Flashcards in Psych Drugs Deck (146):
Goals of ACUTE tx for schizophrenia
1. Relieve distressing psychotic symptoms
2. Induce remission
3. Minimize adverse effects
Goals of MAINTENANCE tx for schizophrenia
1. Prevent relapse
2. Prevent re-hospitalization
3. Improve quality of life
3 hypothesis of schizophrenia pathophysiology
1. Serotonin Hypothesis
2. Dopamine Hypothesis
3. Glutamate Hypothesis
For good antipsychotic therapy, you want ______% of the mesolimbic system blocked. Adverse effects rise when ____% of receptors are blocked.
60% = therapeutic
80% = Adverse effects
Which dopamine receptors (D1 or D2) do antipsychotic meds block?
1st generation or typical antipsychotics we need to know for exam (4)
Name the others...
--Thioridazine, Mesoridazine, Trifluoperazine, Thiothixine, Loxapine, Molindone, Pimozide
Typical antipsychotics block D2 receptors in these four Dopamine pathways...
4.) Tubero-infundibular (Tubero-hypophyseal)
A low dose, high potency typical antispychotic includes _______, ________, and _______.
The side effects...
Greater potential for extrapyramidal side effects, hyperprolactinemia
A high dose, low potency typical antipsychotic includes ______.
The side effects...
More likely to cause sedation, orthostatic hypotension, anticholinergic and antihistaminergic side effects
What is the advantage of an orally disintegrating tablet?
Pt's cannot "cheek" meds because they dissolve and still get into the system.
Of the 4 FGA (first generation antipsychotics) we must know, which come in an immediate acting IM dosage often used for psych emergencies.
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
What is the black box warning on thiordazine and mesoridazine?
What are the cardiovascular adverse effects of FGAs?
QT prolongation (torsades)
What are the endocrinological adverse effects of FGAs?
In levels > 60 mg/ml: amenorrhea, galactorrhea, gyneocmastia, anovulation, sexual dysfunction, osteoporosis
4 type of extrapyramidal side effects (EPSEs)?
1.) Acute Dystonia
4.) Tardive Dyskinesias
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)
--> Diazepam (valium) or Lorazepam (ativan) via slow IV push
Repeat if either does not provide relief in 15 min (IV) or 30 min (IM)
T/F: Acute dystonia usually occurs when pts have been taking their FGA medication for > 1 month.
Rarely occurs beyond 1st month of therapy
What is the number one reason why pts stop taking antipsychotics
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)
4 cardinal symptoms of pseudoparkinsonism
1. Akinesia, bradykinesia, dec. motor activity
2. Resting tremor (pill-rolling)
3. Cogwheel rigidity
4. Postural abnormalities
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
Alternative tx for pseudoparkinsonism in pts who cannot be put on a anticholinergic
Amantadine (Symmetrel) 100-400mg/day BID or QID
When should the Abnormal Involuntary Movement Scale (AIMS) be performed
every 6 months
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
Risk factors for developing tardive dyskinesia
1. Inc. age
3. Poor antipsychotic response
4. Diabetes mellitus
5. Mood disorders
6. Female gender
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
Dopamine pathway functions v. Serotonin pathway functions
DA: Reward (motivation), Pleasure, euphoria, motor function, compulsion, perseveration
5-HT: Mood, memory, processing, sleep, cognition
A pt presents w/ mainly positive symptoms. Which atypical is better? First generation or second generation?
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
Largest risk factor for developing acute dystonia
Immediate-release IM administration of antipsychotic med!
Also, high-potency antipsychotic drugs (FGAs)
Number one reason why FGAs are not used very much anymore...it's what separates FGAs from SGAs
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
_______ is the active metabolite of risperidone
Treatment goals for major depression disorder
1. Reduce symptoms
3. Prevent further episodes of depression
4. Evalulate for hospitalization: suicide risk, physical state of health, support system, presence of psychotic features
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
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
_____% pts w/ varing types of depression improve w/ drug therapy
How long does it take for symptoms to resolve after you start pharm tx?
