Transcript Gen Principles on Psychopharmacology Amaury Delgado

GENERAL PRINCIPLES IN
PSYCHOPHARMACOLOGY
Dr Amaury Delgado-Hernandez ST5
General Adult Psychiatry
DR AMAURY DELGADO HERNANDEZ
ST5 IN GENRAL ADULT PSYCHIATRY
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PAPER 1 EXAM OF THE
RCPSYCH
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History and Mental State
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Descriptive Psychopathology 24
Cognitive Assessment
10
Neurological Examination
10
Assessment
16
Description and Measurement 6
Diagnosis
12
Classification
8
Aetiology
12
Prevention of Psychological Disorder
6
This breakdown is intended as a general
guide to the content of Paper 1 and is
subject to change
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Paper 1 pass rate for December 2011=
54.8%
• Basic Psychopharmacology
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Human Psychological Development
Social Psychology
Basic Psychological Processes
8
4
14
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Dynamic Psychopathology
12
Basic Psychological Treatments
8
History of Psychiatry
8
Basic Ethics and Philosophy of Psychiatry
8
Stigma and Culture
8
PROGRAMME
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History of Psychopharmacology
Classification
Placebo Effect
Drug Approval
Ethnopharmacology
Pharmacokinetics
Pharmacodynamics
Type of Adverse Reaction
Mechanism of side effect
BRIEF HISTORY
1915 Macht and Mora coined the term psychopharmacology when studying
opioids
1931 Sen & Bose (Plant Rauwolfia)=Reserpine.
1949 Cade in Australia discovered the use of Lithium compound in mania.
1950-1952 Delay and Deniker antipsychotic properties of Chlorpromazine
1952 Iproniazid anti-tuberculosis with antidepressant effect (mood lifting
properties)
1954 First BZD Chlordiazepoxide in Austria Leo Sternbach
1955-1958 Klein TCA (Kuhn) and MAOIs.(Klein)
1958 Janssen synthesised butyrophenone (Haloperidol)
1963 Cheese reaction was proposed by Blackwell.
1970 Fluoxetine tested but not taken until 1987
CLASSIFICATION
ACCORDING TO MOLECULES
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Aliphatic phenothiazinestriflupromazine
Piperidine derivativesPiperazine derivativesprophenazine,
Butyrophenones–
ThioxanthenesZuclopenthixol
Dihydroindoles –
Diphenylbutylpiperidine –
Dibenzoxapine –
Benzisoxazole derivativeSubstituted benzamidesDibenzodiazepine Dibenzothiazepine Thienobenzodiazepine BenzisothiazoleArylpiperidylindole
Chlorpromazine, promazine,
Thioridazine
Trifluoperazine, Fluphenazine,
Haloperidol, Droperidol
Thiothixene, Flupenthixol,
molindone
pimozide (long t1/2)
loxapine
risperidone
Amisulpride, Sulpiride
Clozapine
Quetiapine
Olanzapine
Ziprasidone
(quinolone) Aripiprazole
CLASSIFICATION
ACCORDING TO MOLECULE
• Tertiary amines –
imipramine, amitriptyline, clomipramine,
dothiepin, trimipramine (also venlafaxine)
• Secondary amines – desipramine, amoxapine, nortriptyline and
protriptyline (also duloxetine) [more potent mg to mg basis; less
sedating; more noradrenergic, less antihistaminic or
anticholinergic than tertiary]
• Hydrazine derivatives - phenelzine, isocarboxazid (greater
hepatotoxicity than tranylcypromine, non hydrazine compound)
• Aminoketone - Bupropion (amphetamine like)
• Azaspironedecanedione Buspirone
• Triazolopyridine - Trazodone, nefazodone.
• Imidazopyridine - Zolpidem
• Pyrazolopyrimidine - Zaleplon
• Cyclopyrrolone - Zopiclone
CLASSIFICATION
ACCORDING TO MA
• SSRIs
citalopram, paroxetine, fluoxetine, sertraline and
fluvoxamine (S enantiomer of citalopram ) -Escitalopram
• SNRIs – serotonin and noradrenaline reuptake inhibitor
venlafaxine, milnacipran, duloxetine
• NARI – Noradrenaline reuptake inhibitor -reboxetine
• NaSSA – Noradrenergic and specific serotonergic antagonist –
Mirtazepine and
• mianserin
• DARI – Dopamine reuptake inhibitor -Bupropion
• RIMA – reversible inhibitor of Monoamine A oxidase moclobemide
• SARI – serotonin antagonist and reuptake inhibitors –
nefazodone, trazodone.
PLACEBO
• “Intervention deliberately used for non-specific psychophysiological
treatment effect”.
• Placebo effect in research: Difference in outcome between
placebo and an untreated control group.
• Nocebo: Placebo that produces significant SE.
• Placebo sag: The fading of the response with chronic and repetitive
administration.
• Best placebo response (pain and disorders of autonomic
sensation Nausea, Bronchial asthma)
• Psychiatric illness (Placebo Response)
• Depression 25-60%/ Mania 25% / Schizophrenia 25-50% / Panic
Disorders 70%
• Placebo fails in degenerative and vascular conditions
DRUG APPROVAL
PreclinicalAnimal studies
2 different animal species tested for Mutagenicity,
carcinogenicity and organ toxicity
Human trialsSmall group of healthy volunteers and safety, tolerability
Volunteer Phase 1 and pharmacokinetics
safety
Human TrialsPatients Phase 2
effectiveness
Hundreds of patients with target disease vs placebo (RCT)
Human Trials
Patients Phase 3
Superiority
Superiority or equivalence to standard looking at
comparative efficacy and tolerance profile. In this phase
the drug undergoes RCT with double-blinding. Looking at
how well it works and side effects
Human Trail
Post-marketing
Drugs undergoes approval, monitoring continues and drug
could be removed if abnormal findings