Exam 3 Flashcards
1
Q
What is the mortality of meningitis?
A
up to 25% depending on the organism
2
Q
In 1995 ______ _____ was 47% of meningitis cases.
A
streptococcus pneumoniae
3
Q
What 1986, _____ _____ was 45% of meningitis cases.
A
haemaphilus influenzae
4
Q
What causes 8% of meningitis cases that is aerobic gram negative bacilli?
A
Listeria monocytogenes
5
Q
What causes 53% of meningitis cases in neonates?
A
Streptococcus agalactiae
6
Q
What pathogen causes meningitis with trauma or CSF shunts?
A
Staphylococcus aureus
7
Q
What is the classic triad of meningitis?
A
fever
neck stiffness
change in mental status (confusion, lethargy, coma)
8
Q
What fraction of patients with meningitis will present with the classic triad?
A
only 2/3
9
Q
What are the long term effects of meningitis if not mortality? (4)
A
hearing loss (10%)
seizure disorders
learning difficulties
neurologic problems (spasticity, paresis, ataxia)
10
Q
What patients with meningitis clinical presentation benefit from CT?
A
immunocompromised h/o CNS disease new onset of seizures papilledema altered consciousness or focal neurological defect
11
Q
How is meningitis diagnosed?
A
CSF examination by lumbar puncture
12
Q
What is seen with meningitis lumbar puncture?
A
gram stain, C&S, cell counts with diff, CSF protein and CSF glucose
13
Q
What are the CNF findings for bacterial meningitis for opening pressure?
A
> 180mm H2O
<20
14
Q
What are the CNF findings for bacterial meningitis for WBC count?
A
1000-5000/mm3
0-10/mm3
15
Q
What are the CNF findings for bacterial meningitis for % of neutrophils?
A
> 80%
16
Q
What are the CNF findings for bacterial meningitis for protein?
A
100-500 mg/dl
10-45
17
Q
What are the CNF findings for bacterial meningitis for glucose?
A
<40 mg/dl
50-100 (normally 2/3 plasma glucose level)
18
Q
What are the CNF findings for bacterial meningitis for gram stain?
A
+ in 60-90%
19
Q
What are the CNF findings for bacterial meningitis for culture?
A
+ in 70-85%
20
Q
What antibiotics (empirical therapy) is used for meningitis?
A
ceftriaxone 2g IV Q12
Dexamethasone
Vancomycin
(1 month-50 years)
21
Q
What is the dosage of ceftriaxone for meningitis empirical therapy?
A
2g IV Q12
22
Q
What antibiotic is prescribed for empirical therapy for meningitis in someone over 50 years old, ETOH and other debilitating disease?
A
Ampicillin \+ ceftriaxone vancomycin dexamethasone
23
Q
What is someone greater than 50 years at increased risk of with meningitis?
A
increased risk of Listeria monocytogenes
24
Q
What is the empiric therapy with a positive gram stain for Gram(+) diplococci S. pneumoniae?
A
Ceftriaxone 2g IV Q 12h
Vancomycin
dexamethasone 10mg Q6h x 4 days
25
What is the empirical therapy for a gram(-)diplococci meningitidis?
Pen G 4MU IV every 24 hours x5-7days
26
What is the empiric therapy for a gram (+) bacilli or coccobacilli : L. monocytogenes?
Ampicillin
| Gentamicin
27
Why is gentamicin being used for empiric therapy for gram (+)?
SYNERGY against gram +
| not for gram - effects
28
What are the findings of dexamethasone with meningitis? (3)
1. reduction in unfavorable outcomes
2. reduction in mortality
3. even better findings in patients with S. pneumoniae meningitis
29
When should adjunctive dexamethasone be used for meningitis?
with documented or suspected S. pneumoniae
30
What is the dose of dexamethasone for meningitis?
10mg every 6 hours x 4 days
31
When should dexamethasone be given in related to antibiotic dose for meningitis?
Give with or 15 minutes prior to antibiotic dose
32
When should dexamethasone not be given to meningitis pts?
If antibiotic has already been started
If patient has septic shock
If NOT caused by s.pneumoniae
33
What is used to measure cognition for AD?
mini-mental status exam
34
What are the neurological changes seen in AD?
reduced:
acetylcholine (ACh)
acetylcholinesterase (AChE)
35
What are the two main objectives in pharm for AD?
