Pharmacotherapy V - Schizophrenia

Front 1

What are the 4 dopamine pathways and what symptoms are associated with each of these pathways?

Back 1

Mesolimbic - Positive symptoms
Mesocortical - Negative and cognitive symptoms
Nigrostriatal - EPS
Tuberofundibular - Hyperprolactinemia

Front 2

What is commonly used to prevent EPS in antipsychotic therapy?

Back 2

Benzatropine - IM if the patient cannot swallow

EPS symptoms - Acute dytonia, pseudoparkinsonism, akathesia

Front 3

Describe the High potency and Mild Potency typical anti-psychotics and their incidence of side effects.

Back 3

High Potency - Increased D2 Blockade, Increased incidence of EPS, Decreased MI antagonism
Fluphenazine
Thiothixene
Trifluperazine

Mild Potency - Decreased risk of EPS and anticholinergic side effects
Molindone
Loxapine
Perphenazine

Front 4

Drugs that cause dopamine blockade can cause extrapyramidyal symptoms like tardive dykinesia. Haloperidol is particularly potent in this effect.

Back 4

You can treat this adverse drug reaction by lowering the dose, d/c (could be irreversible), switch to an atypical
Use anticholinergics only when indicated and for the shortest time possible (may be a risk factor for tardive dyskinesia)

Front 5

Aripiprazole has the most mild side effect profile with only (+) sedation.

Ziprasidone is also mild with (+) prolactin elevation and (++) QTc prolongation

Quetiapine has (++) weight gain, glucose abnormalities, lipid abnormalities, sedation and hypotension

Back 5

Olanzapine has (+++) weight gain, glucose abnormalities, lipid abnormalities and (+) sedation, hypotension and anti-cholinergic side effects

Clozapine has the same side effects as Olanzapine but worse

Risperidone has many side effects

Front 6

Haloperidol, Perphenazine and Thioridazine are typical anti-psychotics and all cause varying degrees of EPS including tardive dyskinesia and prolactin elevation

Back 6

Olanzapine and Clozapine cause weight gain

Quietiapine is used for sleep. Doesn't do anything for psychosis at 50 mg (low doses) and is expensive. Need at least 200 mg doses to be effective.

Try aripiprazole first.

Front 7

It is important to know what to do if the patient experiences an initial increase in dyskinetic symptoms after conversion from a first generation anti-psychotic to a second generation anti-psychotic.

Back 7

This is withdrawal-emergent dyskinesia. The symptoms may look worse before they get better. Do not go back to the other agent.

Front 8

Patients on sustained FGA's without a dose decrease after the development of TD, the likelihood of reversibility diminshes and can become permanent!

Back 8

AKA - Get the patient off of the FGA or lower the dose immediately if they develop Tardive Dyskinesia!

Front 9

Why could Buproion (Wellbutrin) worsen positive symptoms of schizophrenia?

Back 9

Bupropion prevents reuptake of DA increasing DA stimulation. This has the opposite effect of what we're trying to accomplish in schizophrenia treatment. This isn't a contraindication however and conversely, Wellbutrin is preferred therapy in patients with shizophrenia who are undergoing smoking cessation.

Front 10

What is Haldol decanoate?

Back 10

The decanoate ester form of haldol. It has a markedly extended duration of effect. It comes in an IM injection.

Front 11

How would you convert a 20 mg Bid dose to haldol decanoate?

Back 11

20 bid = 40 mg qd
40 mg daily x 10-15 x po dose
40 x 10 = 400 mg every month
Max initial dose is 100 mg and the rest canb e given over 3-7 days
Continue PO dose for a month after first injection.

Front 12

Case #2

Back 12

Case #2

Front 13

From Dipiro's handbook: What agents are considered first choice treatment?

Back 13

Second generation anti-psychotics except clozapine (olanzapine, risperidine, quitiapine, ziprasidone and aripiprazole) These agents cause few or no EPS, little to no tardive dyskinesia and little effect on serum prolactin levels

Front 14

What should be considered in individuals where adherence is an issue?

Back 14

A long acting or depot injectable anti-psychotic (risperidone microspheres, haloperidol decanoate or fluphenazine decanoate)

Front 15

Anti-psychotics are highly lipophilic and highly protein bound. They all are metabolized via the CYP P450 pathway, except this drug.

Back 15

Ziprasidone

Front 16

Stage 1: SGA
Stage 2: Different SGA
Stage 3: Clozapine (Consider moving straight to clozapine is patient has a history of suicidality, violence, or substance abuse)

Back 16

Stage 4: Clozapine + SGA

Front 17

How would you initiate treatment?

Back 17

Titrate over the first few days to an average effective dose. After 1 week at a stable dose, a modest dosage increase may be considered. If there is no improvement in 3-4 weeks at therapeutic doses, then an alternative antipsychotic should be considered.

Front 18

If control of agitation is needed, what are your options.

Back 18

You can use an IM injection of the antipsychotic
You can also use Lorazepam 2 mg prn in combination with the maintenance anti-psychotic.

Front 19

What are your goals of therapy?

Back 19

Week 1 - Decrease agitation, hostility, anxiety and aggression and normalization of sleep and eating patterns

Week 2 - Improve socialization, self-care habits and mood.
Dose titration may occur every 1-2 weeks as tolerated.

Front 20

For how long should therapy be continued?

Back 20

For at least 12 months after remission of the first psychotic episode.

Continuous treatment is necessary in most patients at the lowest effective dose.

Front 21

How do you want to transition between anti-psychotics?

