Wq Pharm - Anti-Psychotics And Mood Stabilizers

Front 1

What are the phenothiazines we NTK (3)?

What else?

Back 1

chlorpromazine
thioridazine
fluphenazine

thioxanthene (starring as himself in his own drug class)

Front 2

What is the butyrophenone we NTK?

Mood stabilizers (3)?

Back 2

haloperidol

lithium, divalproex, topiramate

Front 3

What are the New Gen atypical anti-psychotics we NTK (6)?

[ACOQRZ]

Back 3

apriprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone

Front 4

Schizo Epidemiology

Onset:
Cause:
Commonality:

Back 4

late teen/early adult
genetic
Common. 1 in 100.

Front 5

What are the cognitive impairment sxs of schizo (3)?

How do they respond to tx?

Back 5

easily distracted -
impaired short term memory -
disorganized, interrupted thought/speech

Poorly

Front 6

What are the 'positive' sxs of schizo (3)?

What causes them?

How do they respond to tx?

Back 6

exaggeration of normal fcns - halluc/delusions - bizarre acts/thoughts

Inc DA activity in limbic sys

Controlled by classic antipsychotics

Front 7

What are the 'negative' sxs of schizo (3)?

How do they respond to tx?

Back 7

Loss of normal fcn - lack of affect/volition/pleasure - antisocial

Respond well to New Gen anti-psychotics

Front 8

What is the main NT resp for schizo?

What are the 3 sites of action for Schizo mechs?

Back 8

DA increase

Nigrostriatal, meso-limbic/meso-cortical, pituitary projections

Front 9

Nigrostriatal sys mech of Schizo

Projects from?
Controls (2)?
Decrease in activity causes (2)?

Back 9

From substantia nigra to caudate putamen

Controls posture & voluntary mvmts

Natural onset = Parkinsons
Drug- induced = Extrapyramidal sxs

Front 10

Meso-limbic/meso-cortical mech of Schizo

Projects from:
Assoc with (2):
Imbalance causes:

Back 10

ventral mesencephalon to limbic sys & neocortex

assoc with higher mental fcn & emotions

imbalance = psychosis

Front 11

Which system is the site of action of most anti-psychotics?

Back 11

The meso-limbic/meso-cortical sys.

Front 12

Pituitary projections in Schizo

How involved?
Action?

Back 12

Some DA neurons project to the mammotrophic cells in the anterior pituitary

Decrease the rls of prolactin

Front 13

What pharmaceutical evidence supports the hypothesis that excessive DA causes Schizo (2)?

Back 13

Drugs that increase DA cause psychosis.

Anti-psychotics work by blocking DA recs.

Front 14

What radiological evidence supports the hypoth that excessive DA causes Schizo?

Back 14

PET scans clearly show increased DA recs in treated and untreated schizos.

Front 15

What anatomical evidence supports the hypoth that excessive DA causes Schizo?

Back 15

Untreated schizos have inc DA recs on autopsy.

DARPP - 32 is a protein regulated by DA recs and is decreased in the prefrontal cortex of schizos

Front 16

What is another mech that is implicated in Schizo?

Back 16

The decreased fcn of glutamate pathways.

Front 17

NMDA rec antagonists have also been implicated in Schizo, what is the mech?

What alleviates bipolar sxs via this mech?

Back 17

Dec NMDA activity leads to dec GABA rls and induces schizo & bipolar sxs

anticonvulsants

Front 18

What is an example of a serotonin stimulator that can cause Schizo sxs?

Back 18

LSD

Front 19

How do the classic anti-psychotics work?

What Schizo sxs are they best for?

Back 19

They block the D2 recs

'Positive' sxs. Little impact on 'negative' sxs.

Front 20

How did phenothiazines come about as an anti-psychotic?

Are phenothiazines classic or New Gen antipsychotics?

Back 20

Were searching for a new histamine & noticed chlorpromazine produced calmness & sedation.

