(psych) psychopharmacology Flashcards
what types of treatment are available in psychiatric medicine?
chemicals (drugs/medicines)
electrical stimulation
structural rearrangement (surgery & orthopaedics)
talking therapies
how are chemicals used in psychiatric medicine?
drugs for psychosis
drugs to treat depression
how is electrical stimulation used in psychiatric medicine?
electroconvulsive therapy for depression
neurostimulation for pain stimulation
how is structural rearrangement used in psychiatric medicine?
psychosurgery
deep brain stimulation for sever depression
how are talking therapies used in psychiatric medicine?
cognitive behaviour therapy (CBT)
exposure for phobias
what is the advantage of classifying psychiatric drugs based on chemical structure?
each drug has a unique structure = extremely precise way of classifying drugs
easy to allocate data
what is the disadvantage of classifying psychiatric drugs based on chemical structure?
no use in clinical decision making as most of the time, clinicians do not know chemical structure of every drug
what is the advantage of classifying psychiatric drugs based on the illnesses they treat?
(e.g. antidepressants, antipsychotics, anxiolytics, hypnotics)
easier for doctors and clinicians to choose a drug to treat the condition
what do hypnotic drugs do?
drugs that induce sleep and are used to treat insomnia
what are the disadvantages of classifying psychiatric drugs based on the illnesses they treat?
(e.g. antidepressants, antipsychotics, anxiolytics, hypnotics)
many psychiatric medicines (e.g. antidepressants, antipsychotics etc) work in several disorders and not just the ones they have been named after
most psychiatric conditions have multiple symptoms and a single medicine may not treat all of them
can be discerning for the patient to find out they have been prescribed e.g. ‘an antipsychotic’ for depression
how are psychiatric drugs classified based on their pharmacology?
using neuroscience-based nomenclature (NbN)
= an app with core pharmacology used to classify psychiatric medicines
what is NbN?
neuroscience-based nomenclature
= an app that contains the core pharmacology used to classify psychiatric medicines
what is the problem with classifying drugs as antipsychotics and antidepressants etc - and how is this overcome?
can be discerning for the patient to find out they have been prescribed e.g. ‘an antipsychotic’ for depression
so instead classify drugs based on target neurotransmitters (e.g. dopamine blocker, serotonin enhancer)
how are drugs classified based on target neurotransmitters?
antipsychotics = dopamine blockers
antidepressants = serotonin enhancer
hypnotic = GABA enhancer
what are antipsychotics also known as?
dopamine blockers
what are antidepressants also known as?
serotonin enhancers
what are hypnotics also known as?
GABA enhancers
which structures do psychiatric drugs (like all drugs) target?
transport proteins (i.e. neurotransmitter re-uptake sites)
enzymes
receptors
ion-channels
where are the targets for psychiatric drugs mostly found?
in the brain
what causes adverse/side effects when taking psychiatric drugs?
when other sites elsewhere in the body are structurally similar to the desired target site, drug can binds to secondary sites and cause side effects
(if unwanted = adverse effects)
which structure, besides the brain, is commonly affected by psychiatric drugs?
liver enzymes
in neuronal transmission, why are reuptake proteins important?
enable the neurotransmitter in the synaptic cleft to be taken back up into the pre-synaptic terminal and then recycled
= prevents continuous activation of the post-synaptic neurone
which is the only neurotransmitter that is not taken back up into the pre-synaptic nerve terminal?
acetylcholine
(Ach is hydrolysed in the synaptic cleft and one of the resultant products, choline, is taken back up into the pre-synaptic neurone)
which two main receptors can a neurotransmitter act on?
post-synaptic membrane receptor (main target)
autoreceptors (on the pre-synaptic neurone)
what is the impact of a neurotransmitter acting on an autoreceptor?
autoreceptors are usually inhibitory
= inhibit Ca2+ influx into pre-synaptic nerve terminal so there is reduced neuronal firing and reduced release of neurotransmitter into the synaptic cleft
what is an autoreceptor?
type of receptor located on the membranes of presynaptic nerve cell
part of a negative feedback loop
which enzyme inhibitors are used for anxiety and depression treatment?
monoamine oxidase inhibitors (MAOIs)
how do monoamine oxidase inhibitors work in treating anxiety and depression?
