Chapter 1, 5, 6, 7, 11, 8, 9, & 10. In this order because this is congruent with the order of the lectures. All the important concepts are in bold. Also contains imagines when needed to clarify.
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Psychopharmacology overzicht neurotransmitters en hun werking
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Psychopharmacology
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Summary psychopharmacology (Kenemans)
Chapter 1
Psychotropic drugs: are substances that influence behavior through an effect on the CNS,
primarily the brain.
Recreational drugs are drugs that people consume because they have a rewarding effect,
this will increase the likelihood that it will be taken again when the next opportunity arises.
When the repeated self-administration is often, this is called addiction.
Psychotropic medication is used to reduce, change or otherwise control problematic
behavior.
1.1 intake
Most common method of administration is pills but is a slow and complicated method has
to pass other organs first before it reaches the bloodstream and brain, also a lot of the active
ingredient is broken down before it reaches the blood.
Injecting or infusing a substance directly in into the bloodstream is a relatively quick way to
increase the amount of the substance in the blood, but also to achieve a fast result in the
brain. Smoking the drugs is similar in regard to speed. Plays a role in the addictiveness.
Insufflation (snorting) is also a fast way. Skin intake (nicotine patch) is extremely slow.
Pills can be packed two ways: the first one being fast which results in the need to take it
more often to ensure the peak blood level is stable. The second is an extended-release
formula to ensure a more constant blood level and a more gradual course of effects on
behavior.
A special category of substances is composed of hormones slow process in comparison to
signals transmitted between neurons via neurotransmitters. Think about melatonin.
1.2 dosing
It’s about the question of how much of a substance should you take to achieve a certain
effect?
It depends on these factors:
- Weight of the person (mg/kg)
- Potency: the amount of drugs it takes to achieve the desirable effects
- Efficacy of the drugs: the relationship between the dose and the occurrence of
certain effects (see also Chapter 5)
- How much someone has/is willing to work to administer the drugs again.
1.3 side effects and therapeutic window
Potency and efficacy can’t be considered separately from the undesirable side effects of a
specific dose. The dose at which the balance swings form positive to negative side effects
differ from individual to individual. depends on context as well as the positive effects
(more positive more likely to immediately consume again).
In principle the higher the dose, the more intense the side effects.
,Therapeutic window: the window is determined on the one hand by the lowest dose that
forms an average lower limit for observing any desirable effect. The upper limit is the highest
dose that results in an unacceptable level of undesirable side effects. the larger the TW
the more suitable it is for treating a symptom or syndrome.
1.4 titration and tolerance
The act of determining the optimal dose is known as titration. Titration also depends on how
long it takes to achieve the desired effects. Most psychoactive drugs the desired effect is
only achieved after chronic administration (±6 weeks).
Tolerance can be developed as a consequence of titration. It’s the reduced desirable or
undesirable effects due to the chronic administration of a substance.
1.5 research into how psychotropic drugs work
The goal of scientific research is to explain phenomena and to make them predictable.
However this is only partially the case in the field of pharmacological research. The goal is
often to determine whether the drugs has the desired effect in a specific group of patients,
without explaining why. This result of this research is a statement regarding the likelihood
that the drug will have a desired effect in a random new patient. usually the last phase in
in the development of a new drug. always preceded by a pre-clinical phase (explanatory).
Many of the current medical applications of psychotropic drugs still rest on accidental
observations of the effects of the substances on behavior, although the substances were
initially intended for other purposes.
1.6 placebo control
Open label study: the drug is administered to a group of patients in full view of everyone
involved, and then the researchers can conclude that it may indeed be due to the substance.
positive results always have to be followed by a placebo control study: comparing two
group of patients or one group with two conditions. One group is administered the drugs the
other will receive a placebo. This is done double blinded. This is done so that expectations of
researchers and patients can be differentiated between ‘real’ results.
Can have different results: a result that the intervention group really performed better than
the placebo. Or the placebo group performed as well as the intervention group. Yet another
possibility is that of a true placebo effect: both experience effects.
1.7 random tests and statistics
the last phase in the development of a new drug usually involves a large scale, double-blind
comparison between two groups of patients. Positive results can still be obtained due to
other factors. Such a demographic factors like age, sex, symptom severity, etc. sample
should be as balanced as possible and representational of the true population.
Still then other factors can contribute to a “false” positive. Can be reduced by getting
baseline measurements, making it possible to determine whether there are any clinical
differences between the groups from the beginning. Can also be used to correct the
eventual clinical results for any a priori differences between the groups. scores after a
treatment as a (percentage) change from the baseline value.
,When the results indicate improvement as well as that the side effects appear to be
acceptable the drug is released on the market. But even then things can go awry, such as
unforeseeable side effects. Whether this has consequences depends on a couple of
considerations:
- statistical: how likely is it? must be quantified. Done by the odds ratio, when its 1
then the effect is equal, when its greater than 5% than it’s a significantly greater
chance.
- How serious are the side effects?
1.8 pre-clinical and clinical research
Clinical research is usually done in three phases:
1. Healthy volunteers are used to see to what extend the drugs is tolerated. This is done
with a titration process. Indicators used are physiological and subjective.
2. Small group of patients with double-blind, placebo-controlled design. Sometimes an
active placebo is used to ensure people really don’t know to which group they
belong (such as an already existing drug)
3. Essentially the same as phase two, to ensure that the findings are indeed a real
positive result, usually done with thousands of patients, preferably in different
countries. At least two independent studies must be conducted. Takes around 3.5
years to complete and cost roughly 30 million euros. When results are positive the
drugs can be registered, sold and prescribed by physicians.
4. Chemist and physicians report any side effects that didn’t occur during the earlier
phases drug is already on the market
Pre-clinical studies usually take years and can utilize animal models.
Chapter 5 principles of psychopharmacology
Psychopharmacology is the discipline that attempts to study the effects of drugs on
behavior, cognition, and emotion. There are two principles that frequently occur in this field
the DRCs and receptor interaction
5.1 dose response curve
x-axis: usually in mg/kg
, A DRC provides insight into how much of a substance must be administered to achieve a
certain effect. This results in a statement of the optimal dose (the quantity) or dosage (the
amount administered to achieve the desired effect.
It provides the sight of the maximum attainable effect of a substance, and it also shows how
the effect develops with gradual increase.
It’s based on the idea that the more you measure, the more you know. And is not exclusively
for psychopharmacology.
5.2 potency, efficacy, and the therapeutic window
Potency: how much of a substance you need to achieve the (desired) effects Quick
effects= very potent
Efficacy: how fast the maximum is achieved with a substance. If its relatively quick, its not
very efficacious.
DRC is dependent on countless of factors, such as history of use and can thus be different for
every individual. Usually in research it’s an average of hundreds of individuals.
The therapeutic window shows the range between the desired and undesirable effects of a
substance. This can be displayed by superimposing the DRCs for two types of effects.
The titration process, described in chapter 1, is usually used in clinical practice to infer the
therapeutic index for an individual. The optimal dose can vary widely between individuals,
and an optimal dose can be determined for each individual patient.
5.3 receptor interaction
The second defining principle is the concept of receptor interaction.
Pre-pulse inhibition (PPI): is a measure for the capacity to regulate excessive amount of
auditory stimulation. Patients with hallucinations have a reduced capacity in this regard.
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