Classic

Front 21

How do the New Gen antipsychotics work?

What Schizo sxs are they best for?

Back 21

They block 5HT2A recs.

'Negative' sxs

Front 22

What recs do both new and classic antipsychotics block that cause most of the side effects (3)?

Back 22

Muscarinic, alpha, and histamine recs.

Front 23

Where are the two locations that classic antipsychotics block DA recs?

Back 23

D2 recs in limbic sys and DA recs in the chemoreceptor trigger zone.

Front 24

Blocked D2 recs

Decreases:

Causes? Different from?

Back 24

Schizo sxs: fear/halluc.

sedation/neuroleptic effect. Different from sedatives/hypnotics.

Front 25

Blocked D2 recs

In autistics (2)?

For vomiting?

What DOESN'T happen?

Back 25

Autistic pts become more responsive & communicative

anti-emetic

It does NOT increase intellectual capacity

Front 26

How safe are the classical antipsychotics?

What are the three main side effects that cause pt non-compliance?

Back 26

Considered safe with a high tx index

sedation, restlessness, ANS sxs

Front 27

What is tardive dyskinesia?

When does it occur in relation to Schizo?

What is the tx (2)?

Back 27

Uncontrollable mvmts of face, trunk, extremities

In 15-25% of ppl tx with classic antipsychotics.

D/C drug and any anticholinergics

Front 28

Which to antipsychotics are LESS likely to cause tardive dyskinesia?

Back 28

clozapine & olanzapine

Front 29

Extrapyramidal effects

Mech?

Sxs (6)?

Back 29

D2 recs in nigrostriatal sys are blocked

Motor control: anxiety, pacing, rocking/akathisia, sustained abnormal postures/dystonia, invol spasms, parkinsons sxs

Front 30

Extrapyramidal effects

Tx?

Which drugs are most likely to cause extrapyramidal ANS sxs (2)?

Back 30

Admin of anticholinergics restore balance to striatal cholinergic & DA activity

thioridazine & fluphenazine

Front 31

Which drug class is less likely to cause extrapyramidal effects?

Why (2)?

Back 31

New Gen atypical antipsychotics

They bind to 5HT2A & D4 recs, and have less affinity for D2 recs

Front 32

Endocrine effects of antipsychotics

Hypothalamus (2):

Prolactin:

Back 32

DA rec blocks in hypothalamus suppress appetite & dereg body temp

increased prolactin

Front 33

Endocrine effects of antipsychotics

Sex hormones in women (2):

In men (3):

Back 33

decreased, causing infertility and dec libido

gynecomastia, infertility, dec libido

Front 34

How does increased prolactin impact pts taking classic antipsychotics (2)?

Back 34

Normally, DA rec activation inhibits prolactin rls. When it's blocked, it causes hyperprolactinemia:

Amenorrhea, lactation

Front 35

Autonomic side effects of classic antipsychotics

Blockade of M, alpha, & hist recs cause:

Specifically, alpha block causes (2):

Histamine blockage causes:

Back 35

Typical M & alpha-block sxs.

orthostatic hypotension & trouble ejaculating

sedation

Front 36

How do seizures tend to occur during tx with antipsychotics?

Use cautiously in (2):

Most common with which 3 classics?

Back 36

They slow the frequency of EEG, cause hypersynchrony.

epileptics and pts withdrawing from CNS depressants

clozapine, olanzipine, & chlorpromazine

Front 37

What is neuroleptic malignant syndrome & sxs (4)?

Tx (3):

Back 37

A life threatening condition causing mm rigidity, catatonia, hyperpyrexia, and changes in BP & HR

MM relaxants (dantrolene) or diazepam & DA agonists (bromocriptine)

Front 38

Chlorpromazine

Drug class:

Consequences at high potency (3):

Low potency:

Back 38

Phenothiazine - prototype

Fewer ANS sxs but more risk for tardive dyskinesia & extrapyramidal sxs

Opposite

Front 39

Chlorpromazine

Administration (2):

Dose:

Back 39

Oral: well abs. IM inj avoids FPM and acts in 30 mins.

