4.8 - Psychopharmacology for psychiatry Flashcards
What are the four different types of treatments in medicine, with examples in psychiatry?
- 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
What are three ways that we can classify psychiatric drugs?
- based on chemical structure
- based on what illnesses they treat
- based on their pharmacology (AKA neuroscience based nomenclature NbN)
Who uses the system of classifying drugs by chemical structure?
WHO uses this system
What is a pro and a con of classifying drugs by chemical structure?
- pro - each drug has a unique structure –> specific identification and easy allocation of data
- con - no use in clinical decision making
What are some examples of classifying drugs based on the illnesses they treat? (4)
- antidepressant
- antipsychotic
- anxiolytic
- hypnotic
What are some pros and cons of classifying drugs by the illnesses they treat?
- 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
How do we classify drugs based on their pharmacology (NbN)?
- 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
What are the four targets that psychiatric drugs work on?
- receptors
- neurotransmitter reuptake sites (channel proteins)
- ion channels
- enzymes
How do drugs that target enzymes work?
- 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)
How do drugs targeting receptors work?
- 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
What is a summary of what antagonists and agonists do?
- antagonists block the endogenous agonist binding to the receptor
- agonists mimic the endogenous agonist and stimulate the receptor
How do drugs targeting reuptake sites work?
- 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
How does the 5-HT system stop itself from releasing too much 5-HT?
Serotonin release acts on presynaptic autoreceptors to inhibit further NT release through negative feedback
How many post-synaptic serotonin receptors are there in the brain and what are the two main ones?
- 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
How do drugs targeting ion channels work?
- 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
How can neurotransmitters be divided into two types?
- FAST acting (on-off switch)
- slow acting (modulators) - about 5% of all neurons
What are the two main fast-acting neurotransmitters and what action do they have?
- glutamate - excitatory and make up >80% of all neurones (called pyramidal cells)
- GABA - inhibitory and make up 15% of neurones (called inter-neurones)
What is the balance of glutamate and GABA (fast NTs) responsible for?
Content of everything we do e.g. memory, movement, vision etc
What neurotransmitters make up slow-acting neurotransmitters?
- dopamine, serotonin, noradrenaline, acetylcholine
- endorphins and other peptides
What is the purpose of the slow-acting neurotransmitters (modulators)?
- emotions
- drives
- valence of memory
What conditions can excess glutamate cause and how can we treat these?
- epilepsy –> Perampanel (blocker)
- alcoholism –> Acamprosate / Ketamine (blockers)
What condition can GABA deficiency cause and how can we treat this?
Anxiety –> benzodiazepines (GABA enhancer)
What conditions can 5-HT deficiency cause and how can we treat these?
Depression and anxiety –> SSRIs and MAOIs (serotonin enhancers)
What condition can excess dopamine cause and how can we treat this?
Psychosis –> dopamine receptor blockers
What condition can excess noradrenaline cause and how can we treat this?
Nightmares –> Prazosin (blocker, used for PTSD)
What conditions can ACh deficiency cause and how can we treat this?
Impaired memory/dementia –> AChE enzyme blockers
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
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
What are partial agonists?
Partial agonists are types of drugs which function similarly to agonist but have a lower max efficacy than full agonists
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)
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)
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
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?
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
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
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
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
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
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)