2-4 weeks (can take longer than that too)
What is the black box warning that ALL antidepressents carry
Increased risk of suicidality in pts 18-24 yo during initial stages of tx
MOA of TCAs
Potentiate activity of NE and 5HT via reuptake blockade
Also block muscarinic, adrenergic, histamine receptors
Besides depression, what are other conditions TCAs can tx
--Nausea w/ chemotherapy
Nortriptyline is the active metabolite of ______.
Desipramine is the active metabolite of _______.
high 1st pass metabolism in liver
highly protein bound
half life: 24hrs
Adverse effects of TCAs
Sexual dysfunction (75%)
Cardiac rhythm changes
Dec. seizure threshold
Narrow TI -- fatal in overdose (torsades)
Contraindications of TCAs
--Benign prostate hyperplasia
Selegiline transdermal patch (Emsam)
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
Mechanism of action of MAOIs
Blocks metabolism of NE, 5HT, and DA via inhibition of the MAO enzyme
Place in therapy: MAOIs
NOT 1ST LINE...Reserved for refractory pts
How long does it take to reach max MAO inhibition?
up to 14 days
Half life of MAOI?
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)
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
What drugs could cause a hypertensive crisis when used w/ MAOIs?
Give the brand name: Fluoxetine
Give the brand name: Sertraline
Give the brand name: Paroxetine
Give the brand name: Citalopram
Give the brand name: Escitalopram
Give the brand name: Fluvoxamine
Which SSRI is only FDA approved for OCD tx
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
Pharmacokinetics of SSRIs
Most have 24 hr half lives
--> Fluoxetine's half life is 7 days
Compared to TCAs and MAOIs, is sedation and wt gain inc. or dec. in SSRIs?
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?
Taper pts off SSRIs slowly over a period of 7-10 days
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)
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!!
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?
What are the 3 mixed 5-HT/NE reuptake inhibitors to treat MDD?
Which type of dosing is used most often (and is considered a 1st line tx for MDD) of Venlafaxine?
Extended-release formulation (XR)
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
Explain dosing of XR Venlafaxine
Titrate: up to 225mg/day in 75mg increments
Once daily dosing
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
Do you need to worry about discontinuation syndrome and serotonin syndrome in Venlafaxine?
What are the FDA indications for using duloxetine?
Side effects of venlafaxine?
Same as venlafaxine but NO dose related increase in BP
MOA of Bupropion (Wellbutrin)
- DA reuptake inhibition (potent)
- Very low reuptake inhibition of NE
- No effect of reuptake of 5-HT
What is an important indication for use of Buproprion?
--> Zyban (bupropion SR)
Usually adunct to seratonin agents
Which antidepressent is contraindicated if one wants to put a pt on buproprion?
What is Nefazodone's black box warning and why we don't see it perscribed anymore?
It can cause life-threatening hepatic failure
What is Trazodone's usual place in therapy?
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
What is the MAO of Mirtazapine (Remeron)?
Selective presynaptic alpha2-receptor antagonist
This enhances NE transmission which increases serotonin firing
How does dosing effect the side effects of Mirtazapine (Remeron)
< 15mg/day = excessive sedation
> 15mg/day = Inc NE transmission which counteracts antihistaminergic-induced sedation
Is St. John's Wort FDA regulated?
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
Can St. John's wort cause serotonin syndrome if used w/ other sertotonin agents?
How often are electroconvulsive therapy tx's?
6-12 treatments (2-3x/week)
A pt is breast feeding but needs to be on an antidepressent. What are your options? (2)
Non-response (50%): dec. in baseline sx
Remission: return to baseline fct
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)
When is lifelong maintenance therapy indicated?
