Pharmacology Specifics – First Generation Antipsychotics Flashcards
1
Q
What are the 11 FDA approved indications for the use of antipsychotics?
A
Schizophrenia bipolar disorder major depressive disorder (adjunctive therapy) Tourette's syndrome severe behavioral problems hyperactivity anxiety hiccups acute intermittent porphyria Nausea/vomiting Tetanus
2
Q
What are the seven non-FDA approved uses for antipsychotics?
A
Dementia (behavioral disturbances)
substance use disorder (reduction in use)
anorexia nervosa (increase body weight) obsessive-compulsive disorder
posttraumatic stress disorder
generalized anxiety disorder
3
Q
What is the mechanism of action for both first and second generation antipsychotics with regard to dopamine receptors?
A
They block post-synaptic D2 dopamine receptors in the mesolimbic system, which has been associated with their antipsychotic effect
4
Q
What is another name for antipsychotics?
A
Neuroleptics
5
Q
How do the first generation and second generation antipsychotics differ in their mechanism of action on serotonin receptors?
A
First generation antipsychotics minimally antagonize serotonin receptors; whereas the second-generation antipsychotics have greater antagonism of serotonin receptors
6
Q
The side effects associated with first and second generation antipsychotics are due to antagonism at which three types of receptors?
A
Histaminic, muscarinic, and Alpha-adrenergic receptors
7
Q
Which generation of antipsychotics are more frequently associated with significant adverse side effects, such as extrapyramidal symptoms (EPS)? What is this due to?
A
First generation antipsychotics
This is due to their higher antagonism of D2 dopamine receptors
8
Q
Thorazine
A
Chlorpromazine
9
Q
Who makes all first generation antipsychotics?
A
Multiple generic manufacturers
Except Orap (pimozide) which is manufactured by Teva and brand-name only
10
Q
What is the route and form of Thorazine? What is the recommended dosage per day?
A
PO, tablets
200-1000 mg per day
BID or TID
11
Q
Prolixin
A
Fluphenazine
12
Q
What is the route and form of Prolixin?
A
PO, IM
Tablets, liquid IM, acute IM, depot
13
Q
What is the recommended PO, IM acute, and IM depot doses of Prolixin?
A
PO
0.5-20 mg per day,
Often given BID with doses larger than 10 mg
IM acute
5-10 mg Q6-8 hrs PRN
IM depot
12.5-25 mg Every 2 weeks
14
Q
Haldol
A
Haloperidol
15
Q
What route and forms does Haldol come in?
A
PO, IM
Tablets, liquid IM, acute IM, depot
16
Q
What are the recommended PO, intramuscular acute, and intramuscular depot doses of Haldol?
A
PO: 0.5-20 mg per day
Intramuscular, acute: 5-10 mg Q6-8 hrs PRN
Intramuscular, depot: 50-200 mg given once monthly
17
Q
What’s the difference between the intramuscular depot shot for Prolixin, and that for Haldol?
A
The dose for Prolixin is 12.5-25 mg, while the dose for Haldol is 50-200 mg
Haldol is given once monthly, while Prolixin is given every two weeks
18
Q
Loxitane
A
Loxapine
19
Q
Navane
A
Thiothixene
20
Q
Which two first generation antipsychotics can be dispensed in capsule form?
A
Navane and Loxitane
21
Q
What is the route of administration for Loxitane? What is the recommended daily dose?
A
PO
25-250 mg per day
22
Q
What is the route of administration for Navane? What is the recommended daily dose?
A
PO
15-30 mg per day
23
Q
Which is more expensive, Loxitane or Navane?
A
Loxitane
24
Q
Trilafon
A
Perphenazine
25
Orap
Pimozide
26
Mellaril
Thioridazine
27
Stelazine
Trifluoperazine
28
What route and form are Trilafon, Orap, Mellaril, and Stelazine dispensed in?
PO; tablets
29
What is the recommended daily dose for Trilafon?
16-64 mg per day
30
What is the recommended daily dose for Orap?
1-10 mg per day
31
What is the recommended daily dose for Stelazine?
2-40 mg per day
32
What is the recommended daily dose for Navane?
15-30 mg per day
33
What is the recommended daily dose for Mellaril?
200-800 mg per day
34
Which first generation antipsychotic in tablet form is the cheapest?
Haldol
35
Which first generation antipsychotics in the tablet form is the second cheapest?
Prolixin
36
Which 2 first generation antipsychotic in the tablet form is the most expensive?
