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.

3. Sometimes The Risks Do Not
Outweigh The Benefits

4. Current Psychotropic Drugs Are Not
“Smart” Drugs
 They travel to every area of the body including the
brain

5. Let’s Follow the Drug
Brain Compartments

6. First Compartment: The Brain Vessels

7. Extracellular Space - Between
Capilaries and Cells

8. Second Compartment: The Space
Between The Cells

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

20. N Methyl D Aspartate Receptors

21. GABA Receptors

22. VOLTAGE SENSITIVE CHANNELS
 Voltage -sensitive sodium channels
 Voltage-sensitive calcium channels

23. Voltage-Sensitive Sodium
Channels
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011

24. Some Mood Stabilizers’
Binding Sites
Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011

25. Voltage-Sensitive Calcium
Channels

26. Alpha 2 Delta Ligands

27. Antihypertensive Calcium Channel
Blockers

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

31. Reversible Enzyme Inhibitor

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

37. Question
The estimated annual rate of TD in
olanzapine treated patients is:
 0.5%
 1.0%
 2.0%
 3%
 4%

39. What happens in the
Tuberoinfundibular pathway?
 With D2 blockade
 With 5HT2A blockade

40. Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011

42. Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011

43. Cardiometabolic Syndrome
Weight gain is mediated by:
 5HT2C
 H1
 M3

44. Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011

45. Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011

47. Stahl SM Stahl’s Essential Psychopharmacology; The Prescriber’s Guide 4th ed 2011