Final psychopharm Flashcards
Paliperidone
Antipsychotic (Invega sustenna)
Available as a long acting injectable
Active metabolite of risperidone
First generation antipsychotics and risks
TD dystonia akathesia parkinsonism Metabolic-wt gain, dyslipidemia, hyperglycemia
clozapine facts
highly effective antipsychotic risk of several side effects least likely to cause EPS used more for refractory pts- most effective CAN CAUSE AGRANULOCYTOSIS
Olanzapine facts
Very effective antipsychotic
chemical derivative of clozapine
reduced EPS, superior to Haldol
Weight gain
First gen antipsychotics names
Haloperidol chlorpromazine (thorazine)
Big concern and side effect seen with risperidone
elevated prolactin levels
secondary negative symptoms of schizophrenia
Social isolation from paranoia
apathy from depression
neuroleptic induced parkinsonism
First Generation antipsychotic receptors facts
65% occupany of striatal D2 receptors is needed for efficacy
Neuro side effects emerge when there is greater than 80% occupancy
High potency conventional agents (haldol and fluvenazine) are highly selective of D2 so they are more likely to cause EPS (dystonia, akathesia, parkinsonism)
akathesia
extremely distressing motor restlessness primarily in lower extremities
CAN BE MISTAKEN FOR PSYCHOTIC AGITATION
DOSE DEPENDENT
CAN SWITCH TO A MED THAT IS KNOWN FOR LESS AKATHESIA
Propanolol can be helpful for akathesia
WHAT TO DO WITH AKATHESIA
LOWER THE DOSE
POSSIBLE PROPANOLOL
POSSIBLE MIRTAZEPINE (antagonizes serotonin 2A-receptors implicated in pathology of akathesia
Dystonia
sustained muscle spasms (anywhere but often neck, tongue, back)
can occur within the first 4 days
dystonia is rare in atypical antipsychotics like quetiapine and clozapine
antipsychotic induced parkinsonism facts
tremor, stiffness, gait disturbance
diminished facial expression
most common in high potency first gen antipsychotics
elderly concerns with first gen antipsychotics
High risk anticholinergic effects -constipation, dry mouth, blurred vision, urinary retention, memory impairment
TD facts
rarely appears right away (less than 6 mo)
Once occurs may be irreversible
Involuntary, choreiform (quick/nonrythmic) movements of mouth tongue and upper extremities.
also possible dystonic form
lifetime risk 50-60%
Lower dose or switch to clozapine
lowering dose or switching may cause withdrawal dyskinesia that may resolve in 6wks
severe cases-tetrabenzine or deep brain stimulation
neuroleptic malignant syndrome facts
Rare, potential lethal complication
hyperthermia
rigidity, confusion,diaphoresis
elevated CPK, leucocytosis
clozapine facts
tricyclic dibenzodiazepine derivative antipscyhotic
for tx resistant schizophrenia or schizoaffective
tx of SI
binds to all 5 dopamine subtypes, muscarinic, histaminergic, cholinergic, and seritonergic
Also modulates glutamatergic NMDA sensitivity and BDNF
Aripiprazole pharmacodynamics and kinetics facts
Abilify
dihydroquinolinone unrelated to other antipsychotics
approved for schizophrenia and bp mania and mixed
partial agonist of D2-30% activity compared to dopamine
high affinity of 5ht1a partial agonist, full agonist 5ht2A
moderate affinity to alpha adrenergic and histamine
CYP 450 2D6 and 3A4
long half life (up to 94 hrs)
2wks needed to achieve steady level after dose initiation or change
What needs to be done with risperidone and paliperidone? And other concerns?
requires careful titration to avoid EPS
Monitoring of hyperprolactinemia
metabolic syndromes
Which two antipsychotics are known to have the highest metabolic liability?
