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PRITE > Pharmacology PRITE Review (JB PPT) Part 1 > Flashcards

Pharmacology PRITE Review (JB PPT) Part 1 Flashcards

1
Q

What is the first pass effect?

A

Phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation

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2
Q

How does Phase 1 metabolism occur? Phase 2?

A

Phase 1 - CYP450 enzymes (i.e., via oxidation)

Phase 2 - Glucuronidation

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3
Q

What is the difference between a pharmacodynamic vs. pharmacokinetic interaction?

A

Dynamic - alteration due to changes in drug binding to a receptor site

Kinetic - alteration due to changes in absorption, distribution, metabolism, or excretion

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4
Q

Important considerations of drug metabolism in the elderly?

A
  • Elderly patients have a decreased GFR
  • Decreased liver Phase 1 oxidation (CYP enzymes)
  • Absorption is UNCHANGED
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5
Q

Important considerations of drug metabolism in newborns?

A
  • Drug absorption and transportation is equivalent to adults at approximately 4 months old
  • GFR and CYP enzymes in children are equivalent to adults at approximately 1 year old
  • Immediately after birth, babies have a lower GFR than adults, but it increases rapidly
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6
Q

Important considerations of drug metabolism in pregnant women?

A
  • Increased GFR and renal blood flow rate

- Increased blood volume and cardiac output (by 30-50%)

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7
Q

List key landmark drug trials in psychiatry.

A
  1. CATIE trial
  2. STAR*D trial
  3. COMBINE trial
  4. 1999 Multimodal Treatment Study of kids of ADHD
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8
Q

Medications involved in CATIE trial + key finding?

A

Olanzapine, perphenazine, quetiapine, risperidone, ziprasidone

Olanzapine was more effective at reducing agitation, hostility, aggression

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9
Q

Key findings of STAR*D trial?

A
  • Depression study
  • Only about 1/3 of patients remit with first antidepressant
  • Typical placebo response is also ~30%
  • Bupropion augmentation is more effective and better tolerated than buspirone
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10
Q

Key findings of COMBINE trial?

A

Any combination of therapies including CBI, naltrexone, or both performed better than any combination that did not include these interventions.

Acamprosate fared poorly compared to various combinations of naltrexone/CBI.

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11
Q

Key finding of 1999 Multimodal Treatment Study of kids with ADHD?

A

Medication alone = medication + psychosocial interventions.

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12
Q

List FDA-approved medications for the treatment of MDD (MAOIs - 4).

A
  1. Isocarboxazid
  2. Phenelzine
  3. Selegiline (MAO-B selective)
  4. Tranylcypromine
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13
Q

List FDA-approved medications for the treatment of MDD (TCAs - 7).

A
  1. Amitriptyline
  2. Clomipramine
  3. Desipramine
  4. Doxepin
  5. Imipramine
  6. Nortriptyline
  7. Trimipramine
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14
Q

List FDA-approved medications for the treatment of MDD (TeCAs - tetracyclic antidepressants - 3).

A
  1. Amoxapine
  2. Maprotiline
  3. Mirtazapine
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15
Q

List FDA-approved medications for the treatment of MDD (NDRI - norepinephrine-dopamine reuptake inhibitors - 1).

A
  1. Bupropion
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16
Q

List FDA-approved medications for the treatment of MDD (SSRIs - 6).

A
  1. Citalopram
  2. Escitalopram
  3. Fluoxetine
  4. Fluvoxamine
  5. Paroxetine
  6. Sertraline
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17
Q

List FDA-approved medications for the treatment of MDD (SNRIs - 4).

A
  1. Desvenlafaxine
  2. Duloxetine
  3. Levomilnacipran
  4. Venlafaxine
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18
Q

List FDA-approved medications for the treatment of MDD (SRI/SRMs - serotonin reuptake inhibitors/modulators).

A
  1. Nefazodone
  2. Trazodone
  3. Vilazodone
  4. Vortioxetine
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19
Q

Augmentation options for the treatment of depression (6)?

