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Psychopharmacology all study questions
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Lecture 1: Introduction, brush up basics (neuroanatomy, neurotransmitters;‘Psychofarmacologie’ chapters 1-4)
Which two overarching classes of psychoactive substances can be discerned based on their use?
Drugs and medicines.
What are the different names that are given to medications once they become available for
prescription, and what is the difference between these names?
WG question 1
You have the molecular name/chemical formula, the code name, the generic name (easier to
communicate) and the brand name. The differences between these names is determined only by the
different producers and dependent of the dosage and dose (tablets or capsules for example.
What is pharmacokinetics and pharmacodynamics? Describe these terms and understand their
difference.
Pharmacodynamics describes the biochemical and psychological effects of substances. It answers
questions like: to what receptors does the substance bind? What effect does the substance have on
the receptor (what does the drug do in the brain)?
Pharmacokinetics describes how psychoactive substances get into the brain (orally, intravenously,
inhaling, sniffing, through the brain but also the blood-brain barrier, digestive tract, liver, lungs, blood
circulation) and how a substance moves through the body. It answers questions like: how do you
administer it? How is it absorbed in the body? It is in some extend quite trivial because it isn’t about
what it exactly does. It is important for, for example, medication why does it work faster/better
for some people than for others.
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.
Types of neurotransmitters: there are neurotransmitters that are being used in a relatively low
number of neurons (<1%), such as NE, DA, 5-HT and they have relatively specific targets for drugs.
There also neurotransmitters that are frequently being used in neurons (about 50% of synapses),
such as GABA, Glu and endocannabinoid receptor in many synapses.
Types of receptors: there are different types of receptors based on their location in the cell. There
are post-synaptic, axodendritic receptors and these are the most typical type. But there are also
presynaptic receptors such as autoreceptors (detect release of neurotransmitter from own neuron),
heterereceptors (modulate synapse from another neuron) and autoreceptors on other locations on
the cell (for example on a dendrite).
Common principles of neurotransmitter synthesis (incl. precursors): precursors are substances that
are needed to construct neurotransmitters. The monoamine catecholamine (DA, NE, E) has the
precursor tyrosine (tyrosine DOPA DA NE E). The monoamine indalomines (5-HT) has the
precursor glucose. The amino acide Glu and GABA have the precursor glucose. ACh has the
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,precursor: choline and lecithine. And the peptides oxitocine and endorphins have the precursors
amino acids.
Degradation (incl. reuptake): degradation is the process that needs to take place in order to end the
reaction. The ending of neurotransmitter activity is determined by a combination of degradation
(metabolism, extra or intercellular) in the synapse and reuptake within the cell. Examples hereof are:
Ach’s degradation happens by the extracellular enzyme AchE and then reuptake takes place. For 5-HT
there is reuptake (and intercellular degradation). For peptides (proteins, amino acid chains)
degradation happens by peptidases and then diffusion.
Principles of communication between cells through receptors and how this influences the chance of
postsynaptic neuron firing an action potential: neuron A sends an electrical signal over the axon to
neuron B. This signal is called an action potential. Incoming Na+ in the dendrite spreads itself
passively to the hillock (axon heuvel). The voltage-gated Na+ cannels open. Voltage gated Na+
cannels on the hillock react to the incoming depolarisation of the dendrite when this depolarisation
achieves the critical threshold. Only then an action potential is generated. The ion cannels open
dependent on the potential, Na+ cannels open faster than K+. The action potential takes place in
about 1 to 2 milliseconds. It moves itself from the hillock to the end of the axon and it regenerates
itself on each next place along the axon during which it doesn’t change its shape. An all or none law
applies: the size and speed of the action potential is independent of the intensity of the stimulus that
causes the action potential. Thus, within the same neuron, all action potentials have the same size
and speed.
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?
WG question 2
The area of illnesses, symptoms or disorders of the behaviour, since psychoactive substances
influence behaviour. Psychoactive substances can manipulate brain en neurotransmitters that
determine behaviour. They influence processes in the brain and hence behaviour, cognition and
affect.
