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Psychiatric Drug Classes > Pharmacology Specifics – Monoamine Oxidase Inhibitors (MAOIs) > Flashcards

Pharmacology Specifics – Monoamine Oxidase Inhibitors (MAOIs) Flashcards

1
Q

What are the 2 FDA approved indications for monoamine oxidase inhibitors?

A

Depression
Especially atypical and refractory depressions

Parkinson disease
Selegiline – oral form

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2
Q

What drug class do monoamine oxidase inhibitors belong to?

A

Antidepressant

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3
Q

What are the 4 non-FDA approved uses for monoamine oxidase inhibitors?

A

Anxiety disorders (phenelzine); i.e., Social anxiety disorder, panic disorder

Alzheimer’s disease (selegiline)

Bulimia nervosa (phenelzine)

PTSD (phenelzine)

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4
Q

What enzymes do monoamine oxidase inhibitors inhibit?

This results in increased levels of which three neurotransmitters?

A

Monoamine oxidase A and B

This results in increased levels of dopamine, serotonin and norepinephrine

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5
Q

What type of MAO inhibitors are phenelzine, selegiline, and tranylcypromine?

A

They are irreversible MAO inhibitors

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6
Q

How long does it take the body to replenish MAO?

A

2 weeks

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7
Q

What should be kept in mind when switching from an MAOI to another antidepressant?

A

It takes approximately two weeks for the body to replenish MAO, therefore there should be a two-week washout period I n order to decrease the risk of toxicity (serotonin syndrome and hypertensive crisis) from drug-drug interactions

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8
Q

What should a clinician do when a patient needs to switch from another antidepressant agent to an MAOI?

A

There should be an appropriate washout period (app. 5 half-lives) when switching from another antidepressant to a monoamine oxidase inhibitor; for most antidepressant agents this is approximately 2 weeks

Fluoxetine and Vortioxetine require a washout period of 5 and 3 weeks, respectively

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9
Q

What specific enzyme does selegiline inhibit at low oral doses? What is it used for the treatment of at low doses?

A

MAO-B

Parkinson disease

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10
Q

At higher doses, how does selegiline impact MAO?

What is it used for the treatment of at higher doses?

A

At higher doses, it is a nonselective MAO inhibitor

It is used for the treatment of depression at higher doses

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11
Q

Via transdermal administration, what is the advantage of selegiline? What does it inhibit?

A

Transdermal administration allows selegiline to avoid first pass metabolism

Selegiline inhibits MAO-A and MAO-B in the CNS selectively and does not affect the MAO activity in the G.I. tract

As a result, adherence to a strict tyramine-restricted diet is not necessarily, specifically with the 6 mg patch

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12
Q

Should patients be instructed to follow a tyramine-restricted diet with the 9 mg and 12 mg patch doses?

A

Yes; due to the lack of supporting evidence of not following such a diet

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13
Q

Nardil

A

Phenelzine

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14
Q

Parnate

A

Tranylcypromine

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15
Q

Emsam

A

Selegiline

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16
Q

Who manufactures Nardil?

A

Pfizer & multiple generic manufacturers

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17
Q

What route and form is Nardil administered in?

A

PO; tablet

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18
Q

What is the recommended daily dose range of Nardil?

A

15-90 mg daily

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19
Q

Who manufactures Parnate?

A

COVIS and multiple generic manufacturers

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20
Q

Similar to Nardil, what route and form is Parnate administered in?

A

PO; tablet

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21
Q

Who manufactures Emsam?

A

Mylan

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22
Q

What is the route and form of administration for Emsam?

A

Transdermal; patch

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23
Q

What is the recommended daily dosage of Parnate?

A

10-60 mg per day

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24
Q

What is the recommended daily dosage of Emsam?

A

6-12 mg per day

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25
Q

Which monoamine oxidase inhibitor is available as a 15 mg tablet only?

A

Nardil

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26
Q

Which monoamine oxidase inhibitor is only available as a 10 mg tablet?

A

Parnate

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27
Q

Emsam, the transdermal patch, is available in which three doses?

A

6 mg, 9 mg, and 12 mg

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28
Q

Which of the monoamine oxidase inhibitor is the cheapest?

