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Flashcards in Psych Drugs Deck (146):
1

Goals of ACUTE tx for schizophrenia

1. Relieve distressing psychotic symptoms
2. Induce remission
3. Minimize adverse effects

2

Goals of MAINTENANCE tx for schizophrenia

1. Prevent relapse
2. Prevent re-hospitalization
3. Improve quality of life

3

3 hypothesis of schizophrenia pathophysiology

1. Serotonin Hypothesis

2. Dopamine Hypothesis

3. Glutamate Hypothesis

4

For good antipsychotic therapy, you want ______% of the mesolimbic system blocked. Adverse effects rise when ____% of receptors are blocked.

60% = therapeutic

80% = Adverse effects

5

Which dopamine receptors (D1 or D2) do antipsychotic meds block?

D2

6

1st generation or typical antipsychotics we need to know for exam (4)

Name the others...

1. Chlorpromazine
2. Fluphenazine
3. Perphenazine
4. Haloperidol

Others:
--Thioridazine, Mesoridazine, Trifluoperazine, Thiothixine, Loxapine, Molindone, Pimozide

7

Typical antipsychotics block D2 receptors in these four Dopamine pathways...

1.) Mesolimbic

2.) Mesocortical

3.) Nigrostriatal

4.) Tubero-infundibular (Tubero-hypophyseal)

8

A low dose, high potency typical antispychotic includes _______, ________, and _______.

The side effects...

Haloperidol
Perphenazine
Fluphenazine

Greater potential for extrapyramidal side effects, hyperprolactinemia

9

A high dose, low potency typical antipsychotic includes ______.

The side effects...

Chlorpromazine

More likely to cause sedation, orthostatic hypotension, anticholinergic and antihistaminergic side effects

10

What is the advantage of an orally disintegrating tablet?

Pt's cannot "cheek" meds because they dissolve and still get into the system.

11

Of the 4 FGA (first generation antipsychotics) we must know, which come in an immediate acting IM dosage often used for psych emergencies.

Haloperidol
Chlorpromazine

12

Adverse effects: what are the antihistaminergic effects and anticholinergic effects of FGAs?

Antihistaminergic = sedation and wt gain

Anticholinergic = Dry mouth, urinary retention, tachycardia, erectile dysfunction, cognitive dysfunction

13

What is the black box warning on thiordazine and mesoridazine?

QT prolongation

14

What are the cardiovascular adverse effects of FGAs?

Orthostatic hypotension
Dizziness
QT prolongation (torsades)

15

What are the endocrinological adverse effects of FGAs?

Hyperprolactinemia
In levels > 60 mg/ml: amenorrhea, galactorrhea, gyneocmastia, anovulation, sexual dysfunction, osteoporosis

16

4 type of extrapyramidal side effects (EPSEs)?

1.) Acute Dystonia

2.) Akathisia

3.) Pseudoparkinsonism

4.) Tardive Dyskinesias

17

Tx w/ a pt taking a typical antipsychotic that develops contraction and arching of back, tongue protrusion, and jaw clenching

IM (or IV) anticholinergic
--> Benztropine mesylate or diphenhydramine (benadryl)

Benzo
--> Diazepam (valium) or Lorazepam (ativan) via slow IV push

Repeat if either does not provide relief in 15 min (IV) or 30 min (IM)

18

T/F: Acute dystonia usually occurs when pts have been taking their FGA medication for > 1 month.

FALSE

Rarely occurs beyond 1st month of therapy

19

What is the number one reason why pts stop taking antipsychotics

Akathisia

20

Tx's that can be done for pts on antipsychotics who present with restlessness and feelings/compulsion to move all the time

BB (Propranolol, Nadolol, Metoprolol)

21

4 cardinal symptoms of pseudoparkinsonism

1. Akinesia, bradykinesia, dec. motor activity

2. Resting tremor (pill-rolling)

3. Cogwheel rigidity

4. Postural abnormalities

22

Tx for pseudoparkinsonism assoc. w/ antipsychotic use

Anticholinergics (benztropine, Trihexphenidyl, Diphenhdramine) and symptoms should begin to solve w/i 3-4 days.

Min. of 2 week tx for full response

23

Alternative tx for pseudoparkinsonism in pts who cannot be put on a anticholinergic

Amantadine (Symmetrel) 100-400mg/day BID or QID

24

When should the Abnormal Involuntary Movement Scale (AIMS) be performed

every 6 months

25

After how long would one be taking an antipsychotic med that you would start to see tardive dyskinesia?

