Exam 4 lecture 3 Flashcards
What are warnings for all antipsychotics
-Boxed warning- increases risk of death in elderly patients treated with antipsychotics for dementia with related behaviors.
-metabolic adverse effects
-EPS
-Risk of somnolence, postural hypotension and motor/sensory instability increases risk for falls and fractures.
- Fall risk assessment should be performed
What are some long acting injections?
Haloperidol deconate
Risperdal Consta
Perseris
Rykindo (risperidone)
Uzedy (risperidone)
Invega Sustenna (paliperidone)
Invega Trinza
Invega Hafyera
Zyprex relprev (olanzapine)
Abilify maintena (aripiprazole)
Abilify Asimtufil
Aristada
Aristada initio
What are things to know Risperdal Consta
Must supplement with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment. (until 3rd injection) (week 4)
1st atypical long acting injection
Things to know about perseris (dose and enzyme substrate)
Abdominal SQ injection- 90 m and 120 mg
3A4 inducers- use 120 mg dose or may need oral supplementation
Things to know about rykindo (dosing)
Every 2 week IM injection
Oral dose overlap is shorter than risperidal consta (7 days vs 21 days)
Things to know about Uzedy (risperidone) (dosing
Abdominal or upper arm SQ injection
Given once monthly or every 2 months
Things to know about Invega susstena (dosing, how to give drug, dose adjustments)
Loading dose then booster, then every 4 weeks (starting every 5 weeks after loading injection)
Initial deltoid booster must be given in deltoid to improve absorption consistency
If loading strategy followed, no need for oral overlap antipsychotic treatment.
May require dose adjustment in moderate to severe renal impairement
Things to know about Invega trinza
May be initiated for patient who has been on a stable monthly IM injection of INVEGA sustenna.
atleast 4 stable invega susstena doses
recommended to be on deltoid, gluteal administration results in lower climax
not recommended if CRCL<50
Things to know about Invega hafyera
Must be initiated after stable invega sustenna for 4 months or stable invega trinza for 3 months
gluteal injection only
Things to know about zyprexa relprev
causes post dose delirium sedation syndrome
Things to know about Abilify maintena
Deltoid or gluteal injection
Must overlap with oral aripiprazole (or another oral antipsychotic) for atleast 14 days after injection.
Abilify maintena dose adjustments for P450 interactions
If taking 2D6 or 3A4 inhibitors for 3A4 inducers for more than 14 days as concomitant therapy.
patients taking 400 mg of abilify maintena
-strong CYP 2D6 OR CYP 3A4 inhibitors adjust dose to 300 mg
CYP2D6 AND 3A4 inhibitors adjust dose to 300 mg
Patients taking 300 mg of abilify maintena
-strong CYP 2D6 OR 3A4 inhibitors- adjust to 200 mg
- sCYP 2D6 AND CYP3A4 inhibitors- adjust dose to 160 mg
Things to know about abilify asimtufii (aripiprazole)
Every 2 month dosing
Gluteal injection only
continue Oral aripiprazole for 2 weeks after 1st injection
Things to know about Aristada (aripiprazole lauroxil)
Overlap with oral aripiprazole for 3 weeks after 1st injection.
Things to know about aristada initio
Developed to avoid need for 21 day oral overlap of antipsychotic
Avoid in patients who are 2D6 poor metabolizers or with strong 3A4 or 2D6
Immediate release antipsychotic injections/psychiatric emergencies
Haloperidol (most common)
chlorpromazine
fluphenazine
Olanzapine IR IM
Loxapine for inhalation
What are notable things to know about olanzapine IR IM
Can not be given at the same time as benzodiazepine IR injection- boxed warning for respiratory depression.
clinical treatment strategies for EPS
Acute dystonia- IM anticholinergic NOW dose
- benztropine 2 mg, diphenhydramine 50 mg)
Drug induced parkinsons- Oral anticholinergics (benztropine, trihexylphenidate, dihenhydramine)
Akathisia- BB (propanolol preferred 1st line)
Benztropine- usually lorazepam
Tardive dyskinesia- VMAT inhibitors
What are the VMAT inhibitors. Notable things about them
Tetrabenzine
Valbenzine- 2D6/3A4 substrate. side effects QTc prolongation
Deutetrabenazine- 2D6 substrate. Side effects QTc prolongation
What is neuroleptic malignant syndrome (NMS)? Symptoms?
Side effects? Treatment?
Life threatening-IS a medical emergency.
symptoms- Hyperpyrexia, tachycardia, labile blood pressure
muscle rigidity- Elevated (significantly) CK, myoglobin
Treatment is supportive
Future antipsychotic use is NOT contraindicated
Metabolic adverse effects of antipsychotics. Rank atypical antipsychotic risk for atypical antipsychotic risk.
