Anxiety And Depression Flashcards
What do you use to treat anxiety
Benzodiazepine
SSRIs
What is the diagnostic criteria for Major Depressive Episode
A. ≥5 symptoms on most days for 2 weeks; that represent a change from previous functioning:
Depressed mood and/or loss of interest must be present
Weight loss/gain; insomnia or hypersomnia; psychomotor agitation/retardation; fatigue; feelings of worthlessness/guilt; decreased concentration; suicidal ideation.
B. Symptoms must cause significant clinical impairment in functioning
C. Episode not attributable to direct physiological effects of a substance or underlying general medical condition
D. The occurrence of the major depressive episode is not better explained by presence of schizophrenia, delusional disorder or any other psychotic disorder.
E. No history of a manic or hypomanic episode
What are the two classifications of Monoamines
(Monoamines -Have one amine group)
- Catecholamines:
-Adrenalin
-Noradrenaline
-Dopamine - Indolamines
-Serotonin
-Histamines
What is the normal pathophysiology of neurotransmitters in nerves ?
-When a nerve travels at a 5HT (serotonin) or noradrenalin nerve terminal, neurotransmitter is released from synaptic vesicles
-Released by exocytosis into the synaptic cleft.
-After transferring into synaptic cleft, neurotransmitter binds to specific receptors on the post synaptic membrane.
-The nerve is probagated or inhibited in this post synaptic membrane depending on receptor type.
-Serotonin and noradrenalin are then released from the receptors and taken back into the nerve terminal via serotonin or noradrenalin reuptake transporters
-Neurotransmitters can also be degraded by enzymes MAO (Monoamines oxidase) and catecholomethyl transferase (COMT) which are found in synaptic cleft and in the nerve terminal.
What is the mono amine hypothesis of Mood
It postulates that brain amines (serotonin and noradrenalin), are important in pathways that function in the expression of mood
A functional decrease in activity of these amines results in depression and a functional increase results in mood elevation.
Hypothesis is based on studies showing that drugs capable of alleviating symptoms of MDD enhance the actions of these neurotransmitters.
What is believed to cause depression in the monoamine theory
-Low levels of monoamine neurotransmitters;
-Upregulation of inhibitory presynaptic and somatodendritic autoreceptors that control monoamine release.
-Upregulation of postsynaptic monoamine receptors
Problems with the monoamine hypothesis of neurotransmitters
-Post-mortem studies do not show decreases in levels of 5-HT or NE
-Although amine activity changes within hours after starting antidepressant therapy, clinical response can take up to 6 – 8 weeks.
-Bupropion (an antidepressant in use) has no activity on brain NE or 5-HT.
What is the neurotrophic hypothesis
The neurotrophic hypothesis postulates that depression arises from abnormalities in neurotrophic pathways that involve brain-derived neurotrophic factors (BDNF).
With resulting changes in the connectivity between structures in the brain that regulate mood and stress response.
BDNF is regulated by monoamines and BDNF expression is reduced when monoamine transmission is impaired, but also in conditions of stress with increased serum cortisol.
Neuroendocrine factors associated with depression
Depression has found to be associated with the hypersecretion of corticotropin releasing hormone (CRH) and cortisol.
These hormones have detrimental effects on neuroplasticity and neurogenesis and may contribute to the suppression of BDNF.
Elevated CRH also depresses serotonergic neurotransmission.
Improved chronic activation of monoamine receptors during treatment with antidepressants, increases BDNF transcription/expression, and appears to down regulate the hypothalamic-pituitary axis and normalize function.
What is the mechanism of action of antidepressants.
Blocks degradation of neurotransmitters: MAOI
Blocks neurotransmitters reuptake:
-Selective SSRI
- SNRI
-TCA
Inhibition of negative feedback by antagonism of auto receptors
How does TCAs inhibit monoamine neurotransmitters reuptake
Antagonism at alpha1 adrenoceptors (vasodilation = hypotension),
Antagonism at histamine (H1) receptors (antihistamine effect = sedation, stimulation of appetite and weight gain),
Antagonism at muscarinic receptors (anticholinergic effects = dry mouth; urinary retention)
Blockage of voltage-gated sodium channels (responsible for lethality in OD)
TCA Adverse effects
Weight gain
Nausea
Constipation
Hypotension
Urinary retention
Tachycardia
Arrhythmia
Blurred vision
Drowsiness
Dry mouth
TCA HBD WUD N
Antagonism at alpha1 adrenoceptors (vasodilation = hypotension),
Antagonism at histamine (H1) receptors (antihistamine effect = sedation, stimulation of appetite and weight gain),
Antagonism at muscarinic receptors (anticholinergic effects = dry mouth; urinary retention)
Blockage of voltage-gated sodium channels (responsible for lethality in OD)
What are the contraindications to TCA
-Acute closed angle glaucoma (pupil dilation which may worsen closure of angle)
-BPH (urinary retention),
-Myocardial infarction or arrhythmias.
-Sudden withdrawal syndrome may also be seen with TCA’s. During long term treatment, doses should be decreased gradually over 4 weeks to avoid agitation, headache, malaise, sweating, GIT upset which can accompany a sudden withdrawal of TCA.
Examples of SSRIs
Citalopram, escitalopram, fluoxetine, paroxetine,
Flu,paro, sertaline. (xetine)
Citalopram(add es to it on the next one)
Mechanism of action of SSRIs
Increases synaptic serotonin concentration by inhibiting serotonin reuptake
