesicles with monoamines cannot be released into synapses Tetrabenazine - treats Huntington’s Chorea by inhibtiting VMAT

95
Q

What drug would be used to control drooling in a Parkinson disease patient?

A

Benztropine - anticholinergic

► Med Misc 10 (44 decks)

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