1. raise cortical acetylcholine levels
| 2. decrease glutamate-medicated neuronal cell death
36
What are the main goals of therapy?
1. minimize behavioral disturbances
| 2. improve symptoms
37
what are 4 drugs FDA approved for managing AD?
donepezil (aricept)
rivastigmine (exelon)
galantamine (razadyne)
memantine (nameda)
38
what are the 3 acetylcholinesterase inhibitors for AD?
donepezil (aricept)
rivastigmine (exelon)
galantamine (razadyne)
39
What medication is a NMDA antagonist for AD?
memantine (Namenda)
40
What medication is most effective for treating AD?
Acetylcholinesterase Inhibitors (AChEIs)
41
How can Acetylcholinesterase Inhibitors (AChEIs) affect AD?
typically results in small improvements and symptoms
most studies involve mild to moderate symptoms
may improve cognition and behavior
42
What happens if side effects develop with Acetylcholinesterase Inhibitors (AChEIs)?
a switch can usually be initiated 24 hours after discontinuation of the first medicine
43
What are the adverse effects of Acetylcholinesterase Inhibitors (AChEIs) mostly related to?
increased ACh
44
What are the adverse reactions of increased Achievement from Acetylcholinesterase Inhibitors (AChEIs)? (6)
```
depression
headache
anxiety
dizziness
stomach pain
insomnia
```
45
What are the Acetylcholinesterase Inhibitors (AChEIs) pronounced adverse effects on the the GI tract? (7)
```
nausea
vomiting
diarrhea (N/V/D)
dehydration
decreased appetite
weight loss
stomach ulcers
```
46
Incidence and seriousness of Acetylcholinesterase Inhibitors (AChEIs), adverse effects are __________ _______.
dose related. and may require drug discontinuation
47
What methods are used for Acetylcholinesterase Inhibitors (AChEIs) to decrease incidence and seriousness of Acetylcholinesterase Inhibitors (AChEIs)?
minimize by starting low and dose titration
48
Who is at risk for dose related SE of Acetylcholinesterase Inhibitors (AChEIs)?
pts <50kg (110lbs)
elderly
both have increased incidence
49
What medication was the first agent approved for moderate to severe AD?
Donepazil (aricept)
50
What is the dosing of Donepazil (aricept)?
starting dose is 5mg daily
increase to 10mg daily after 4-6 weeks
may increase to 23mg daily after 3 months
51
What time of day should Donepazil (aricept) be given?
HS with or without food
52
What dosage of Donepazil (aricept) is available only brand name?
23mg Extended release Tablet
53
What medication is approved for mild to moderate AD?
Galantamine (Razadyne)
54
What are the MOI of Galantamine (Razadyne)? (2)
inhibits AChE & stimulates nicotinic receptors
| stimulates at non-ACh site (allosteric modulation)
55
What is important to remember about renal adjustment for Galantamine (Razadyne) for AD?
moderate renal impairment: max dose of 16mg/day
DONT use with severe renal impairment
56
What is important to remember when converting to Galantamine (Razadyne) with poor tolerability with donepezil or rivastigmine?
wait until side effects subside or allow 7 days washout prior to giving Galantamine (Razadyne).
57
What is important to remember when converting to Galantamine (Razadyne) with no intolerance to donepezil or rivastigmine?
begin galantamine the day after stopping.
58
What is a transdermal patch approved for severe AD?
rivastigme (exelon)
59
How does rivastigme (exelon) compare to oral medication for AD?
less N/V/D
similar rates of bradycardia & syncope as oral forms
PATCH doses are immediately therapeutic (not oral-titrate)
60
How can allergic contact dermatitis be prevented with rivastigme (exelon)?
rotate application sites
don't reuse the same site for 14 days
recommended: upper/lower back
alternate sites: chest/upper arm
61
What is the unique MOA of rivastigme (exelon)?
"pseudoirreversible"
| Inhibits G1 AChE> G4 AChE
62
What is significant about the metabolism and elimination of rivastigme (exelon)?
results in fewer drug-drug interactions
63
What medication for AD is a N-methyl-D-aspartate (NMDA) antagonist?
mementine (nameda)
64
What medication was recently approved for mod-severe AD that results in cognitive improvement when added to ACHIs?
mementine (nameda)
65
mementbine (nameda) side effects are _____ and _____.
infrequent; mild
66
What is the dosage in renal impairment for mementine (nameda)?
mid to moderate: no adjustment
| severe impairment: 5mg BID
67
What monoamine neurotransmitters changes are seen in the symptoms of depression? (3)
norepinephrine (NE)
Serotonin (5-hydroxytryptamine; 5-HT)
Dopamine (DA)
68
What agents block reuptake/metabolism of amines making them effective for depression?
