Pharmacology of psychosis Flashcards
In which ways can we classify drugs?
based on chemical structure - used by WHO, easy to allocate data but no use in clinical decision making
based on which illnesses they treat e.g. antidepressant, antispychotic
based on pharmacology: neuroscience based nomenclature (dopamine blocker, serotonin enhancer)
What is Chlorpromazine?
First ever drugs for schizophrenia
What is Haloperidiol?
The 2nd anti schizophrenia drug
What may be the con to classifying drugs based on which illnesses they treat?
May treat more than one illness
most psychiatric disorders have multiple symptoms and a single med may not treat them all
Which drugs are an example of enzyme blockers?
monoamine oxidase inhibitor
acetylcholinesterase inhibitors for dementias
lithium blocks glycogen synthase kinase for mood stability
Which drugs are an example of receptor targeting medicines? 3
Dopamine receptor blockers for schizophrenia
Serotonin receptor subtype antagonists for depression
histamine receptor antagonists for sleep
Can you give some agonist examples which stimulate receptors? 2
benzodiazepines - enhance GABA to allow for sleep
Guanfacine enhance noradrenaline, helps ADHD
Why do some drugs target reuptake sites?
Reuptake sites are were neurotransmitters are recovered and recycled.
this would increase the neurotransmitter concentration in the synapse to enhance the post synaptic receptor activity
What drugs are examples of reuptake site targeting medicine? 3
Citalopram - enhances serotonin for depression and anxiety
desipramine - noradrenaline re-uptake inhibitor for depression
methylphenidate- dopamine uptake inhibitor enhances dopamine for ADHS
How does Amfetamine work for ADHD?
Switches the reuptake site direction to enhance release
Describe the 5 HT neuron reuptake system?
the 5HT - serotonin releasing neuron.
Once the serotonin is released it is taken back up at the pre synaptic membrane by 5HT 1B/D receptors which inhibits its own further release
and also uptaken by the 5HT 1A
If these are both blocked by SRIs then serotonin will increase
–> post synaptic 5HT1A is an inhibitory receptor, serotonin release dampens down activity where that receptor is and can help anxiety
Which drugs are example of ion channel targeters?
Usually block the channels
Sodium channel blockers : sodium valproate - epilepsy and mood stabilisation
carbamazepine - epilepsy and mood stabilisation
Calcium channel:
Gabapentin and pregabalin - epilepsy and anxiety
Which fast acting neurotransmitters are there?
Excitatory - Glutamate, pyramidal cells and 80% of neurons
Inhibitory - GABA, interneurons and 15% of neurons
- both are amino acids
What slow acting modulating neurotransmitters are there?
5% of neurones
dopamine, serotonin, noradrenaline, acetylcholine
endorphins and peptides
drives emotions, Valence of memory etc
What if glutamate is in excess?
Epilepsy
Alcoholism
How to treat excess glutamate?
Parampanel - blocker
Acampriosate - blocker
ketamine - blocker
Wat if GABA is deficient?
Anxiety
How to treat GABA deficiency?
Benzodiazepines - GABA enhancer
What if 5-HT is deficient?
Depression
Anxeity
How to treat 5-HT deficiency?
SRIs
MAOIs
(serotonin enhancers)
What happens if Dopamine is in excess?
Psychosis
How to treat Dopamine excess?
dopamine receptor blocker
What happens if noradrenaline is in excess?
Nightmares
How to treat noradrenaline excess?
Prazosin- acts as blocker
What if acetylcholine is deficient?
Imapired memory / dementia
How to treat acetylcholine deficency?
Acetylcholine esterase enzyme blockers
which drugs treat depression?
- check slide 20
What are partial agonists?
lower max efficacy than full agonists
= Improved safety – especially in overdose
= In states of high neurotransmitter or excess agonist medicine can act as an antagonist
- check slide 21 graph
What examples of partial agonists are there?
buprenorphine < heroin
aripiprazole < haloperidiol
varenicline < nicotine
WHat are inverse agonists?
Opposite effects to agonists
GABA – pro-cognitive - ? dementias
Histamine – increased attention – ADHD
What are receptor subtypes used for?
e,g, GABA a receptors
5 different proteins make up a receptor so there can be different combinations of stimulation
What is allosteric modulation?
some drugs may work on the same site as the natural neurotransmitter
others work on different sites on the target proteins
e,g
GABA-A receptor is an ion-channel linked receptor
GABA binds to the GABA receptor = orthosteric site
This binding enhance chloride ion conductance
-> inhibits neurons -> calm the brain
Benzodiazepines – barbiturates –alcohol – neurosteroids
All act at allosteric sites on the same protein complex
They enhance the action of GABA -> sedation,
sleep, reduce anxiety, anti-epilepsy
Are GABA B receptors ion channels?
– they are Gprotein coupled receptors. Some Glutamate receptors are ion channel linked and others are Gprotein linked.
why may two drugs for schizophrenia have differing side effects?
both are dopamine blockers
due to their chemical structures have different side effects
Haloperidiol: Very selective for the dopamine receptor - Adverse effects due to dopamine receptor block
Clozapine: Non-selective – lots of adverse effects due to off-target effects
E.g. sedation - weight gain – metabolic syndrome
How do the side effetcs to amitriptyline and citalopram differ?
Amitriptyline: One of the first antidepressants - ‘‘tricyclic” structure
- adverse effects from histamine and acetylcholine receptor blockade
Citalopram : A selective serotonin reuptake inhibitor(SSRI) – adverse effects driven solely by increased serotonin