Plasma concentration varies, so dose must be individualized

Front 40

Chlorpromazine

t1/2:

Metab (2):

Back 40

24-48 hrs

liver. slow.

Front 41

Chlorpromazine

Uses (6):

Which ones are best tx for emesis (2)?

Back 41

Tx of schizo, N/V, pre-anesthetic, premature ejac, relief from pruritis, tx of psychotic episodes in W/D pts.

prochlorperazine & compazine

Front 42

Main anticholinergic side effects of phenothiazines (3):

Main alpha-block side effects of phenothiazines (2)?

Back 42

blurry vision, retention, dec GI motility

postural hypotension, inhib of ejaculation

Front 43

Main CV side effects of phenothiazines (4):

Back 43

Negative inotropic action (like quinidine): prolonged QT & PR, blunted T-waves, ST depression

Front 44

Serious side effects of phenothiazines (4)?

Back 44

Extrapyramidal sxs, endocrine sxs, tardive dyskinesia, neuroleptic malignant syndrome much like classic antipsychotics

Front 45

Misc side effects of phenothiazines (3):

Back 45

Mild jaundice in 2-4th wk of tx
Decreased seizure threshold
retinal deposits (thioridazine)

Front 46

Clozapine

Drug Class:

Best for:

Why?

Back 46

NG atypical antipsychotic

'negative' sxs of schizo

Greater meso-cortical & limbic system specificity

Front 47

Clozapine

Unlikely to cause (3):

Huge drawback:

Back 47

Extrapyramidal sxs, tardive dyskinesia, or hyperprolactinemia

Very expensive due to required weekly blood monitoring for agranulocytosis

Front 48

Clozapine

Uses (3):

Back 48

Tx schizo, delusions & psychosis in Parkinson's, reserved for pts who don't respond to classics or have bad side effects from classics

Front 49

Clozapine

Worst side effect:

Others (2):

Back 49

Poss agranulocytosis

Same as classic antipsychotics - secondary to M, alpha, & H rec blockages.

Front 50

Clozapine

Main mech:

Also binds:

Prefers ___ recs over ___ recs:

Back 50

Blocks D4 recs in limbit system & cerebral cortex instead of striatum.

5HT2A recs, M, H & alpha recs

D4 over D2 recs

Front 51

Clozapine

PHK (2):

Back 51

Oral: well abs
Liver metab

Front 52

Olanzapine

Drug class:

Similar to:

Main difference:

Why?

Back 52

NG atypical antipsychotics

Clozapine

Improves BOTH 'positive' and 'negative' sxs

Higher affinity for 5HT2A recs

Front 53

Olanzapine

Uses (2):

PHK (2):

Back 53

Same as clozapine, plus tx of bipolar

t1/2: long, so QID is okay
Liver metab

Front 54

Olanzapine

Side effects (5):

Does NOT cause:

Back 54

Similar to clozapine, plus sedation OR akathisia, hyperglycemia, constipation, activates anticholinergics

agranulocytosis, like clozapine

Front 55

Olanzapine

Why caution in DM pts?

Back 55

Hyperglycemia is a side effect

Front 56

Risperidone

Drug class:

First line drug for:

Treats both:

Back 56

NG atypical antipsychotic

Tx of psychosis

'Positive' & 'negative' sxs

Front 57

Risperidone

Tends to work when:

PHKs (4):

Back 57

Other neuroleptics fail

Oral: well abs
High PP binding
Metabs to an active metab
t1/2 varies genetically

Front 58

Risperidone

Mech (3):

Also enhances:

Back 58

Blocks D2, 5HT2A, & alpha recs

DA transmission in basal ganglia, resulting in less risk of extrapyramidal sxs & tardive dyskinesia

Front 59

Risperidone Side Effects

CV (2):

CNS (4):