Biogenic amine hypothesis
69
What are medical conditions that can cause depression? (5)
```
Hypothyroidism
Addison or Cushings Disease
Pernicious Anemia
Severe anemia
HIV/AIDS
```
70
What are the antihypertensives that can cause depression?
clonidine (Catapres)
| Diuretics
71
What other mediations besides HTN meds that can cause depression?
oral contraceptives
steroids
ACTH
72
What are the factors that increase risk of suicide?
```
suicidal plans/attempts
male genders (females attempt more but males succeed)
single or living alone
inpatient status
feelings of hopelessness
```
73
What should be done for patients that are high risk of suicide?
immediately refer
74
What are the 3 phases of depression treatment?
acute phase: 3 months
continuation phase: 4-9 months
Maintenance phase: 12-36 months (prophylaxis)
75
What does the duration of therapy for depression depend on?
Depends on risk of recurrence
76
How often should pt be evaluated for treatment in acute phase?
evaluate weekly or twice a month
continue until substantial improvement occurs
77
During the acute phase of depression what should happen with <50% improvement (non response, partial response) at 4 weeks?
change meds and consider non adherence
78
What amounts should be prescribed to patients in acute phase depression?
do not presribe large amounts to seriously depressed patients
79
All patients should complete this phase of depression( usually 3 months)
acute phase
80
During continuation phase what might be indicated by residual symptoms (partial remission)?
reccurence
early relapse
chronic course
81
How long is the continuation phase?
4 months minimum AFTER the acute phase. should continue treatment until symptoms have resolved
82
When should you consider discontinuation of depression treatment?
consider if no recurrence or relapse during continuation phase
83
What might be a side effect of early discontinuation of depression treatment?
higher risk of relapse
taper medication over several weeks
84
How long is the maintenance phase of depression treatment last? how does it effect recurrence?
12-36 months
| decreases recurrence by 2/3
85
When is maintenance indicated for depression patients?
```
yearly episodes
impairment from mild residual symptoms
chronic major depression
severe episodes
high risk of suicide
```
86
What is a non pharmacological therapy for depression?
psychotherapy to all those willing
87
When is psychotherapy 1st line for depression?
mild-moderate depression
88
The initial choice of antidepressants is made empirically based on: (7)
```
previous response history
pharmacogenetics
presenting symptoms (fatigue vs agitation)
drug-drug interaction potential
side effect profile
patient preference
cost
```
89
What class of medication is superior to other antidepressants for major depression?
Selective Serotonin Reuptake Inhibitors (SSRIs)
90
Why are Selective Serotonin Reuptake Inhibitors (SSRIs) considered 1st line for major depression?
due to overdose safety and tolerability
fewer anticholinergic and cardiovascular adverse effects than TCAs
91
What is a common side effect of Selective Serotonin Reuptake Inhibitors (SSRIs)?
decreased libido
92
What happens if Selective Serotonin Reuptake Inhibitors (SSRIs) are stopped abruptly?
withdrawal syndrome
93
What Selective Serotonin Reuptake Inhibitors (SSRIs) is less likely to cause withdrawal syndrome?
fluoxetine (prozac)- metabolite has longer half life; improves adherence
94
When are Selective Serotonin Reuptake Inhibitors (SSRIs) contraindicated?
patients on or recently (5-6 weeks) taken off MAOIs (Serotonin syndrome)
95
What is the first Selective Serotonin Reuptake Inhibitors (SSRIs) approved for children?
fluoxetine (prozac)
96
What is the black box warning of fluoxetine (prozac)?
increased suicidal ideation in children and adolescents
97
Why is fluoxetine (prozac) once daily dosing?
active metabolite with longer halflife than other SSRIs
98
When is fluoxetine (prozac) used with caution?
pts with bipolar disorder because one metabolite persists for weeks and may aggravate the manic state
99
What is the maximum dose od fluoxetine (prozac)?
