Inhoudsopgave
PSYCHOPHARMACOLOGY.............................................................................................. 1
COLLEGE 1. INTRODUCTION ................................................................................................. 2
COLLEGE 2. PRINCIPLES OF PSYCHOPHARMACOLOGY – INCLUSIEF VOORBEREIDENDE VIDEO’S ............... 7
3. REFRESHER ON NEUROANATOMY AND PHYSIOLOGY ............................................................... 16
COLLEGE 4. STIMULANTS – INCLUSIEF VOORBEREIDENDE VIDEO ................................................... 24
COLLEGE 5 – PHARMACOLOGY OF DEPRESSION ....................................................................... 38
COLLEGE 6. CLINICAL PART OF PSYCHOPHARMACOLOGY............................................................ 47
COLLEGE 7. ANTIPSYCHOTICS ............................................................................................ 52
COLLEGE 8. ANTIPSYCHOTICS & BIPOLAR DISORDER – CLINICAL ASPECTS...................................... 61
COLLEGE 9. THE PHARMACOLOGY OF ANXIETY ......................................................................... 65
COLLEGE 10. COGNITIVE ENHANCEMENT............................................................................... 75
COLLEGE 11. DEPENDENCE ............................................................................................... 81
COLLEGE 12. HORMONES.................................................................................................. 93
COLLEGE 13. PSYCHEDELICS (INCLUSIEF VOORBEREIDENDE VIDEO) .............................................. 97
1
,College 1. Introduction
Psychopharmacology: studies the influence of substances in biological processes.
Focusses on their effects on behavior, but also on cognition and effect, incl. their
mechanisms in the brain
Pharmacokinetics: how does a substance move through the body?
- Principles lecture
To be distinguished from pharmacodynamics:
- To what receptors does the substance bind?
- What effect does the substance have on the receptor?
- Interactions with neurotransmitter
Neurotransmission: many sites of actions
- Neurons
- Action potential
- Synapse
- Transmitter
o Synthesis
o Release
o Degradation
- Receptor
→ refresher lecture next week Tuesday
Knowledge from serendipity…:
- First insights from folklore (e.g. alcohol)
- Later developments often coincidence
… to hypothesis-based research
- Research programs in pharmaceutical industry and universities for targeted drug
discovery
2
,What are hypotheses based on?
1. Basis knowledge
o How neurotransmitter levels are de- or increased
o Which brain cells/regions are involved in a brain function
o Which kind of substances may affect a neurotransmitter
o Which kinds of substances may affect a certain type of brain cell
o What are potential beneficial and side effects of a substance
→ preclinical research
2. Clinical knowledge
o Which brain functions are involved in a psychiatric disorder
o Which brain cells/regions are involved in a psychiatric disorder
o What is known about levels of neurotransmitters in a disorder
o Different subtypes of a disorder that may require different treatment
→ clinical research
Hypothesis-based research
- Starts with knowledge from the literature
- What is known about a (clinical) phenomenon
o Which neurotransmitter may affect this function?
o Which substances medicines ay affect this NT?
o What patient characteristics may influence whether a certain approach
will work (and for a given patient)?
o Is the substance prone to side effects / toxicity / addiction
o Do the beneficial effects outweigh the side effects?
- What is now known and would be important to find out?
What can a new substance be prescribed?
- New compounds must be admitted by a regulatory board
- NL: CBG, college ter beoordeling van geneesmiddelen
- Europe: EMA: Europe Medicine Agency
- US: FDA – food & drug administrations
- Registration for medications is based on research into: efficacy, administration
routes & safety
Registration: Drug safety
- Therapeutic index = relation between the toxic dose and the effective dose = TD50
/ ED50
o Dose at which 50% shows dangerous side effects (TD50) vs. the dose at
which 50% has the intended effect (ED50)
o Should this be a small or a large number? ED high, TD low
3
, ▪ The product is safer, the bigger the distance is
- Drug interactions
o At level of the brain
o At level fo metabolism, e.g. liver enzymes
→ can be helpful or harmful
- Toxicity (harmful effects)
o Unexpected effects; often temporary (desensitization → principles)
o Unexpected effects: e.g. allergies
Registration
- To be admitted by CBG, EMA, FDA
o Preclinical phases (animal research precedes administrations in humans)
▪ Efficacy: animal models not always predictive for effect in humans
▪ Administration: does the substance survive the gastro-intestinal
system? And the blood-brain barrier?
▪ Safety: are there no serious side effects, even when administered
systematically
o Clinical trials (in humans)
▪ Phase 1: non-toxic, tolerable: whether human subjects tolerate the
substance. If the substance is sufficiently safe, phase 2 starts
• How safe should a compound be before moving forwards
depends on: severity of disease that may be cured or
alleviated by the drug & whether there is already an
alternative treatment
4