Transcript PSYCHOPHARMACOLOGY

‫‪PSYCHOPHARMACOLOGY‬‬
‫דר' שאולי לב‪-‬רן‬
‫מרכז לבריאות הנפש "שלוותה"‬
Neurotransmitters
Classical
Neurotransmitters
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Acetylcholine
Monoamines
Dopamine
NE
Serotonin (5-HT)
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Amino acids
GABA
Glycine
glutamate
Neuropeptides
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Somatostatin
Vasopressin
Prolactin
GH
Oxytocin
Groups of drugs
Anti-psychotics
Anti-cholinergic
Anti-depressants
Mood stabilizers
Sedatives
Classical/typical anti-psychotics
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Chlorpromazine – 1954
Dopamine hypothesis
Dopamine receptor antagonists (DRD2)
Also antagonize α-1, central & peripheral
cholinergic receptors, H1
• High potency vs low potency
High potency  EPS
Low potency  peripheral /
systemic AE
Classical / typical anti-psychotics
Phenotiazines
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Aliphatics (chlorpromazine, levomepromazine,
clotiapine)
Piperazines (perhpenazine, fluphenazine)
Piperidines (thioridazine, pericyazine)
Thioxanthines (flupenthixol, zuclopenthixol)
Butyrophenones (haloperidol)
Diphenylbutylpiperidine (pimozide, penfluridol)
Benzamides (sulpiride)
EPS = extrapyramidal syn.
Medication induced movement disorder
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Parkinsonism
Acute dystonia
Acathisia
Tardive dyskinesia
NMS
Treatment of NMS
Discontinuation of dopamine antagonist
Monitoring vital signs, electrolytes, renal
output
Symptomatic treatment of fever
IV dantrolene/bromocriptine/amantadine
After symptoms subside – switch to
atypical anti-psychotic
Non-EPS AE
• Dopamine
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endocrine effects: gallactorhea, impotence,
amenorrhea, anorgasm
• ACh
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Dry mouth, mydriasis, blurred vision, constipation,
urinary retention, central anticholinergic effect
• α1
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Orthostatic hypotension
• H1
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sedation
Cardiac effects: QT, PR elongation, T
wave changes, arrhythmias
Hematological efffects: agranulocytosis
Dermatological effects: allergic dermatitis,
photosensitivity (chlorpromazine)
Ophtalmological effects: retinal
pigmentation (thioridazine – irreversible,
chlorpromazine – benign)
Hepatological effects: obstructive jaundice
Neurologic : seizures
Atypical anti-psychotics
5-HT2 > DRD2
Improve positive and negative symptoms
Lower incidence of EPS
Atypical anti-psychotics
Risperidone (risperdal)
Olanzapine (zyprexa)
Clozapine (leponex)
Quetiapine (seroquel)
Ziprasidone (geodon)
Dispulpride (solian)
Adverse effects
Metabolic
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Weight gain, glucose intolerance,
hypercholesterolemia
Hematological
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agranulocytosis (clozapine)  weekly/monthly CBC
Sialorrhea – clozapine
Genitourinary – clozapine
In addition: similar AE to typical anti-psychotics
but to a lesser degree.
Long acting anti-psychotics
• Indicated mainly for patients with low compliance
to treatment
• IM:
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Haloperidol - Halidol decanoas
Fluphenazine – Modiket
Zuclopenthixol – Clopixol depot
Flupenthixol – Fluanxol depot
Risperidone – Risperidal consta
• PO:
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Penfluridol – Semap
Drug of choice…
Depends on:
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Pharmacodynamics & pharmacokinetics
Diganosis, major symptoms, past treatments
Demographics – age, support group,
substance abuse
Medical issues
Other – availability, price, personal experience
Groups of drugs
Anti-psychotics
Anti-cholinergic
Anti-depressants
Mood stabilizers
Sedatives
Anticholinergics
Used for treatment of medication-induced
movement disorder
Antimuscarinic
Trihexyphenidyl (artane), Biperiden
(dekinet), orphenadrine citrate (flexin)
Risk of anticholinergic intoxication
Treatment of medication-induced
movement disorders
Parkinsonism
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anticholinergics, amantadine
Acute dystonia
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anticholinergics (IM)
Akathisia
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beta-blockers, BZ
Tardive dyskinesia
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clozapine, (vit E?)
Groups of drugs
Anti-psychotics
Anti-cholinergic
Anti-depressants
Mood stabilizers
Sedatives
Causes of Disability by Illness Category
United States and Canada
15-44 years old
Mental Illness*
Alcohol and drug use
Injuries, including self-inflicted
Respiratory disease
Musculoskeletal disease
Sense organ disease
Cardiovascular disease
Migraine
Infectious disease, excluding HIV
0
5
10
15
20
25
30
35
WHO World Health Report 2002
40
Causes of Disability by Specific Illness
United States and Canada
15-44 years old
Unipolar depression
Alcohol use
Drug use
Bipolar disorder
Schizophrenia
Hearing loss
Migraine
Iron deficient anemia
Diabetes mellitus
0
5
10
15
20
25
30
WHO World Health Report 2002
Anti-depressants
5HT
Serotonin
and
NorepinephrineNE in the brain
Limbic System
Prefrontal
Cortex
Raphe Nuclei
(5-HT source)
Cooper JR, Bloom FE. The Biochemical Basis of Neuropharmacology. 1996.