80mg/daily
100
What SSRI blocks serotonin reuptake at lower doses; blocks domain reuptake at HIGHER doses?
paroxetine (Paxil)
sertaline (Zoloft)
101
Since paroxetine (Paxil) blocks dopamine reuptake at higher doses it may help contribute to its ______ action.
antidepression
102
What is the maximum dose of paroxetine (Paxil)?
50mg/daily
103
What is the maximum dose of sertaline (Zoloft)
200mg daily
104
What is one of the oldest SSRIs?
fluvoxamine (Luvox)
105
What SSRI may cause or worsen sexual dysfunction?
fluvoxamine (Luvox)
106
What is the maximum dose of fluvoxamine (Luvox)?
300mg daily
107
Medication that is FDA approved to treat symptoms of major depression?
citalopram (Celexa)
108
What was the FDA warning for citalopram (Celexa)?
>40mg daily may prolong QT interval
109
When should citalopram (Celexa) be avoided?
congenital long QT syndrome
other drugs causing QT prolongation
or at high risk for Torsades de pointes
110
What is the maximum dose of citalopram (Celexa)?
40mg daily (used to be 60mg)
111
What is the S-isomer of citalopram?
escitalopram (Lexapro)
112
What medication may help reduce the frequency and severity of hot flashes in perimenopausal women?
escitalopram (Lexapro)
113
What is the maximum dose of escitalopram (Lexapro)?
20mg daily
114
What are the newer 2nd generation agents for depression?
Mixed 5-HT/NE Reuptake inhibitors
115
What class of medications are SNRIs?
Mixed 5-HT/NE Reuptake inhibitors
116
What are the "dual action" antidepressants?
Mixed 5-HT/NE Reuptake inhibitors
117
What medication can block monoamine uptake more selectively than TCAs WITHOUT cardiac conduction effects like TCAs
Mixed 5-HT/NE Reuptake inhibitors
118
What are the Mixed 5-HT/NE Reuptake inhibitors agents? (3)
venlafaxine (Effexor)
duloxetine (cymbals)
desvenlafaxine (pristiq)
119
What medication is superior for severe depression than other SSRIS or TCAs that is also effective for chronic pain?
venlafaxine (Effexor)
120
What medication may double the risk of miscarriage?
venlafaxine (effexor)
121
What is the O-desmethylvenlafaxine (metabolite) of venlafaxine?
desvenlafaxine (Pristiq)
122
What medication is 10x more effective at blocking serotonin than NE uptake?
desvenlafaxine (Pristiq)
123
Medication with higher rates of discontinuation syndrome?
desvenlafaxine (Pristiq)
124
What is duloxetine (Cymbalta) FDA approved for? (3)
major depressive disorder
neuropathic pain
fibromyalgia pain
125
Prescribers observed that duloxetine (Cymbalta) is not chosen a lot because there are so many other options given what side effect?
hepatic disorders and drug interactions
126
When is duloxetine (Cymbalta) not recommended?
CrCl <30ml/min
| with hepatic impairment
127
What medication inhibits both NE & dopamine reuptake with NO action on serotonin?
bupropion (Wellbutrin)
128
How does bupropion (Wellbutrin) compare to TCAs and SSRIs?
similar in efficacy to TCAs and SSRIs
less N/D, somnolence and sexual dysfunction than SSRIs
effective alternative or adjunctive for SSRI non responders
129
What are mixed serotonin/NE reuptake inhibitors that are effective for all depressive subtypes?
Tricyclic antidepressants (TCAs)
130
What are common side effects of Tricyclic antidepressants (TCAs) and why their use is limited?
```
anticholinergic effects
sedation
orthostatic hypotension
seizures
cardiac conduction abnormalities
```
131
What are the commonly available Tricyclic antidepressants (TCAs) agents?
tertiary amines
secondary amines
high risk of death with overdose
132
What are the older 1st generation agents, irreversibly, non selecting binding MAO-A&B?
monoamine oxidase inhibitors (MAOIs)
133
monoamine oxidase inhibitors (MAOIs), are antidepressants with similar effects to _____.