Back 59

Prolongs QT, postural hypotension/reflex tachy

Agitation, anxiety, insomnia, HA

Front 60

Risperidone Side Effects

Other/Misc (3):

Back 60

nausea, weight gain, hyperprolactinemia

Front 61

Ziprasidone

Drug Class:

Also works as/mech:

Back 61

NG atypical antipsychotic

antidepressant secondary to either 5HT2A agonism or inhib of 5HT reuptake

Front 62

Ziprasidone

PHK (2):

Back 62

Oral or IM ok
Liver metab by CYP3A4 - poss interactions

Front 63

Ziprasidone Side Effects

CV:

CNS (2):

Other:

Back 63

Prolongs QT

Lowers sz threshold, sedation to the point of impairment initially

hyperprolactinemia

Front 64

Quetiapine/Seroquel

Drug class:

Similar to:

Tx of both:

Back 64

NG atypical antipsychotic

Clozapine

'Positive' & 'negative' sxs of schizo

Front 65

Quetiapine/Seroquel

PHK:

Does NOT cause (3):

Back 65

VERY well tolerated

NO agranulocytosis, extrapyramidal sxs, hyperprolactinemia

Front 66

Quetiapine/Seroquel Side Effects

GI (4):

CNS (2):

CV:

Back 66

Weight gain, constip, dyspepsia, xerostomia

dizziness, drowsiness

Orthostatic hypotension

Front 67

Loxapine

Drug class:

But acts like:

First or last resort & why?

Back 67

NG atypical antipsychotic

phenothiazines

Drug of last resort bc it decreases the sz threshold even more

Front 68

Pimozide

Drug class:

Acts like & why?

Biggest risk for:

Back 68

NG atypical antipsychotic

haloperidol, is a D2 blocker

Extrapyramidal sxs

Front 69

Loxapine

Sedative & anticholinergic effects ranking:

CV side effects:

Use:

Back 69

Moderate

Prolongs QT

Tx for tics in Tourette's

Front 70

Molindone

Drug Class:

Mech:

Back 70

NG atypical antipsychotic

Blocks D2 recs

Front 71

Molindone Side effects

CNS (3):

GI (2):

CV (3):

Back 71

Moderate sedation, or increased motor activity, mild euphoria

xerostomia, constipation

hypotension, sinus tachy, syncope

Front 72

Molindone

Risk of:

Back 72

Extrapyramidal sxs

Front 73

Apriprazole

Drug class:

Mech (2):

Back 73

DA system stabilizer (new class)

DA recs are activated when DA is low and blocked when DA is high. Considered a partial agonist of D2, 5HT1A recs

Front 74

Apriprazole

Uses (2):

Also works on ___ recs (3):

Back 74

anti-psychotic and for drug-resistant depression

5HT2A, alpha, & histamine recs

Front 75

Apriprazole

PHK (2):

Does NOT cause (4):

Back 75

Oral: well abs
Liver metab CYP3A4 & 2D6

QT elongation, hyperprolactinemia, extrapyramidal sxs, weight gain

Front 76

Apriprazole Side Effects

CV:

CNS (3):

GI:

Back 76

Orthostatic hypotension

Szs, sedation, dec temp regulation

Hyperglycemia, dec motility

Front 77

Apriprazole

Use with caution in (2):

Back 77

DM pts (hyperglycemia)

Elderly (dec GI motility)

Front 78

CIs of all antipsychotics and why (3):

Back 78

Anticholinergics: inc side effects

Sedative-hypnotics: inc sedation

Anti-HTNs: unpredictable sxs secondary to alpha blocking

Front 79

Why is carbemazepine CI with antipsychotics?

What else causes this effect?

Back 79

Carbemazepine's activation of liver enzymes causes increased metabolism and decreased concentration of antipsychotics

Smoking

Front 80

Iloperidone

Drug Class:

First or last choice and why?

