2.18: AntiPsycho Flashcards
(54 cards)
1
Q
Indications for antipsychotics?
A
- Schizophrenia
- Bipolar disorder
- Major depression
- Delirium / dementia
- Substance induced psychosis
- Tourettes
- OCD
- Anxiety / Agitation
- Autism
2
Q
What are the 4 dopamine (DA) tracts?
A
- Mesolimbic
- Mesocortical
- Nigrostriatal
- Tuberoinfundibular
3
Q
Which of the dopamine (Da) tracts seems to be sources of psychosis?
A
- Mesolimbic: hyperactivity in this region leads to symptoms
- Also where antipsychotics work
4
Q
What is the dopamine hypothesis?
A
- Psychosis caused by too much dopamine
- Antipsychotics were blocking DA receptors: those with higher affinity = more affective
- Drugs that increased DA increased psychosis
- Schizos seen to have increase DAr
5
Q
What is FGA?
A
First generation antipsychotics
6
Q
Problem with dopamine hypothesis of antipsychos?
A
- FGAs were not very effective with negative signs
- 35% ptns relapsed annually
- 30% didnt have adepuate response
7
Q
Which are the FGA’s?
A
Low Potency: 1. Chlorpromazine: ***Most important to remember 2. Thioridazine 3. Perphenazine 4. Thiothixene: moderate potency High potency 1. Haloperidol ****Most important 2. Fluphenazine 3. Trifluoperazine
8
Q
MOA of antipsychotics?
A
- Block D2 receptors in mesolimbic tract
* ***Occur when 60% of receptors here are blocked
9
Q
How do side effects of antipsychotics occur?
A
- Unintended D2 blockage in nigrostriatal and tuberoinfundibular tracts: Increased prolactin / EPS
- Muscarinic receptors
- Adrenergic receptors
- Histamine receptors
* ***Occurs when 80% of receptors here are blocked
10
Q
Window of antipsychotics?
A
> 60%
11
Q
Side effects for low potency FGAs?
A
Chlorpromazine: Corneal deposits
Thioridazine: retinal deposits
12
Q
What does increased prolactin cause?
A
- **Caused by tuberoinfundibular tracts interaction:
1. Gynecomastia
2. Galactorrhea
3. Sexual dysfunction
4. Menstrual irregularity/infertility
13
Q
Dopaminergic side effects of chlorpromazine?
A
- Extrapyramidal
- Increased prolactin
- Decreased bone density
14
Q
What are the histaminic side effects of chlorpromazine?
A
- Sedation
2. Weight gain
15
Q
What are the adrenergic side effects of chlorpromazine?
A
- Orthostasis: fall risk
16
Q
What are the muscarinic effects of chlorpromazine?
A
"Anticholinergic" 1. Blurred vision 2. Urinary retention 3. Dry mouth 4. Constipation "Cant pee, cant see, cant spit, cant shit"
17
Q
Relation of dopamine and ACh?
A
- In nigrostriatal pathway, dopamine suppresses Ach
- When DA blocked, ACh suppression is released = EPS
- Low potency antipsychotics are anticholinergic = self treating for EPS
18
Q
What is EPS?
A
Extrapyramidal systems
19
Q
How do identify FGAs?
A
- “Phenothiazines” end in “azine”
- Haloperidol and thiothixene exceptions
20
Q
Side effects of high potency antipsychotics?
A
- Dopaminergic side effects are greater
2. NO muscarinic, adrenergic, or histaminic side effects are seen
21
Q
What are the EPS side effects?
A
“Drug induced movement disorders” (50 - 90% develop):
EPS:
1. Parkinsonian: resting tremor, bradykinesia, stiffness
2. Dystonia
3. Akathisia
4. Tardive dyskinesia: involuntary movement (20-50%)
22
Q
What is dystonia? Who is at higher risk?
A
- Sustained abnormal posture / muscle contraction
- Made worse by activity
- Young males at higher risk
- Often seen early in treatment, may be reported as allergy
23
Q
What is akathisia?