TCAs
134
What are monoamine oxidase inhibitors (MAOIs) not considered 1st line?
due to risk of "serotonin syndrome"
| numerous drug-drug interactions
135
What are the common monoamine oxidase inhibitors (MAOIs)?
phenelzineu (Nardil)
| selegiline (Eldepryl)
136
What are the potentially life threatening adverse drug reactions of serotonin syndrome? (4)
therapeutic drug use with SSRIs
intentional self poisoning with SSRIs
Interaction between 2 drugs (SSRI + another drug)
tyramine-containing foods while on MAOIs
137
Why is patient counseling critical for serotonin syndrome?
dietary and medication restrictions (for MAOIs)
| early symptom recognition (pts and clinicians)
138
What is the usual triad of serotonin syndrome?
mental status changes
autonomic hyperactivity
neuromuscular abnormalities
139
How often does serotonin syndrome occur in SSRI overdoses?
14-16%
140
what are the notable autonomic findings of serotonin syndrome?
shivering
diaphoresis
mydriasis
141
What are the clinical presentations of serotonin syndrome besides the notable autonomic findings?
labile blood pressure/hypertension
| hyperthermia >41C is critical
142
What is the treatment for serotonin syndrome?
STOP precipitating agent!
TEMP
5-HT 2A antagonist; cyproheptadine
monitor & treat hypotension
143
What should you do if temp is greater than 41C with serotonin syndrome?
```
immediate sedation with benzodiazepines (diazepam)
neuromuscular paralysis (vecuronium-nondepolarizing)
orotracheal intubation
```
144
What is significant about Triazolopyridines? (4)
newer, mixed- action agents
less sexual and sleep associated side effects
pharmacologically similar to TCAs
fewer anticholinergic side effects
145
How does nefazodone (Serzone) work?
blocks 5-HT 2A receptor and serotonin reuptake
efficacy similar to SSRIs
less sexual and sleep related side effects
146
What are the recent reports of nefazodone (Serzone) ?
hepatic toxicity
| black box warning of possible liver failure
147
What is significant of mirtazapine (remeron)?
efficacy is similar to the TCAs and SSRIs
| fewer Uses especially sexual and sleep side effects
148
What is significant about trazadone (desyrel)?
```
less anticholinergic (dry mouth, constipation and tachycardia)
less sexual side effects than most TCAs
```
149
Why is trazadone (desyrel) not associated with increased appetite and weight gain?
limited by dizziness, orthostatic hypotension & sedation
| caused by potent alpha 1 blockade
150
What medication is FDA apprised for adjunctive depression on 11/20/07, that was originally approved as an "atypical" antipsychotic agent
aripiprazole (abilify)
151
What is the US lifetime prevalence of Schizophrenia?
1% (0.6-1.9%)
152
What is the lifetime prevalence of suicide in Schizophrenia?
10%
153
What is the genetic risk factor of schizophrenia if 2nd degree relative has it?
3%
154
What is the genetic risk factor of schizophrenia if 1st degree relative has it?
10%
155
What is the genetic risk factor of schizophrenia if BOTH parents have it?
40%
156
What is the genetic risk factor of schizophrenia in monozygotic twins?
48%
157
Schizophrenia is NOT ______
split personality
158
What is schizophrenia?
a chronic disease of thought & affect (expression)
159
What are the acute psychotic episodes of schizophrenia? (3)
```
auditory hallucinations (especially voices)
delusions (fixed false beliefs)
Ideas of influence (external forces control their actions)
```
160
What are the symptom classifications of schizophrenia? (3)
Positive (most obvious/dramatic)
Negative (functional impairment)
Cognitive
161
What are the characteristics of positive schizophrenia?
suspiciousness, unusual thought content (delusions), hallucinations, conceptual disorganization
162
What are the characteristics of negative schizophrenia?
affect flattening, logia(inability to speak, anhedonia(total loss of pleasure things, avocation(lack of desire, drive or motivation to pursue meaningful goals
163
What are the characteristics of cognitive schizophrenia?
impaired attention, impaired working memory, impaired executive function
164
What is the mainstay of treatment for schizophrenia?
pharmacotherapy
165
What is the mainstay for non pharmacological treatment for schizophrenia?
psychosocial rehab
166
What is included in the lab work up for schizophrenia prior to pharmacotherapy?
```
vitals
CBC
electrolytes
LFTs
renal function
ECG
fasting glucose
lipid studies
thyroid function
urine drug screen
```
167
Why is it important to do lab work up for schizophrenia prior to starting pharmacotherapy?
baseline
| rule out medical or substance abuse causes
168
What is the rational of "Dopamine Hypothesis" pharmacotherapy for schizophrenia?
acute psychotic episodes increase dopamine neurotransmission
| results in hypersensitivity to stimuli
169
What is the rational of "Dysregulation Hypothesis" for schizophrenia pharmacotherapy?
