1b Psychopharmacology for Psychiatry

Question 1

What are the four classifications of treatments in medicine?

Answer 1

1. Chemical eg Drugs
2. Electrical Stimulation - eg Neurostimulation
3. structural rearrangement - eg Surgery and orthopaedics
4. Talking therapies eg CBT

Question 2

What are the pros and cons of classifying drugs based on their chemical structure?

Answer 2

Pro- each drug has a unique structure = a fact  easy to allocate data

Con – no use in clinical decision making

Question 3

What are the pros and cons of classifying drugs based on which illnesses they treat?

Answer 3

Pro - easy for doctor to make a diganosis as

Cons: Con –1. many psychiatric medicines work in several disorders

most psychiatric disorders have multiple symptoms and a single medicine might not treat them all

Question 4

what are the four drug targets?

Answer 4

Receptors
Neurotransmitter reuptake sites
Ion channels
Enzymes

Question 5

Which body enzymes are particular unwanted targets for brain medication/

Answer 5

Liver enzymes

Question 6

What is the only neurotransmitter that isn’t retaken up by the pre-synaptic neurone?

Answer 6

Acetylcholine

Question 7

How do receptor antagonists and agonists work in general respectively?

Answer 7

Antagonists work by blocking the endogenous agonist neurotransmitter from binding to its receptor

Agonists mimic the endogenous neurotransmitter and therefore stimulate the receptor

Question 8

What is citalopram and how does it work?

Answer 8

SRI - enhances serotonin (= serotonin reuptake inhibitor or SRI)– for depression and anxiety

Question 9

What is desipramine and how does it work?

Answer 9

noradrenaline reuptake inhibitor (NRI)= enhances noradrenaline - for depression

Question 10

Which drug acts on the reuptake site to increase dopamine concentration? and for what condition?

Answer 10

Amfetamine for ADHD

Question 11

What are the two 5HT receptors in the body

Answer 11

1) 5HT1A - inhibitory receptor. When we enhance serotonin, we increase stimulation of 5HT1A which dampens down activity of the neurones where the receptor is and so reduces conditions like anxiety and depression.

2) 5HT2A - psychedelic drugs work on this to produce their profound disturbance of consciousness and altered states of hallucinations. Might be involved in schizophrenia, eating and regulation of sleep.

Question 12

Which medications are used to treat epilepsy and for mood stabilization?

Answer 12

Sodium channel blockers - sodium valproate and carbamazepine

Question 13

Which medications block calcium channels?

Answer 13

Gabapentin and pregabalin

Question 14

What are two main classes of neurotransmitters?

Answer 14

Fast acting and slow acting

Question 15

What are the two types of fast acting neurotransmitters?

Answer 15

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 two types of slow acting neurotransmitters?

Answer 16

dopamine – serotonin – noradrenaline -acetylcholine
endorphins and other peptides

Question 17

What condition does an excess of glutamate result in and how is it fixed?

Answer 17

Epilepsy and Alcoholism - use perampanel, ketamine or acamprostate as a blocker

Question 17

What condition does an deficit of GABA result in and how is it fixed?

Answer 17

Anxiety - Use benzodiazepines as GABA enhancers

Question 18

What condition does a 5-HT deficiency result in?

Answer 18

Anxiety and Depression - use SRIs and MAOIs as serotonin enhancers

Question 19

What condition does an excess of dopamine result in and how is it fixed?

Answer 19

Psychosis - dopamine receptor blockers

Question 20

What condition does an excess of noradrenaline cause and how is it fixed?

Answer 20

Night mare and use Prazosin

Question 21

What does a deficit of ACh result in and how is it fixed?

Answer 21

Impaired memory / dementia - used acetylcholine esterase enzyme blockers

Question 22

What are partial agonists?

Answer 22

Partial agonists – lower max efficacy than full agonists

Question 23

What is the benefits of partial agonists?

Answer 23

Improved safety – especially in overdose
In states of high neurotransmitter or excess agonist medicine can act as an antagonist

Question 24

What are inverse agonists?

Answer 24

Opposite effects to agonists

Question 25

What is allosteric modulation?

Answer 25

Work on different sites on the target proteins eg 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

Question 26

What type of receptor is GABA-B?

Answer 26

Gprotein coupled receptor - Some Glutamate receptors are ion channel linked and others are Gprotein

Question 27

What determines the side effects experienced by a drugh?

Answer 27

The number of targets it binds to - more targets = more side effects

Question 28

What is an ortho-steric receptor?

Answer 28

These are the receptor that the natural transmitter works on.

eg.

dopamine blockers in schizophrenia

GABA binding to GABA receptor

Question 29

What effect does GABA binding to the receptor then have?

Answer 29

Enhances Cl- conductance → inhibits neurons → calms the brain

Question 30

What subunit of the GABA receptor do Benzodiazepines work on?

Answer 30

Gamma sub unit

Question 31

Compare drug selectivity of amitriptyline and citalopram as 5-HT reuptake blockers

Answer 31

Amitriptyline → One of the first antidepressants - “tricyclic” structure

adverse effects from histamine and acetylcholine receptor blockade

Citalopram → selective serotonin reuptake inhibitor(SSRI) – adverse effects driven solely by increased serotonin

Question 32

Compare drug selectivity of haloperidol and clozapine for treatment of schizophrenia

Answer 32

Haloperidol → 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