Clozapine
Olanzapine
clozapine class and action
tricyclic dibenzodiazepine derivative binds to several CNS receptors FDA approved for schizophrenia, schizoaffective, SI peak plasma levels reached in 2 hrs CYP 1A2, 3A4, 2D6
clozapine lab requirements
To initiate clozapine:
wbc’s at least 3500
ANC at least 2000
weekly cbc x 6mo then biweekly for 6 mo, then monthly if they stay stable
additional cardiac and neuro possible side effects with clozapine
myocarditis, cardiomyopathy (0,01-0,2%) present like flu like illness, cp, reduced ejection fraction, elevated CPK, T wave changes
Seizures- 5-10%- usually caused by rapid dose escalation or increased plasma concentrations
Obesity, DM(markedly reduced insulin sensitivity), dyslipidemia
Methylphenidate
IR- behavioral effects peak at 1-2 hrs
Dissipate within 3-5
More rapidly absorbed and peaks sooner than Ritalin(similar pharmacokinetic profile)
equal racemic mixture of d,l-threo-MPH
concerta
racemic mixture of d,l-threo-MPH 50/50 (essentially methylphenidate)- osmotic release oral system (OROS) labeled for 12 hrs of coverage
instead of Methylphenidate 3x daily
focalin
primary active form of MPH d-threo isomer available in immediate and extended release
10mg of MPH is equivalent to 5mg of d-MPH
Daytrana
MPH through the skin via transdermal system
effects within 2 hrs and 3 hrs after removal
doesnt do first pass metabolism so lower doses may be needed than oral doses
Good for pts’ who can’t tolerate PO
Quillivant
AKA MEROS
oral suspension MPH
may be useful for children who cant tolerate pills or experience skin reactions to the patch
Amphetamine forms
dextroamphetamine (dex;dexadrine)
Mixed amphetamine salts (MAS;Adderall)
Lisdexamphetaminedimesylate (Vyvance;LDX)
DEX facts
Behavioral effects peak in 1 to 2 hrs
half life 4-6hrs
MAS/Adderall contains
equal portions of 4 amphetamine salts
the 2 isomers have different pharmacodynamic properties
some pts with ADHD preferentially respond to one isomer over another.
efficacy of MAS is well established in youth and adults
extended release delivers immediate release then 4 hrs later delayed release
LDX/vyvanse
amphetamine prodrug lysine(amino acid) linked to d-amphetamine
prodrug is metabolically hydrolyzed in the body to release d-amphetamine to reduce abuse liability.
Melatonin
Hormone secreted by the pineal gland helps regulate circadian rythms
concerning side effects: Migraines, nightmares, aggression
stimulants interactions and side effects
Monitor with simpathomimetic (pseudoephedrine) and TCA’s
MAOIs contraindicated with stimulants
nausea, dry mouth, difficulty falling asleep, obsessiveness, rebound phenomena, anxiety, irritability, dysphoria, wt loss
ATMX/atomoxetine
Strattera
unscheduled
blocks NE reuptake- increasing synaptic NE
increases dopamine in the frontal lobes
cmax occurs 1-2 hrs
plasma half life 4-5 hrs,CNS affects over 24 hrs
metabolized cyp2d6
If pt taking other 2d6 meds like fluoxetine, paroxetine, quinidine may need lower doses of ATMX
0.5-1.4mg/kg/d
early response up to 10 wks for full effects
may be good for pt’s with substance abuse issues
side effects of ATMX/Strattera
children- decreased appetite, dyspepsia, dizzyness
adults- dry mouth, insomnia, nausea, decreased appetite, constipation, dizzyness, decreased libido, sweating, difficulty attaining or maintaining erection.
watch for any signs of hepatitis or si
clonidine facts
alpha adrenergic agonist primarily used for HTN
extended delivery (Kapvay) approved for ADHD youth 6-17
less effective than stimulants but good for traumatized children, ODD and ADHD, and ADHD sleep disturbances
clonidine side effects
abrupt withdrawal- rebound htn extreme caution with beta or ca channel blockers (ok with stimulants) sedation dry mouth vivid dreams depression confusion
Guanfacine facts
most selective alpha 2 adrenergic agonist
mimics binding of NE in the PFC
possible less sedation than clonidine and longer duration of action
milder CV profile
guanfacine adverse effects
sedation
irritability
depression
buproprion facts
modulates NE and Dopamine
often used in pts with ADHD and comorbidities
buproprion side effects
more stimulating than other antidepressants-irritability
exacerbate tics
drug induced seizures
irritability during marijuana withdrawal
TCA’s for ADHD
effective but less robust than stimulants
may be useful in comorbid anxiety, depression, tics, depression but potential cardiotoxicity
Modafinil facts
novel stimulant distinct from amphetamine approved for narcolepsy activates hypothalamic regions not for kids SJS potential to exacerbate mania
Meds for sedation in ETOH withdrawl
Diazepam 10-20mg every 1-2 hrs until sedation achieved
Chlordiazepoxide 50-100mg
Lorazepam -shorter acting for elderly or liver disease
phenobarbitol to augment benzo’s and prevent ICU admit
DT facts
Generally occurs 24-72 hrs after abstinence disorientation (person, place, time) tremor hyperactivity fever marked wakefullness increased autonomic tone hallucinations can last 2-3 days can resolve with sleep prognosis good with meds can cause convulsions, coma, death
Wernickie’s encephalopathy facts
opthalmoplegia ataxia mental disturbance nystagmus disorientation exhaustion/lethargy dehydration
fetal alcohol spectrum disorder signs
epicanthal folds (upside v down folds) flat nasal bridge small upper lip smooth philtrum (above upper lip) railroad track ears small palpebral fissures (eyes)
GAD critera
EGADS. Im so MISERA-ble Excessive General Anxiety Daily (most days) Six months
3 or more: Muscle tention Irritability Sleep disturbance Energy Restlessness Attention
Alzheimers
disease cause by destruction of acetylchoine releasing neurons
(ACH-remember autonomic, contraction, hippocampus)
ACH
Autonomic-PSNS-bradycardia, gi motility,salivation, sexual arousal
Contraction-Muscle
Hippocampus-learning, memory, awakeness, attention
What can risperidone do?
