PSYC650 Psychopharmacology Antipsychotics And Sedative-Hypnotics.
Transcript of PSYC650 Psychopharmacology Antipsychotics And Sedative-Hypnotics.
How many people with Sz respond well to
classical antipsychotics?
A li
ttle
over
80%
Rough
ly 5
0%
About
35%
Aro
und 15
%
25% 25%25%25%
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Do not respond at all
1. A little over 80%
2. Roughly 50%3. About 35%4. Around 15%
Respond marginally
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&feature=related
http://www.youtube.com/watch?v=0E7x1mPa3iM&NR=1
Extrapyramidal Side Effects
• About 30% of people who take classical antipsychotics– Akathisia (fidgety)– Dyskenisia (impaired voluntary movement)– Dystonia (muscle spasms in head and neck)– Oculogyric crisis (fixed eyeballs)– Torticullis (tilted head)– Hypersalivation– Parkisnonian symptoms
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!
Uses…
• 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– Barb’s bind to receptor near GABA receptor– Causes retention of GABA – Increases influx of Cl-– Inhibiting 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
• About a zillion of them• Chlordiazepoxide (Librium): prototypic• Lorazepam (Ativan)• Clonazepam (Klonopin)• Diazepam (valium)• Alprazolam (xanax)• Estazolam (ProSom)• Triazolam (Halcion)
Benzo ADRs
• 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
• 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
Benzodiazepines __________ binding at the _____________
receptor
Fac
ilita
te, G
ABA
Fac
ilita
te, 5
-HT
Inhi
bit, G
ABA
Inhi
bit, 5
-HT
25% 25%25%25%
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1. Facilitate, GABA
2. Facilitate, 5-HT3. Inhibit, GABA4. Inhibit, 5-HT
Your patient on Haldol seems agitated, and when
he’s not pacing, he’s rocking back and forth.
What’s most likely?
Dys
tonia
Aka
this
ia
Par
kins
onism
Tar
dive
dysk
ines
ia
25% 25%25%25%1. Dystonia2. Akathisia3. Parkinsonism4. Tardive
dyskinesia
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