A
  1. Bupropion
  2. Atypical antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone)
  3. Buspirone
  4. Lithium
  5. Liothyronine (T3)
  6. Mirtazapine
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20
Q

MDD with atypical features?

A

A. Mood reactivity (mood brightens in response to positive events)
B. 2 or more of the following:
1. Hypersomnia
2. Increased appetite/weight gain
3. Leaden paralysis (heavy feeling in arms and legs)
4. Interpersonal rejection sensitivity (persistent lifelong trait that may be exacerbated during periods of depression; characterized by sensitivity to rejection and/or criticism)

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21
Q

Key treatment of atypical depression?

A

MAOI

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22
Q

MDD with melancholic features?

A

A. One of the following is present during the most severe period of the current episode:

  1. Loss of pleasure in all, or almost all, activities
  2. Lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens)

B. 3+ of the following:

  1. Distinct quality of depressed mood characterized by profound despondency, despair, and/or moroseness or by so-called empty mood
  2. Depression worse in the morning
  3. Early-morning awakening (at least 2 hours before usual)
  4. Marked PMA/PMR
  5. Significant anorexia or weight loss
  6. Excessive or inappropriate guilt
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23
Q

List the selective MAOIs.

A

MAO-A: clorgiline and moclobedmie

MAO-B: selegiline (at low doses)

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24
Q

List the non-selective MAOIs.

