Transcript Gen Principles on Psychopharmacology Amaury Delgado

Psychotropi
c Drugs
Nefazadone
Droperidol /
Thioridazine
Sertindole
Thalidamide
Nomifensine
Clozapine
MAOIs
Mianserine
Adverse effect detected by
post-marketing surveillance
Hepatotoxicity
QT prolongation
Sudden Death (cardiac)
Phocomelia
Hepatotoxicity
agranulocytosis
Cheese Reaction
Blood dyscresias
ETHNOPHARMACHOLOGY
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Caucasians (Lower Plasma level of TCA)
Maximal Haloperidol concentration following RT Asian> Caucasians (Lin at
al 1983)
CYP2D6 Caucasians higher rate of poor metabolizers (7%), East Asian
lower (1%)
Ultrarapid metabolizers North Africans (33%) needing high dosages
40% of Asians and 60% South American Native Indians lack Aldehyde
Dehydrogenase
Caucasion better SSRI response (long form 5_HT transporter
polimorphism)
ETHNOPHARMOCHOLOGY
African American
Asians
Increased Diagnosis of Schizophrenia but
decreased diagnosis of depression
More side effect with Lithium and TCA
Better to start at half of standard dosage
of all psych medication
Higher Tardive Dyskinesia with
antipsychotics
Clozapine better effect at lower dosage,
higher risk of agranulocytosis
Better rapid responders to TCA and
lorazepam but poor response to
fluoxetine
Slower metabolizers of TCA
More depot medication prescribed
GENDER DIFFERENCES
Women
Men
Superior antipsychotic response
Men will require dosages twice as high for
effective maintenance
Higher antipsychotic plasma level than men
when using same dosages
CYP1A2 more active in men, therefore
metabolize olanzapine and clozapine faster
Volume of distribution of lipophilic drugs is
higher in women (Blood volume is lower but lipid
concentration is higher) This prolongs half life of
antipsychotics
More common acute dystonia
More common TD and Pulmonary embolism
(rare problem seen in drugs with affinity for
5HT2A
PHARMACOKINETICS
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What happens to drugs once administered (What the body does to the
drug)
Routes of administration: enteral (oral, rectal and SL) and parenteral
(IM, IV, intrathecal, peritoneal, inhalation, skin). Advantages and
disadvantages.
How single and multiple dosing of different formulations affect plasma
concentration---Time relationship
Bioavailability: How much of a given drug reaches its target, It depends
on Absorption/ Distribution/ Metabolism / Excretion
Distribution: Free and bound , BBB crossing → target tissue and other
tissue
First-Order Kinetic: Rate of absorption or elimination is directly
proportional to the amount of drug remaining. (The higher the plasma
concentration the longer remains in the body)
Zero-order kinetic: a fixed amount of drug is absorbed or eliminated for
each unit of time independent of drug concentration (e.g saturation of
enzymes or controlled released)
METABOLISM
1-Aims to produce polar
compounds for renal
elimination
2-Liver is the main site
3-Metabolise to active
compounds=Phase 1
or inactive Phase 2
4-First pass Metabolism=
Drugs is absorbed from GI
into portal circulation and
metabolized in liver before
reaching systemic
circulation
EXCRETION
1-Ionised
states allows
passive
diffusion
2-Ph affect
rate of
elimination
METABOLISM
• Chemical transformation by the body: reducing lipid solubility and
altering biological activity. Eg: Diazepam→Oxazepam.
• By hepatomicrosomal and nonmicrosomal enzyme systems and two
phases: phase I and phase II
• Phase 1: Oxdn, redn, hydrolysis →may or may not be active but
shorter T1/2
• Phase 2: Combining with endogenous molecules, usually
glucoronides→ ↑H2O soluble.
• Now, if MW 300+ then through bile or otherwise → blood→ kidneys.
• Also in plasma, lung, kidney and skin.
P450 INDUCTION OR
INHIBITION
Inducers
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Carbamazepine
Phenytoin
Burbiturates
Chronic EtOH
Cigarette smoking
Others such as
Rifampicin,
griseofulvin
Inhibitors
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Ranitidine
Ciprofloxacin
Erythromycin
Valproate
Fluoxetine, paroxetin
TCAs
Antipsychotics