Clozapine and olanzapine have the highest risk
Ziprasidone, lurasidone and aripiprazole have the least risk.
Monitoring parameters for metabolic advrese effects of antipsychotic
Weight every 4 weeks
BP, fasting lipids, FPG/A1C, baseline, 12 weeks and yearly
Define Sedative, anxiolytic, hypnotic, narcotic
Sedative- Calms anxiety, reduces excitement and activity. Does not produce drowsiness or impair performance
anxiolytic- antianxiety relieves anxiety without sleep or sedation (not all anxiolytics are sedatives)
Hypnotic- Induces sleep, implies restful, refreshing sleep not hypnotized
Narcotic- Actually means “sleep producing, now refers to opioids or illegal drugs
What is the reticular formation? Where is it found?
It is an intricate system composed of loosely clustered neurons in what is otherwise white matter.
The reticular formation extends through the central core of the medulla oblongata, pons and midbrain.
What are the stages of sleep
Wakefulness
NREM
REM
stages of NREM?
Stage 1 (dozing)
stage 2 (unequivocal sleep)
stage 3 (voltage increase, frequency decrease)
stage 4- delta waves
What are factors that regulate sleep
Age
Sleep history
Drug ingestion
Circadian rhythms
what are some biological regulators of sleep
-Neurotransmitters (almost all) (main target for current medications is GABA)
-Neuromodulators
What are GABAergic neurotransmitters
GABAa receptors
GABAb receptors
GABA transporters (GAT-1)
GABA-T (transaminase)
GABA receptor is a ______ channel complex
Chloride
where to BZDs bind to
Alosteric sites (alpha 1 and gamma 2)
How do BZds affect GABA action
Facilitate GABA action., increase frequency.
What are some ligands acting at the BZD receptor
Benzodiazepines- Increase frequency
non BZDs (Z hypnotics)- BZ receptors of A1
BZD antagonist- Flumazenil
How do BZDs modulate GABA receptor
increase frequency of channel opening
How do barbiturates affect modulation of GABA receptors
Increase duration of channel opening and direct effects on GABA (high doses)
SAR of benzodiazepines
1 position alkylation is the source of active metabolites.
Annealating the 1-2 bond with an electron rich ring yields high affinity and decreased half life
which bzd has long half life? BZDs that have a long half life have what in common?
diazepam.
slow elimination rates- all have active metabolites.
What does diazepam treat
Diazepam- prototypical BZD used as anxiolytic, for alcohol withdrawal and for treatment of convulsive disorders (seizures), Accumulation of metabolites.
What BZD drugs have intermediate elimination rates?
clonazepam (anticonvulsant)
- tolerance may develop with prolonged use, used as an anticonvulsant.
Which BZD drugs are rapid elimination rates
Midazolam
-rapid anesthesia
why are barbiturates more dangerous than BZDs
Barbiturates may cause coma. BZDs have an asymptote at anesthesia (ceiling effect)
BZDs increase the frequency of GABA receptors
What are some pharmacologic properties of BZDs
Decrease REM
Decrease stage 3 and 4
Anticonvulsant activity
toxicology of BZD (side effects, precautions and interactions, drug dependence and abuse)
side effects- dose dependent (sedation, confusion, weakness)
precautions and interactions- Alcohol, pregnancy and breast feeding.
Drug dependence and abuse- abuse potential low vs barbiturates
Benzodiazepine antagonist drug? Use?
Flumazenil
Treat BZD overdose
What are the non benzodiazepine drugs? What site do they act on?
Z hypnotics- act at BZD binding site (BZ1 receptor)
Zolpiden (ambien)- short term treatment of insomnia
Zaleplon (sonata)- short term treatment of insomnia (7=10 days)
Eszopiclone- Long term use
Z hypnotics common features
Metabolism- CYP3A4
Overdose treatment- Flumazenil
Side effects- cause less negative effects on sleep patterns than BZD
Sleep driving, sleep cooking, sleep eating (warn your residents) (know for exam)
What other illicit uses do BZDs and non BZDs have
BZDs (clonazepam, flunitrazepam)- roofies
Non BZDs (Zolpidem)- Sexual assault dangers
Barbiturates classifications
Long acting- Phenobarbital
Short to intermediate acting- Pentobarbital
What do barbiturates cause
Respiratory depression- death
KNOW FOR EXAM. Compare BBT, BZD and Z hypnotics
BBT- bind all GABA a 1-5, Increase the duration of channel opening and DIRECT EFFECTS on GABA channel
BZDs- bind to all GABA a-1-5, increase the FREQUENCY of GABA channel
Z hypnotics- bind to GABA BZ receptors of a1, increase frequency of GABA channel opening
What is the use and limitation of flumazenil
Treats overdoses, but not for BBT