Pt's w/ high risk of recurrence (>2 previous episodes)
Depression that does not achieve remission after 2 optimal antidepressant trials is referred to as....
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
Therapeutic uses of benzodiazepines
1. Treatment of anxiety
2. Muscle disorders
4. Sleep disorders
6. Withdrawal from ETOH
What are two good benzodiazepines to use in the elderly population and in a pt w/ hepatic dysfunction?
BZD Adverse Effects
-Sedation (will build a tolerance in 2 weeks)
-Diminished motor skills (driving caution)
-Elderly more sensitive (give lower doses)
-Respiratory depression at high doses or low doses combined w/ ETOH
What happens if you abruptly discontinue a BZD?
Rebound anxiety, insomnia, seizures
Antidote for BZD overdose
What is the 2nd line agent in GAD?
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
Antidepressants are considered the tx of choice for long-term management of anxiety. Which antidepressants?
3 types of sleep disorders
1. Difficulty falling asleep (sleep latency)
2. Difficulty staying asleep (total sleep time)
3. Non-restorative sleep
Which tx has the best outcome when it comes to sleep disorders?
4 Hypnotic Drugs
4. Melatonin agonist
3 benzo's used to treat sleep disorders
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.
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
Zolpidem (Ambien), Zaleplon (Sonata), and Eszopiclone (Lunesta) are all _______.
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?
--Need at least 4 hours available for sleep after taking it
How to bzd effect REM sleep and non-REM sleep?
They decrease REM sleep and increase non-REM sleep (Stage 2)
What is the #1 sleep aid in the US?
What is the 1st line agent used for pts w/ insomnia that are prone to substance abuse?
_____ is a melatonin receptor agonist
Can antihistamines such as benadryl be used as long term sleep aids?
NO! Tolerance develops after 3 days of continued use
MOA of Suvorexant
Orexin receptor antagonist
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
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
FDA approves lithium in what?
Tx of acute mania and maintenance tx of BPI
MOA of Lithium (in a broad sense)
interacts w/ 5-HT, DA, GABA, Glutamate, NE
What is the therapeutic level of lithium that we aim for?
Each 300mg of Li+ results in approximately _____mEq/L
Pharmacokinetics of Lithium
NO protein binding
Excreted unchanged in the urine
Half life: 18-27 hrs
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%)
When are adverse effects of lithium most often seen?
At peak serum concentrations --> 1.2hrs post dose
Lithium adverse effects: later in therapy
1. Nephrogenic diabetes insipidus
3. Cardiac effects
4. Benign reversible leukocytosis
5. Dermatologic effects
6. Wt. gain
7. Decreased libido, sexual dysfunction
8. Renal disease
When are plasma concentrations taken for lithium maintenance therapy?
8-12 hours after last dose
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)
- Serum electrolytes
- Pregnancy test
A pt shows plasma concentrations of >2.0 mEq/L. What adverse effects would you expect to see at these plasma concentrations?
How do you treat lithium toxicity?
Drugs that increase lithium levels (dec. lithium clearance)
Drugs that decrease lithium levels (inc. lithium clearance)
MOA of Valproic Acid
Increase GABA levels
Antikindling properties (may dec. rapid cycling and mixed states)
Valproic acid adverse effects
Mild and transient inc. in LFTs
What can Valproic acid also be used to tx?
What is the therapeutic plasma concentration of VPA?
A person who has levels _____ has Valprocic acid toxicity. What are the effects seen when this happens?
New onset tremor
What are the monitoring parameters for VPA?
- Serum concentration
- CBC w/ differential
- Chemistry panel w/ electrolytes
- Liver function tests
What is carbamazepine's place in therapy?
NOT 1st LINE!!
More of a last line
Adverse effects of carbamazepine
CNS toxicity (60%)
Hyponatremia (don't give w/ lithium)
Carbamazepine toxicity occurs at serum levels _____. These symptoms are:
> 15 mcg/mL
Cardiac conduction changes