1B psychopharmacology for psychiatry Flashcards
What 4 different types of treatments are there in medicine (with psych examples)?
- Chemical- drugs/medicines e.g. fdrugs for psychosis or depression
- Electrical stimulation e.g. ECT for depression or 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 three ways can we classify drugs by?
- Based on chemical structure
- Based on what illness they treat (e.g. antidepressants, antipsychotics, anxiolytics, hypnotics)
- Based on pharmacology aka neuroscience based nomenclature
What are the pros and cons of chemical structure classification?
- Pro - each drug has unique structure, so there’s specific identification and easy allocation of data
- Con- no use in clinical decision making
What are the pros and cons of classifying drugs based on what illness they treat?
- Pro
- easy for Drs to choose a drug as docs make diagnosis
- Cons
- many psychiatric medicines work in several disorders (e.g. antidepressants also treat anxiety and OCD)
- most psychiatric disorder have multiple symptoms and a single medicine might not treat them all e.g. in depression we get anhedonia, libido loss, appetite loss, poor concentration etc
How do we classify drugs based on pharmacology?
- We classify drugs based on the neurotransmitters they target
- e.g. instead of antidepressant - we can say serotonin enhancers
What are the 4 targets that drugs work on?
- Receptors
- Ion channels
- Enzymes
- Channel proteins
How do drugs that target receptors work + give examples?
- Most are receptor blockers (antagonists)
- dopamine receptor blockers for schizophrenia
- serotonin receptor subtype antagonists for depression
- Histamine receptor antagonists for sleep
- Some stimulate receptors (agonists)
- Benzodiazepines enhance GABA for sleep
- Guanfacine enhances noradrenaline for ADHD
How do drugs that target ion channels work + give examples?
Some drugs block channels so reduce neuronal excitability
- Sodium channels
- Sodium valproate- epilepsy and mood stabilisation
- Carbamazepine- epilepsy and mood stabilisation
- Calcium channels
- Gabapentin and pregabalin- epilepsy and anxiety
How do drugs that target enzymes work + give examples?
generally they block enzyme activity
- E.g. monoamine oxidase inhibitors for anxiety and depression (blocks breakdown of serotonin)
- Acetylcholinesterase inhibitors for dementia (block breakdown of ACh)
- Lithium blocks glycogen synthase kinase for mood stability (stabilises neurones)
Why are reuptake site targeting drugs useful?
Most neurotransmitters are recovered and recycled via reuptake sites
How do drugs targeting reuptake sites work + give examples?
- Many drugs block reuptake sites to increase neurotransmitter conc in the synapse to enhance post-synaptic receptor activity
- Citalopram- enhances serotonin (serotonin reuptake inhibitor) for depression and anxiety
- Desipramine- noradrenaline reuptake inhibitor (NRI) to enhance NA for depression
- Methylphenidate- dopamine reuptake inhibitor (DRI) to enhance dopamine for ADHD
- Some drugs switch the reuptake site direction to enhance release
- E.g. amphetamine for ADHD
Give an example of a neurotransmitter system
5-HT
How does the 5-HT system stop itself from releasing too much 5HT?
Serotonin release acts on presynaptic autoreceptors to inhibit further NT release through negative feedback
How can the effects of NT be divided into 2 types?
- Fast acting (on-off switch)
- Slow acting (modulators) (5% of all neurons)
What 2 NTs come under fast acting NTs and what action do they have?
- Glutamate- are excitatory and make up ≥80% of all neurones (called pyramidal cells)
- GABA- are inhibitory and make up 15% of neurones (called inter-neurons)
What is the balance of glutamate and GABA responsible for?
Content of everything we do e.g. memory, movement, vision etc
What NTs make up slow acting (modulators)?
- Dopamine, serotonin, noradrenaline, acetylcholine
- Endorphins and other peptides
What is the purpose of slow acting NTs?
- Emotions
- Drives
- Valence of memory
What conditions can excess glutamate cause + give treatments?
- Epilepsy
- Perampanel: blocker
- Alcoholism
- Acamprosate: blocker
- Ketamine: blocker
What condition can GABA deficiency cause + what is the treatment?
