Antipsychotic Drugs Flashcards
1
Q
definition of psychosis
A
- major mental disorder w/ following symptoms
1. personality is seriously disorganized
2. contact w/ reality is impaired
3. ability to think, perceive, and judge is impaired
4. ability to communicate and relate to others is impaired
5. can’t cope w/ environment
6. can’t meet ordinary demands of life
2
Q
criteria for schizophrenia
A
- 2 or more, each present for a significant proportion of time for 1 month
1. delusions
2. hallucinations
3. disorganized speech
4. grossly disorganized or catatonic behavior
5. negative symptoms - social/occupational dysfunction
- at least 6 months
- substance abuse and general medical conditions have been ruled out
- in presence of autism, hallucinations or delusions present for over 1 month
3
Q
positive symptoms of schizophrenia
A
- delusions, hallucinations, disorganized speech, disorganized or catatonic behavior
4
Q
negative symptoms of schizophrenia
A
- impoverished thoughts
deficits of attention
blunt affect
lack of initiative
5
Q
dopamine receptors
A
- D1 : activated by AC (Gs)
2. D2 : Gi
6
Q
Typical antipsychotics MOA
A
- dopamine D2 blockers
- produces extrapyramidal symptoms (EPS)
- elevated PRL levels
- equally effective but differ in potency/side effects
- largely effective for positive symptoms
7
Q
Atypical antipsychotics MOA
A
- share D2 and 5HT2A antagonism in common
- addition of 5HT2A blockade my reduce EPS and improve efficacy for negative symptoms
8
Q
What are the antipsychotics
A
phenothiazines
thioxanthenes
butyrophenones and diphenylbutylpiperidines
9
Q
Phenothiazines
A
- Aliphatic side chain: chlropromazine, low potency
- Piperazine group side chain: fluphenazine, perphenazine. Potent
10
Q
Butyrophenones
A
Haloperidol - high potency
11
Q
Clozapine
A
low potency, atypical
12
Q
Risperidone
A
5HT2/D2 antagonist
- limited EPS at low doses
- only approved agent for use in kids and teens
13
Q
Aripiprazole
A
D2 partial agonist - reduces actions of full agonist
- 5HT2A antagonists, 5HT1A partial agonists
- lower incidence of side effects
14
Q
Ziprasidone
A
5HT2A, 5HT1a, 5HT2C/D2 antagonist
- limited EPS
15
Q
Lurasidone
A
D2 and 5HT2A antagonist
5HT1A partial agonist
risk of EPS present
16
Q
Neuroleptic syndrome
A
suppression of spontaneous movements and complex behavior
- reduced initiative and interest in environment
- decreased manifestations of emotion or affect
- psychotic symptoms disappear over time
17
Q
CNS effects of antipsyhcotics
A
- Cerebral cortex - minimal adaptive changes in dopamine system, can lower seizure thresholds
- Basal Ganglia - initially increase DA metabolism, synthesis and firing rate. Antipsychotics don’t really occur here
- Limbic system - thought to be site of antipsychotic effects, anticholinergics don’t block therapeutic effect
- Hypothalamus - increased PRL, little tolerance, avoid in pts w/ established breast carcinoma
- Brainstem - little effect on respiration, decreased vasomotor reflexes at low doses
- CTZ -
18
Q
What effect do the following have on Prl secretion?
