antidepressants Flashcards
Describe Major Depressive disorder or unipolar depression
- disturbances in affect with NO MANIC EPISODES
- treated by antidepressant drugs
define bipolar disorder (manic depression)
- perioids of depression alternating with periods of mania
- treated by mood-stabilzing drugs
- prevalent, heterogeneous and recurrent MENTAL ILLNESS
- Symptoms: depressed mood, anhedonia (loss of pleasure) and loss of interest in life, appetitie changes, fatigue, etc
describe the problems with chemical antidepressants
- only work in a subset of patients (1/3 of patients, they dont work)
- Delay of therapeutic response - takes weeks or months of regular dosing before most patients derive therapeutic benefit
- Side effects can limit usage - elderly are equally responsive to antidepressants, but are more likely to experience adverse side effects
describe the 2 major hypotheses of depression
1) Monoamine/biogenic amine hypothesis
–> deficiency in level of 5-HT, NE and DA
–> all currently available antidepressants enahnce the synaptic availability of monoamines
2) neurotrophic hypothesis
–> loss of neurotrophic growht factosr (brain derived neurotrophic factor, BDNF) leads to neuronal atrophy and death
–> BDNF –> TRK-B receptors leading to ICNREASED NEURONAL SURVIVAL AND GROWTH
–> antidepressants increase BDNF in the brain
describe Antidepressant mech of action
- Goal is to increase levels of monoamines (5HT and NE) in the neuronal synapse
1) block enzymatic degradation by monoamine oxidase (MAO)
2) block re-uptake into the presynaptic terminal by inhibiton of transporters
3) inhibiton of presynaptic autoreceptors
4) binding specific possynaptic receptors (5HT2)
describe wine and cheese reaction
- Patients taking MAO-A inhibitors need to AVOID FOODS HIGH IN TYRAMINE (cheese, smoked meats and fish, fava beans, chianti wines and beers that contain yeast, chocolate and coffee)
–> possibly fatal interaction with tyramine resulting in release of catecholamines in the synames
–> decrease in MAO-A + increase in tyramine results:
- increased NE circulation
- overwhelming vasoconstriction = HYPERTENSIVE CRISIS
- headaches, intracranial bleeding, stroke, MI, etc
Describe the mechanism of MAOI
- Increase synaptic availability of NE and 5HT by blockign their catabolism via inhibition of MAO enzymes (MAO-A or MAO-B)
–> MAO-A = targets tyramine, NE, 5HT and DA
–> MAO-B = targets mainly DA
MAOI overdose signs
- hyperthermia, sizures, shock, delirium and comatose state
describe principals of antidepressant tx
- Require administration for 2-4 weeks to reach therapeutic benefit
- Safety of antidepressants primary concern
–> TCA = cardiotoxicity
–> SSRI’s are safer in overdose
- MAOI’s, TCA’s and SSRI’a should NOT be combined!!! SIDE EFFECTS CAN BE FATAL
**CAREFUL WHEN CHANGING MEDS**
What are the PK considerations to giving antidepressants
- Most all inhibit CYP isozymes (2D6, 3A4)
–> Paroxetine, fluoxetine, and fluvoxamine potent inhibitors of CYP2D6
0 Never combine TCAs and SSRIs –> long half lives, need longer time to clear before switching meds
–> leads to serotonin syndrome and TCA toxicity
describe TX of Bipolar disorders
- Lithium –> maintenance tx, slow onset of action
–> drug of choice for controlling manic and depressive phases of disorder (mood-stabilizing agent)
- Valproic acid and carbamazepine – tx of acute manic
Define discontinuation syndrome
- Sudden discontinuation of short half-life SSRIs may cause ADVERSE SIDE EFFECTS IN SOME PATIENTS 1-7 days after stopping
–> PAROXETINE, SERTRALINE –> dizziness, paresthesia, anxiety
Describe Serotonin SYndrome
- Occurs usually in combo with another SSRI, MAOIs, TCAs when switching medication
- FLUOXETINE has to be discontinued for 4-5 weeks prior to using other antidepressants, other need to be discontinued for 2 weeks
- SYMPTOMS
–> lethargy, restlessness, mental confusion, flushing, diaphoresis, tremor
List the 6 Selective serotonin reuptake inhibitors (SSRI’s)
- Fluoxetine
- sertraline
- paroxetine
- citalopram
- escitalopram
- fluvoxamine
