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Drugs and the brain
1. Drugs and the
Brain
Psychotropic Medications -
Effects and Adverse Effects
Adonis Sfera, MD
Neurovascular coupling
2. Why Do We Get Side Effects From
Drugs?
Any time you alter you body chemistry
you will have some form of side effect.
The benefits of the medication will
often outweigh the cost of the side
effects by improving heath or allowing
people to function in daily life.
It is up to us to decide.
9. The Firewall (Blood Brain Barrier)
The
blood-brain barrier (BBB) is located
between the blood vessels (capilaries)
and the extracellular space of the brain.
10. Blood Brain Barrier (BBB)
Endotelialcells
Astrocyte endfeet
Trans-cellular
passage of drugs
Passage of drugs
from the
bloodstream to the
brain is dependent
on the ability of the
molecules to
penetrate through
cell membranes.
11. Crossing the Membranes
Penetration of a molecule from the bloodstream to the neurons
and glial cells is dependent on the compound's liposolubility.
12. Targets of psychotropic drugs
30% of psychotropic drugs target transporter
proteins
30% of psychotropic drugs target G protein
linked receptors
20% of psychotropic drugs target ligand-
gated ion channels
10% of psychotropic drugs target voltage
sensitive ion channels
10% of psychotropic drugs target enzymes
13. Transporter Protein and G Protein
(60% of psychotropic drugs)
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
14. Ligand Gated Ion Channels, Voltage Sensitive
Ion Channels and Enzymes
(40% of psychotropic drugs)
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
15. Transporter Proteins
Transporters are receptors that bind neurotransmitters (they go in
and out of the neuronal membrane 12x)
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
16. All Antidepressants (except MAO inhibitors)
Target and Block Transporter Proteins
Serotonin Transporter(SERT); Norepinephrine Transporter(NET);
Dopamine Transporter(DAT)
17. Antidepressants Bind to
Transporters
1. When Na binds to the
transporter, serotonin also
binds and renders the
transporter ready.
2. When the antidepressant
binds to the transporter it
displaces serotonin and Na,
blocking the transporter
Stahl SM Stahl’s Essential Psychopharmacology;
The Prescriber’s Guide 4th ed 2011
18. G Protein Linked Receptors
G protein linked receptors (7 transmembrane regions, one intracellular
and one extracellular portion)
19. Ligand-Gated Ion Channels (20%
of Psychotropic Drugs)
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
28. Enzymes Directly Targeted by
Psychotropic Drugs
Some Enzymes Create New
Molecules.
Others Destroy Existing
Molecules.
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s
Guide 4th ed 2011
29. Enzymes as Targets of Psychotropic
Drugs
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
30. Irreversible Enzyme Inhibitor
An irreversible inhibitor of an enzyme binds
to the enzyme in such a way that
permanently prevents a substrate from
binding.
Stahl SM Stahl’s Essential Psychopharmacology; The
Prescriber’s Guide 4th ed 2011
32. Dopamine Pathways
I wish I could inhibit only the mesolimbic pathway, but I cannot
because the drugs are not “smart”.
33. All antipsychotics (typical
and atypical) are
dopamine D2 blockers, but
unfortunately they affect
other receptors as well
-adverse effects
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
34. Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011
35. Tardive Dyskinesia (TD)
Up regulation of the postsynaptic dopamine
receptors.
5% of patients maintained on typical
antipsychotics will develop TD in 1 year (25%
in 5 years).
TD in elderly can be as high 25% in the first
year of treatment
Kane JM in Bloom FE, Kupfer DJ, Psychopharmacology: The fourth generation of
progress. Philadelphia Raven 1996
National Alliance on Mental illness. Tardive dyskinesia Available at
www.nami.org/ContentGroups/Helpline1/Tardive_Dyskinesia.html
36. Question
Which of the following risk factors for the
development of TD is most important?
Age
Gender
Mood disorders
Substance abuse