A

Isocarboxazid, phenelzine, selegiline (at high doses), tranylcypromine

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25
List the reversible MAOIs.
Moclobemide
26
List the irreversible MAOIs.
Clorgiline, isocarboxazid, phenelzine, selegiline, tranylcypromine
27
How do dietary restrictions vary for MAO-A vs. MAO-B?
MAO-A - must follow diet; MAO-A is found in the gut and uses tyramine as a substitute MAO-B - no dietary restrictions needed (unless taking at very high doses)
28
What is the purpose of the dietary restriction when taking MAOIs?
Tyramine-induced hypertensive crisis
29
Substrates of MAO-As?
Serotonin Norepinephrine Dopamine Tyramine
30
Substrates of MAO-Bs?
Dopamine | Phenylethylamine
31
Tissue localization of MAO-As?
``` Brain Gut Liver Placenta Skin ```
32
Tissue localization of MAO-Bs?
Brain Platelets Lymphocytes
33
Formulations of selegiline?
Oral | Transdermal patch
34
How is moclobemide unique compared to other MAOI-A's?
Fewer tyramine dietary restrictions
35
Treatment of MAOI hypertensive crisis?
Phentolamine Calcium channel blockers (e.g., nifedipine) Nitroprusside Nitroglycerin
36
MAOIs increase risk of ___ when taken with certain other medications.
Serotonin syndrome
37
Treatment options for anxiety?
1. SSRI 2. SNRI 3. Buspirone 4. Mirtazapine 5. Propranolol 6. Gabapentin
38
MOA - buspirone?
5-HT1A agonist
39
MOA - gabapentin?
Indirectly acts as a GABA agonist by modulating voltage-gated calcium channels (VGCC)
40
FDA-approved medications for anxiety (antihistamine)?
Hydroxyzine (non-specific anxiety)
41
Adverse effects of antihistamines like hydroxyzine?
Dizziness Dry mouth Headache Sedation
42
FDA-approved medications for anxiety (benzodiazepines)?
1. Alprazolam (non-specific; panic disorder) 2. Chlordiazepoxide (non-specific) 3. Clonazepam (panic disorder) 4. Diazepam (non-specific) 5. Lorazepam (non-specific) 6. Oxazepam (non-specific)
43
Adverse effects of benzodiazepines?
Appetite change Cognitive problems Fatigue Somnolence
44
FDA-approved medications for anxiety (SSRIs)?
1. Escitalopram (GAD) 2. Fluoxetine (panic disorder) 3. Fluvoxamine (social anxiety disorder) 4. Paroxetine (GAD, panic disorder, PTSD, social anxiety disorder) 5. Sertraline (panic disorder, PTSD, social anxiety disorder)
45
FDA-approved medications for anxiety (SNRIs)?
1. Duloxetine (GAD) | 2. Venlafaxine (GAD, panic disorder, social anxiety disorder)
46
Adverse effects of SSRIs/SNRIs?
Diarrhea, headache, HTN, insomnia, nausea, sexual dysfunction, somnolence
47
What is buspirone approved for and what adverse effects can it cause?
Non-specific anxiety Dizziness, headache, nausea
48
Which LAIs are FDA-approved for bipolar maintenance in addition to schizophrenia?
1. Abilify Maintena | 2. Risperdal Consta
49
List the two first generation LAIs.
1. Prolixin decanoate (fluphenazine) | 2. Haldol decanoate
50
List the 8 second generation LAIs.
1. Abilify Maintena (aripiprazole monohydrate) 2. Aristada (aripiprazole lauroxil) 3. Aristada Initio (aripiprazole lauroxil) 4. Invega Sustenna (paliperidone palmitate) 5. Invega Trinza (12-week) 6. Risperdal Consta 7. Perseris (risperidone subcutaneous) 8. Zyprexa Relprevv (olanzapine)
51
List the LAIs that require PO overlap.
1. Prolixin decanoate 2. Abilify Maintena 3. Aristada (unless giving Aristada Initio IM + 1 PO dose 4. Risperdal Consta
52
List the medications FDA-approved for acute bipolar depression.
1. Olanzapine/fluoxetine (Symbyax) 2. Quetiapine + quetiapine XR 3. Lurasidone
53
List the medications FDA-approved for acute bipolar mania.
1. Lithium 2. Chlorpromazine 3. Divalproex + ER 4. Olanzapine 5. Risperidone 6. Quetiapine + XR 7. Ziprasidone 8. Aripiprazole 9. Carbamazepine ER 10. Asenapine
54
List the medications FDA-approved for bipolar maintenance.
1. Lithium 2. Lamotrigine 3. Olanzapine 4. Aripiprazole 5. Quetiapine + XR 6. Risperidone LAI 7. Ziprasidone
55
Which mood stabilizer is NOT FDA-approved for bipolar maintenance?
Depakote
56
Which medication should NOT be used fo treatment of acute mania?
Lamotrigine
57
What is the best treatment for acute mania?
(Lithium or Depakote) + antipsychotic
58