Back 21

The first agent should be tapered and discontinued over 1-2 weeks after the second anti-psychotic is
is initiated.

Front 22

Clozapine has shown superiority over other anti-psychotics in RCT's for the management of treatment-resistant schizophrenia. At what dose do you want to initiate Clozazpine?

Back 22

Try a 12.5 mg test dose to test for hypotension. If this is tolerated, try 25 mg at bedtime, then 25 mg bid after 3 days and then increased in 25 mg increments every 3 days until a dose of at least 300 mg is reached.

Front 23

What types of agents are used in augmentation therapy?

Back 23

Mood stabilizers (lithium, valproic acid, carbamazepine)
SSRI's
Beta Blockers

Front 24

Which drugs yield the most anti-cholinergic side effects?

Back 24

Clozapine and Olanzapine

Front 25

How can you treat dystonia?

Back 25

IM or IV formulations

Benzotropine 2 mg (anti-cholinergic)

Diazepam 5 mg (benzodiazepine)

Front 26

What is akathisia?
Which anti-psychotics have the lowest risk for this?
How is it treated?

Back 26

A state of inner restlessness

Propranolol appears to be effective
Diazepam is conflicting
Quetiapine and Clozapine appear to have the lowest risk for this.

Front 27

What is pseudoparkinsonism?

Back 27

4 Cardinal symptoms = akinesia or bradykinesia, tremor, rigidity, postural abnormalities

The first line strategy for patients with TD is to switch them to Clozapine, where there are no reports of TD.

You can also simply switch them to an SGA at the earliest signs of TD.

Front 28

What are 2 short term consequences and a long term consequence for men and women of high prolactin levels?

Back 28

Women - Amenorrhea, Loss of libido
Men - Impotence, Loss of libido

Long-term - Osteoporosis (women), Low bone density (men)

Front 29

Describe the prevalence of hyperprolactinemia amongst the atypical anti-psychotics.

Back 29

Risp > Olan = Zip = Quet = Cloz > Ari

Ari decreases prolactin levels

You can switch agents if this adverse reaction occurs, but if the patient is stable on the medication, consider just lowering the dose.
You could also add ari.P

Front 30

PORT schizophrenia guidelines: Clozapine should be offered to people who continue to experience persistent and clinically significant positive symptoms after 2 adequate trials of other anti-psychotic agents

Back 30

Should be considered for people who exhibit persistent suicidal thoughts or behaviors

Should be considered for people with persistent symptoms of hostility and/or display persistent violent behaviors

Front 31

Describe the DDI's associated with Clozapine. (4)

Back 31

Ciprofloxacin - Increases clozapine levels and side effects (monitor side effects)
Clonazepam - Respiratory depression (monitor for altered response)
Cigarette smoking - Decreased clozapine levels by 20-40% (monitor and increase dose if needed)
Carbamazepine (Increased risk of agranulocytosis - CONTRAINDICATION - Use Lamotrigine)

Front 32

What are some disease state interactions with Clozapine?

Back 32

DM II
HTN
Hyperlipidemia
Parkinson's Disease
Alcoholism

Front 33

Why would you avoid Wellbutrin in a patient taking Clozapine?

Back 33

Clozapine is most associated with lowering the seizure threshold and could be dangerous in combination
Alcohol is another risk factor for this

Front 34

Why would you avoid Chantix in a schizophrenic patient?

Back 34

Increased risk of worsening psychiatric illness

Front 35

What happens if a patient taking clozapine quits smoking?

Back 35

The hydrocarbons from cigarette smoking is a CYP 1A2 inducer of which clozapine is a substrate.
If the patient quit smoking, clozapine levels would therefore increase because the induction is no longer present.

Front 36

Which atypical antipsychotic has the most anti-cholinergic side effects?

Back 36

Clozapine

Front 37

If a patient has high TG levels, how would you counsel them while on clozapine?

Back 37

Alcohol consumption

Front 38

How do you want to monitor a patient on Clozapine?

Back 38

Baseline labs (WBC > 3,500 and ANC > 2,000)
First 6 months - weekly blood draws
6-12 months - Biweekly blood draws
> 12 months - Monthly blood draws thereafter

Front 39

What should you instruct a patient to do who has missed a dose for more than 48 hours?

Back 39

You must restart slowly. If you start too high of a dose too quickly, your blood pressure can drop, especially when you stand up.
Missing the occasional dose (no more than once a week) isn't usually a big problem.

Front 40

What is recommended first line for treatment of acute positive symptoms in people with first-episode schizophrenia?

Back 40

Anti-psychotics other than clozapine and olanzapine.

No significant short term differences between FG's and SG's. Difference only lies in ADR profiles.

Front 41

Why is Olanzapine not considered first line?

Back 41

Due to its association with significant metabolic risks and weight gain. Considered a second line agent.

Front 42

Why is Clozapine not considered a first line agent?

Back 42

It is the most efficacious, but

most dangerous - Most likely to cause anti-cholinergic effects, lower seizure threshold, orthostatic hypotension, weight gain, affect insulin and leptin levels, diabetes, obesity and dyslipidemia
Possible agranulocyotis and strict monitoring requirements
Compliance is key
Multiple drug interactions

Front 43

What is the advantage of using typical anti-psychotics versus atypicals?

Back 43

Cost

Front 44

What makes an atypical anti-psychotic atypical?

Back 44

Little to no EPS
Minimal increase in prolactin
Decrease in both (+) and (-) symptoms
5HT2A antagonism
Fast receptor dissociation from D2 receptors