Locus Ceruleus
(NE Source)
Functional domains of Serotonin and Norepinephrine1-4
Serotonin (5-HT)
Sex
Depressed
Mood
Anxiety
Norepinephrine (NE)
Concentration
Appetite
Vague Aches
and pain
Interest
Aggression
Irritability
Motivation
Thought
process
References:
1. Adapted from: Stahl SM. In: Essential Psychopharmacology:
Neuroscientific Basis and Practical Applications: 2nd ed. Cambridge
University Press 2000.
2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35.
4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.
TCAs (Tricyclic anti-depressants)
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Inhibit reuptake of NE + serotonin
Antagonist to muscarinic, H1, H2, adrenergic
receptors
AE: anticholinergic, sedation, weight gain,
orthostatic hypotension, cardiac
TCAs
Imipramine (tofranil)
Clomipramine (anafranil)
Amitriptyline (elatrol)
Doxepin (gilex)
Nortryptyline (nortylin)
Maprotiline (melodil)
MAO-I
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Inhibit degradation of biogenic amines
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Risk of tyramine (hypertensive) crisis
Treated with α-adrenergic antagonist, diuretic, beta-blocker
SSRIs (Serotonin Specific
Reuptake Inhibitors)
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Low side effect profile
AE: Sexual, GI, weight gain, headaches,
insomnia/sedation, EPS, agitation
Sexual AE are the most common AE of SSRIs
(50-80-%)
SSRIs
Fluoxetine (prozac)
Paroxetine (seroxate)
Fluvoxamine (favoxil)
Sertraline (lustral)
Citalopram (cipramil)
Escitalopram (cipralex)
Serotonin Syndrome
May occur when administrating an SSRI
concurrent with a MAO-I, L-tryptophan or lithium
Includes:
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Diarrhea
Restlessness
Extreme agitation, hyperreflexia, autonomic instability
Myoclonus, seizures, hyperthermia, rigidity
Delirium, coma, status epilepticus, CV collapse, death
Treatment includes removing the offending
agent + intensive supportive care
additional anti-depressants
Venlafaxine (SNRI)
Mirtazapine (α-2 antagonist, H1
antagonist, 5-HT2,3 antagonist)
Trazodone (relative serotonin specific, α-1
antagonist)
ECT (electroconvulsive therapy)
Phototherapy
TMS (transcranial magnetic
stimulation)
VNS (vagus nerve stimulation)
Groups of drugs
Anti-psychotics
Anti-cholinergic
Anti-depressants
Mood stabilizers
Sedatives
Mood Stabilizers
Lithium
Lithium
Uncertain therapeutic mechanism
AE:
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GI: gastric distress, weight gain
Neurological: tremor, cognitive
Renal: polyuria, secondary polydipsia
Hypothyroidism
Cardiac
Dermatological
Risk of lithium toxicity
Blood level of lithium is available
Contraindicated in 1st trimester (ebstein’s
anomaly)
Anticonvulsants
Valproate
Carbamazepine
Blood level is attainable
Contraindicated in pregnancy (neural tube
defects)
Anticonvulsants cont.
Lamotrigine
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Increasing data regarding effects on bipolar
depression
May carry lower risk during pregnancy
compared to other anticonvulsants (further
studies needed)
Risk of dermatologic AE (including life
threatening Stevens-Johnson syndrome
Slow titration to avoid side effects)
Groups of drugs
Anti-psychotics
Anti-cholinergic
Anti-depressants
Mood stabilizers
Sedatives
SEDATIVES
BZ (benzodiazepines)
Sedative, muscle relaxant, anticonvulsant
BZ
Diazepam (valium)
Lorazepam (lorivan)
Clonazepam (clonex)
Alprazolam (xanax)
Brotizolam (bondormin)
Dangers
Dependance
Overdose (treat with flumazenil)
Accidents (i.e. while driving, falls common
among elderly)
Antihistamines
H1 antagonists
Also carry some antimuscarinic activity
Used as:
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Sedative
Treatment for medication induced movement
disorder
Common in practice: Promethazine
(phenergan)
Buspirone
5-HT1A agonist
Takes 2-3 weeks for full effect
Most commonly used for General Anxiety
Disorder (GAD)
A word for the wise…
Classify the drug according to the major
groups
Knowledge of the Mechanism of action /
receptor activity facilitates remembering
both disorder hypotheses, drug activity
and adverse effects.