Preferred treatment for rapid cycling?
Depakote
59
Preferred treatment for mixed episodes?
Depakote
60
Lab work-up for patients who develop rapid cycling must include what and why?
TSH; new onset rapid cycling bipolar is associated with hypothyroidism
61
Recommended dosing of Depakote?
Weigh-based - 15-20 mg/kg/day
62
Treatment options for OCD?
1. Clomipramine (TCA; only FDA-approved TCA for OCD) 2. Fluvoxamine (SSRI, only approved for OCD) 3. Other SSRIs
63
Treatment options for PTSD?
1. FDA-approved - paroxetine and sertraline | 2. Off-label - prazosin
64
Medications approved for treatment of MDD in pediatrics?
Fluoxetine, escitalopram, sertraline, fluvoxamine, clomipramine
65
Medications approved for treatment of OCD in pediatrics?
Fluoxetine, escitalopram
66
Medications approved for treatment of GAD in pediatrics?
Duloxetine
67
First-line treatments of ADHD?
Methylphenidate and amphetamine
68
Alternative treatments for ADHD?
Alpha-2-agonists: clonidine (Kapvay), guanfacine (Intuniv) Atomoxetine (Strattera; SNRI) Bupropion (Wellbutrin; NDRI)
69
DSM-5 definition of tics?
Sudden, rapid, recurrent, non-rhythmic motor movement or vocalization
70
DSM-5 definition of Tourette's Disorder?
A. Both multiple motor and one or more vocal tics present at some time during the illness, although not necessarily concurrently. B. Tics may wax and wane in frequency but have persisted for >1 year since first tic onset C. Onset before age 18
71
DDx for Tourette's
Persistent (chronic) motor or vocal tic disorder
72
Commonly used medications for treatment of Tourette Syndrome?
Alpha-agonists: clonidine, gunafacine Antipsychotics: haloperidol, fluphenazine, pimozide, risperidone Dopamine depleter: tetrabenazine
73
FDA-approved treatment of Tourette's
Haloperidol | Pimozide
74
Medications used to treat anorexia/bulimia?
Mirtazapine Fluoxetine Olanzapine + fluoxetine Cyproheptadine (appetite stimulant)
75
Medications used to treat binge-eating?
Lisdexamfetamine (Vyvanse) Topiramate Sibutramine (appetite suppressant)
76
FDA-approved medications to treat anorexia?
None
77
FDA-approved medications to treat bulemia?
Fluoxetine
78
FDA-approved medications to treat binge-eating?
Lisdexamfetamine (Vyvanse)
79
Treatment for narcolepsy?
No single treatment - medications are used to target symptoms
80
List 4 common features of narcolepsy.
1. Excessive daytime sleepiness 2. Cataplexy 3. Sleep paralysis 4. Hyponagogic/hypnopompic hallucinations
81
What is the best diagnostic marker of narcolepsy?
Cataplexy (sudden episode of bilateral muscle weakness triggered by the onset of strong emotions) - examples include buckling/unlocking of knees, head or jaw dropping, facial muscle flickering, sagging of jaw/weakness in arms, garbled speech/voice
82
Treatment options for excessive daytime sleepiness in narcolepsy?
1. Modafinil, armodafinil 2. Methylphenidate, dextroamphetamine, amphetamine-dextroamphetamine 3. Sodium oxybate
83
Treatment options for cataplexy in narcolepsy?
Venlafaxine Fluoxetine Clomipramine Sodium oxybate
84
Which narcolepsy treatment can target both daytime sleepiness and cataplexy?
Sodium oxybate (GHB)
85
Medications FDA-approved for treatment of autism or ID?
None
86
Medications FDA-approved for pediatric irritability/aggression in autism?
Risperidone | Aripiprazole
87
Off-label medication classes used for patients with ASD and/or ID?
1. SGAs (targeting irritability, aggression, self-injury, severe tantrums) 2. Alpha-2 agonists (inattention, hyperactivity) 3. Stimulants (inattention, hyperactivity) 4. SSRIs (anxiety-related symptoms) 5. Anti-epileptics (irritability, repetitive behaviors)
88
FDA-approved treatment for dementia?
1. Donepezil - MILD TO SEVERE 2. Galantamine - MILD TO MODERATE 3. Rivastigmine - MILD TO MODERATE 4. Memantine - MODERATE TO SEVERE memory impairment
89
MOA of donepezil/galantamine/rivastigmine?
Cholinesterase inhibitor
90
MOA of memantine
NMDA receptor agonist
91
Medications to treat symptoms of Parkinson's disease?