A
- Feeling of restlessness and need to move
- Women 2x risk of men
24
Q
What is tardive dyskinesia?
A
- Classically seen from taking DA blockers
- Involuntary movements
- Classically seen in lower face and tongue
- Does not remit even after taken off drugs
25
What are SGAs?
Second Generation antipsychotics
26
What are the endings of the SGAs?
1. "idone"
2. "Apine"
3. Aripiprazone
27
Broad mechanism of the SGAs?
- Dual antagonism of DA / 5HT receptors
28
What does blocking D2 receptors in nigral striatal pathway lead to?
- Extrapyramidal side effects
- Tardives
* **Our target is blocking D2 in mesolimbic system, at higher [] in other tracts other D2 receptors begin to be blocked leading to side effects
29
Impact of 5HT on DA?
- When serotonin binds Dopaminergic neuron, DA release is decreased
30
Why is it important that SGAs are blocking 5HT?
- Blocking 5HTr releases more DA into synapse
- This DA is competing with the drug to bind DA receptor
- at > 80% binding of drug, side effects are seen
- By releasing more DA via dual action, we compete with Drug for DA-receptors = decreased side effects
31
What is the hit and run concept?
SGAs bind more loosely to DA receptor meaning it works enough to get antipsychotic effects but not long enough for EPS
32
Side effect profile of SGAs?
- Less extra pyramidal side effects via over blockade of DA in areas outside of mesolimbic
- Side effect profiles vary for histamine and muscarinic receptors and are often worse in this regard than haloperidol
33
What are some metabolic syndromes?
1. Weight Gain
2. Hyperlipidemia
3. Glucose intolerance
34
New side effects found in SGAs?
Metabolic syndromes
35
Which SGAs have least weight gain?
1. Ziprasidone
| 2. Aripiprazole
36
Mechanisms of Aripiprazole?
- Partial antagonism of DA-r
- In low DA environment, binds DA-r acting as agonist keeping 65% or receptors blocked
* ***Keeps % un therapeutic window
37
Cost benefit of clozapine?
```
Benefit:
1. Great efficacy for negative symptoms
2. Great efficacy in patients unresponsive to others
3. Lowers risk of suicide
Costs:
1. Agranulocytosis
2. Myocarditis
3. Decreased seizure threshold
```
38
When can clozapine be used?
Only after 2 other drugs have failed
39
What is agranulocytosis?
Bone marrow stops producing blood cells
40
More commone side effects of clozapine?
1. Weight gain
2. Very sedating
3. Metabolic Syndrome
4. Anticholinergic
41
What is NMS?
"Neuroleptic malignant syndrome"
- Can be caused by SGA or FGA: same risks for all DA blockers
- Dopamine system goes haywire
42
Signs of NMS?
1. Mental status changes
2. Muscle rigidity: Increased CPK
3. Fever
4. Dysautonomia
43
Treatment for NMS?
1. Stop meds
2. Supportive
3. Dantrolene
4. Bromocriptine: D2 agonist
44
What has black box warning of sudden death?
- FGAs and SGAs
| - Seen in elderly, usually CV in nature
45
Who should you take extra care in prescribing antipsychotics to?
Elderly: sudden death black box warning
46
Protein binding of anti psychotics? Halflife?
- Highly protein bound
- Unbound portion crosses BBB for effects
- 20 hours
47
Longest 1/2 life of antipsychotics?
Aripiprazole: 72 hours
| - Most others are 20
48
Which drug has risk of increased qTc interval as side effect?
Ziprasidone
49
Which drug has long lasting injectable form?
1. Risperidone
2. Olanzapine
3. Aripiprazole
4. Haldol
* **Good for patient with low compliance
50
Drug only available in sublingual form?
Asenapine
51
What is risperidone metabolized to?
Palliperidone
52
How is paliperidone excreted?
80% renal
53
What to use if patient has liver disease?
Paliperidone
54
What to avoid if patient has renal disease?
Paliperidone