- Anxiety
- Benzodiazepines: GABA enhancer
What conditions can 5-HT deficiency cause and how do we treat them?
- Depression
- Anxiety
Treated using SRIs and MAOIs: serotonin enhancers
What condition can excess dopamine cause and how do we treat it?
Psychosis
Treated with dopamine receptor blockers
What conditions can excess noradrenaline cause and how do we treat it?
Nightmares
Treated with prazosin: blocker used for PTSD
What conditions can ACh deficiency cause and how can we treat it?
Impaired memory/dementia
Treated using AChesterase enzyme blockers
What types of drugs treat depression?
- MAOI- monoamine oxidase inhibitors
- TCA- tricyclic antidepressants
- SSRI- selective serotonin reuptake inhibitors
- SNRI- serotonin-noradrenaline reuptake inhibitors
- NRI- noradrenaline reuptake inhibitors
- DRI- dopamine reuptake inhibitors
What are partial agonists?
Partial agonist 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 antagonist
- When there’s a deficit of NT, it can act as an agonist
Give examples of partial agonists and what they are usually preferred over
E.g. buprenorphine < heroin
E.g. aripiprazole < haloperidol
E.g. varenicline < nicotine
What are inverse agonists?
- These drugs have the opposite effects to agonists
- e.g. inverse agonists for histamine increase attention so can be used to target ADHD
What receptor subtypes do GABA-A receptors have?
- 5 separate proteins that make up a receptor in multiple different combinations
- Most common is alpha2beta2gamma1 found in the cortex- different combinations found in different parts of brain
What are allosteric vs orthosteric receptors?
- Orthosteric- the receptor on the target protein where the natural transmitter works on
- Allosteric- a different receptor on the target protein
Describe ortho/allosteric receptors on the GABA-A receptor
- GABA-A receptor is an ion channel linked receptor
- GABA binds to the orthosteric GABA receptor sites- there are 2
- This binding enhances Cl- conductance → inhibits neurones → calms the brain
- Benzodiazepines, barbiturates, alcohol, neurosteroids act at allosteric sites on the same protein complex
- They enhance the action of GABA → sedation, sleep, reduce anxiety, anti-epilepsy
Describe drug selectivity
- Some drugs are very selective and only bind to few receptors, meaning they have minimal adverse affects
- However some drugs can bind to multiple receptors and are therefore not selective. This means they can produce a lot of adverse affects
Explain the difference in selectivity between haloperidol and clozapine
Haloperidol: very selective
Clozapine: not very selective
They are both drugs used to treat schizophrenia.
- Haloperidol- D2 receptor antagonist but also has off target effects on alpha1 receptor
- Clozapine- D2 receptor antagonist, 5HT1A partial agonist, 5HT2 antagonist but has off target effects on H1 receptor, M1-4 receptor and alpha-1 receptor causing side effects like sedation, weight gain and metabolic syndrome
Explain the difference in selectivity between amitriptyline and citalopram
- These drugs treat depression as 5HT reuptake blockers
- Amitriptyline- is a serotonin and noradrenaline uptake blocker but also a powerful H1 receptor, 5HT2 receptor and muscarinic M1-4 receptor blocker which gives side effects
- Citalopram- very selective SSRI since it only works on serotonin transporter
What are the different sorts of GABA receptors?
- GABA-A
- GABA-B
What is the GABA-A receptor?
The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel.
Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system.
What happens upon activation of GABAAR?
Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring.
What is the GABA-B receptor?
GHB binds with low affinity to GABAB receptors which are inhibitory via GIRK channels.
What happens upon activation of GABA-B receptor?
Activation of which leads to K+ extrusion and hence membrane hyperpolarisation.
The week agonist properties of GHB are observed only at central GABAB receptors located post-synaptically but does not interact with GABAB in the spinal cord and has no affinity (or only minimal affinity) for the BDZ and alcohol preferring GABAA receptor. Although GHB does not have a direct effect on GABAA receptors activation of GABAB receptors can increase synthesis of several neuroactive steroids that positively modulate the GABAA receptor although this warrants further investigation.
