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Psychofarmacology Hoorcolleges (Cijfer 9,8)

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Dit document bevat uitgebereide, gedetaileerde aantekeningen van alle hoorcolleges gegevens tijdens het vak 'Psychofarmacologie'.

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  • April 9, 2024
  • 63
  • 2022/2023
  • Class notes
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PSYCHOFARMACOLOGY
LECTURE 1: INTRODUCTION TO PSYCHOPHARAMCOLOGY AND TO
THE COURSE
Overview of the course
Assessment
• Assignments: 30%
o Assignment 1 heeft inspanningsverplichting en voor assignment 2 krijg je cijfer
• Exam: 70%

Psychopharmacology in bird’s eye view
What is pharmacology?
• Pharmacology studies the influence of substances on biological processes, c.q., living beings.
• Psychopharmacology focuses on their effects on behaviour, cognition and affect, incl. their
mechanisms in the brain. -> What does the drug do with the person.

Why is this of interest?
• What are the effects of psychoactive substances that you use?
o We use a lot of psychoactive substances daily: cigarettes, energy drink, alcohol, coffee.
• Some have some (clinical) applications.
o Ritalin voor betere concentratie, medicijn tegen zware depressie, vapes met fentanyl,
verslaving voor nicotine, drugsgebruik
• Development of future applications
o Never fear, cannabinoids are here
o Ethical??
o Niet iedereen haalt een voordeel uit een bepaalde psychotherapie. Er is dus een noodzaak
aan nieuwe medicatie ontwikkelen.

Pharmacodynamics/kinetics
• Pharmacokinetics: ‘How does a substance move through the body?’
o Where does it go?
o How long works it?
-> What does the body do with the drug?
• To be distinguished from pharmacodynamics:
o To what receptors does the substance bind?
o What effect does the substance have on the receptor?
-> What does the drug do with body?
• In psychopharmacology this means: interactions with neurotransmitters

Where do psychoactive drugs act?
Neurotransmission
• Neurons
• Action potential
• Synapse
• Transmitters: synthesis, release, degradation
• Receptor

,Influencing neurotransmission – Points of engagement
around the synapse
Points of engagement drugs:
• Amount of transmitters
o Synthesis (presence precursor (1), activity of enzymes
(2))
o Uptake of transmitter in (3) and release from (4)
vesicles
• Blocking or modulating receptor (5, pre/post synaptic)
• Ending influence through
o Reuptake (6)
o Degradation (7, extra/intracellular)

The basis for our knowledge on psychopharmacology
From serendipity to hypothesis based research
• First insights from folklore (e.g., alcohol)
• Later developments often coincidence
o E.g., the discovery of penicillin
• Research programs in pharmaceutical industry and universities for targeted drug discovery

What are hypotheses based on?
• Preclinical research: Basis knowledge, e.g. about:
o How neurotransmitter levels are de- or increased
o Which brain cells/regions are involved in a brain function
o Which kinds 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
• Clinical research: Clinical knowledge, e.g. about:
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 if a disorder that may require different treatment
--> Find a treatment that is the best for a specific patient.

Hypothesis-based research
• Starts with knowledge from the literature
• What is known about a (clinical) phenomenon?
o Which neurotransmitter (NT) may affect this function?
o Which substances (medicines) may 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 not known and would be important to find out?

When can a new substance be prescribed?
• New compounds must be admitted by a regulatory bard
• NL: CBG, College ter Beoordeling van Geneesmiddelen
o Beoordeelt en bewaakt de werkzaamheid, risico’s en kwaliteit van geneesmiddelen.
• Europa: EMA, Europe Medicine Agency

,• US: FDA, Food & Drug Administration
• Registration for medications based on research into: efficacy and safety

Registration
To be admitted by CBG / EMA / FDA
• Preclinical phases (animal research precedes first administration in humans):
o Efficacy (NB: animals models not always predictive for effect in humans!)
o Administration (Does the substance survive the gastro-intestinal system? And the blood-
brain barrier?)
o Safety (Are there no serious side effects, even not when administered ‘systemically’ (e.g.,
orally)?)
• Clinical trials (in humans):
o Phase 1: non-tocix, tolerable
o Phase 2: limited efficacy studies
o Phase 3: large, multi-center studies

Drug safety
• Therapeutic index = relation between the toxic dose and the effective
dose = TD50 / ED50
• TD50 / ED50: dose at which 50% shows dangerous side effects (TD50)
versus the dose at which 50% has the intented effect (ED50)
• Should this be a small or a large number?
o More toxic (less safe): lage TI
o Less toxic (more safe): hoge TI
• Drug interactions
o ‘Don’t drink alcohol with the use of this drug’
• Toxicity (harmful effects)
o Expected effects; often temporary
o Unexpected effects: e.g., allergies

Animal research: sense, ethics
Er wordt veel dieronderzoek gedaan, maar daardoor kunnen mensen wel 23,5 jaar langer leven door
de medicatie die is ontwikkeld.

Timeframe introduction new medication – Preclinical phase




Phases in drug research
Four phases in human drug research:
• Phase 1: Is the substance safe?
o In the first phase researchers test whether human subjects (most often healthy volunteers)
tolerate the substance. If the substance is sufficiently safe, phase 2 starts.

, o Cost/benefit consideration!
o How safe should a compound be before moving forward depends on:
- Severity of disease that may be cured or alleviated by the drug
- Whether there is already an alternative treatment.
o Consider chemotherapy for cancer for which no cure exists, vs. drugs for a non-fatal disease
that can already be cured by existing treatments. (NB chemo is typically not tested in
healthy individuals b/c of the many side effects.)
• Phase 2: Does it work?
o In phase 2, sick people take the place of the healthy. Aim is now to test whether the
substance really works against the disease. Most often this phase starts with a small number
of patients who take the new drug.
• Phase 3: Does it work, and is it better than other existing drugs?
o When the results in phase 2 are good, larger trials start with larger number of patients. In
this phase, the new drug is first tested against a placebo and then against existing
treatments.

What’s in a name?
• Chemical name/ formula: N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine
• Codename: LY110140
• Generic name, easier to communicate: fluoxetine
• Brand name (®)
o Patent holder: ‘Prozac’ (Eli-Lilly) -> 16,10 euro
o After the patent expires, it is also sold under the generic name (fluoxetine) -> 7,08 euro
• What are the different names that are given to medications once they become available for
prescription, and what is the difference between these names?

Timeframe introduction new medication
• Clinical phases 1-3; precede registration
• After registration phase 4; side effects, optimal dosing




Phases in drug research
• When the results are satisfactory, after phase 3 follows registration by CBG, EMA, and/or FDA of
the substance as an official medication. Physicians may now prescribe the drug to their patients.
• Phase 4: What are the effects in the long term?
o Even after a drug has been registered, research continues. This is mostly focussed on side
effects in the long term, or the optimal treatment duration. But often the medicine is tested
for its effects on other diseases as well.  Phase 4 is important because major side effects
usually do not come to light until this phase (example: rimonabant)

What’s in a name…
• Drugs versus medicines
• Related to their purpose: a medicine aims to cure, a drug does not necessarily have the purpose.
• Hence: all medicines are drugs, whereas not all drugs are medicines
• And medication? Defined as the process of treating an illness with medicine

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