12.1 Anti-Psychotics

Question 1

What is the theory of the mechanism of depression

Answer 1

Caused by a reduction in monoamines (NA, 5HT)

Maybe a loss of receptors

Question 2

How do we treat Depression?

Steps

Answer 2

Mild 1) CBT and Therapy
Moderate/Severe 2) Specific MOA inhibitor e.g. SSRIs
3) Non selective MOA-i e.g TCA, SNRIs

Question 3

How do we diagnose depression?

How do we grade it?

Answer 3

Need to have 2 or more of: low mood, low energy and lack of enthusiasm for thinks would normally enjoy for at least 2 weeks

We grade it mild, moderate or severe, by secondary symptoms (e.g. suicidal/harmful thoughts, withdrawal from society, previous incidences, FHx)

Question 4

What is depression?

Answer 4

Depression is a feeling of low mood or lack of energy. It can range from being mild, with mood/cognitive changes, to severe which can experience hallucinations

Question 5

What are SSRIs?
What do we treat with them?
How do they work?
Pharmacokinetics?

Advantages?

Disadvantages?

Answer 5

Selective Serotonin Reuptake Inhibitors
Depression

Absorbed: Gut
Metabolised: Liver

Have a Long Half Life, less withdrawal
Safe in Overdose!

Takes 2 weeks to affect and longer to maximise

Question 6

ADRs of SSRIs

Answer 6

Increased energy/motivation can cause suicide
Mania
Extrapyramidal symptoms - Tremor
GI - nausea, vomiting, diarrhoea
Citalopram can cause Long QT

Question 7

DDIs with SSRIs

Answer 7

Metabolised by CYP450

Risk of Bleeding with NSAIDs

Question 8

How do you remember the ADRs of SSRIs?

Answer 8

Sleep - insomnia
Sex - dysfunction
Sweat - anxiety
Stomach - Nausea

Question 9

What are TCAs?
Pharmacokinetics?
Example?

Answer 9

Tricyclic Amines
They act on Muscarinic ACh receptors, Histamine receptors
And they block the reuptake of NA and 5HT

Oral and well absorbed
Lipophillic
Variable 1st Pass Effect
Long Half Life

Amylotriptiline

Very Dangerous if OD (arrhythmia, narrow TW)

Question 10

ADRs of TCAs

Answer 10

Postural Hypotension
Loss of Glandular Secretions (mACh - dry mouth, constipation)
Long QT and Tachycardia
Weight Gain
Sedation
Nausea
Nephrotoxic

Question 11

What is an SNRI?

Answer 11

Serotonin Noradrenaline Reuptake Inhibitor
Used for Unipolar Depression

Short Half Life so withdrawal!

Duloxetine

Question 12

ADRs of SNRIs?

Answer 12

Same as SSRIs but more
Sleep Disturbances
Hypertension
Hyponatraemia

Question 13

What is Schizophrenia?

Caused by?

Answer 13

Mental illness with psychotic symptoms
Thought to be caused by an increase in Dopamine

Change in nigrostriatal (extarpyramidal signs), mesolimbic (emotional response), mesocortical (arousal)

Doesn’t explain negative symptoms of PS, maybe 5HT /glutamate involved

Question 14

How do we treat schizophrenia?

How successful is treatment for PS?

Answer 14

1st Gen D2 Antagonists (Ergot Derived)
Atypicals e.g clozapine
1/3 better, 1/3 ok, 1/3 get worse

Question 15

How do D2 antagonists work?

ADRs

Answer 15

They block the D2 receptors in the striatum, this inhibits dopamines action on the indirect pathway. This reduces psychotic symptoms

extrapyramidal symptoms
Can cause hyperprolactinaemia
Weight Gain
Hypotension
Sedation
Can lead to Parkinsonism - tardive dyskinesia
Takes days/weeks to work

Question 16

What are the symptoms of PS?
Positive
Negative

Answer 16

Hallucinations, Delusions, Disturbed Thoughts/Behaviour

Withdrawal, Anxiety, Unusual Speech

Question 17

What is an example of a D2 antagonist?

Answer 17

Haliperidol

Question 18

What is an atypical antipsychotic?
ADRs?

An example? Specific ADRs

Answer 18

Have fewer extrapyramidal symptoms so are first line!

Hyperprolactinaemia
Weight Gain (A LOT)

Clozapine - only use in hospital as need to monitor FBC closely
Agranulocytosis

Question 19

How do we treat anxiety?

Answer 19

CBT and psychological intervention

or antidepressant or antipsychotic may work
May use a benzodiazepine to sedate

Question 20

What is anxiety?

What NTs are believed to be linked?

Answer 20

Fear which is disproportionate to the situation
Sweating, Pale, Tachycardia, Nausea, Lightheaded

NA, 5-HT, GABA

There is usually a cycle of fear and avoidance, leading to the belief that the only cure is avoidance

Question 21

How do we use benzodiazepines in anxiety?

PK?

Answer 21

Act on GABA receptors to sedate

Oral
High Bioavailability
Lipid Soluble
Half Life
Renally Excreted

Question 22

ADRs with Benzodiazepines?

Anxiety

Answer 22

Dependence
Tolerance
Addictive
Drowsy, Hypotension, Teratogenic, Blurred Vision

Question 23

What do you give if you KNOW it’s a benzodiazepine OD?

Answer 23

Flumazenil to antagonise the GABA receptor sites

Question 24

What is Bipolar Disorder?

Answer 24

Manic Depression

Question 25

What are the signs of mania?

Answer 25

Talking really fast
Jumping Topics
Elation
Overactivity
Can't sit still
Poor judgement
Delusions

Question 26

What do we treat Bipolar with?

Answer 26

NOT anti-depressants as could worsen mania

Mood stabilisers - Lithium, Anti-epileptics (Sodium Valproate)

Question 27

ADRs of Lithium
(Bipolar)

Things to monitor

Answer 27

Lithium is Nephrotoxic (U and E)
Risk in Pregnancy
Thyroid dysfunction

Weight Gain
Memory Problems
Thirst and Polyuria

Question 28

PKs of Lithium

Mechanism of Action?

Answer 28

A: Oral, Once a day
D: Slow release
M: Has a narrow TW (MONITOR)
E: Renal

Competes with Ca2+, Affects 5HT levels

Question 29

What do you do in a lithium OD?

Answer 29

Support and give fluids
Anticonvulsants

Dialysis

Question 30

How do you treat dementia?

Answer 30

AChesterase inhibitors
NMDA antagonists - memantine

They slow the progression of mild (ACh) and moderate + (NMDA) disease