1. Dopamine precursors (levodopa) 2. Dopamine agonists (pramipexole, ropinirole, bromocriptine, pergolide, cabergoline) 3. COMT inhibitors (entacapone, tolcapone) 4. MAO-B inhibitors (selegiline, rasagiline) 5. Anticholinergics (benzotropine, trihexyphenidyl) 6. Other - amantadine
92
MOA carbidopa/levodopa?
Levodopa - converted in the brain to dopamine | Carbidopa - prevents levodopa from being converted into dopamine in the peripheral circulation
93
Compare pros and cons of Carbidopa/levodopa compared to direct dopamine agonists.
L-Dopa: significantly improves mobility; does not slow disease progression, increased doses needed to maintain efficacy Dopamine agonists: less motor fluctuations than L-Dopa; does not slow disease progression, not as effective, causes daytime sleepiness, hallucinations, impulsivity
94
Pros/cons of anticholinergics (benztropine, trihexyphenidyl) in Parkinson's?
+ helpful to relieve tremor and may ease dystonia - side effects (blurred vision, dry mouth, constipation, urinary retention, hallucinations)
95
MOA of MAO-B inhibitors and COMT inhibitors in Parkinson's?
Prolongs the effect of L-dopa by blocking its metabolism
96
Pros/cons of MAO-B and COMT inhibitors in Parkinson's?
Mao-B: may have mild antidepressant effect; small benefit, multiple interactions COMT: improves mobility, may lead to increased L-Dopa side effects
97
FDA-approved medication for treatment of Psychosis in Parkinson's? Typical correct answer for treatment of psychosis in Parkinson's (not FDA-approved)
Pimavanserin Quetiapine and clozapine
98
Why are quetiapine and clozapine the best options for treatment of psychosis in Parkinson's?
D2 antagonism worsens motor features of Parkinson's Quetiapine and clozapine ahve very low affinity for D2
99
MOA - pimavanserin?
Atypical antipsychotic | Antagonist/inverse agonist at 5-HT2A and 5-HT2C (to a lesser extent)
100
Classes of medications used to treat insomnia?
1. Antidepressants (mirtazapine, trazodone, doxepin --> FDA-approved) 2. Anti-histamines (hydroxyzine, diphenhydramine) 3. Melatonin (OTC melatonin supplements; ramelteon) 4. Orexin receptor antagonists (suvorexant) 5. Z drugs (Zaleplon, zolpidem, eszopiclone) 6. Benzodiazepines (temazepam)
101
Similarities and differences of Z-drugs and benzos?
Not structurally related, but similar MOA - both allosterically modulate GABA-A receptors, binding occurs in nearby areas of the alpha subunit Z-drugs do not significantly alter sleep architecture like benzodiazepines, better safety profile (less respiratory depression)
102
What condition should be ruled out as a potential etiology of RLS?
Iron deficiency anemia
103
Treatment of RLS?
Dopamine agonists (ropinirole, pramipexole, rotigotine patch are FDA-approved; pergolide, though not FDA-approved) Gabapentin enacarbil
104
Rx premature ejaculation
SSRIs in high doses (paroxetine on PRITE)
105
First-step in treating TD?
Switch from FGA to an SGA with lower D2 affinity (clozapine, quetiapine)
106
Medications used to treat TD?
FDA-approved: valbenazine, deutetrabenazine Not FDA-approved: tetrabenazine
107
Indications for tetrabenazine?
Huntington's Tourette's Hemibalism TD
108
Treatment of ALS + MOA?
Riluzole (glutamate antagonist
109
St. John's wart (aka hypericum perforatum) is sometimes used for depression - it increases risk for what adverse event?
Serotonin syndrome
110
What is valerian root used for?
Sleep (hypnotic)
111
Risk asociated with ginko biloba?
Bleeding
112
Pain indication for the following TCAs: 1. Amitriptyline 2. Desipramine 3. Doxepin 4. Nortriptyline
1. Amitriptyline - chronic pain 2. Desipramine - post-herpetic neuralgia 3. Doxepin - limited data for LBP 4. Nortriptyline - post-herpetic neuralgia (All off-label)
113
Contraindications to TCA use
Concurrent use/use within 2 weeks of MAOIs, MI (acute recovery period), glaucoma (doxepin), tendency for urinary retention (doxepin); caution in elderly due to risk for postural hypotension; sedating
114
Pain indication for the following SNRIs: 1. Duloxetine 2. Milnacipran 3. Venlafaxine
1. Duloxetine - chronic MSK; neuropathic; fibromyalgia 2. Milnacipran - fibromyalgia 3. Venlafaxine - GAD, mDD, panic disorders, SAD
115
___ are generally not the preferred antidepressants for neuropathic pain but may be useful for ___.
SSRIs; fibromyalgia