Occurs late in therapy...typically 1 year after start of agent

26

Risk factors for developing tardive dyskinesia

1. Inc. age
2. EPSEs
3. Poor antipsychotic response
4. Diabetes mellitus
5. Mood disorders
6. Female gender

27

A pt comes to you after being on a FGA for 1 and 1/2 years with abnormal involuntary movements that do not occur during sleep. How would you go about treating this?

Discontinue therapy and start on an atypical agent...Clozapine

28

Dopamine pathway functions v. Serotonin pathway functions

DA: Reward (motivation), Pleasure, euphoria, motor function, compulsion, perseveration

5-HT: Mood, memory, processing, sleep, cognition

29

A pt presents w/ mainly positive symptoms. Which atypical is better? First generation or second generation?

First generation

30

Dose Forms:
Why would an immediate-acting IM injection be used? What FGA come in this form?

Why would a long-acting depot formulation be used? What FGA come in this form?

For acute psychotic episodes...Haloperidol and Chlorpromazine

For non-compliant patient's...Haloperidol and fluphenazine

31

Largest risk factor for developing acute dystonia

Immediate-release IM administration of antipsychotic med!

Also, high-potency antipsychotic drugs (FGAs)

32

Number one reason why FGAs are not used very much anymore...it's what separates FGAs from SGAs

Tardive Dyskinesia

33

Monitoring parameters for all antipsychotic agents

1. EPSEs q6 months
2. Lipid panel, fasting glucose q6 months
3. Vital Signs multiple times daily during dose titration
4. Weight gain and waist circumference weekly

34

_______ is the active metabolite of risperidone

Paliperidone

35

Treatment goals for major depression disorder

1. Reduce symptoms
2. Remission
3. Prevent further episodes of depression
4. Evalulate for hospitalization: suicide risk, physical state of health, support system, presence of psychotic features

36

3 Tx Phases of MDD

1. Acute Phase (6-8 wks)
--Goal: Remission of symptoms

2. Continuation Phase (4-9 mos)
--Goal: Eliminate residual symptoms and prevent relapse

3. Maintenance Phase (12-36mos)
--Goal: prevent recurrence

37

What is the choice of agent based on for MDD since they ALL HAVE EQUAL EFFICACY AT COMPARABLE DOSES

--Pt's hx of response
--Pharmacogenetics (familial response)
--Subtype of depression
--Concurrent medical hx
--Potential for drug-drug interactions
--ADR
--Cost

38

_____% pts w/ varing types of depression improve w/ drug therapy

65-70%

39

How long does it take for symptoms to resolve after you start pharm tx?

2-4 weeks (can take longer than that too)

40

What is the black box warning that ALL antidepressents carry

Increased risk of suicidality in pts 18-24 yo during initial stages of tx

41

MOA of TCAs

Potentiate activity of NE and 5HT via reuptake blockade

Also block muscarinic, adrenergic, histamine receptors

42

Besides depression, what are other conditions TCAs can tx

--Enuresis
--Migraines
--Nausea w/ chemotherapy
--Neuralgia
--Urticaria
--OCD

43

Nortriptyline is the active metabolite of ______.

Amitriptyline

44

Desipramine is the active metabolite of _______.

Imipramine

45

TCA pharmacokinetics

high 1st pass metabolism in liver

highly protein bound

highly lipophilic

half life: 24hrs

46

Adverse effects of TCAs

Sexual dysfunction (75%)
Cardiac rhythm changes
Tachycardia
Orthostatic hypotension
Wt. gain
Sedation
Dec. seizure threshold
Narrow TI -- fatal in overdose (torsades)

47

Contraindications of TCAs

--Benign prostate hyperplasia
--Closed-angle glaucoma
--Cardiac disease
--Hepatic impairment
--Elderly patients

48

3 MAOIs

Phenelzine (Nardil)
Tranylcypromine (Parnate)
Selegiline transdermal patch (Emsam)

49

Dosing of Selegiline transdermal patch...why it is important

Comes in 6mg/24hrs, 9mg/24 hrs, and 12mg/24hrs

It is a selective MAO-B inhibitor at 6mg

Non-selective inhibitor at 9mg & 12mg

50

Mechanism of action of MAOIs

Blocks metabolism of NE, 5HT, and DA via inhibition of the MAO enzyme

51

Place in therapy: MAOIs

NOT 1ST LINE...Reserved for refractory pts

52

How long does it take to reach max MAO inhibition?

up to 14 days

53

Half life of MAOI?

