Psych Drugs Flashcards
1
Q
Goals of ACUTE tx for schizophrenia
A
- Relieve distressing psychotic symptoms
- Induce remission
- Minimize adverse effects
2
Q
Goals of MAINTENANCE tx for schizophrenia
A
- Prevent relapse
- Prevent re-hospitalization
- Improve quality of life
3
Q
3 hypothesis of schizophrenia pathophysiology
A
- Serotonin Hypothesis
- Dopamine Hypothesis
- Glutamate Hypothesis
4
Q
For good antipsychotic therapy, you want ______% of the mesolimbic system blocked. Adverse effects rise when ____% of receptors are blocked.
A
60% = therapeutic
80% = Adverse effects
5
Q
Which dopamine receptors (D1 or D2) do antipsychotic meds block?
A
D2
6
Q
1st generation or typical antipsychotics we need to know for exam (4)
Name the others…
A
- Chlorpromazine
- Fluphenazine
- Perphenazine
- Haloperidol
Others:
–Thioridazine, Mesoridazine, Trifluoperazine, Thiothixine, Loxapine, Molindone, Pimozide
7
Q
Typical antipsychotics block D2 receptors in these four Dopamine pathways…
A
- ) Mesolimbic
- ) Mesocortical
- ) Nigrostriatal
- ) Tubero-infundibular (Tubero-hypophyseal)
8
Q
A low dose, high potency typical antispychotic includes _______, ________, and _______.
The side effects…
A
Haloperidol
Perphenazine
Fluphenazine
Greater potential for extrapyramidal side effects, hyperprolactinemia
9
Q
A high dose, low potency typical antipsychotic includes ______.
The side effects…
A
Chlorpromazine
More likely to cause sedation, orthostatic hypotension, anticholinergic and antihistaminergic side effects
10
Q
What is the advantage of an orally disintegrating tablet?
A
Pt’s cannot “cheek” meds because they dissolve and still get into the system.
11
Q
Of the 4 FGA (first generation antipsychotics) we must know, which come in an immediate acting IM dosage often used for psych emergencies.
A
Haloperidol
Chlorpromazine
12
Q
Adverse effects: what are the antihistaminergic effects and anticholinergic effects of FGAs?
A
Antihistaminergic = sedation and wt gain
Anticholinergic = Dry mouth, urinary retention, tachycardia, erectile dysfunction, cognitive dysfunction
13
Q
What is the black box warning on thiordazine and mesoridazine?
A
QT prolongation
14
Q
What are the cardiovascular adverse effects of FGAs?
A
Orthostatic hypotension Dizziness QT prolongation (torsades)
15
Q
What are the endocrinological adverse effects of FGAs?
A
Hyperprolactinemia
In levels > 60 mg/ml: amenorrhea, galactorrhea, gyneocmastia, anovulation, sexual dysfunction, osteoporosis
16
Q
4 type of extrapyramidal side effects (EPSEs)?
A
- ) Acute Dystonia
- ) Akathisia
- ) Pseudoparkinsonism
- ) Tardive Dyskinesias
17
Q
Tx w/ a pt taking a typical antipsychotic that develops contraction and arching of back, tongue protrusion, and jaw clenching
A
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
Q
T/F: Acute dystonia usually occurs when pts have been taking their FGA medication for > 1 month.
A
FALSE
Rarely occurs beyond 1st month of therapy
19
Q
What is the number one reason why pts stop taking antipsychotics
A
Akathisia
20
Q
Tx’s that can be done for pts on antipsychotics who present with restlessness and feelings/compulsion to move all the time
A
BB (Propranolol, Nadolol, Metoprolol)
21
Q
4 cardinal symptoms of pseudoparkinsonism
A
- Akinesia, bradykinesia, dec. motor activity
- Resting tremor (pill-rolling)
- Cogwheel rigidity
- Postural abnormalities
22
Q
Tx for pseudoparkinsonism assoc. w/ antipsychotic use
A
Anticholinergics (benztropine, Trihexphenidyl, Diphenhdramine) and symptoms should begin to solve w/i 3-4 days.
Min. of 2 week tx for full response
23
Q
Alternative tx for pseudoparkinsonism in pts who cannot be put on a anticholinergic
A
Amantadine (Symmetrel) 100-400mg/day BID or QID
24
Q
When should the Abnormal Involuntary Movement Scale (AIMS) be performed
A
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
