Comprehensive summary of ALL literature concerning Task 4 (Biological substrates of anxiety disorders), summarized per article. Written in English, with Dutch clarifications. All tasks of this course are also available as a bundle! GGZ2024 - Anxiety Disorders
Mechanism of action of the drugs heel belangrijk!
Laatste slide college gebruiken voor het lezen van Delgado
Neuroimaging - the process of producing images of the structure or activity of the
brain or other part of the nervous system by techniques such as magnetic
resonance imaging or computerized tomography.
Engelse namen Kalium en Natrium opzoeken! ivm actiepotentiaal etc.
GABA = benzodiapine !! causes that CL- goes in the cell, so it becomes more
negative inside so it become very difficult om over de drempel te gaan no
fire! Werkt kalmerend! zegt dat een gevaar wel meevalt wel heel
verslavend.
GABA is an agonist it induces the efect versterkt de werking)
Beta-blockers are antagonist het maakt het moeilijkers voor een
neurotransmitter om te binden moeilijker om tot fire te komen) het blokkeert de
werking)
Fear network
General model of anxiety:
Spider amygdala says this is important) insula subjective feelings I feel
fear/anxious) ACC approach, avoidance what should I do), responding)
PTSD – hippocampus memory)
OCD – striatum motoric) & orbitofrontal obsessions)
Dual path model of le doux zie foto!! En foto bord college highroad is
thinking zie ook Wikipedia.
Emotional stimulus thalamus high road sensory cortex) amygdala
emotional response
o Makes sure you give an appropriate response, it only takes more
time because another brain section is used.
Emotional stimulus thalamus low road amygdala emotional
response
o Easier road in case of fight or ight PA)
Learning goals:
1. What medication exist to treat anxiety? Focus on GABA,
betablockers, Noradrenergin and serotenergic system, SSRIs, TCA,
Bendoziapine SSRIs TCA vooral bij stemming
a. Specifc indications for diferent anxiety disorders.
b. What are the mechanisms of these action of these drugs?
c. What are side-efects of medication for anxiety?
Meyer, J.S., & Quenzer, L.F. (2013). Psychopharmacology: drugs, the brain, and
behavior. Sunderland MA, Sinauer.
Drugs for treating anxiety
Drugs that are used to relieve verlichten) anxiety are called anxiolytics. Many
of these belong to the class of sedative-hypnotics, which is part of a still larger
category, the CNS depressants.
CNS depressants include barbiturates, benzodiazepines and alcohol. All these
drugs reduce neuron excitability prikkelbaarheid).
, Anxiolytics – relieve the feelings of tension and worry and signs of stress. They
have minimal side efects such as sedation verdoving). This drugs increase
behaviours which are normally suppressed onderdrukt) by anxiety or
punishment.
Side efects:
Drugs that relieve anxiety often also
produce a calm and relaxed state, with
drowsiness slaperigheid) and mental
clouding vertroebeling), incoordination,
and prolonged reaction time. At higher
doses, these drugs also induce sleep,
and they are therefore sometimes called
hypnotica.
At the highest doses, CNS depressants
induce coma and death, although even
at therapeutic doses they can be fatal if
combined with other drugs .
Classic sedative-hypnotic drugs afect the functioning of many types of neurons
in the CNS central nervous system), their primary mechanism of action involves
enhancing GABA transmission.
GABA is the major inhibitory neurotransmitter in the nervous system it has
receptors on most cells in the CNS to exert widespread inhibitory efects.
The GABA A receptor complex regulates a Cl- channel that increases Cl-
current into the cell to move the membrane potential farther away from the
threshold drempel) for firing. therefore, GABA agonists produce a local
hyperpolarization, or inhibitory postsynaptic potential, and inhibit cell firing.
When benzodiazepines bind to their BSZ side on the GABAA complex, they
enhance the efect of GABA by increasing the number of times the channel
opens. owever, in the absence of GABA, the benzodiazepines have no efect on
Cl- channel opening. The presence of a BDZ alters the physical state of the
receptors, increasing the receptor affinity for GABA so that GABA opens the
channels more easily.
1. Efect of GABA
2. Efect of GABA + BDZ
3. Efect of GABA + BDZ + antagonist umazenil prevents the BDZ-induced
enhancement on GABA, but not GABA itself).
4. efect of GABA+BDZ+ GABA antagonist prevents GABA from opening the
channel & the presence of BD has no further efect).
Benzodiazepines
Alles wat op –pam eindigt is een BZD
Langdurende BZP worden ook gebruikt als hypnotic/spierverslapper
Chlordiazepoxide Librium) was the first benzodiazepine to be introduced. It
represented the first true arixiolytic that targeted anxiety without producing
excessive sedation verdoving). It has a low incidence of tolerance, a less severe
withdrawal syndrome than barbiturates, and a very safe therapeutic index.
Others – diazepam Valium), oxazepam Serax), urazepam Dalmare)
All BDZs have a common molecular structure and a similar mechanism of
action.
The choice of a particular BDZ for a given therapeutic situation depends
primarily on the speed of onset and the duration of drug action.
, o The onset of action is determined by the drug’s lipid solubility
oplosbaarheid) – the most soluble are quickest to be absorbed and
moved through the blood-brain-barrier to initiate the drug efect.
o The duration of action is determined by 1) diferences in their method
of biotransformation and 2) the extent of redistribution to inactive
depots such as skeletal muscle and fat.
Many have active metabolites, making them long acting.
Therapeutic efects:
o BDZs are useful for presurgical anesthesia: the patient is conscious but
is less aware of his surroundings and is quite relaxed not for deep
anesthesia).
o Most popular use is anxiety relief: they relieve the sense of worry and
fearfulness, and the physical symptoms associated with anxiety with
less mental clouding, loss of judgment, and motor incoordination than
is typical of other sedative-hypnotica.
o Some BDZs are useful muscle relaxants and others are anticonvulsants
for the management of particular forms of epilepsy.
o Preventing acute alcohol and barbiturate withdrawal symptoms
ontwenning).
Advantages of BDZs over other sedative-hypnotics:
o igh therapeutic index
A higher therapeutic index is preferable to a lower one: a patient
would have to take a much higher dose of such a drug to reach
the toxic threshold than the dose taken to elicit the therapeutic
efect.
o Availability of a competitive antagonist to reverse overdose.
o Lower change of physical dependence, withdrawal and abuse potential.
BDZ partial agonists – produce less of an efect than the BDZs. It was thought
that the partial agonist would relieve anxiety with reduced side efects. Blijkt
bij dieren wel te werken, maar bij mensen niet.
Bijwerkingen – minder goed concentreren, slaperig/sufer zijn
Antidepressants – relieve anxiety and depression – het probleem hiermee is
dat het eerst erger wordt bv. je wordt eerst veel angstiger, daarom stoppen veel
mensen er in de eerste fase mee).
Anxiety and depression very often occur at the same time and a single drug can
be used for both conditions. But several antidepressant have beneficial efects in
treating anxiety apart from their antidepressant action.
In OCD – the SSRI’s clomipramine Anaf- ranil), uoxetine Prozac),
uvoxamine Luvox), and sertraline Zoloft) have been found efective in
reducing symptoms, possibly because they enhance 5- T function by blocking
reuptake of the monoamine.
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