A

Nardil

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29
Q

What is the recommended starting dose for Nardil in an adult patient? How much should it be safely increased per day? What’s the maximum recommended daily dose?

A

7.5-15 mg twice per day

It can be increased by 15 mg per day weekly

Maximum daily dose is 90 mg

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30
Q

What’s the maximum recommended daily dose of Nardil?

A

90 mg

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31
Q

What is the starting dose for the Emsam transdermal patch? How much is the dose safely increased? At what interval?

A

The starting dose is 6 mg per day (24 hours)

Increase by 3 mg per day at 2-week intervals

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32
Q

What is the maximum recommended daily dose of Emsam?

A

12 mg per day

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33
Q

What is the recommended starting dose for Parnate? How much should it be increased per day and at what interval?

A

The starting dose is 10 mg, 2x per day

It should be increased by 10 mg per day at 2-3 week intervals

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34
Q

What is the recommended maximum daily dose of Parnate?

A

60 mg per day

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35
Q

Generally speaking, how should monoamine oxidase inhibitors be managed in geriatric patients?

A

Start at the lowest dose, and titrate slowly, while assessing for side effects, such as orthostatic hypotension and potential drug-drug interactions

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36
Q

How should phenelzine be used in geriatric patients with regard to starting dose, increasing dose, and maximum dose?

A

Starting dose = 7.5 mg total daily

Increase by 7.5 mg per day weekly

Maximum dose = 60 mg per day

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37
Q

What’s the maximum dose of the selegiline transdermal patch used in geriatric patients?

A

Maximum dose of 6 mg per day (24 hours)

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38
Q

How should tranylcypromine be managed in geriatric patients, in other words, is a dose adjustment necessary?

A

No dose adjustment is needed, but start at the lowest dose, and increase gradually

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39
Q

Generally speaking, monoamine oxidase inhibitors should be avoided in which two specific types of patients?

A

They should be avoided in patients with hepatic and/or renal impairment due to the risk of reduced clearance, elevated levels and increased incidence of side effects

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40
Q

Which two specific monoamine oxidase inhibitors are contraindicated in patients with severe renal impairment?

A

Phenelzine (Nardil) and tranylcypromine (Parnate)

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41
Q

With regard to use during pregnancy, what category are monoamine oxidase inhibitors?

A

Category C

42
Q

Has the safety of monoamine oxidase inhibitors during pregnancy been established?

A

No

43
Q

Monoamine oxidase inhibitors are generally not recommended during pregnancy for what two reasons?

A

Due to the risk of hypertensive crisis and the need for dietary restrictions

44
Q

What is the recommendation for breast-feeding while using monoamine oxidase inhibitors?

A

When possible, avoid use. There’s little information about monoamine oxidase inhibitors and breast-feeding but we do know that it can pass into breastmilk.

45
Q

What does the black box warning for monoamine oxidase inhibitor use in pediatric populations state?

A

Not recommended for use in the pediatric population

46
Q

Since monoamine oxidase inhibitors nonselectively inhibit monoamine oxidase, what medications should be coadministered with caution?

A

Medications that can further increase norepinephrine, dopamine and serotonin

47
Q

What may happen if noradrenergic agents are used in conjunction with monoamine oxidase inhibitors?

A

Hypertensive crisis

48
Q

What may happen if serotonergic agents are used in conjunction with monoamine oxidase inhibitors?

A

Serotonin syndrome

49
Q

Monoamine oxidase is naturally found in many organs. What are two examples? Therefore, what does nonselective inhibition of monoamine oxidase mean?

A

The liver and intestines; it means that nonselective inhibition of monoamine oxidase can result in various side effects

50
Q

Monoamine oxidase inhibitors block the metabolism of which amino acid? Which neurotransmitter is released? What may result?

A

Tyramine; it increases norepinephrine release; hypertensive crisis may result

51
Q

What kind of diet is necessary for someone on a monoamine oxidase inhibitor?

A

A restricted diet that is low in tyramine

52
Q

What are two common side effects during early monoamine oxidase inhibitor treatment initiation?

A

Headache and insomnia

53
Q

There is a high incidence of which cardiovascular side effect with the use of monoamine oxidase inhibitors, why?

