Download PSY650-Antipsychotics-Sedative-Hypnotics

PSYC650
Psychopharmacology
Antipsychotics
And Sedative-Hypnotics
How many people with Sz
respond well to classical
antipsychotics?
A little over 80%
Roughly 50%
About 35% Respond marginally
Around 15% Do not respond at all
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Psychopathology
Refresher
• Positive Symptoms
– Classical Antipsychotics
• Negative Symptoms
– Atypical Antipsychotics
• The Dopamine Hypothesis
Mechanisms of Action
• Classicals are usually D2 and D2-like receptor
antagonists
• Atypicals antagonize D2-like receptors plus
some 5-HTa action
– LSD
– The serotonin hypothesis of negative symptoms
Some Pharmacokinetics
• Long half-lives, so a 1ce daily dose usually
suffices
– Often at night to capitalize on sedating effects
• Elders Beware:
– Mostly metabolized in liver
– Can induce tachycardia
– Anticholinergic reactions
Other General ADRs
• Lowers seizure threshold
• Can induce parkinsonian symptoms
– Especially Haldol
– Can be rectified with anticholinergic drugs
• Beware…exacerbation of cholinergic ADRs
• Monitor for dry mouth, disorientation, agitation, confusion, etc.
• If too bad may need to provide a cholinergic agonist (physostigmine)
http://www.youtube.com/watch?v=OVAUDAn7Tco&f
eature=related
http://www.youtube.com/watch?v=0E7x1mPa3iM&NR=1
Extrapyramidal Side
Effects
• About 30% of people who take classical
antipsychotics
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Akathisia (fidgety)
Dyskenisia (impaired voluntary movement)
Dystonia (muscle spasms in head and neck)
Oculogyric crisis (fixed eyeballs)
Torticullis (tilted head)
Hypersalivation
Parkisnonian symptoms
Tardive Dyskinesia
Tardis
• Sometimes irreversible
• Anticholiergics sometimes given to prevent EPS
can exacerbate tardis
Phenothiazines
• Early 1950’s
• Aliphilactics
– Largactil (chlorpromazine—Thorazine)
– Fewer ADR but lower in potency
• Anticholinergic, TD, EPS, menstrual changes, weight gain
• Piperazines
– EPS, TD, sometimes anticholinergic, weight changes, orthostatic
hypotension, abnormal lactation
– prochlorperazine (Compazine)
• Excellent antiemetic
– Fluphenazine (Prolixin)
• Can do shots 1ce-2ce per month
Phenothiazines-Piperidines
• Includes thioridazine (Mellaril)
– Similar to aliphiliactics but less sedating and has
fewer EPS
– Anticholinergic, weight changes, menstrual, lactation,
orthostatic hypotension
– Long term-high dose: Lens opacity & Retinal
pigmentation (esp bad with Mellaril)
Butyrophenones
• Droperidol (Inapsine), haloperidol (Haldol)
• Similar to phenothiazines, but faster with less
ACH
• Haldol can be injected as a long-term depot
bound substance
• Droperidol is effective as an antiemetic
– Often given for nasuea associated with anasthesia
• EPS, blood disorders, lactation and menstrual
difficulties, postural hypotension, sedation, TD
Atypicals
• Clozapine (Clozaril), olanzapine (Zyprexa), risperidone
(Risperdal)
• Treatment-resistant clients
• Negative symptoms
• Fewer ADRs
– Anticholinergic, antihistaminic
– Serotonin-related symptoms (10-40% patients): constipation,
drowsiness, headache, hypersaliation, hypotension,
tachycardia
– Neutropenia (2% patients) decrease in neutrophil count in
blood. Increases susceptibility to bacterial and fungal
infections
• Fatal!
Sedative Hypnotics
Uses…
•
•
•
•
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Depresses CNS
Anxiety
Sleep disturbances
Not for depression-associated anxiety
If on stimulant, wait for stimulant effects to
wear off
– “Wide awake drunk”
Dreaming of Drugs
• Some sedative hypnotics suppress REM, others
suppress N-REM
• May be desirable to prescribe a drug that
suppresses the stage at which another disorder
‘strikes’
– N-REM: Night terrors
– REM: Nocturnal angina
• Beware REM rebound
Barbiturates
• Lots of legends around name
– St. Barbara’s day 1903
– “Barbara’s Urates”
• Over 2,500 barb’s synthesized and 50 marketed
• Now about 10 are “going strong”
– Benzo’s knocked them out of the market
• Better marketed
• Lower abuse potential
• Higher TI
Barbituarates:
Pharmacokinetics and
Pharmacodynamics
• Vary in potency, depending on lipid solubility
– Most lipophilic is thiopental (Pentothal)
• Metabolized in liver
– Enzyme induction
• Probably GABA-ergic
–
–
–
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Barb’s bind to receptor near GABA receptor
Causes retention of GABA
Increases influx of ClInhibiting transmission
Barbiturates: ADRs
• CNS depression
– Normal and transient
– Slow breathing, low BP
• OD: Respiratory depression, coma, kidney failure, cardiovascular
collapse, death
• Little use other than sedation
– Tolerance can occur in as little as 2 weeks
• Sometimes therapeutic adjunct
• Paradoxical effect on elderly and young
• Can cause insomnia
– More frequent and intense dreaming
– Angina
– Exacerbates gastric ulcers
Benzodiazepines
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About a zillion of them
Chlordiazepoxide (Librium): prototypic
Lorazepam (Ativan)
Clonazepam (Klonopin)
Diazepam (valium)
Alprazolam (xanax)
Estazolam (ProSom)
Triazolam (Halcion)
Mechanism of Action
• Probably GABA
• Largely in amygdala and thalamus
– Probably via Cl- channels
Benzo ADRs
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Best anxiolytics, buts…
REM suppression at high doses
Short acting benzo’s may have rebound insomnia
Amnestic effects
Confusion
Motor coordination
Disorientation
Lethargy
Oversedation
Some reports of tachycardia
Benzo Dependence
• Withdrawal comes in 3 phases:
1. Rebound anxiety and insomnia
– could last several days, depending on T-1/2
– Starts 1-4 days after drug removal
2. Anxiety, difficulty concentrating, headache,
irritability, sleep problems
– Lasts about 1-3 weeks
3. Anxiety
– May last several months
Benzoverdose
• May have to administer a BZ antagonist
– Flumazenil
– T-1/2 of 1 hour
• Need to be careful to monitor and readminister as needed
• Watch for withdrawal as well
Miscellaneous:
Chloral Hydrate
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Knock out drops
Quite a few interactions
Active metabolite trichloroethanol
Tolerance
OD potential
Severe nausea (take with meals to prevent
vomiting)
Miscellaneous Others
• Buspirone
– Only mildly sedating
– Serotonergic
• Methqualone
– High abuse potential
– Once thought to be an aphrodesiac
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Benzodiazepines __________
binding at the _____________
receptor
Facilitate, GABA
25% 25% 25% 25%
Facilitate, 5-HT
Inhibit, GABA
Inhibit, 5-HT
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Dystonia
Akathisia
Parkinsonism
Tardive dyskinesia
D
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2.
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4.
Your patient on Haldol seems
agitated, and when he’s not pacing
he’s rocking back and forth.
25% 25%
25% 25%
What’s most
likely?
10