1-4 hrs

54

The big adverse effects associated w/ MAOI

1.) HTN Crisis...occurs after eating tyramine containing foods (pizza, beer, red wine, cheese)

2.) Serotonin Syndrome...occurs w/ use of other antidepressents,narcotic analgesics, St. John's wort, linezolid (so MAOIs are monotherapy)

55

Which drug/dose form could you use if a pt refuses to go on a strict dietary restriction for thyramine?

Selegiline transdermal patch at 6mg/24 hrs

56

What drugs could cause a hypertensive crisis when used w/ MAOIs?

--Ephedrine
--Pseudoephedrine
--Phenylephrine

57

Give the brand name: Fluoxetine

Prozac

58

Give the brand name: Sertraline

Zoloft

59

Give the brand name: Paroxetine

Paxil

60

Give the brand name: Citalopram

Celexa

61

Give the brand name: Escitalopram

Lexapro

62

Give the brand name: Fluvoxamine

Luvox

63

Which SSRI is only FDA approved for OCD tx

Fluvoxamine (Luvox)

64

MOA of SSRIs

Serotonin is usually removed fro synapse by reuptake sites of PREsynaptic neurons. These are blocked by SSRIs allowing 5HT to remain active in synapses longer

NO EPI OR DA INVOLVEMENT

65

Pharmacokinetics of SSRIs

Most have 24 hr half lives
--> Fluoxetine's half life is 7 days

Hepatically metabolized

66

Compared to TCAs and MAOIs, is sedation and wt gain inc. or dec. in SSRIs?

Decreased

67

A patient who recently discontinued their SSRI medication comes in complaining of nightmares, crying spells, and poor concentration. What can this be attributed too and how do we prevent this?

Discontinuation Syndrome

Taper pts off SSRIs slowly over a period of 7-10 days

68

A pt has trouble falling asleep at night. Which SSRI is best recommended?

1. Sertraline (zoloft)
2. Fluoxetine (Prozac)
3. Paroxetine (Paxil)
4. Citalopram (Celexa)
5. Escitalopram (Lexapro)

Paroxetine (Paxil)

69

Describe the washout period for fluoxetine (Prozac)

5 wk washout after discontinuation before starting an MOAI

It's only a 2 wk washout for all other SSRIs!!

70

If a pt needs to be started on an SSRI but has many other co-morbidities (many medications including things like phenytoin and warfarin) what are the drug options?

Sertraline (Zoloft)
Citalopram (Celexa)
Escitalopram (Lexapro)

71

What are the 3 mixed 5-HT/NE reuptake inhibitors to treat MDD?

Venlafaxine (Effexor)
Duloxetine (Cymbalta)
Desvenlafazine (Pristiq)

72

Effexor

Venlafaxine

73

Cymbalta

Duloxetine

74

Pristiq

Desvenlafazine

75

Which type of dosing is used most often (and is considered a 1st line tx for MDD) of Venlafaxine?

Extended-release formulation (XR)

76

MOA of Venlafaxine

Mixed 5-HT/NE reuptake inhibitor

5HT > NE...3-5x greater when doses are < 200mg/day

Weak DA reuptake inhibitor

No significant affinity for adrenergic, muscarinic, or histaminergic receptors

77

Explain dosing of XR Venlafaxine

Start: 75mg/day
Titrate: up to 225mg/day in 75mg increments

Once daily dosing

78

A pt is prescribed 225mg of XR Venlafaxine. What side effects are expected?

>200mg/day --> Noradrenergic effects are more prominent relative to serotonergic activity --> dose dependent increase in diastolic BP

79

Do you need to worry about discontinuation syndrome and serotonin syndrome in Venlafaxine?

Yes.

80

What are the FDA indications for using duloxetine?

MDD
Diabetic Neuropathy
Fibromyalgia

81

Side effects of venlafaxine?

Same as venlafaxine but NO dose related increase in BP

82

MOA of Bupropion (Wellbutrin)

- DA reuptake inhibition (potent)

- Very low reuptake inhibition of NE

- No effect of reuptake of 5-HT

83

What is an important indication for use of Buproprion?

Smoking cessation!
--> Zyban (bupropion SR)

Usually adunct to seratonin agents

84

Which antidepressent is contraindicated if one wants to put a pt on buproprion?

MAOI

85

What is Nefazodone's black box warning and why we don't see it perscribed anymore?

It can cause life-threatening hepatic failure

86

What is Trazodone's usual place in therapy?

Sleep aid.