Describe the most common mechanisms of modulation of neurotransmission along which
psychoactive substances exert their influence on the brain.
WG question 3
?
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.
In the preclinical phases animal research precedes administration in humans. These phases consist of
efficacy (note that animal models aren’t always predictive for the effect in humans), administration
(does the substance survive the gastro-intestinal system or the blood-brain barrier?) and safety (are
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,there serious side effects when administered systematically?). Then the clinical trials (in humans)
follow. In the first phase it is investigated if the drug is non-toxic and tolerable. In the second phase,
limited efficacy studies are preformed to find out if the substance really works against the disease.
And in the third and last phase large, multi-center studies are performed in which it is determined if
the drug works and if it is better than other existing drugs. When the results in phase 2 are good,
larger trials start with a larger number of patients. In this phase the new drug is first tested against a
placebo and then against existing treatments. When the results are satisfactory, after phase 3 follows
registration of the substance as an official medication. Physicians may now prescribe the drug to
their patients. In this fourth phase the effects of the substance in the long term are being described.
Even after a drug has been registered, research continues. This is mostly focused 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 four is basically an optimisation of application.
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?
The brain mechanisms that cause the disorder in humans may differ from the brain mechanisms in
the animals in which the substances are tested first. Also, there could be problems with
administering substances, which already occur naturally in the brain. Also, very different
combinations of symptoms fall under the same diagnosis, which makes it hard to develop just one
medicine that works against all of the symptoms. The working mechanism of a substance can be
counterproductive because of this. Practical hindrances for, for example Ritalin could be that the pills
don’t work long enough for a kid to get through an entire day at school or it could take to long before
it works because of the oral administration. Then lastly, there are also financial hindrances, since
clinical drug research is a long and costly process.
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 ones.
WG question 4 [questions 5 and 6 are below under Lecture 2
?
Describe the golden standard in executing (psycho)pharmacological research: placebo –controlled
and double-blind. Why are these aspects of importance?
Because it is important to know whether a substance really works the way you want it to and you can
only test this by comparing it with a placebo. It is also very important that this comparison is
performed double-blind so no expectations, either from the participant or the investigator, can
influence the outcome of the study.
Which result will allow the conclusion that a placebo (fake pill) medicine may be useful in treatment?
When the real medicine doesn’t provide significant better results as the placebo.
What is an active placebo?
An active placebo is a placebo that produces noticeable side effects. This is important when a
treatment has side effects while the control doesn’t, because patients who experience side effects
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, may then correctly guess that they are receiving treatment. If patients are able to discriminate
between treatment and placebo at a rate greater than chance, the experiment is not truly blind.
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?
WG question 7
Evidence-based medicine means that the medicine is tested with the golden standard and from its
efficacy is determined through meta-analysis. The conflicting interests of patients, treating
physicians, pharmaceutical industry and policy-makers mean that the credibility of different sources
of information that you can find, for example on the internet, decreases.
Lecture 2: Principles of psychopharmacology (dose-response-curve, receptor-interaction,
pharmacokinetics, tolerance etc; Kenemans chapter 5)
Give a definition of psychopharmacology.
Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking
and behaviour.
(See also Kenemans, paragraph 1.2) What is a dose-response-curve (DRC)?
A dose-response curve is a curve that represents response as a function of 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?
It is not, it depends on dose but there also exist differences between individuals in how they react to
a certain dose of a substance.
What type of responses in a DRC and the relationship between them are especially relevant for
medications?
The minimum dose for a noticeable effect, the maximum effect and the highest dosage with
minimum side effect.
What is efficacy? Potency? Therapeutic window?
Efficacy is the maximum effect (the psychological effect).
Potency is the minimum dose for a noticeable effect.
The range within the lowest dosage with maximum therapeutic effect and the highest dosage with
minimum side effects, forms the therapeutic window.
Which considerations are relevant for the individual titration of the optimal dose of a substance?
The side effects and individual differences.
What is receptor interaction?
?
What is the relationship between receptor interaction and statistical interaction?
?
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