Since inhibitory neurons are modulated by dopamine, serotonin, acetylcholine norepinephrine; these became targets for the new antipsychotics
170
In schizophrenia, antipsychotic efficacy is proportional to what?
dopamine (D2) affinity
171
Non D2 (dopamine) receptors are associated with what?
side effects and adverse effects
172
What was the MOA of the first generation antipsychotics?
Dopamine antagonism, especially D2
| "typical antipsychotic"
173
Older term applies to antipsychotic drugs with prominent D2-dopamine receptor antagonism and risk of adverse extrapyramidal symptoms
neuroleptic
174
What is called the "typical" antipsychotic?
neuroleptic
175
What is the MOA of "atypical" antipsychotics?
act on multiple receptors not just D2
| Second Generation Antipsychotics-SGAs
176
What is the preferred term of neuroleptics?
First Generation Antipsychotics (FGA)
177
What are the first generation antipsychotics?
fluphenazine (Prolixin)
Haloperidol (Haldol)
long acting depot injection formulations available but highly potent
178
What is the result of first generation antipsychotics (FGA)?
immediate D2 receptor blockade
179
How long does it take for first generation antipsychotics (FGA) therapeutic effect to develop?
6-8 weeks
180
What does the efficacy of FGAs correlate with?
decreased presynaptic release of dopamine
181
For FGAs what is the result of greater than 60% D2 blockade?
clinical response
182
For FGAs what is the result of greater than 70% D2 blockade?
hyperprolactinemia
183
For FGAs what is the result of greater than 80% D2 blockade?
increased risk of extrapyramidal symptoms
184
What are the adverse effects of FGAs?
```
sedation
dystonias/parkinsonism movement disorders
anticholinergic effects
orthostatic hypotension
seizures
hyperprolactinemia
moderate weight gain
prolonged QT interval
```
185
What are anticholinergic effects?
```
constipation
urinary retention
blurry vision
tachycardia
dry eyes, mouth and throat
```
186
What antipsychotics have the worst increase in QTc baseline to the least? (3)
Thioridazine (Mellaril)- worst
Ziprasidone (Geodon)
Haloperidol (Haldol)-least
187
What are the early neurological effects of FGAs? (3)
Acute dystonia- muscle spasms of tongue, face, neck and back (mimic seizures)
Akathisia (motor restlessness, pacing foot tapping)
Parkinsonism (bradykinesia, rigidity, variable tremor)
188
When is the maximal risk of acute dystonia associated with FGAs?
1-5 days
189
What is acute dystonia treated with in FGA adverse effects?
diphenhydramine IM
| benztropin IM
190
When does akathisia present with FGA adverse effects?
5-60 days
191
When does Parkinsonism present with FGA adverse effects?
5-30 days
192
What are the late neurological effects of FGAs (3)?
Neuroleptic Malignant Syndrome
Tardive dyskinesia
Perioral tumor
193
When does Neuroleptic Malignant Syndrome present with FGA adverse effects? What is the mortality?
weeks
| 10% mortality
194
When does Tardive dyskinesia present as an adverse effect of FGAs?
after months- years of treatment
195
What is rabbit syndrome? and when does it present as an AE of FGAs
Perioral tremor
| months- years
196
What is significant about Neuroleptic Malignant Syndrome treatment?
antiparkinson agents NOT effective
197
When is Neuroleptic Malignant Syndrome more common?
pts on high potency FGAs
depot FGAs
dehydrated or exhausted patients
198
What is the treatment for Neuroleptic Malignant Syndrome?
discontinue the antipsychotic
The DA agonist bromocriptine reduces rigidity, fever and CK in up to 94% of patients
Another DA agonist, amantadine works in up to 63%
199
What is the antipsychotic recommended after neuroleptic malignant syndrome?
use only SGAs for rechallenge post NMS
200
What are the second generation antipsychotics, early agents?