A

Orthostatic hypotension

Due to an accumulation of Octopamine which occupies alpha or beta adrenergic receptors and blocks sympathetic activity

54
Q

What two things should be monitored routinely in patients taking monoamine oxidase inhibitors?

A

Heart rate and blood pressure

55
Q

What other side effect may occur with monoamine oxidase inhibitor use?

A

Moderate weight gain may occur

56
Q

What are the common side effects associated with phenelzine, Selegiline, and tranylcypromine use?

A

Orthostatic hypotension, weight gain, G.I. symptoms, xerostomia, transaminitis, headache, dizziness, sedation, weakness, sexual dysfunction

57
Q

What’s the difference (With regard to side effect) between the activity of tranylcypromine in comparison to phenelzine selegiline?

A

Tranylcypromine can be more activating

Therefore, patients may report restlessness, anxiousness, insomnia and other adverse effects of stimulation

58
Q

What are two occasional side effects associated with the use of phenelzine?

A

Worsening of depression and hypertensive crisis (with certain foods)

59
Q

What are two occasional side effects associated with the use of the selegiline transdermal patch?

A

Decreased systolic pressure and hypertensive crisis (with certain foods)

60
Q

What is an occasional side effect associated with the use of tranylcypromine in patients with depression?

A

Worsening of depression

61
Q

What are 6 adverse drug reaction with the use of phenelzine?

A

Leukopenia, liver necrosis, edema of glottis, seizure, suicidal ideation and behavior

62
Q

What are 3 rare adverse drug reaction with the use of selegiline (transdermal patch)?

A

Suicidal ideation and behavior, atrial fibrillation

63
Q

What are 7 rare adverse drug reactions associated with the use of tranylcypromine?

A

Agranulocytosis, anemia, leukopenia, thrombocytopenia, hepatitis, suicidal ideation and behavior

64
Q

Under normal circumstances, MAO-A inactivates which neurotransmitter when ingested?

A

Tyramine

65
Q

Monoamine oxidase blocks the degradation of tyramine resulting in elevated systemic levels of this neurotransmitter. Subsequently, the release of which neurotransmitter is increased? What may be the potential result of this?

A

Norepinephrine; hypertensive crisis (also known as “cheese reaction”

66
Q

What type of diet should patients receiving monoamine oxidase inhibitor therapy be placed on? How long after discontinuation of the drug should the diet be maintained?

A

Tyramine-Restricted diet

Diet should be maintained for two weeks after monoamine oxidase inhibitor discontinuation

67
Q

What type of restricted diet should patients using the 6 mg selegiline transdermal patch be placed on?

A

This is the exception!

These patients do not need to adhere to a tyramine-restricted diet

68
Q

What beverages should be avoided in patients using monoamine oxidase inhibitors?

A

Tap beer; Chianti wine

69
Q

In general, what types of food should be avoided in patients taking monoamine oxidase inhibitors?

A

Avoid aged, smoked, fermented and pickled foods

70
Q

What type of breads and cereals should be avoided in patients using monoamine oxidase inhibitors?

A

Cheese bread and crackers

71
Q

What types of dairy products should be avoided while using monoamine oxidase inhibitors?

A

Cheeses (aged cheese, American, Camembert, cheddar, Gouda, Gruyere, Parmesan, provolone, Romano, Roquefort, Stilton)

72
Q

What meat/fish/poultry should be avoided in patients taking monoamine oxidase inhibitors?

A

Aged chicken and beef liver; dried and pickled fish; shrimp paste; summer or dry sausage; dried meats (i.e. salami, cacciatore); meat extracts; liverwurst; caviar

73
Q

What type of starches should be avoided in patients taking monoamine oxidase inhibitors?

A

Soybean; tofu

74
Q

What types of vegetables should be avoided in patients using monoamine oxidase inhibitors?

A

Sauerkraut; fava bean pods (not beans); kimchi

75
Q

What type of fruit should be avoided in patients taking monoamine oxidase inhibitors?

A

Overripe avocado; overripe fruit; canned figs

76
Q

What type of soups should be avoided in patients taking monoamine oxidase inhibitors?