Orap and Trilafon
37
How should first generation antipsychotics be adjusted in patients with renal insufficiency or renal failure?
No dosage adjustment needed
38
With regard to pregnancy, what category are the first generation antipsychotics in?
Category C
39
How should the dosage of first generation antipsychotics be adjusted for patients with liver failure or liver disease?
They should be used with caution in patients with liver disease, especially chlorpromazine and perphenazine because they are both metabolized by the liver
40
What are the two options for the starting recommended dose of Thorazine?
10 mg
3-4 times per day
25 mg
2-3 times per day
41
How should Thorazine be increased?
One can increase by 20-50 mg per day
42
What is the maximum recommended dose of Thorazine per day?
400 mg
43
What is the recommended intramuscular dose of Thorazine?
Intramuscular dose is 25 mg
| It can be repeated in 1 hour if needed
44
What's the recommended starting oral dose of Haldol? How much should it be increased per day?
1 mg per day or twice daily
It should be increased by 1-2 mg per day
45
What's the maximum recommended dose of Haldol per day?
100 mg per day
46
What's the initial, recommended long-acting intramuscular dose of Haldol?
10-20 times the total oral dose
47
What should be done if the initial long-acting intramuscular dose of Haldol is greater than 100mg?
It should be administered in separate doses one week apart
48
After giving the initial dose, the following month, what dose of long-acting intramuscular Haldol should be given?
10-15 times the total oral dose
49
What's the maximum, recommended, long-acting intramuscular dose of Haldol?
450 mg
50
What is the recommended starting dose of Orap? How should the dose be gradually increased?
The recommended initial dose is 1-2 mg per day in divided doses
The dose should be gradually increased every other day
51
What is the maximum recommended dose per day of Orap?
10 mg
52
What type of biogenetic testing should be done for doses greater than 4 mg with the use of Orap?
CYP2D6 genotyping should be done
53
What is the recommended starting oral dose for Navane? What is the maximum recommended dose per day?
1-2 mg per day in divided doses
The maximum dose is 60 mg per day
54
What is the intramuscular dose of Navane?
4 mg, 2-3 times per day
| Maximum dose of 60 mg per day
55
What is the recommended starting oral dose of Stelazine? What is the maximum dose per day?
2-5 mg twice per day
The maximum dose is 40 mg per day divided doses
56
What is the recommended intramuscular dose of Stelazine? What is the maximum dose given per day?
An intramuscular dose of 1-2 mg can be given every 4-6 hours as needed
The maximum dose is 6 mg per day
57
What is the recommended starting dose of Prolixin? What is the maximum dose per day?
2.5-10 mg per day in divided doses every 6-8 hours
The maximum dose is 40 mg per day
58
What is the conversion from oral dosing to intramuscular dosing for Prolixin?
The intramuscular dose is 1.25 times the oral dose every 2-4 weeks
59
What is the recommended starting oral dose for Trilafon? What is the maximum recommended dose per day
4 mg, 2-4 times per day
The maximum dose is 64 mg per day
60
What is the recommended starting dose for Loxitane? How much should this medication be increased per day? What is the maximum recommended dose?
Starting dose is 10 mg twice per day
It should be increased by 10 mg per day
The maximum dose is 250 mg per day
61
What is the recommended starting dose for Mellaril? How much should it be gradually increased per day? What is the maximum dose recommended?
Starting dose is 50 mg, 3x per day
It should be gradually increased by 50 mg per day
The maximum dose per day is 800 mg
62
What are the 6 doses for the tablet option of Haldol?
0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg
63
What is the dosage for the liquid form of Haldol?
2 mg/mL
| 120 mL bottle
64
What is the dose for acute intramuscular, depot Haldol administration?
5 mg/mL
| 1 milliliter vial
65
What are the dosing options for intramuscular, depot administration of Haldol?
50 mg/mL
5 mL multidose vial
100 mg/mL
1 mL vials
66
What are the 4 tablet options for the administration of Prolixin?
1 mg, 2.5 mg, 5 mg, 10 mg
67
What are the 2 options for liquid administration of Prolixin?
2.5 mg/5 mL
480 mL
5 mg/mL
120 mL
68
What is the acute dose of intramuscular administration of Prolixin?
2.5 mg/mL
| 10 mL vial
69
What is the dose for intramuscular, depot administration of Prolixin?
25 mg/mL
| 5 mL vial
70
What are the 2 tablet options for Orap?
