Depression

Question 1

Depression

Answer 1

chemical imbalance

Major Depressive Disorder:
-dysphoric &/or loss of interest/pleasure in nearly all activities

May be d/t inflammation in the brain (microglia = inc secretion

Major drug classes = act at the synapse
-can take for 6-12months + then stop or need to be on the meds for rest of life, diff variables (don’t get same response)

• # diff tests that = predictive of improving mood, no actual biological test to confirm
• can’t really use animal modes b/c how do you know the animal is experiencing depression
• to get same symptoms = need to stress the animal a lot
• look for loss of pleasure (norm = like sugar, abnormal =/= like-during stress)

Question 2

Bipolar Disorder

Answer 2

wide fluctuations in mood (cycle between depression + mania)

• cycle = variable (few hrs to months)
• depression
• mania: elevated, expansive irritable, inflated self-esteem, dec need for sleep, inc tendency to talk, distractible, goal oriented, hyper-sexuality

Question 3

Depression Treatments

• General Info
• Side Effects
• Metabolism
• Interactions

Answer 3

SSRIs + SNRIs

• don’t change gene expression
• not too selective-many side effects
• consequence of blocking NA reuptake = inc HR, BP (SNS)
• most receptors = GPCRs that NT act on (60% of all drug targets)
• changes intracellular signalling, receptor density, gene exp + trophic factors

NE selective: Oxaprotiline
DA selective: Bupropion
5HT selective: Citalopram

Side Effects

• agitation
• seizures
• sedation
• dec BP
• anti-ACh effects
• GI effects
• sexual effects
• cardiac effects

Metabolism

• metabolized by CYP2D6
• potential interactions with other hepatic metabolized drugs
• titrate dose for elderly
• generally safe with less CV + antimuscarinic effects (xerostomia - dry mouth)
• extensive stimulation of 5HT pathways (insomnia, anxiety, irritability, dec’ed libido, erectile dysfunction, anorgasmis, ejaculatory delay)
• GI = nausea + diarrhea
• discontinuation with short lived drugs = trigger WD

Interactions

• can’t eat a lot of tyramine or Tyr
• inc risk of bleeding (some NSAIDs + SSRIs)
• Don’t use SSRI/SNRI with MAOi
• > normally only block tx’ers partially, but with combo = block completely (high toxicity)
• don’t use if 5HT syndrome
• > autonomic, cognitive, hyperthermia all b/c excessive 5HT

Question 4

Tricyclic Antidepressants

Answer 4

high # of side effects

not too selective

Question 5

Serotonin Receptors

Answer 5

• 7 types tot. (all GPCRs)
• 1 + 5 = inhibitory
• 2 = change IP3 + DAG
• Mainly change cAMP
• increase cell firing rate if NT amplified

Question 6

Oxaprotiline

Answer 6

NE selective SSRIs + SNRIs

Question 7

Bupropion

Answer 7

DA selective SSRIs + SNRIs

• enhances NA + D neurotransmission
• inhibition of NET or DAT (unclear)
• might be presynaptic

Question 8

Citalopram

Answer 8

5HT selective SSRIs + SNRIs

Question 9

Antidepressants

Answer 9

• 3rd gen = used clinically
• 1st gen = high side effects
• > nonspecifically block transporters
• > CV side effects
• > lower epilepsy threshold
• > xerostomia
• > used to constrict blood vessels in local anesthesia

Question 10

MAOi

Answer 10

2 types of MAOs -> A & B
blocks the metabolism of NT
some inhibitors = more selective for B
-can target MAOb without affecting MAOa (which is present in the GI tract)
*only @ low doses*
-reversible competitive inhibitors
-potential toxic effects
-interactions with food (tyramine)
(modest amounts in processed cheeses, meat, fruit + veggies)

Question 11

5HT2 Antagonists

Answer 11

Used with SSRIs + SNRIs

inhibit reuptake or block post-synaptic binding