116
Pain indication for the following SSRIs: 1. Fluoxetine 2. Paroxetine
Neuropathic pain (off-label for both)
117
FDA-approved indication (pain management) for the following anticonvulsants: 1. Carbamazepine 2. Gabapentin 3. Pregabalin 4. Topiramate 5. Depakote
1. Carbamazepine - trigeminal neuralgia 2. Gabapentin - Post-herpetic neuralgia 3. Pregabalin - Post-herpetic neuralgia, diabetic neuropathy, fibomyalgia, polyneuropathy 4. Topiramate - migraine prophylaxis 5. Depakote - migraine prophylaxis
118
MOA - SSRI
Selectively inhibits the reuptake of 5-HT at the presynaptic neuronal membrane
119
MOA - SNRI
Inhibits reuptake of both serotonin and norepinephrine at the pre-synaptic membrane; also weakly inhibits dopamine reuptake
120
MOA - NDRI (example)
Norepinephrine and Dopamine Reuptake Inhibitor; Bupropion; inhibits reuptake of both norepinephrine and dopamine at the pre-synaptic membrane
121
MOA - SARI (examples)
Serotonin Antagonist and Reuptake Inhibitor; trazodone and nefazodone; antagonist at the serotonin receptor; also inhibits the reuptake of serotonin as well as NE and/or dopamine
122
MOA - NaSSA (example)
Noradrenergic and Specific Serotonergic Antidepressant (Mirtazapine); antagonist at the alpha-2-adrenergic receptor fo the presynaptic membrane causes increased release of NE. Also antagonizes certain serotonin receptors.
123
MOA - TCA
Inhibits reuptake of both 5HT and NE at the presynaptic membrane
124
MOA - MAOI
Inhibits activity of monoamine oxidase, which prevents degradation of serotonin, norepinephrine, and dopamine
125
SSRI with the longest half-life?
Fluoxetine
126
SSRI with the shortest half-life?
Fluvoxamine (NOT PAXIL)
127
Antidepressant (all categories) with shortest half-life?
Trazodone
128
Antidepressants that have active metabolites that extend their duration of action?
Sertraline | Fluoxetine
129
Mirtazapine MOA?
Antagonist at alpha-2-adrenergic, 5HT2A-2C, H1
130
Which antidepressant is not serotonergic?
Bupropion
131
Uses for bupropion?
``` Smoking cessation Weight loss ADHD "Treat" antidepressant-related sexual dysfunction (switch or add) Adjunctive depression treatment ```
132
MOA - buspirone?
5HT-1A pre-synaptic (full agonist) 5HT-1A post-synaptic (partial agonist, especially hippocampus and cortex) D2, D3, D4 (antagonist) A1-adrenergic (agonist)
133
MOA of vortioxetine?
Antagonist: 5HT3A, 5HT7, 5HT1D, beta-1 receptor Agonist: 5HT1A Partial agonist: 5HT1B
134
MOA of vilazodone?
SSRI and 5HT1A partial agonist
135
MOA of L-minacepran?
SNRI in extended-release formulation
136
MOA of mifepristone?
Glucocorticoid receptor antagonist Progesterone antagonist Studied as an adjunct to antidepressants in psychotic depression
137
Discuss nortriptyline's curvilinear dose curve.
Can sometimes see improvement in depression symptoms by decreasing the dose; can have a plateau or decline effect at higher plasma concentrations
138
Impact of bupropion on REM sleep
Increases
139
MOA - gabapentin?
Inhibits calcium channels, specifically acting at the alpha-2-delta subunit of voltage-dependent calcium channels; mimics GABA but does not bind GABA receptors
140
MOA - baclofen?
GABA-B agonist
141
MOA - benzodiazepines?
GABA-A modulator/agonist
142
MOA - barbitureates?
GABA-A agonist (can open the GABA-A channel in the absence of GABA)
143
MOA - Z-drugs?
GABA- A modulator/agonist
144
MOA - EtOH
GABA-A agonist
145
MOA - flumazenil?
GABA-A receptor antagonist
146
Compare the MOA of benzos vs. barbiturates.
Bind to GABA-A receptor at different allosteric sites Facilitate GABA action - Barbiturates increase duration of opening of chloride channel - Benzodiazepines increase frequency of opening of chloride channel Membrane hyperpolarization CNS depression
147
Liver-safe benzodiazepiens + why?
Lorazepam, Oxazepam, Temazepam Metabolized via liver glucuronidation (instead of CYP), don't generate active metabolites
148
What is the most rapidly orally absorbed benzo?
Diazepam
149
Diazepam is metabolized to what three metabolites?
Nordiazepam Temazepam Oxazepam

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