PH3113 - Psychiatric Disease and its Pharmacology 6 Flashcards
What is neuroleptic malignant syndrome (NMS)?
Its a rare life threatening side effect of antipsychotic medications
- hyperthermia
- fluctuating level of consciousness
- muscle rigidity
- autonomic dysfunction
- pallor
- tachycardia
- labile BP
- sweating
- urinary incontinence
Associated with change in dose or formulation or initiating new medication using combinations of antipsychotic medications
What is the NICE guidance on choosing anti-psychotic medications?
Decision should be made by the service user and healthcare professional together
- taking into account the views of the carer if the service user agrees
Benefits and side effects of each drug
- metabolic
- weight changes
- diabetes
- extrapyramidal
- akathisia
- dyskinesia
- dystonia
- cardiovascular
- QT interval prolongation
- hormonal
- plasma prolactin
What is the Mental Health Act (1983)?
Main piece of legislation that covers the assessment, treatment and rights of people with a mental health disorder
Give examples of affective disorders?
Major depressive disorder
- recurrent depressive episodes
Bipolar I disorder
- manic episodes and depressive episodes
Bipolar II disorder
- predominant depression
- milder manic episodes
Cyclothymia
Dysthymia
- persistent depressive disorder
What is the leading cause of disability in developed countries?
Major depressive disorder
- fourth leading cause worldwide
What is the prevalence of major depressive disorder?
Genetics and environmental factors
- 40/60
Lifetime prevalence of major depressive disorder in the US is 1 in 6 people
- 10 - 20 %
- gender difference
- more common in women
- more likely to seek help
- age on onset highly variable
- peak in men is old age
- peak in women is middle age
- direct and indirect costs are significant
- loss of productivity
- strongly associated with suicide
What are the symptoms of major depressive episode?
Low mood
Loss of interest/ pleasure from normally pleasurable activities
- anhedonia
Reduced energy
- fatigue
Low self-esteem
Feelings of guilt
Inability to think/concentrate
Altered psychomotor activity
Sleep disturbance
- early morning wakening
Altered appetite
Suicidal thoughts
How is major depressive disorder diagnosed?
2 core symptoms plus 2 or more of the minor symptoms present for most of the day and on most days for at least two weeks
What is the aetiology of major depressive disorder?
Biological
- genetic factors - polygenic
- 15% prevalence in first degree relative
- 5% in background population
- monoamine hypothesis
- alterations in the hypothalamic-pituitary axis (HPA) and immune system
Environmental/psychological
- early life adversity
- personality traits
- anxiety
- impulsivity
- obsessionality
- stressful life events
- physical illness
What is the prognosis of major depressive disorder?
Episodes tend to last for approximately 3 - 6 months
Approximately 50 - 80% of patients who have one episode of major depression will go on to have a second
- 80 - 90% of those having a second episode will have a third episode
Significant risk of suicide
- 7% in men
- 1% in women
Risk of recurrence increased by
- family history
- female gender
- social factors
- co-morbid psychiatric illness
- longer duration of episode
- co-morbid medical illness
Which hormones does the monoamine hypothesis involve?
Dopamine
- DA
Serotonin
- 5-HT
Noradrenaline
- NA
What are serotonergic and noradrenergic signalling linked with?
Mood regulation
Motivation/reward
Sleep
Pain perception
What is the process of noradrenergic signalling?
Vesicular monoamine transporter blocked by reserpine
- VMAT
Negative feedback through alpha-2 autoreceptor agonism
Noradrenaline transporter facilitates the uptake of noradrenaline
What is the process of serotonergic signalling?
Vesicular monoamine transporter blocked by reserpine
- VMAT
Negative feedback through 5HT(1A/1B) autoreceptor agonism
5-HT transporter facilitates the uptake of 5-HT
What is the monoamine theory of depression?
Many clinically effective drugs have defined neurochemical actions on monoamines in CNS
- 5-HT and noradrenaline
- firstly imipramine
- marketed as an antihistamine but prototype tricyclic anti-depressant
- iproniazid
- intended for tuberculosis but found to be an monoamine oxidase inhibitor
- anti-hypertensive reserpine induced depression
- VMAT blockade
- tryptophan depletion
- reduces 5-HT synthesis
- depressive symptoms
- increased activity in the subgenual cingulate cortex
- anti-depressants and deep brain stimulation reduce the activity of this area
- everything pointed to monoaminergic involvement in depression pathogenesis
