12.1 Anti-Psychotics Flashcards
What is the theory of the mechanism of depression
Caused by a reduction in monoamines (NA, 5HT)
Maybe a loss of receptors
How do we treat Depression?
Steps
Mild 1) CBT and Therapy
Moderate/Severe 2) Specific MOA inhibitor e.g. SSRIs
3) Non selective MOA-i e.g TCA, SNRIs
How do we diagnose depression?
How do we grade it?
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)
What is depression?
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
What are SSRIs?
What do we treat with them?
How do they work?
Pharmacokinetics?
Advantages?
Disadvantages?
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
ADRs of SSRIs
Increased energy/motivation can cause suicide Mania Extrapyramidal symptoms - Tremor GI - nausea, vomiting, diarrhoea Citalopram can cause Long QT
DDIs with SSRIs
Metabolised by CYP450
Risk of Bleeding with NSAIDs
How do you remember the ADRs of SSRIs?
Sleep - insomnia
Sex - dysfunction
Sweat - anxiety
Stomach - Nausea
What are TCAs?
Pharmacokinetics?
Example?
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)
ADRs of TCAs
Postural Hypotension Loss of Glandular Secretions (mACh - dry mouth, constipation) Long QT and Tachycardia Weight Gain Sedation Nausea Nephrotoxic
What is an SNRI?
Serotonin Noradrenaline Reuptake Inhibitor
Used for Unipolar Depression
Short Half Life so withdrawal!
Duloxetine
ADRs of SNRIs?
Same as SSRIs but more
Sleep Disturbances
Hypertension
Hyponatraemia
What is Schizophrenia?
Caused by?
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
How do we treat schizophrenia?
How successful is treatment for PS?
1st Gen D2 Antagonists (Ergot Derived)
Atypicals e.g clozapine
1/3 better, 1/3 ok, 1/3 get worse
How do D2 antagonists work?
ADRs
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
What are the symptoms of PS?
Positive
Negative
Hallucinations, Delusions, Disturbed Thoughts/Behaviour
Withdrawal, Anxiety, Unusual Speech
What is an example of a D2 antagonist?
Haliperidol
What is an atypical antipsychotic?
ADRs?
An example? Specific ADRs
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
How do we treat anxiety?
CBT and psychological intervention
or antidepressant or antipsychotic may work
May use a benzodiazepine to sedate
What is anxiety?
What NTs are believed to be linked?
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
How do we use benzodiazepines in anxiety?
PK?
Act on GABA receptors to sedate
Oral High Bioavailability Lipid Soluble Half Life Renally Excreted
ADRs with Benzodiazepines?
Anxiety
Dependence
Tolerance
Addictive
Drowsy, Hypotension, Teratogenic, Blurred Vision
What do you give if you KNOW it’s a benzodiazepine OD?
Flumazenil to antagonise the GABA receptor sites
What is Bipolar Disorder?
Manic Depression
What are the signs of mania?
Talking really fast Jumping Topics Elation Overactivity Can't sit still Poor judgement Delusions
What do we treat Bipolar with?
NOT anti-depressants as could worsen mania
Mood stabilisers - Lithium, Anti-epileptics (Sodium Valproate)
ADRs of Lithium
(Bipolar)
Things to monitor
Lithium is Nephrotoxic (U and E)
Risk in Pregnancy
Thyroid dysfunction
Weight Gain
Memory Problems
Thirst and Polyuria
PKs of Lithium
Mechanism of Action?
A: Oral, Once a day
D: Slow release
M: Has a narrow TW (MONITOR)
E: Renal
Competes with Ca2+, Affects 5HT levels
What do you do in a lithium OD?
Support and give fluids
Anticonvulsants
Dialysis
How do you treat dementia?
AChesterase inhibitors
NMDA antagonists - memantine
They slow the progression of mild (ACh) and moderate + (NMDA) disease