Cause markedly elevated serum prolactin levels (due to dopamine blockade)
what are young pt’s at risk for with first gen antipsychotics
Dystonia during the first week
cognitive dysfunction in schizophrenia
decline of attention, memory and executive functions. Not very responsive to antipsychotic agents
what do you look for in antipsychotic induced parkinsonism?
Tremor and rigidity along with diminished facial expression that can be mistaken for depression. Gait disturbance.
Anticholinergic agents in the elderly concern?
constipation, dry mouth, dental caries, blurred vision, urinary retention, memory impairment =DRY
LT use in elderly should be avoided.
Chlorpromazine and clozapine ++++
Quetiapine ++
Perphenazine ++
TD s/s and risk factors
Old age
greater than 6 mo first generation neuroleptic exposure
Hx of parkinsonian side effects
DM
risk is reduced with 2nd gen antipsychotics
NMS s/s
Rigidity/fever/ALOC - TRIAD
(gradually evolves in the following order) confusion rigidity diaphoresis mutism autonomic instability (HR, BP, sweating) hyperthermia elevated cpk
two 2nd gen antipsychotics with few or no cardiac effects
Olanzapine and aripiprazole
clozapine, risperidone, quetiapine, ziprasidone, iloperidone can cause what?
alpha adrenergic side effects-Orthostatic hypotension so they need careful dose titrations
clozapine causes more tachycardia and hypotension than others.
consider intervention when antipsychotic metabolic changes of ?
5% wt gain
1 point increase in BMI
1 in or greater waist circumference
criteria met for metabolic syndrome (obesity, triglycerides 150>, HDL <40men <50 women, BP 130/85>, fasting blood glucose 100>
Quetiapine has high affinity for what receptors? Metabolized by?
5HT2a, A1 and A2 adrenergic, Histaminergic
CYP3A4
short half life (6hrs) still usually prescribed once daily
ziprasidone facts
differs from other antipsychotics with moderate reuptake of serotonin and norepiephrine(noradrenaline)
Absorption greatly increased with a meal within 1 hr and decreases half life
known for not causing wt gain, normalizing lipids and lowering prolactin levels
monitor cardiac risk factors
Aripiprazole mech of action and facts
Partial agonist of D2(so not associated with eps)
affinity to sertonergic, histaminergic and alpha 1 adrenergic receptors
CYP2D6 and 3A4
75-94 hr half life. Needs two weeks to achieve steady state drug levels following a dose change.
known for less prolactin elevation(good choice for a pt with other antipsychotic induced hyperprolactinemia), less akathesia, less need for tx of eps
Iloperdone facts
Finapt
High affinity for d2 and 5th2a
tx of schizophrenia
titrate slowly for orthostatic hypotension
Lurasidone facts
Latuda
High affinity for D2 and 5ht2a
Half life of 18hrs
absorption increased with food-must take with 350 cal
can increase prolactin levels, eps (including akathesia)
serious side effects from clozapine and ?
fluvoxamine and erythromycin-
Obtundation and CV effects
drugs that induce hepatic metabolism (like carbamazepine and phenobarb, phenytoin) can lower antipsychotic concentrations and can cause loss of therapeutic efficacy.
ziprazidone and iloperidone caution
significantly effect cardiac conduction so should not be combined with low potency phenothiazines or antiarrhythmics
Memantine facts
Normalizes levels of glutamate(neurotransmitter involved in learning and memory- glutamate in excessive quantities contributes to neurodegeneration)
NMDA antagonist
Cholinesterase inhibitors for AD
Donazepil (aricept)
Rivastigmine
Galantamine
Tx for frontotemporal dementia and what to avoid
SSRI’s for tx of symptoms
Antipsychotics and mood stabilizers sparingly
Avoid cholinesterase inhibitors and memantine- may exacerbate neuropsych sx
Tx of vascular dementia
control of vascular risk factors-high cholesterol, HTN, inactivity, DM, etoh,
cigarettes and hyperhomocystinemia