Used less for depression d/t its orthostatic hypotension, dizziness, and sedation effects but its immediate-release formulation is often used to help pts sleep

87

What is the MAO of Mirtazapine (Remeron)?

Selective presynaptic alpha2-receptor antagonist

This enhances NE transmission which increases serotonin firing

88

How does dosing effect the side effects of Mirtazapine (Remeron)

< 15mg/day = excessive sedation

> 15mg/day = Inc NE transmission which counteracts antihistaminergic-induced sedation

89

Is St. John's Wort FDA regulated?

No.

90

What drug interactions would you see if taking St. John's Wort?

St. John's Wort is a potent CYP3A4 inducer...therefore it will decrease levels of the following drugs
-HIV drugs
-Digoxin
-Oral contraceptives
-Warfarin

91

Can St. John's wort cause serotonin syndrome if used w/ other sertotonin agents?

YES!

92

How often are electroconvulsive therapy tx's?

6-12 treatments (2-3x/week)

93

A pt is breast feeding but needs to be on an antidepressent. What are your options? (2)

1. Sertraline

2. Paroxetine

94

Evaluating responses:
-Non-response
-Partial respone
-Partial Remission
-Remission

Non-response (50%): dec. in baseline sx

Remission: return to baseline fct

95

What is the proper length of time for a pt to be considered having an adequate trial of an antidepressant

6-8 weeks at a max dosage (up to 12 weeks in the elderly)

96

When is lifelong maintenance therapy indicated?

Pt's w/ high risk of recurrence (>2 previous episodes)

97

Depression that does not achieve remission after 2 optimal antidepressant trials is referred to as....

Resistant depression

98

What are your options in tx'ing resistant depresiion

1. Switch to another antidepressent

2. Augmentation w/ another antidepressant, lithium, T3, atypical antipsychotic, ECT, psychotherapy

99

Therapeutic uses of benzodiazepines

1. Treatment of anxiety
2. Muscle disorders
3. Seizures
4. Sleep disorders
5. Pre-anesthetics
6. Withdrawal from ETOH

100

What are two good benzodiazepines to use in the elderly population and in a pt w/ hepatic dysfunction?

1.) Lorazepam

2.) Oxazepam

101

BZD Adverse Effects

-Sedation (will build a tolerance in 2 weeks)
-Amnesia
-Impaired judgement
-Diminished motor skills (driving caution)
-Elderly more sensitive (give lower doses)
-Respiratory depression at high doses or low doses combined w/ ETOH

102

What happens if you abruptly discontinue a BZD?

Rebound anxiety, insomnia, seizures

103

Antidote for BZD overdose

Flumazenil

104

What is the 2nd line agent in GAD?

Buspirone

105

MOA Buspirone

Serotonin partial agonist

It has the anxiolytic effects w/o marked sedation...no anticonvulsant or muscle relaxing properties

NO cross-tolerance w/ alcohol or BZD

106

Antidepressants are considered the tx of choice for long-term management of anxiety. Which antidepressants?

Venlafaxine
Paroxetine
Sertraline

Other SSRIs

107

3 types of sleep disorders

1. Difficulty falling asleep (sleep latency)

2. Difficulty staying asleep (total sleep time)

3. Non-restorative sleep

108

Which tx has the best outcome when it comes to sleep disorders?

Sleep hygiene

109

4 Hypnotic Drugs

1. BZD
2. Barbiturates
3. Anti-histamines
4. Melatonin agonist

110

3 benzo's used to treat sleep disorders

1. Triazolam
2. Flurazepam
3. Temazepam

111

Which is the most common benzo used for sleep disorders? Why?

Temazepam...it has an intermediate half life which means it can help pts fall asleep as well as stay asleep.

112

Discuss the half lives of Triazolam, Flurazepam, and Temazepam

Triazolam: short 1/2 life (helps pts fall asleep)

Flurazepam: long 1/2 life (helps pts stay sleep)

Temazepam: intermediate 1/2 life

113

Zolpidem (Ambien), Zaleplon (Sonata), and Eszopiclone (Lunesta) are all _______.

Non-BDZ hypnotics

114

A new mother comes in complaining of frequent nighttime awakenings in which she has trouble falling back asleep after feeding her infant. What should you prescribe and advise?

Zaleplon
--Need at least 4 hours available for sleep after taking it

115

How to bzd effect REM sleep and non-REM sleep?

They decrease REM sleep and increase non-REM sleep (Stage 2)

116

What is the #1 sleep aid in the US?

