psychopharmacology Flashcards
What are some therapeutic methods in psychiatry?
- chemicals - drug/medicines (eg antidepressants)
- electrical stimulation (ECT for depression)
- structural rearrangement (psychosurgery/deep brains stimulation for depression)
- talking therapies (CBT or exposure for phobias)
How are drugs classified?
- based on chemical structure
- based on illnesses they treat (problem is that many drugs can treat many disorders)
- based on pharmacology (what it targets - uses neurotransmitter as basis of what drug does)
What are the usual targets for medicines in psychiatry?
- receptors
- neutrotransmitter reuptake sites
- ion channels
- enzymes.
Targets in brain but can affects systems elsewhere eg. Liver enzymes
What are drug that blocks enzyme activity?
- monoamine oxidase inhibitors for anxiety and depression (monamines = dopamine, serotonin, norephineprhine)
- acetylcholinesterase inhibitors for dementia (ach)
- lithium blocks glycogen synthase kinase for mood stability
What are drugs that target receptors?
Receptor blockers (antagonists) eg
- dopamine receptor blockers for schizo
- serotonin receptor subtype antagonists for depression 3. histamine receptor antagonists for sleep.
Receptor agonists (enhancers) –>
- benzodiazepines enhance GABA for sleep
- guanfacine enhance noradrenaline for ADHD
What is difference between agonists and antagonists?
Agonists mimic endogenous agonist and stimulate the receptor. Antagonists block the endogenous agonist binding to receptor
What are some examples of drugs blocking reuptake sites?
Most neurotransmitters recovered & recycled via reuptake sites. Drugs block these reuptake sites to increase concentration of ns in synapse to enhance post-synaptic activity
1. citalopram enhances serotonin (serotonin reuptake inhibitor SRI) for depression
2. desipramine is noradrenaline reuptake inhibitor NRI for depression
3. methylphenidate is dopamine reuptake inhibitor DRI for ADHD.
Some switch reuptake site direction to enhance release.
How does the 5-HT system work?
Serotonin can stimulate many receptors. Taken up by reuptake sites. Can act pre-synaptically on auto-receptors to inhibit its ns release. We increase serotonin by inhibiting reuptake.
-Most important receptors are 5HT1A receptor (inhibitory - dampens down activity in neurones where receptor is to reduce anxiety and depression) & 5HT2 receptor (psychedelic drugs work to these to give effect - maybe involved in schizophrenia, involved in regulation of sleep and eating.
What are some drugs that target ion channels?
Block channels to reduce neuronal excitability eg.
- sodium channels eg. Sodium valprotate (epilepsy & mood stabilisation) eg. Carbamazepine
- calcium channels - gabapentin & pregabalin for epilepsy & anxiety
What are the imprortant neurotransmitters in our body?
fast acting (on/off switch) –> 1. excitatory - glutamate (pyramidal cells - regulate brain function) 2. inhibitory GABA neurones . We need balance of these for memory, movement, vision.
Slower acting (neuromodulators) - dopamine, serotonin, noradrenaline, acetylcholine, endorphins –> emotions drives, valence of memories (lay down tone and relevance)
What does glutamate excess cause & treatment?
Epilepsy & alcoholism. Treatment: perampanel - blocker for epilepsy, acamprosate & ketamine blockers for alcoholism
What does GABA deficiency cause + treatment?
Anxiety. Bezodiazepines (GABA enhancer)
What does 5-HT deficiency cause? treatment?
Depression/anxiety. SRI & MAOIs - serotonin enhancers
What does dopamine excess cause + treatment?
Psychosis, dopamine receptor blockers
What does noradrenaline excess cause + treatment?
Nightmares, prazosin - blocker
What does acetylcholine deficiency cause + treatment?
Impaired memory/dementia Acetylcholinesterase enzyme blockers
• Where do most drugs that treat depression act?
On 5HT systems
What are partial agonists?
Have lower maximal efficacy than full agonists (safety in overdose).
-Effect determined by ongoing level of neurotransmitter - if a lot can block it acting as antagonist. If deficit can act as agonist.
Eg. In psychosis can dampen dopamine with dopamine antagonists but gives side effects, giving partial agonist (asipiprazole) can act as blocker of dopamine if in excess, and as agonist if low (allow normal motor function - less side effects).
What are examples of partial agonists?
Aripiprazole (dopamine - psychosis), buprenorphine (pain & addiction), varenicline (smoking cessation)
What are inverse agonists?
Bind to same receptor binding site as agonist but antagonises agonist effects, exerting opposite effect by suppressing spontaneous receptor signalling.
Eg. In alcohol impaired memory, inverse agonist turns off GABA system
What are receptor subtypes?
Eg. GABA-A .
GABA has many receptor subtypes with many binding sides (5 separate proteins make up receptor)
What is allosteric modulation?
Drugs that work on different site as endogenous neurotransmitter
eg. In GABA-A receptor (ion channel linked receptor) GABA binds to GABA receptor (orthosteric site), enhancing CL- conductance, inhibiting neurones, calming brain. Benzodiazpeines/barbitruates/acl/neurosteroids all act on allosteric site on same complex enhancing action of GABA for sedation, sleep, anxiety, anti-epilepsy
What is drug selectivity?
Ability of drug to bind one target (eg haloperidol selective for dopamine receptor causing side effects there due to block), other drugs that are less selective can cause adverse effects due to off target effect bind somewhere else) to chemically similar receptors for example
