**_🤯Psychiatry🤯 - Psychopharmacology for Psychiatry

Question 1

What are the types of treatment in medicine?

Answer 1

Question 2

Can psychiatric drugs be classified based on chemical structure?

Answer 2

Not really
Image shows 2 anti-schizophrenia drugs
Totally different structure yet both treat the same disease

Question 3

What are the cons of classifying psychiatric drugs based on the illness that they treat?

Answer 3

Many psychiatric medicines work in several disorders
-antidepressants also treat anxiety and OCD (obsessive compulsive disorder)
–some antipsychotics used as add on (augmentation)
Most psychiatric disorders have multiple symptoms and a single medicine might not treat them all
(e.g. symptoms in depression include – anxiety-insomnia-low mood-agitation-loss of pleasure- loss of appetite- poor concentration -loss of libido with likely different neurotransmitter mechanisms)

Question 4

So how are psychiatric medicines classified?

Answer 4

By their pharmacology
e.g. target neurotransmitters
(Instead of antipsychotic – we can say dopamine blocker
Instead of antidepressant – we can say serotonin (or with some drugs noradrenaline or dopamine enhancer)
Instead of hypnotic or anxiolytic – we can say GABA enhancer)

Question 5

What are the two different GABA receptors?

Answer 5

GABA-A
GABA-B

Question 6

Outline the GABA-A receptor

Answer 6

An ionotropic receptor
Its endogenous ligand is GABA - the major inhibitory neurotransmitter in the nervous system
Upon activation, selectively conducts Cl- through its pore
Causes hyperpolarisation of the neuron, inhibiting successful action potentials

Question 7

Outline the GABA-B receptor

Answer 7

GHB binds with low affinity to GABAB receptors which are inhibitory via GIRK channels
Activation of which leads to K+ extrusion and hence membrane hyperpolarisation
Weak agonist properties of GHB are observed only at central GABA-B receptors located post-synaptically, but does not interact with GABA-B in the spinal cord and has no affinity (or only minimal affinity) for the BDZ and alcohol preferring GABA-A receptor

Question 8

Which GABA receptor does treatment of alcoholism target?

Answer 8

Treatment of alcohol dependence has received the most attention regarding modulation of the GABAB receptor via agonism
GABAB receptor agonism therefore has the potential to treat all aspects of alcohol dependence which include:
-Alleviating acute withdrawal
-Initiating and maintaining abstinence
-Reducing craving and craving-related relapse

Question 9

Which systems do medicines work on in psychiatry?

Answer 9

All work on one [occasionally two] of 4 different systems:
Receptors
Neurotransmitter reuptake sites
Ion channels
Enzymes

Question 10

What system is particularly vulnerable to side effects from psychiatric medicines?

Answer 10

Liver enzymes

Question 11

Give some examples of enzyme targeting medicines

Answer 11

Generally drug treatments block enzyme activity
Monoamine oxidase inhibitors [MAOIs] for anxiety and depression
Acetylcholinesterase inhibitors for dementias
Lithium blocks glycogen synthase kinase for mood stability

Question 12

Outline receptor targeting medicines

Answer 12

Question 13

What are the roles of reuptake sites in psychiatric pharmacology?

Answer 13

Most neurotransmitters are recovered and recycled via reuptake sites
Many psychiatric drugs block these reuptake sites so increase neurotransmitter concentration in the synapse to enhance post-synaptic receptor activity
(Citalopram – enhances serotonin (= serotonin reuptake inhibitor or SRI)– for depression and anxiety
Desipramine – noradrenaline reuptake inhibitor (NRI)= enhances noradrenaline - for depression
Methylphenidate – dopamine reuptake inhibitor (DRI)- enhances dopamine - for ADHD)
Some switch the reuptake site direction to enhance release
(e.g. amphetamine for ADHD)

Question 14

What is the mechanism of action of epilepsy medications?

Answer 14

Block channels and reduce neuronal excitability
Sodium channels
(Sodium valproate - epilepsy and mood stabilisation
Carbamazepine - epilepsy and mood stabilisation)
Calcium channels
(Gabapentin & pregabalin – epilepsy anxiety)

Question 15

What are the fast acting neurotransmitters?

Answer 15

FAST acting (on-off switch)
Excitatory – glutamate = > 80% of all neurons - pyramidal cells
Inhibitory – GABA = 15% - inter-neurons
Content e.g. of memory, movement, vision etc..

Question 16

What are the slow acting neurotransmitters?

Answer 16

Slow acting (modulators) – about 5% of all neurons
Dopamine – serotonin – noradrenaline - acetylcholine
Endorphins and other peptides
Emotions, drives, valence of memory etc…

Question 17

Briefly outline the neurotransmitters involved in various psychiatric disorders
(Glutamate, GABA, 5-HT, Dopamine, Noradrenaline, Acetylcholine)

Answer 17

Question 18

What system is targeted by depression-treating drugs?

Answer 18

5-HT system

Question 19

What is the significance of partial agonists?

Answer 19

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
(e.g. buprenorphine < heroin
e.g. aripiprazole < haloperidol
e.g. varenicline < nicotine)

Question 20

What are inverse agonists?

Answer 20

Antagonists bind to a receptor but do not activate it. Instead, they block or reduce the effects of an agonist Antagonists simply prevent the receptor from being activated without changing the receptor’s baseline
Inverse agonists, on the other hand, bind to a receptor and actively reduce its baseline (constitutive) activity. While antagonists have no effect on the receptor in the absence of an agonist, inverse agonists decrease the receptor’s activity even if no agonist is present, effectively producing the opposite effect of an agonist

Question 21

Give an example of the orthosteric site of a receptor

Answer 21

GABA binds to the GABA receptor = orthosteric site
This binding enhance chloride ion conductance - inhibits neurons - calm the brain

Question 22

What are allosteric sites?

Answer 22

Different site to the natural (endogenous) neurotransmitter of a receptor
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