```
clozapine (Clozaril)
rispeidone (Risperdal)
olanzapine (Zyprexa)
quetiapine (Seroquel)
ziprasidome (Geodon)
aripiprazole (Ability)
```
201
What are the second generation antipsychotics, later agents?
palpiperidone (Invega)
Iloperidone (Fanapt)
asenapine (Saphris)
lurasidone (Latuda)
202
What is the MOA of second generation antipsychotics?
all are B2 antagonists; less tightly bound
D1, D4 antagonism
Norepinephrine and Serotonin antagonism
203
What is significant about second generation antipsychotics compared to first generation?
second generation have significantly less risk of extrapyramidal effects but tradeoff is increased risk of metabolic effects (especially weight gain)
204
What is the benefit of second generation antipsychotics (atypical antipsychotics)?
-few or no acutely occurring extrapyramidal side effects
enhanced efficacy (especially for negative symptoms & cognition)
absence of tardive dyskinesia
205
What is the only SGA to fulfill all criteria?
clozapine
206
What are the side effects of second generation antipsychotics? (7)
```
moderate to severe weight gain (olanzapine, clozapine)
diabetes mellitus
seizures (clozapine)
nocturnal salivation (clozapine)
agranulocytosis (clozapine)
myocarditis (clozapine)
lens opacities (clozapine)
```
207
The first atypical antipsychotic drug that is FDA approved despite risk of agranulocytosis?
Clozapine (clozaril)
| risk of death (0.013%)
208
When is clozapine prescribes? What must be done if prescribed?
reserved for patients who fail on other agents
| weekly CBCs x 6 months; then every 2 weeks
209
What is significant about early 2nd generation antipsychotics?
virtually no EPS
reduced risk of tardive dyskinesia
especially good for "negative" symptoms
significantly less relapse than first generation
210
What is the rate of relapse of second generation, risperidone?
25%
211
What is the rate if relapse first generation anti psychotic?
40%
212
What is the 9-OH metabolite of risperidone?
Paliperidone (Invega)
213
What is the SGA that has increased risk of orthostatic hypotension
Iloperidone (Fanapt)
214
What is the SGA oral dissolving sublingual tablet?
Asenapine (Saphris)
215
How is Asenapine (Saphris), the SGA taken?
SL!
| do not chew or swallow due to increased risk of anaphylaxis & angioedema
216
What are the 3 phases of schizophrenia treatment?
1. acute phase
2. stabilization phase
3. maintenance phase
217
What is the initial goal for treatment of first (acute) psychotic episode?
to calm agitated patients
218
Why is immediate treatment important in first (acute) psychotic episode?
immediate treatment improves long term outcome
219
What so most psychiatrists usually prescribe for treatment of first (acute) psychotic episode?
SGA (other than clozapine)
| decreased anger & anxiety usually seen in 24-48 hours
220
When is maximal improvement seen in the treatment of first (acute) psychotic episode?
seen by 6-8 weeks
221
Suicide risk _______, as other symptoms improve.
INCREASES
222
What are the indications of clozapine use for schizophrenia?
lack of response with other SGAs
| intolerable side effects of other antipsychotics
223
When are FGAs usually prescribed for schizophrenia?
typically NOT 1st line therapy
may be used before a SGA if chronically ill patients had a precious satisfactory response
224
What is the pharmacotherapeutic algorithm for stage 1?
only for patients with FIRST schizophrenic episodes
| SGAs are considered 1st line
225
What is the pharmacotherapeutic algorithm for stage 2?
chronically ill patients recently started on antipsychotics
or new onset patients with poor response to stage 1
mono therapy with a FGA or SGA (not clozapine)
choose a different antipsychotic than used in stage 1
226
What is the pharmacotherapeutic algorithm stage 3?
switch to clozapine (mono therapy)
Increased efficacy for suicidal behavior
Consider earlier in suicidal patients
monitor CBC weekly for agranulocytosis
227
What is the pharmacotherapeutic algorithm stage 4?
continue clozapine
| add an additional antipsychotic (combination therapy)
228
What is the pharmacotherapeutic algorithm stage 5?
trial of mono therapy AP
| use a FGA or SGA not previously used
229
pharmacotherapeutic algorithm stage 6?
consider combination therapy
when switching APs:
overlap 2nd agent for 1-2 weeks
taper & D/C 1st agent (taper clozapine slowly)
230
What is combination therapy?
involves using 2 APs simultaneously
231
What is augmentation treatment?
addition of a non antipsychotic drug to an antipsychotic drug
232
What are the augmentation guidelines? (4)
use only in inadequately responding patients
augmentation agents are rarely effective for schizophrenia if used alone
Augmentation responders usually improve rapidly
If symptoms so not improve, D/C the augmentation agent
233
What are the mood stabilizers? (3)
Lithium
Valproic acid
Carbamazepine
234
What are the augmentation gents? (3)
mood stabilizers
selective serotonin reuptake inhibitors
beta- blockers
235
What are the beta blockers used for augmentation agents?
anti-aggressive effect
propranolol
pindolol
nadolol
236
What is important to know about the combination therapies (steps 4-6)
combo trails should be time limited to 12 weeks
| if no improvement, taper 1 medication then discontinue
237
In general a series of ______ is preferred over _______ combinations
mono therapies; AP
238
What is important to note about stabilization (maintenance) treatment?