Trazodone

117

What is the 1st line agent used for pts w/ insomnia that are prone to substance abuse?

Trazodone

118

_____ is a melatonin receptor agonist

Ramelteon

119

Can antihistamines such as benadryl be used as long term sleep aids?

NO! Tolerance develops after 3 days of continued use

120

MOA of Suvorexant

Orexin receptor antagonist

121

Describe the catecholamine hypothesis (one of the neurochemical theories of bipolar disorder

Mania related to excess NE and DA

Depression related to decreased NE, 5-HT, and DA

122

Describe the permissive theory/hypothesis (one of the neurochemical theories of bipolar disorder)

In both mania and depression there is an underlying decrease in serotonin w/ increased NE activity resulting in mania or decreased NE activity resulting in depression

123

FDA approves lithium in what?

Tx of acute mania and maintenance tx of BPI

124

MOA of Lithium (in a broad sense)

interacts w/ 5-HT, DA, GABA, Glutamate, NE

125

What is the therapeutic level of lithium that we aim for?

0.8 mEq/L

126

Each 300mg of Li+ results in approximately _____mEq/L

0.3

127

Pharmacokinetics of Lithium

Rapidly absorbed
Widely distributed
NO protein binding
Not metabolized
Excreted unchanged in the urine
Half life: 18-27 hrs

128

Adverse effects of lithium: early in therapy

GI distress (will eventually build a tolerance)
Polydipsia, polyuria, nocturia (70%)
Fine hand tremor (50%)
HA, memory impairments, confusion, poor concentration, impaired motor performance (40%)
Muscle weakness and lethargy (30%)

129

When are adverse effects of lithium most often seen?

At peak serum concentrations --> 1.2hrs post dose

130

Lithium adverse effects: later in therapy

1. Nephrogenic diabetes insipidus
2. Hypothyroidism
3. Cardiac effects
4. Benign reversible leukocytosis
5. Dermatologic effects
6. Wt. gain
7. Decreased libido, sexual dysfunction
8. Renal disease

131

When are plasma concentrations taken for lithium maintenance therapy?

8-12 hours after last dose

132

What should you be monitoring if a pt is on lithium therapy?

- Plasma concentration
- Renal fct
- Thyroid fct
- ECG (baseline, q6mos then yearly when on 1+yrs of lithium therapy)
- CBC
- Serum electrolytes
- Pregnancy test

133

A pt shows plasma concentrations of >2.0 mEq/L. What adverse effects would you expect to see at these plasma concentrations?

Seizures
Cardiac arrhythmias
Neurological impairment
Kidney damage
Coma
Death

134

How do you treat lithium toxicity?

Dialysis (hemodialysis)

135

Drugs that increase lithium levels (dec. lithium clearance)

Thiazide diuretics
NSAIDs
ACE inhibitors
Fluoxetine
Salt-restricted diets

136

Drugs that decrease lithium levels (inc. lithium clearance)

Caffeine
Theophylline

137

MOA of Valproic Acid

Increase GABA levels
Antikindling properties (may dec. rapid cycling and mixed states)

138

Valproic acid adverse effects

GI upset
Tremor
Mild thrombocytopenia
Somnolence
Dizziness
Wt. gain
Mild and transient inc. in LFTs
Rash
Alopecia

139

What can Valproic acid also be used to tx?

Seizures
Bipolar Disorder
Migraines

140

What is the therapeutic plasma concentration of VPA?

50-125 mcg/mL

141

A person who has levels _____ has Valprocic acid toxicity. What are the effects seen when this happens?

>200

Visual hallucinations
New onset tremor
Motor restlessness
Deep sleep
Coma

142

What are the monitoring parameters for VPA?

- Serum concentration
- CBC w/ differential
- Chemistry panel w/ electrolytes
- Liver function tests

143

What is carbamazepine's place in therapy?

NOT 1st LINE!!

More of a last line

144

Adverse effects of carbamazepine

CNS toxicity (60%)

GI

Hyponatremia (don't give w/ lithium)

Wt. gain

Agranulocytosis

Dermatologic reactions

145

Carbamazepine toxicity occurs at serum levels _____. These symptoms are:

> 15 mcg/mL

Ataxia
Choreiform movements
Diplopia
Nystagmus
Cardiac conduction changes
Seizures
Coma

146

Monitoring parameters of carbamazepine

1. Serum levels q1-2 weeks during first two months of therapy; then q3-6mos during maintenance

2. CBC w/ differential

3. Liver function tests

4. Serum electrolytes

5. Dermatologic monitoring