L30 - Depression Flashcards
MAJOR DEPRESSIVE DISORDER – sustained for at least how long? Symptoms? Manic episodes?
At least 2 weeks, depressed mood, energy, interest/pleasure in activities, low self-esteem, feelings of guilt, inability to concentrate, sleep disturbances (eg early morning awakening), changes in appetite etc. Anxiety. Pessimism and melancholy. Suicidal thoughts and attempts are common. NO manic episodes.
BP AFFECTIVE DISORDER/MANIC DEPRESSION – sustained for at least how long? Symptoms?
At least 1 week, swings of mood from extreme elation and hyperexcitability (mania e.g. extreme – hyperactivity, excited or hypomania) to extreme melancholia and withdrawal. > Depressive than the periods of elevated mood.
During manic phases – risk taking tasks heightened/lessened
Heightened e.g. buying expensive things, sexual indiscretions
ECT – Electroconvulsive therapy
A last resort when drugs don’t work – but apparently, it works the same way as the drugs do on the receptors.
When will beneficial effects from antidepressive treatment first become apparent? How long will optimal beneficial effects take?
Until 1-3 weeks of treatment. Optimal beneficial effects may take 6-8 weeks.
TCA – Example, Pharmocology, SE
- Amitriptyline
- Inhibitors of neuronal uptake of NA and 5HT
- Antagonists at a1 adrenoceptors, MuscR (anti SLUD if antagonist used), histamine H1- and H2-receptors and 5-HT receptors (in high concentrations).
SE: anti-cholinergic, CV (postural hypotension, arrhythmias causing changes in ECGs, increased HR as MuscR (vagus) is blocked), CNS, weight gain.
.Similar in structure to phenothiazines. Major difference – in 3D, tricyclics are more “buckled” ie the rings are at angles to each other.
SSRI – Example, low/high TI, SE
Fluoxetine - Increases level of 5-HT in synaptic cleft
High therapeutic index – minimal toxicity in overdose unless combined with other drugs e.g. TCAs or neuroleptics.
SE: insomnia, agitation, sexual dysfunction (made Fluoxetine not as popular), GIT disturbances, restlessness (anxiety present), increases suicidality
MAO I - – Example, Side Effects
Moclobemide – reversible competitive inhibitors of MAO A (RIMAs)
Side effects: dizziness, nausea, insomnia.
- MAO is in the gut – there is lots of food containing tyramine e.g. cheese, vegemite (indirectly acting sympathomimetic) goes into blood stream and gets converted into NA causing increased BP (if you have MAOI then you can’t stop this)….hydrazines and non-hydrazines are irreversible and wipe out MAO completely
- Originally developed from the anti-TB drug isoniazid. These drugs increase levels of noradrenaline, 5-HT & dopamine.
BP Disorder – Example, Low/high TI? Side effects
Lithium carbonate – discovered by accident, Low TI (toxic in low amounts), mood stabilizer
-Very low therapeutic index (2-3) – if you double or triple the concentration of the recommended dose, you can get toxicity. Plasma levels must be monitored very regularly otherwise serious toxicity may result.
Side effects: renal (replaces Na+ ions in the body), thyroid (lower active thyroid resulting in goitre), neurological (shakes, convulsions, coma, death)
Mechanism of action of drugs used in affective disorders – compare before (old theory) and after (new theory)
BEFORE - TCA and MAO inhibitors were effective in depression through increasing availability of NA, 5-HT and other neurotransmitters in the CNS, either by blocking neuronal uptake or breakdown of the transmitters.
NOW – it is thought that adaptive changes in receptors are more important in the mechanism of action of antidepressants, such as a reduction in -adrenoceptor sensitivity or numbers, desensitization of 5-HT2 receptors and 2-adrenoceptors.
Lithium carbonate, the mechanism of action
Unknown. Evidence suggests that interactions with second messenger systems may play a role.
Lowered or heightened levels of BDNF or malfunction of its Trk B receptor plays a role
Lowered
Major depression is associated with neuronal loss in hippocampus and PFC - how is this reversed?
ECT or exercise works by inhibiting or reversing this loss by stimulating neurogenesis