A

Soup which contain aged cheese, flavor cubes or meat extract, fava bean pods (not beans); or miso soup

77
Q

Should soy sauce and marmite be avoided in patients using monoamine oxidase inhibitors?

A

Yes

78
Q

What about the consumption of chocolate and monoamine oxidase inhibitors?

A

It should be used in moderation

79
Q

What type of medications may interact with monoamine oxidase inhibitors and cause hypertensive crisis?

A

Stimulants (amphetamines, methylphenidate)

Decongestants (phenylephrine, pseudoephedrine), levodopa, and bupropion

It can cause hypertension, headache, stiff neck, nausea, vomiting, sweating

80
Q

Which medications can cause serotonin syndrome when used in conjunction with monoamine oxidase inhibitors?

A

Antidepressants (SSRIs, SNRIs, TCAs, buspirone, St. John’s wort)

Tramadol, meperidine, dextromethorphan, and ecstasy (MDMA)

Can cause confusion, restlessness, sweating, hyperthermia, autonomic instability, tremor, clonus, Muscle rigidity, incoordination

81
Q

How is phenelzine absorbed?

A

Rapidly and well

82
Q

What percentage of bioavailability does selegiline (transdermal patch) provide?

A

75%

83
Q

How is tranylcypromine absorbed?

A

It’s absorbed rapidly, individual absorption variation

84
Q

What organ metabolizes phenelzine, Selegiline, and tranylcypromine?

A

The liver

Selegiline (CYP2B6, CYP3A4, CYP2C9)

Tranylcypromine (CYP2A6, CYP2C19, CYP2D6)

85
Q

What organ is responsible for excreting the monoamine oxidase inhibitors?

A

The kidney

Tranylcypromine is mostly excreted via urine and some by feces

86
Q

While data is not available for the protein binding of phenelzine tranylcypromine, what percentage of selegiline (transdermal patch) is bound to protein?

A

90%

87
Q

True or false: the half-life of monoamine oxidase inhibitors is related to the duration MAO activation (two weeks)

A

False

88
Q

What is the half-life of Tranylcypromine?

A

1.5-3.5 hours

89
Q

What is the half-life of phenelzine?

A

11.6 hours

90
Q

What is the half-life of selegiline (transdermal patch)?

A

18-25 hours

91
Q

While the distribution of phenelzine is not known due to data not being available, what is the distribution for tranylcypromine and selegiline?

A

Selegiline (transdermal patch): 1854 L

Tranylcypromine: 3.09 L per kilogram

92
Q

What type of patients are monoamine oxidase inhibitors reserved for? Why?

A

Patients that have had poor responses to multiple other antidepressants

Due to relatively poor tolerability, necessity of dietary restrictions and potentially fatal drug interactions

93
Q

How far in advance of an elective surgery should monoamine oxidase inhibitors be discontinued? Why?

A

10 days

To decrease the risk of developing significant hypertension with co-administration of adrenergic agents (ie, epinephrine, norepinephrine, phenylephrine, ephedrine, etc.)

94
Q

Selegiline may cause false positives for what type for the urine detection of what type of drugs? Why?

A

Amphetamine/methamphetamine

This is because its metabolites include amphetamine and methamphetamine

95
Q

Which part of the selegiline transdermal patch should be avoided?

A

Avoid touching the sticky side of the patch; if this occurs, wash hands with soap and water

96
Q

How should the selegiline transdermal patch be rotated?

A

Upper torso, upper thigh or outer surface of upper arm

97
Q

What type of temperature exposure should be avoided with use of the transdermal patch?

A

Avoid heat exposure to the application site (i.e. heating pad, hot tub, etc.), which may increase absorption

98
Q

Can the selegiline transdermal patch be worn during routine activities such as bathing, and swimming? What happens if it falls off?

A

Yes; if the patch falls off, replace with a new patch and continue routine schedule

99
Q

True or false: one should avoid cutting the selegiline transdermal patch.

A

True

100
Q

Before what type of procedure should the selegiline transdermal patch be removed? Why?

A

Prior to an MRI

It may contain metal

101
Q

Can a selegiline transdermal patch be used in patients with a latex allergy?

A

Yes

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