1 mg, 2 mg
71
What are the 4 tablet options for, both, Stelazine and Navane?
1 mg, 2 mg, 5 mg, 10 mg
72
What are the 4 tablet dosing options for Trilafon?
2 mg, 4 mg, 8 mg, 16mg
73
What are the 4 tablet dosing options for Loxitane?
5 mg, 10 mg, 25 mg, 50 mg
74
What are the 4 tablet dosing options for Mellaril?
10 mg, 25 mg, 50 mg, 100 mg
75
What are the 5 tablet dosing options for Thorazine?
10 mg, 25 mg, 50 mg, 100 mg, 200 mg
76
Which are the two cheapest antipsychotic options for tablets?
Mellaril and Haldol
77
Which are the two relatively most expensive antipsychotic tablet options?
Orap and Trilafon
78
What is the recommended course of action for the use of chlorpromazine, loxapine, Pimozide, thioridazine, thiothixene, and Trifluoroperazine in geriatric patients?
Start a low dose, and gradually increase as needed while monitoring for side effects
79
What is the recommended course of action for the use of haloperidol in geriatric patients?
Start at 0.5 mg daily-twice per day
gradually increase to 2 mg, 3x per day if needed
The initial IM dose is 10-15 times the total oral daily dose
80
What is the recommended course of action for the use of Fluphenazine in geriatric patients?
Start at 1-2.5 mg per day and increase gradually
81
What is the recommended course of action for the use of perphenazine in geriatric patients?
Start at 2 mg, 2x per day and gradually increase as needed/tolerated
82
How should the first generation neuroleptics be adjusted for patients with renal insufficiency or renal failure?
No dosage adjustment needed
83
How should first generation antipsychotics be adjusted in patients with liver disease?
They should be used with caution in patients with liver disease
84
Which two first generation antipsychotics are known to be metabolized by the liver?
Chlorpromazine and perphenazine
85
What is the general recommendation for the use of first generation antipsychotics in a post partum mother who is breast-feeding?
Generally speaking, there is insufficient data for the use of first generation antipsychotics during nursing and breast-feeding should be avoided
86
Which two first generation antipsychotics are not recommended for patients less than 12 years of age?
Perphenazine and Thiothixene
87
Which medication has safety and efficacy that is not established in children?
Loxapine
88
What is the pediatric dosing for Haldol?
Starting dose is 0.05 mg per kilogram per day divided into 2-3 doses
increase by 0.5 mg per day weekly
89
What is the pediatric dosing for pimozide?
Starting dose is 0.05 mg per kilogram per day, which can be increased every third day with the maximum dose of 0.2 mg per kilogram per day not to exceed 10 mg per day
90
What is needed for doses of pimozide greater than 0.05 mg per kilogram in pediatric patients?
A GYP2D genotype
91
What is the pediatric dosing for fluphenazine?
0.25-0.75 mg,
1-4 times per day
92
What is the pediatric dosing for chlorpromazine?
Starting dose is 0.25 mg per pound Q4-6hrs PRN
Maximum dose is 200-400 mg per day
Intramuscular dose is 0.25 mg per pound every 6-8 hours PRN
93
What is the pediatric dosing for Trifluoroperazine?
Starting dose is 1 mg, 1-2 times per day
It can gradually increase to a maximum of 15 mg per day
Similar doses can be used for the intramuscular form
94
What type of adjustment needs to be made for first generation antipsychotic use in pediatric patients with renal disease?
No adjustment needed
95
Generally speaking, all the neuroleptics have a black box warning of increased mortality in elderly patients with what condition?
Dementia
96
Thioridazine and Pimozide also have a black box warning for what specific cardiac side effects?
QTC interval prolongation
97
Patients on IV haloperidol are at a higher risk for which two specific cardiac side effects?
QTC prolongation and torsades de pointes
98
What are the 15 most common side effects associated with first generation antipsychotic use?
EPS, orthostatic hypotension, dry mouth, increased sweating, photosensitivity, blurred vision, retinitis pigmentosa, epithelial keratopathy, constipation, tardive dyskinesia, akithesia, dizziness, sedation, parkinsonism, nasal congestion
99
What are 3 occasional side effects seen with first-generation antipsychotic use?
Prolonged QTC interval
Paralytic ileus
Obstipation
100
What are 12 rare side effects associated with first generation antipsychotic use?