- All typicals
- Risperidone
- Clozapine
- Olanzapine
- Ziprasidone
- Quetiapine
- Aripiprazole
A
- increased
- increased
- little increase
- little increase
- little increase
- no increase
- no increase
19
Q
clinical consequences of sustained hyperPRL
A
sexual dysfunction, amenorrhea, gynecomastia/galactorrhea, hypoestrogenism/osteopnia
20
Q
other organ system effects of antipsychotics
A
- ANS - complex and unpredictable
- renal system - chlorpromazine may be antidiuretic
- Hepatic system - no characteristic effects, may be toxin in pts w/ liver dz
- Endocrine system - chlorpromazine (impaired glucose tolerance, decreases insulin release). Clozapine, risperidone, aripiprizole, ziprasidone, olanzepine, and quetiapine all increased risk of type 2 DM
- CV system - direct effects on heart and vessels and indirect effects via CNS and ANS. Mild orthostatic hypotension. (more w/ chlorpromazine, thioridazine. less w/ haloperidol, loxapine, risperidone. tolerance develops)
- Misc : may increase Ach turnover (basal ganglia), inverse relationship btw antimuscarinic potency and EPS
21
Q
Side effects of antipsychotics
A
- high TI
- anticholinergic effects: nasal stuffiness, dry mouth, blurred vision, constipation, CV
- acute dystonia, akathesia, parkinsonian syndrome, NMS, perioral tremor, tradive dyskinesia
- jaundice
- blood dyscrasis
- skin rxn
- wt gain
22
Q
what is acute dystonia
A
muscle spasma: facial grimacing, torticollis, oculogyeric crisis
- treat w/ anticholinergic antiparkinsonian agents
23
Q
What is akathesia
A
- strong subjective feelings of distress or discomfort often referrred to the legs. “ants in pants”
- treat by decreasing dose, add antiparkinsonian agent, antianxiety agent or propranolol
24
Q
Parkinsonian syndrome
A
- akinesia, mask facies, decreased arm movement, rigidty, tremor
- treat w/ anticholinergic antiparkinsonian agent, amantadine
25
NMS
rare, fever, severe parkinsonism w/ catatonia
- fluctuations in coarse tremor intensity
- autonomic instability
- elevated creatine kinase
- myoglobinemia
- high morality
26
treatment for NMS
- stop antipsyhcotic
- supportive care
- dantrolene or bromocriptine
27
Perioral tremor
rare, rabbit syndrome
| - treat w/ anticholinergic agent, stop neuroleptic
28
Tardive dyskinesia
repetitive, quick choeriform movements of face eyelids, mouth, tongue, extremities or trunk
- no real treatment
- discontinue antipsychotic
- symptoms fade w/ time
29
Jaundice side effect
- occurs 2nd-4th week w/ chlorpromazine
- HSR rxn
- mild
change agents
30
Blood dyscrasis side effect
mild leukocytosis, leukopenia (may be a sign of impending agranulocytosis), eosinophilia
- especially important when using clozapine
31
Skin rxn side effect
- urticaria or dermatitis
- 5% of pts on chlorpromazine
- more common w/ phenothiazines
- occurs in 1st 8 weeks
- skin clears w/ discontinuation
- photosensitivty
32
Wt gain side effect
- clozapine, olanzapine more likely
- risperidone, quetiapine - intermediate risk
- ziprasidone, aripiprazole, asenapine - less likely
- increased risk of type 2 DM, HTN, and HLD
33
incidence of metabolic syndrome on atypical antipsychotis
1. olanzapine - high
2. quetiapine - mod
3. risperidone - mod
4. zisprasidone - low
5. aripiprazole - low
34
PK of antipsychotics
- highly lipophilic
- highly protein and membrane bound
- accumulates in high blood supply tisssue
- crosses placental barrier and enters breast milk
35
metabolism of antipsychotics
- oxidation main route: hepatic microsomal oxidase and conjugation
- most metabolites inactive
36
drug interactions of typical antipsychotics
- metabolized by 2D6 and 3A4
- dont' induce CYP enzymes
- may inhibit 2D6 and raise levels of many TCAs and SSRIs
37
Treatment for following disorders
1. schizophrenia
2. bipolar disorders w/ psychotics features
3. schizoaffective disroder
4. major depressive disorder w/ psychotic features
1. antipsychotics
2. mood stabilizers and/or antipsychotics
3. antipsychotics, w/ mood stabilizers and/or antidepressants
4. ECT and/or antidepressant med and/or antipsychotics
38
long acting depot antipsychotics
1. slow release, combined w/ base AP w/ a fatty acid (decanoic acid)
2. alcohol group of drug is esterified by acid = increased solubility in oil
3. considered for pts w/ several relapses, pts who have compliance problems, when oral absorption is poor
39
Misc uses for antipsychotisc
1. N/V
2. Alcoholic hallucinosis
3. neuropsychiatric diseases marked by movement disorders: tourettes, HD, intractable hiccup
40
What are the 2nd gen antipsychotics
```
Aripirazole
Clozapine
Olanzapine
Palperidone
Quetiapine
Risperidone
Ziprasidone
```
41
What 2nd gens are more likely to casue DM and weight gain
Clozapine and olanzapine
| - palperidone, quetiapine, risperidone also do both but a bit less
42
2nd gens that cause EPS
- Risperidone -most likely
- Palperidone and Aripirazole - next
- Ziprasidone and Olanzapine
43
2nd gens that cause QT prolongation
- Ziprasidone - most
| - others do a little
44
2nd gens that cause PRL secretion
1. most = risperidone and palperidone
| 2. next = ziprasidone and olanzapine
45
2nd gen drugs w/ highest potential for CYP interactions
Aripiprazole
Quetiapine
Risperidone
Ziprasidone
