4.8 - Psychopharmacology for psychiatry Flashcards
1
Q
What are the four different types of treatments in medicine, with examples in psychiatry?
A
- chemical - drugs/medicine(+ immunotherapy) e.g. drugs for psychosis or depression
- electrical stimulation e.g. ECT for depression, neurostimulation for pain syndromes
- structural rearrangement - surgery and orthopaedics e.g. psychosurgery/deep brain stimulation for severe depression
- talking (psycho) therapies e.g. CBT or exposure to phobias
2
Q
What are three ways that we can classify psychiatric drugs?
A
- based on chemical structure
- based on what illnesses they treat
- based on their pharmacology (AKA neuroscience based nomenclature NbN)
3
Q
Who uses the system of classifying drugs by chemical structure?
A
WHO uses this system
4
Q
What is a pro and a con of classifying drugs by chemical structure?
A
- pro - each drug has a unique structure –> specific identification and easy allocation of data
- con - no use in clinical decision making
5
Q
What are some examples of classifying drugs based on the illnesses they treat? (4)
A
- antidepressant
- antipsychotic
- anxiolytic
- hypnotic
6
Q
What are some pros and cons of classifying drugs by the illnesses they treat?
A
- pro - easy for doctors to choose a drug as doctors make diagnosis
- con 1 - many psychiatric medicines work in several disorders e.g. antidepressants also treat anxiety and OCD, some antipsychotics used as add on treatment for depression
- con 2 - most psychotic disorders have multiple symptoms and a single medicine may not treat them all e.g. in depression there is anhedonia, libido loss, low mood, anxiety, insomnia, appetite loss etc
7
Q
How do we classify drugs based on their pharmacology (NbN)?
A
- core pharmacology used to classify medicines
- we classify drugs based on the neurotransmitters they target
- e.g. instead of antipsychotic - dopamine blocker
- e.g. instead of antidepressant - serotonin enhancer
- e.g. instead of hypnotic/anxiolytic - GABA enhancer
8
Q
What are the four targets that psychiatric drugs work on?
A
- receptors
- neurotransmitter reuptake sites (channel proteins)
- ion channels
- enzymes
9
Q
How do drugs that target enzymes work?
A
- generally drug treatments block enzyme activity
- e.g. MAOIs for anxiety and depression (block breakdown of serotonin)
- e.g. AChE inhibitors for dementia (block breakdown of ACh)
- e.g. lithium blocks glycogen synthase kinase for mood stability (stabilises neurones)
10
Q
How do drugs targeting receptors work?
A
- most treatments are receptor blockers (antagonists)
- e.g. dopamine receptor blocker for schizophrenia
- e.g. serotonin receptor subtype antagonists for depression
- e.g. histamine receptor antagonists for sleep
- some stimulate receptors = enhancers (agonists)
- e.g. BZs enhance GABA for sleep
- e.g. guanfacine enhances NA for ADHD
11
Q
What is a summary of what antagonists and agonists do?
A
- antagonists block the endogenous agonist binding to the receptor
- agonists mimic the endogenous agonist and stimulate the receptor
12
Q
How do drugs targeting reuptake sites work?
A
- most NTs are recovered and recycled via reuptake sites
- many psychiatric drugs block these reuptake sites so increase NT concentration in synapse to enhance post-synaptic receptor activity
- e.g. citalopram (SSRI) enhances serotonin for depression and anxiety
- e.g. desipramine (NRI) enhances noradrenaline for depression
- e.g. methylphenidate (DRI) enhances dopamine for ADHD
- some switch the reuptake site direction to enhance release
- e.g. amphetamine for ADHD increases dopamine
13
Q
How does the 5-HT system stop itself from releasing too much 5-HT?
A
Serotonin release acts on presynaptic autoreceptors to inhibit further NT release through negative feedback
14
Q
How many post-synaptic serotonin receptors are there in the brain and what are the two main ones?
A
- 14
- 5HT1A - inhibitory receptor which dampens activity in the neurons it is in to reduce anxiety and depression
- 5HT2A - psychedelic drugs work on this to have hallucinogenic effects - might be involved in schizophrenia and is involved in eating and regulation of sleep
15
Q
How do drugs targeting ion channels work?
A
- some drugs block channels to reduce neuronal excitability
- e.g. sodium valproate and carbamazepine block sodium channels - epilepsy and mood stabilisation
- e.g. gabapentin and pregabalin block calcium channels - epilepsy and anxiety
16
Q
How can neurotransmitters be divided into two types?
A
- FAST acting (on-off switch)
- slow acting (modulators) - about 5% of all neurons
17
Q
What are the two main fast-acting neurotransmitters and what action do they have?
A
- glutamate - excitatory and make up >80% of all neurones (called pyramidal cells)
- GABA - inhibitory and make up 15% of neurones (called inter-neurones)
18
Q
What is the balance of glutamate and GABA (fast NTs) responsible for?