block the breakdown of serotonin and noradrenaline so greater concentrations remain in the system to stimulate wellbeing and a better mood
which enzyme inhibitors are used for depression treatment?
acetylcholinesterase inhibitors
how do acetylcholinesterase inhibitors work in treating dementias?
block the breakdown of acetylcholine so more remains to make up for the acetylcholine deficit in dementia
which enzyme inhibitors are used for mood stability treatment?
glycogen synthase kinase inhibitors
how does lithium work for mood stability treatment?
lithium blocks glycogen synthase kinase for mood stability
what are agonists?
mimic the endogenous agonist and stimulate the receptors
what are antagonists?
block the endogenous agonist binding to the receptors
give examples of antagonists
dopamine receptor blockers (for schizophrenia)
histamine receptor blockers (for sleep)
give examples of agonists
benzodiazepines enhance GABA (for sleep)
guanfacine enhances noradrenaline (for ADHD)
why do some psychiatric drugs block reuptake sites?
to increase neurotransmitter concentration in the synapse to enhance post-synaptic receptor activity
(e.g. citalopram, desipramine, methylphenidate)
how does citalopram work?
binds to and inhibits the serotonin re-uptake transporter to enhance serotonin in the CNS
to treat depression and anxiety
how does desipramine work?
binds to and inhibits the noradrenaline re-uptake transporter to enhance noradrenaline in the CNS
to treat depression
how does methylphenidate work?
binds to and inhibits the dopamine re-uptake transporter to enhance dopamine in the CNS
to treat ADHD
how does amfetamine work?
bind to re-uptake transporters and switch the re-uptake site direction so release of neurotransmitter into the synaptic cleft is enhanced
what is amfetamine used for?
to treat ADHD
which drugs bind to reuptake proteins?
citalopram
desipramine
methylphenidate
amfetamine
where does serotonin act in the CNS?
acts on auto-receptors to inhibit serotonin release (negative feedback)
acts on post-synaptic receptors (5HT1a) to dampen activity in the post-synaptic neurone, reducing anxiety and depression
what is the effect of psychiatric drugs blocking ion channels?
reduces neuronal excitability
which psychiatric drugs block sodium channels and why?
sodium valproate and carbamazepine
= reduce sodium influx into pre-synaptic neurones
= reduced stimulation of action potentials
= reduce neuronal excitability
= cannot recruit neurones in an epileptic focus so no seizures
to treat epilepsy and enable mood stabilisation
which psychiatric drugs block calcium channels and why?
gabapentin and pregabalin
= reduced neuronal excitability
to treat epilepsy and anxiety
what is the main excitatory neurotransmitter?
glutamate
approx 80% of all neurones
what is the main inhibitory neurotransmitter?
GABA
approx 15% of all neurones
what are the two types of neurotransmitter?
fast-acting (inhibitory or excitatory)
slow-acting (modulators e.g. dopamine, serotonin, noradrenaline, acetylcholine)
give examples of fast-acting neurotransmitters
glutamate (excitatory)
GABA (inhibitory)
give examples of slow-acting neurotransmitters
dopamine
serotonin
acetylcholine
noradrenaline
endorphins and other peptides
what is the function of fast-acting neurotransmitters?
involved in memory, movement and vision
what is the function of slow-acting neurotransmitters?
modulators
emotions, drives, valence of memory
what happens to neurotransmitter levels in epilepsy?
excess glutamate
how is epilepsy treated pharmacologically?
perampanel - glutamate (AMPA) receptor antagonist
what happens to neurotransmitter levels in alcoholism?
excess glutamate
how is alcoholism treated pharmacologically?
acamprosate
ketamine
= both glutamate (NMDA) receptor antagonists
what happens to neurotransmitter levels in anxiety?
GABA deficiency
how is anxiety treated pharmacologically?
benzodiazepines
= GABA enhancers
what happens to neurotransmitter levels in depression/anxiety?
5HT (serotonin) deficiency
how is depression(/anxiety) treated pharmacologically?