Back 80

Serotonin-DA rec agonist

QT prolongation and many other side effects make this a last choice anti-psychotic drug

Front 81

Investigational drugs

Drug class/mech:

Tx which sx (that no other drugs can treat):

PHK:

Back 81

Selective M1/M4 rec agonists

improves cognitive fcn in Schizos

Well tolerated

Front 82

Uses of antipsychotics

In Schizo (2):

Back 82

Minimizes sxs & exacerbations.
IM inj of haloperidol & fluphenazine improves compliance.

Front 83

First-line drugs for Schizo (3):

If pt unresponsive to these or had tardive dyskinesia, use:

Back 83

risperidone, quetiapine, olanzepine due to low side effects

clozapine

Front 84

Uses of antipsychotics

In Depression or mania with psychosis (2):

Back 84

Use in combo with mood stabilizers, benzos, or antidepressants at first. Improvements seen within 48 hrs.

Front 85

Uses of antipsychotics

Choices for Tourette's (2):

Choice for ALZ:

For emesis (2):

Back 85

halperidol or pimozide

risperidone to control agitation & hyperactivity.

prochlorperazine & compazine

Front 86

Which antipsychotics cause hyperglycemia & weight gain (4)?

Sedation (3)?

Back 86

olanzapine, risperidone, quetiapine, phenothiazines

phenothiazines, quetiapine, apriprazole

Front 87

Which antipsychotics cause prolonged QT (4)?

Which one of these is most likely to cause it?

Back 87

Risperidone, ziprasidone, pimozide, iloperidone

Risperidone

Front 88

Bipolar Affective Disorder

AKA:

Epidemiology (2):

Probable cause:

Back 88

Manic depression

1-2% of the population
Strong genetic component

lack of GABA activity

Front 89

General tx of bipolar

Usually (3):

Also (3):

Often a combo of (2):

Back 89

Lithium, valproic acid, carbemazepine

Gabapentin, lamotigine, olazapine

Antidepressants & anti-psychotics

Front 90

Lithium

Mech (4):

Uncouples:

Back 90

Unsure. Known that it decreases rls of NE & DA, dec prod of IP3 & DAG, increases ACH.

G-proteins from recs, probably causing major side effects.

Front 91

What 2 types of recs are known to be uncoupled from G-proteins by lithium?

Back 91

TSH recs & ADH recs

Front 92

Lithium

PHK (4):

Back 92

Slow onset - takes 5-6 days to achieve steady-state.

Rapid oral abs

Peaks in 0.5-2 hrs

Dose varies with pt.

Front 93

Lithium

How is the optimal dose determined?

What is the optimal dose typical range?

Back 93

Serum [lithium] is measured 10-12 hrs after last dose.

0.6-1.2 mEq/L

Front 94

Lithium

Excretion & rate:

Other excretion concerns:

Back 94

RExc at 50% within 24 hrs.

Lithium reabs in PT of kidney, so it competes with Na reabs.

Front 95

How do lithium and Na interact?

Why do we care?

Back 95

Decreased Na = increased lithium activity in body since they compete for reabs in PT.

Means we can use dialysis & saline to tx lithium OD

Front 96

Lithium Side Effects

CNS (6):

GI transient (4):

GI other:

Back 96

Tremor, HA, poor memory & concentrtion, confusion, lethargy, weakness

Nausea, diarrhea, bloating, anorexia

Weight gain

Front 97

Lithium Side Effects

Renal issue, mechanism, and result:

Failure?

Back 97

Can cause nephro diabetes insipidus because lithium blocks ADH action. The CT cannot conserve water, so pt gets polyuria, polydipsia, edema (Na retention) and chronic interstitial nephritis.

Renal failure is not common

Front 98

How are the renal complications of lithium use treated if they occur?

What tx is ineffective for these renal issues?

Back 98

Amiloride blocks lithium from entering CT.

vasopressin

Front 99

Lithium Side Effects

Thyroid issues & mech:

Result?

Back 99

Lithium blocks thyroxine synth & rls, and decreases body's sensitivity to TSH by uncoupling the TSH rec from its G-protein.