A
Content of everything we do e.g. memory, movement, vision etc
19
Q
What neurotransmitters make up slow-acting neurotransmitters?
A
- dopamine, serotonin, noradrenaline, acetylcholine
- endorphins and other peptides
20
Q
What is the purpose of the slow-acting neurotransmitters (modulators)?
A
- emotions
- drives
- valence of memory
21
Q
What conditions can excess glutamate cause and how can we treat these?
A
- epilepsy –> Perampanel (blocker)
- alcoholism –> Acamprosate / Ketamine (blockers)
22
Q
What condition can GABA deficiency cause and how can we treat this?
A
Anxiety –> benzodiazepines (GABA enhancer)
23
Q
What conditions can 5-HT deficiency cause and how can we treat these?
A
Depression and anxiety –> SSRIs and MAOIs (serotonin enhancers)
24
Q
What condition can excess dopamine cause and how can we treat this?
A
Psychosis –> dopamine receptor blockers
25
What condition can excess noradrenaline cause and how can we treat this?
Nightmares --> Prazosin (blocker, used for PTSD)
26
What conditions can ACh deficiency cause and how can we treat this?
Impaired memory/dementia --> AChE enzyme blockers
27
What types of drugs treat depression? (8)
- MAOI - monoamine oxidase inhibitors
- TCA - tricyclic antidepressants
- SSRIs - selective serotonin reuptake inhibitors
- receptor antagonists
- SNRIs - serotonin-noradrenaline reuptake inhibitors
- NRIs - noradrenaline reuptake inhibitors
- DRIs - dopamine reuptake inhibitors
- melatonin agonist
28
What are multimodal drugs for depression?
- work on two different targets
- e.g. Vilazodone - SSRI + 5HT1A agonist
- e.g. Vortioxetine - SSRI + multiple other 5-HT receptor effects
29
What are partial agonists?
Partial agonists are types of drugs which function similarly to agonist but have a lower max efficacy than full agonists
30
Why are partial agonists useful?
- improved safety - especially in overdose
- in states of high NT or excess agonist, partial agonist medicine can act as an antagonist (and when there is a deficit of NT it can act as an agonist)
31
What are some examples of partial agonists and what other drug they act like when being antagonists?
- aripiprazole - haloperidol (psychosis)
- buprenorphine - heroin (pain and addiction, safer alternative)
- varenicline - nicotine (smoking replacement)
32
Why is aripiprazole (partial agonist) better than haloperidol for psychosis?
- aripiprazole acts like haloperidol (dopamine antagonist) when there is too much dopamine but as dopamine agonist when there is too little
- important as we need some dopamine for normal motor function and haloperidol completely blocks dopamine activity so would have its own negative side effects
33
What are inverse agonists?
- opposite effects to agonists
- not antagonists as they do not block receptor
- e.g. inverse agonists for histamine increase attention --> treat ADHD?
34
What receptor subtypes do GABA-A receptors have?
- 5 separate proteins that make up a receptor in multiple different combinations
- most common is alpha1beta2gamma2 found in cortex - different combinations found in different parts of the brain
35
What are allosteric vs orthosteric receptors?
- orthosteric - receptor on target protein where the natural (endogenous) neurotransmitter works on
- allosteric - a different receptor/site on the target proteins
- drugs act on orthosteric/allosteric site
36
Describe how different things bind to orthosteric/allosteric sites on the GABA-A receptor.
- GABA-A receptor is an ion channel-linked receptor
- GABA binds to orthosteric GABA receptor sites --> enhances Cl- conductance --> inhibits neurons --> calms the brain
- BZs, barbiturates, alcohol, neurosteroids act at allosteric sites on the same protein complex --> enhance the action of GABA --> sedation, sleep, reduce anxiety, anti-epilepsy
37
What is drug selectivity?
- some drugs are very selective and only bind to a few receptors = minimal adverse effects
- however some drugs can bind to multiple receptors and are therefore not selective = many adverse effects
38
Compare the drug selectivity of haloperidol and clozapine (dopamine receptor blockers for schizophrenia).
- haloperidol - selective - D2 receptor antagonist but also off-target effects on alpha1 receptor
- clozapine - not selective - D2 receptor antagonist, 5HT1A partial agonist, 5HT2 antagonist but has off-target effects on H1, M1-4 and alpha1 receptors causing side effects like sedation, weight gain and metabolic syndrome
39
Compare the drug selectivity of amitriptyline and citalopram (5HT reuptake blockers for depression).
- amitriptyline - SNRI but also powerful H1, 5HT2, alpha1 and muscarinic M1-4 receptor blockers = side effects
- citalopram - very selective SSRI since it only works on serotonin transporter (adverse effects driven solely by increased serotonin)