1) selective serotonin reuptake inhibitors (SSRIs)
= prevent serotonin reuptake back into the pre-synaptic neurone
OR
2) monoamine oxidase inhibitors
= block breakdown of serotonin and noradrenaline
what happens to neurotransmitter levels in psychosis?
excess dopamine
how is psychosis treated pharmacologically?
dopamine receptor blockers
what happens to neurotransmitter levels in nightmares?
excess noradrenaline
how are nightmares treated pharmacologically?
prazosin
= blocks adrenoreceptors, preventing activation by adrenaline/noradrenaline
what happens to neurotransmitter levels in dementia/impaired memory?
acetylcholine deficiency
how is dementia/impaired memory treated pharmacologically?
acetylcholinesterase enzyme inhibitors
what are multimodal drugs?
drugs that work on two different targets at the same time
what classes of drugs act on 5HT systems to treat depression?
monoamine oxidase inhibitors (MAOIs)
tricyclic antidepressants (TCAs)
selective serotonin re-uptake inhibitors (SSRIs)
5HT receptor antagonists
serotonin-noradrenaline reuptake inhibitors (SNRIs)
melatonin agonist (?)
what is an inverse agonist?
an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist
‘antagonises the effects of an agonist’
give an example of an inverse agonist
inverse agonist for histamine receptor can increase attention in ADHD
how is inverse antagonism used for ADHD treatment?
inverse agonist for histamine receptor can increase attention in ADHD
(histamine usually sedates so inverse agonist has the opposite effect)
how can inverse antagonism be used to reverse alcohol’s amnestic effect?
amnestic effect of severe alcoholism could be reversed by giving a5IA
= improves functionality of hippocampus to improve memory again
what are partial agonists?
ligands that bind to the agonist recognition site but trigger a response that is lower than that of a full agonist at the receptor
why are partial agonists preferred in some cases?
improved safety (especially in overdose)
how does a partial agonist act when there is excess neurotransmitter?
in excess neurotransmitter, partial agonist will have antagonising effects (blocking the receptor)
what determines the effect of a partial agonist and how?
the ongoing levels of neurotransmitter present
how does a partial agonist act when there is a deficit in neurotransmitter?
acts as an agonist (as required) to produce the desired outcome
how many parts are there to a GABA receptor?
five different proteins make up the receptor
what is an orthosteric site?
the sites for binding of the substrates or competitive inhibitors of enzymes and agonists or competitive antagonists of receptors
what is an allosteric site?
sites to which binding will result in a conformational change (far from the orthosteric site)
give an example of orthosteric site binding
the GABAa receptor is an ion-channel linked receptor
the neurotransmitter GABA binds to the GABA receptor’s orthosteric site
= enhanced chloride ion conductance
= inhibits neuronal excitability and activation
= calms the brain
give an example of allosteric site binding
benzodiazepines, barbiturates, ethanol (alcohol), neurosteroids
= all act at allosteric sites (sites away from the orthosteric site) on the same protein complex
= enhance the action of GABA allosterically without interacting at the GABA orthosteric site directly
= sedation, sleep, reduced anxiety, anti-epilepsy
what are the binding sites available on the GABA ion channel?
GABA
benzodiazepines
neurosteroids
ethanol
barbiturates
which two dopamine receptor blockers are used to treat schizophrenia?
haloperidol and clozapine
= block dopamine neurotransmission
how does haloperidol compare to clozapine in terms of drug selectivity?
haloperidol = very selective for the dopamine receptor (potent dopamine receptor blocker)
but some side effects
how does clozapine compare to haloperiodol in terms of drug selectivity?
clozapine has a very low drug selectivity - binds to numerous receptors
= increased risk of off-target side effects
(weight gain, sedation, metabolic syndrome)
which two serotonin reuptake inhibitors are used to treat depression?
amitriptyline and citalopram
= both block the serotonin transporter and prevent serotonin reuptake
how does amitriptyline compare to citalopram in terms of drug selectivity?
binds to numerous transporters and receptors
= huge burden of side effects due to many off-target actions
how does citalopram compare to amitriptyline in terms of drug selectivity?
much more selective as it binds only to the serotonin transporter
= not many side-effects unless due to excess serotonin
what are the impacts of off-target effects in overdose?
can have a huge impact
= can lead to cardiac or brain toxicity (increased binding to undesired sites where can be very dangerous)