Agranulocytosis, aplastic anemia, leukopenia, jaundice, neuroleptic malignant syndrome, priapism, seizure, lupus, torsades, jaundice, anaphylactic reaction, erythroderma photosensitivity, seizure
101
What is the bioavailability of fluphenazine in the oral form and intramuscular form?
Oral = 2.7%
Intramuscular = 100%
102
What is the bioavailability of chlorpromazine in the oral form and the intramuscular form?
Oral = 32%
Intramuscular = 100%
103
What is the bioavailability of perphenazine in the oral form and the intramuscular form?
Oral = 40%
Intramuscular = 100%
104
What is the bioavailability of pimozide in the oral form?
>50%
105
What is the bioavailability of thioridazine in the oral form?
>60%
106
What is the bioavailability of Haldol in the oral form and the intramuscular form?
Oral = 60-70%
Intramuscular = 100%
107
What is the bioavailability of loxapine, thiothixene, and trifluoperazine in the oral form?
100%
108
Where are all of the first generation antipsychotics metabolized?
In the liver
109
All of the first generation antipsychotics are excreted by the kidneys except for which specific one?
Trifluoperazine
It's excreted via the feces
110
Aside from trifluoperazine, what two other first generation antipsychotics are also found to be excreted partially in the feces?
Loxapine and thioridazine
111
Which specific liver enzyme is responsible for metabolizing perphenazine?
CYP2D6
112
Pimozide, in addition to being metabolized by CYP2D6 is also metabolized in the liver by which two other specific enzymes?
CYP1A2
| CYP3A4
113
What percentage of Haldol is bound to protein?
>90%
114
What percentage of chlorpromazine is bound to protein?
90-99%
115
What percentage of fluphenazine and perphenazine is bound to protein?
91-99%
116
What percentage of Loxapine is bound to protein?
97%
117
What percentage of pimozide, thioridazine, thiothixene and trifluoperazine is bound to protein in the body?
99%
118
What is the half-life of chlorpromazine?
6 hours
119
What is the half-life of perphenazine?
9-12 hours
120
What is the half-life of trifluoperazine?
12 hours
121
What is the half-life of loxapine?
8 hours
122
What is the half-life of Haldol in the oral form?
14-37 hours
123
What is the half-life of thioridazine?
21-24 hours
124
What is the half-life of Fluphenazine in the oral form?
33 hours
125
What is the half-life of thiothixene?
34 hours
126
What is the half-life of pimozide?
55 hours
127
What's the half-life of the long-acting intramuscular form of fluphenazine?
6-9 days
128
What's the half-life for the long acting intramuscular form of Haldol?
3 weeks
129
What is the distribution of loxapine in the body?
Unknown
130
What is the distribution of Haldol in the body?
9.5-22 L per kilogram
131
What is the distribution of perphenazine in the body?
10-34 L per kilogram
132
What is the distribution of pimozide in the body?
10-46 L per kilogram
133
What is the distribution of thioridazine in the body?
18 L per kilogram
134
What is the distribution of chlorpromazine and trifluoperazine in the body?
160 L per kilogram
135
What is the distribution of fluphenazine in the body?
168-220 L per kilogram
136
Why are antipsychotics called neuroleptics?
Early researchers saw that these drugs "seized neurons", causing motor and behavioral slowing in animals
137
Are there differences in efficacy among neuroleptics i.e., first and second generation antipsychotics?
Yes, there are small but significant differences in efficacy
138
Are there differences in side effects among the medications?
Yes, there are substantial differences
139
True or false: some second-generation antipsychotics can cause more adverse effects than first generation antipsychotics
True
140
What has research shown about the effectiveness of second-generation anti-psychotics vs. Haldol?
Some second generation antipsychotics are more effective than Haldol, which caused more EPS
141
What did an important multiple-treatment meta-analysis show regarding the use of clozapine vs. other neuroleptics?
The research showed that clozapine was significantly more effective than other neuroleptics
It also showed that amisulpride, olanzapine, and risperidone were the next most effective neuroleptics
142
Which first generation antipsychotic is associated with pigmentary retinopathy?
Thioridazine
143
Which first-generation antipsychotic is approved for the treatment of tics in Tourette syndrome?
Haldol
144
Besides haloperidol, what other first generation antipsychotic is approved for use in Tourette syndrome?
What is this other antipsychotic also used for off-label?
Pimozide
Also used off label for schizophrenia
145
Which first-generation antipsychotic needs to be discontinued gradually to avoid withdrawal symptoms?
Pimozide