1st presentation may respond sooner
meds may reduce symptoms, but are not curative
all symptoms may not abate
239
The stabilization (maintenance) treatment prevents relapse. What is the % of relapse vs drug and placebo?
18-32% on drug
| 60-80% on placebo
240
How long should the stabilization (maintenance) treatment occur?
continue at least 12 months past remission
241
When are long-acting depot injectable APs used?
recommended in unreliable (non adherent) patients
NOT used as 1st line therapy
look for side effects as a cause of non adherence
242
What are the long acting depot injectable APs?
haloperidol decanoate-Haldol (FGA)
fluphenazine decanoate- Prolixin (FGA)
Risperidone microspheres- Risperdal (SGA)
243
How is haloperidol decanoate prescribed? (sustained release)
use 10-15 times the oral daily dose
round dose up to nearest 50mg
give dose via deep IM (NOT IV) injection every month
Overlap with PO haloperidol for 1st month
244
What is the immediate release of haldol injection?
haldol lactate
245
How is fluphenazine decanoate (Prolixin) given?
use 1.2 times the oral daily dose
use 1.6 times PO dose for more acutely ill patients
Round dose up tp nearest 12.5 mg interval
Overlap with PO fluphenazine for 1 week
246
What is the only SGA depot agent ; needs reconstitution
Risperidone microspheres (Risperdal)
247
What is the optimum dose of risperidone microspheres (Risperdal)?
25-50mg
higher doses show no benefit but more EPS
248
What type of bipolar disorder is associated with at least 1 episode of MANIA and affects 1% of the worldwide population?
Bipolar I Disorder
249
What type of bipolar disorder is associated with at least 1 episode of HYPOMANIA?
Bipolar II Disorder
250
What is important to rule out in bi-polar disorder?
amphetamine abuse
| pheochromocytoma
251
What was bipolar disorder originally called?
Manic-Depression
252
What is the unique hallmark of bipolar disordeR?
mania
253
What is bipolar disorder characterized by?
elevated mood
overactivity
lack of need for sleep
increased optimism
254
What is sufficient for diagnosis of bipolar disorder?
a single manic episode not caused by amphetamine abuse or pheochromocytoma
255
What are the types of bipolar disorder?
one manic episode then frequent depressive episodes
alternating episodes of mania and depression annually
mania every few years without a depressive episode
256
What are rapid cyclers of bipolar disorder?
patients with > 4 manic or depressive cycles year
257
What percentage of people with bipolar disorder have family history?
50%
258
What is the risk of bipolar disorder in the siblings on affected patients?
10%
259
What are the non-treatment endangers of acute mania? (medical emergency)
marriage job and patients life
260
What treatment is effective in acute mania?
Antipsychotic drugs
261
What treatment is important in acute mania with violent patients?
rapid onset drugs like short acting injectables
262
What treatment is good in acute mania for patients that are compliant?
newer "atypical" secondary antipsychotic agents
263
What are the mood stabilizers that can be used for acute mania?
lithium
valproic acid
carbamazepine
264
What is the treatment for bipolar depression? (3)
SSRIs
TCAs
MAOIs
265
What can happen when giving antidepressants in bipolar depression?
pt may switch from depression to mania
266
When should antidepressants not be used in bipolar depression?
pts with h/o dangerous mania episodes
267
Lithium is a classic mood stabilizer for prophylaxis of bipolar disorder and bipolar depression, what is the trough level for seizure and death?
> 2.5mEq/L
268
How often should blood levels be drawn when starting lithium for bipolar disordeR?
2x per week until stable
269
When should trough samples be collected for lithium in bipolar disorder pts?
just prior to next dose
270
In bipolar disorder, _____ was found more more effective than ______ for suicide prevention
lithium prophylaxis; valproate
