Psychopharmacology 2020-2021
Study questions per lecture – weeks 1 & 2, lectures 1,2 & 3
Lecture 1: Introduction, brush up basics (neuroanatomy, neurotransmitters;
‘Psychopharmacology’ chapters 1-4)
- Which two overarching classes of psychoactive substances can be discerned based on
their use?
It can either be therapeutic or recreational
- What are the different names that are given to medications once they become available
for prescription, and what is the difference between these names?
One is the name of the substance and the other names are brand names
- What is pharmacokinetics and pharmacodynamics? Describe these terms and understand
their difference.
Pharmacokinetics is about what the body does with a substance. Things like
excretion, half-life and metabolism. Pharmacodynamics is about what the drug does
to your body, like: what is the effect on the neurotransmitters? What are side effects?
What happens inside the body that is facilitated by the drug.
- Considered known (part of the prerequisites; self-study if unfamiliar): types of
neurotransmitters, types of receptors, common principles of neurotransmitter synthesis
(incl. precursors), degradation (incl. reuptake), principles of communication between
cells through receptors and how this influences the chance of the postsynaptic neuron
firing an action potential.
Neurotransmitter release from the presynaptic terminal consists of a series of
intricate steps: 1) depolarization of the terminal membrane, 2) activation of voltage-
gated Ca2+ channels, 3) Ca2+ entry, 4) a change in the conformation of docking
proteins, 5) fusion of the vesicle to the plasma membrane, with subsequent release
of neurotransmitter into the synaptic cleft.
Precursers:
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Monoamines (singe amine group)
- Catecholamines: DA, NE, E
* Precurser: tyrosine -> DOPA -> DA -> NE -> E
Indolamines: 5-HT
* Precursor: tryptophan
Amino acid
- Glu, GABA
* Precursor: glucose
ACh
* Precursor: choline/lecithin.
Peptides
- oxytocin, endorphines
*Precurser Amino Acids
- Medications have a certain indication, meaning the illness, symptoms or disorder for
which they are prescribed. In general, within which area do the indications for
psychoactive substances fall?
Psychiatric / mental problems.
- Describe the most common mechanisms of modulation of neurotransmission along
which psychoactive substances exert their influence on the brain.
Psychoactive substances can have an excitatory or inhibitory effect on several
mechanisms. It is possible for there to be an effect in the postsynaptic receptors or
autoreceptors, which would be done by agonists or antagonists. It is also possible for
substances to affect the reuptake signal which would modulate the amount of
neurotransmitter that stays in the presynaptic gap and the time it remains there.
Amount of transmitters:
Synthesis (presence precursor, activity of enzymes)
Uptake of transmitter in and release from vesicles
Blocking or modulating receptor (pre/post synaptic)
Ending influence through
Reuptake
Degradation (extra/intracellular)
- Many of the currently used psychoactive substances have been discovered by
serendipity, but once every so often new medications are developed on purpose through
hypothesis-driven research lines. Describe in broad terms the (pre)clinical development
phases which a new medicine has to pass before it can be made available to patients.
1. Registration
2. Preclinical phases (animal research before humans)
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3. Clinical trials (in humans)
Phase 1: non-toxic, tolerable
Phase 2: limited efficacy studies
Phase 3: large, multi-center studies
Four phases in human drug research:
1: is it safe?
2: does it work?
3: does it work and is it better than other existing drugs
4: What are the long term effects? (physicians may describe the drug to patients
in this phase)
- In the development of new medicines, there are many bottle necks. What are the most
important conceptual bottle necks (think for example of brain mechanisms that cause the
disorder)? And what are the most important practical hindrances (for example, think of
pharmacokinetic properties)? And what are financial hindrances?
I don’t know what bottle necks are, but practical hindraces are the therapeutic index,
drug interactions, unexpected effects like allergies and toxicity.
- There are various reasons why most psychoactive substances not only exert their main
(intended) effect, but also unwanted side-effects. Describe the two most important
reasons.
They do not selectively bind! Most substances bind to more than just the receptor
that you want them to bind to. So it can also alter other systems/mechanisms in the
brain, and even the body. For example excess serotonin not only affects your mental
state but also has an effect on your gastric intestinal system.
-The receptors are “all over the body” → you have them in your brain, stomach,
kidneys, etc. → side effects
- Describe the golden standard in executing (psycho)pharmacological research: placebo –
controlled and double-blind. Why are these aspects of importance?
Placebo controlled removes the influence of a placebo effect. It shows the contents of
the substance really work, instead of the psychological aspect of taking medication
Double-blind research means both participants and researchers don’t know in what
group the participants are. They could be either in the placebo group or the
experimental group. This is important so researchers can act differently or biased
towards the group they didn’t give the placebo.
- Which result will allow the conclusion that a placebo (fake pill) medicine may be useful in
treatment?
The result that placebo in depression with low severity has more effect than SSRIs
- What is an active placebo?
An active placebo produces side-effects to convince its user that they took the real
drug
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- What is meant with ‘Evidence-based medicine’? Why is this important? What do the
conflicting interests of patients, treating physicians, pharmaceutical industry and policy-
makers mean for the credibility of the different sources of information that you can find,
for example on the internet?
There has to be scientific research for medicine. Pharmaceutical industry wants to put
their medicine on the market asap, which means they try to pay researchers for
showing that their drug is safe. This means there is conflict of interest and is unsafe
for the patients.
Lecture 2: Principles of psychopharmacology (dose-response-curve, receptor-interaction,
pharmacokinetics, tolerance etc; Kenemans chapter 5)
- Give a definition of psychopharmacology.
Psychopharmacology means the study of trying to understand the effect of a drug on
behavior.
- (See also Kenemans, paragraph 1.2) What is a dose-response-curve (DRC)?
On the X-axis: increasing dosage of substance
On the Y-axis: subjective report/objective observation of behavior/brain
process/concentration of (other) substance in brain or body
Useful to determine minimum dose for a noticeable effect (potency) and the
maximum effect (efficacy) and the expected effect of a given dose
- See Kenemans Fig. 5.2: Does the DRC for one particular substance always look the same?
What does it depend on? How about differences between individuals?
Age can be important, as the speed of metabolism can be important to the effect of a
drug
- What type of responses in a DRC and the relationship between them are especially
relevant for medications?
The DRC can visualize what dose is needed to see effect, what the maximum
attainable effect will be and what the therapeutic window is for a drug
- Wat is efficacy? Potency? Therapeutic window?
Efficacy: physiological effect of the drug. Efficacy = 0 means entire receptor is blocked,
so theres no effect. The efficacy on the DCR curve is the maximum attainable desired
effect
Potency: The amount of drug needed for an effect. If a drug is highly potent, only a
tiny amount oh mg will be prescribed. This is were the first effects start to take place.
Therapeutic window: This is the window where you can prescribe drugs safely
without overdosing. This can be done by: the dosis where the first undesired effects
happen – the dosis where the maximum desired effect is reached.
- Which considerations are relevant for the individual titration of the optimal dose of a
substance?
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