Chapter 13: Antidepressants Flashcards
(35 cards)
Monoamine Theory of Depression?
- originate from: reduced activity in NE, SE and DA systems
- Current focus is on: 5-HT dysfunction (decreased activity)
Glucocorticoid Theory of Depression?
- Heightened HPA-axis activity leads to elevation of stress hormone levels (cortisol)
- Stress–> Hypothalamus: CRH–> Pituitary: ACTH–> Adrenal Cortex: Cortisol –(inhibits): Hypothalamus, Pituitary
- > Cortisol stimulates Prefrontal Cortex, Amygdala and Hippocampus…Amygdala stimulates hypothalamus and the other two inhibit.
Problems in living theory?
- depression is NOT a disease
- stressors can cause changes in the physiology and functioning of the brain
What are the first generation AD’s?
- Monoamine Oxidase Inhibitors
L> first ever: Iproniazid (1950) originally used to treat TB- unwanted SE such as liver damage - Tricyclic Antidepressants - safer
L> firs: imipramine
What is the difference between new MAOIs vs old ones?
- they are reversible
- less likely to effect diet or cause liver damage
What are the second Generation AD’s?
- SSRI’s: first choice….
L> Prozac = first…..slightly different than Tricyclic
L> less SE
What are the third generation AD’s?
- SNRI’s : effecting SE and NE
* do not effect muscarinic acetylcholine receptors…therefore do not produce SE associated with older AD’s
- enhancing NE treats tiredness and loss of energy etc
Neurophysiology:
1. First Gen AD’s
I) MAOI’s
- inhibit monoamine oxidase causing NE, SE, DA to float freely in cytoplasm
- new ones are selective for MAO-A(degrades all three) or B(DA mostly)
- some new ones are reversible
- low doses = B, high= A
Neurophysiology:
- First Gen AD’s
- tricyclic
- block reuptake of 5-HT and NE
- block muscarinic acetylcholine receptors and they antagonize histamine and adrenergic receptors.
Neurophysiology:
2. Second and Third Gen AD’s
-SSRI : block reuptake of SE..Build up in synapses prolonging stimulation (fluoxetine - Prozac)
- SNRI: block reuptake of 5-HT and NE and in some cases DA
L> Bupropion ( NE and DA but not Sert!) aka Wellbutrin
L> goes against SE hypothesis
L> Zyban= smoking cessation aid!
*both are Bupropion
Which absorbs faster: TCA’s or SSRIS and SRNIs
- TCAS
Do they undergo significant first pass metabolism?
- yes via digestive system and liver
- alcohol inhibits this therefore increasing the amount of drug being reabsorbed from a specific dose.
BUT SSRIs and SNRIs barely react with alcohol
Do they readily cross the blood brain barrier and placental ?Where do they become concentrated ?
YES
- kidneys, lungs, liver and brain can be found in breast milk!
Excretion?
MAOI (2-4 hours) >SSRI (15-25 hours) > TCA (24 hours, single dose daily)
Excretion and Fluoxetine?
- extremely long half life
- nearly 4 days
- active metabolite norfluoxetine has one of 7-15 days
Effects on the body?
- MAOI?
- TAC?
- SSRI
- tremors, weight gain, blurry vision, dry mouth and lowering of BP and postural hypotension. Can have dangerous SE when in combination with foods with tyramine (cheese, beer, wine, chocolate)…MAOI-A metabolizes it normally and B picks up whatever was missed. It can cause sweating, nausea and increased bp…headaches, internal bleeding and even stroke or death. (cheese effect)
- also drugs such as Amph, decongestants and nose drops release NE which potentiates MAOI
Effects on the Body?
2. TAC
- ANS……PD specifically
- dry mouth, constipation, blurred vision, ringing in ears and retention of urine
Effects on the Body?
3. SSRI
- nausea, gastrointestinal probs, agitation, headache, dizziness, sweating , nervousness
- cause weight loss
Bupropion SE
- restlessness, agitation, tremor, constipation, nausea, headache, dry mouth and loss of appetite.
- seizures
Why is serzone no longer sold ?
- risk of liver damage
MAOI’s effect on sleep?
- insomnia or sedation
TAC effect on sleep?
- drowsiness (anticholinergic effect )
Fluoxetine effect on sleep?
- reduces REM but increases vividness of dreams
Bupropion effect on sleep?
- increases REM