Dec thyroid fcn

Front 100

Lithium Side Effects

Pregnancy:

Back 100

Ok to use, but dose must be increased because of increased renal clearance, and care must be taken to dec dose after delivery.

Front 101

Lithium Toxicity

Mild toxicity levels and sxs (5):

Back 101

>2.0 = mild. NVD, fasciculations, hyperreflexia, fine tremor, slurred speech, poor memory & concentration

Front 102

Lithium Toxicity

Serious tox levels & sxs (7):

Back 102

>2.5 = severe. Ataxia, agitation, nystagmus, tonic-clonic twitch, szs, resp issues, coma, death.

Front 103

Lithium Toxicity

Tx:

Back 103

dialysis & saline (remember that inc Na = dec lithium reabs)

Front 104

Valproic acid

Drug Class/uses:

Efficacy for mood stabilization:

Back 104

anticonvulsant, mood stabilizer

Greater than or equal to lithium

Front 105

Valproic acid

PHK:

Mech:

Back 105

Rapid onset

Unknown. Poss GABA stim

Front 106

Valproic acid Side Effects

CNS (3):

Other (4):

Back 106

Drowsy, ataxia, tremor

hair changes, decreased platelet agg, transient inc in liver enzymes, weight gain

Front 107

Lamotigine

Drug class/use:

Efficacy for mood stablization:

Back 107

Anticonvulsant used as mood stabilizer

Equal to lithium

Front 108

Lamotigine Side Effects

CNS (5):

Other (2):

Does NOT cause:

Back 108

HA, ataxia, dizzy, double vision, sedation

Possibly serious rash, nausea.

NO weight gain

Front 109

Topiramate

Drug Class:

Uses (7):

Back 109

Anticonvulsant

Anticonvulsant, mono tx for bipolar, tx of alcoholism, prevent migraines, prevent essential tremor, prevents binge eating.

Front 110

Topiramate

Often used with SSRIs to do what:

Back 110

Offset weight gain, since Topiramate usually causes weight loss

Front 111

Gabapentin/Neurontin

Drug Class:

Ok for short term use as:

Analogue of:

Back 111

Anticonvulsant

Mood stabilizer

GABA - inc GABA rls

Front 112

Gabapentin/Neurontin

Side effects (6):

Pregnancy:

Back 112

drowsy, weight gain, ataxia, blurry vision, HTN, back pain

Not recommended

Front 113

Carbemazepine/Tegretol

Drug class:

Often combined with:

Efficacy as mood stablizer:

Back 113

Anticonvulsant

Lithium at first, then lith is w/d.

Worse than lithium

Front 114

Carbemazepine/Tegretol

Mech:

Back 114

Unknown. Poss PM stabilization.

Front 115

Carbemazepine/Tegretol Side Effects

GI (3):

CNS (4):

Back 115

NVDC, abd pain, anorexia

drowsy, dizzy, fatigued, ataxia (CNS toxicity in 60% of pts)

Front 116

Carbemazepine/Tegretol Side Effects

Hemo (5):

Hemo warning signs (3):

Back 116

aplastic anemia, agranulocytosis, thrombocytopenia, leukopenia, eosinophilia

sore throat, fever, bruising

Front 117

Carbemazepine/Tegretol Side Effects

Major Side Effect:

AKA:

Type:

Back 117

Stevens-Johnson syndrome

erythema multiforme

HS rxn

Front 118

Sxs of Stevens-Johnson syndrome secondary to carbemazepine (2):

Requires ___ for ___ before Rx.

Back 118

fever, lesions

genetic testing for presence of HLA-B*1502

Front 119

Carbemazepine/Tegretol

Increased toxicity with (7):

Not recommended in:

Back 119

cimetidine, erythromycin, isoniazid, verapamil, diltiazem, propoxyphene, fluoxetine because they decrease the metab of carbemazepine.

Pregnancy.