Antidepressant pharm Flashcards
What is the biogenic amine hypothesis and some evidence to support it?
depression may result from low activity of NE or 5HT. Evidence: reserpine depletes DA, NE, and5HT and can precipitate major depressive disorder in patients; iproniazid and tricyclic antidepressants can elevate mood and incr. 5HT
What are some problems wit the biogenic amine hypothesis?
antidepressants take weeks to work, but increases in amines occur almost immediately
amine depletion in “normal” people don’t cause depression- though they can precipitate relapses in people who are predisposed to depression.
No direct evidence
What should I know about theories around changes in receptors and depression? (why proposed as a theory for MOA of antidepressants; problems with the theory)
antidepressants cause a decr. in the amt of beta adrenergi, a2 AR and 5HT receptors. Maybe this helps?
But, time course of changes doesn’t match time course of antidepressant efficacy, this isn’t seen in other effective antidepressant therapies (ECT), and sometimes beta-AR blockade can CAUSE depressive symptoms
What should I know about monamine sensitivity and depression?
incr. amine levels in synapse initially lead to decreased release from aminergic neurons. but then autoreceptors are desensitized and neurtransmitter release is increased. increased release and transporter blockade results in an increase in post-synaptic mono-amine activity. Post-synaptic receptors not desensitized in the same way as pre-synaptic receptors.
These effects also seen with ECT and 5HT agonists
What are the theories about depression and CRF?
CRF = corticotrophin releasing factor CRF directly and indirectly influences brain function by acting as a neurotransmitter and by acting as a hypothalamic factor that increases the release of ACTH from the pituitary. ACTH increases glucocorticoid release by the adrenal gland. CRF is high in patients with current depression, as are cortisol levels. CRF receptors found at nuclei of Rafhe and at locus ceruleus. no definitive proof of role- but CRF receptor antogonists one potential new class of anti-depressants.
What is the theory of Durman and Nestler about the causes of depression (they sort of localize)
hippocampal atrophy, perhaps from elevated glucocoritoids that reduce BDNF nuerotrophic factors. NE and 5HT might increase BDNF production. Hippocampal loss is a problem because hippocamus is important for memory, learning, HPA (hypothalamus pituitary adrenal system) mudulation, emotional rresponse.
What evidence supports the idea that depression may be based in hippocampal abnormailites?
stress decreases hippocampal BDNF (which should be around to increase synapses in the hippocampus and increase survival of 5HT nuerons)
stress and gglucocorticoid cause hippocampal atrophy and weakened neurotrophin levles
What are the other receptors in the brain that may be abnormal in depressed patients?
ACh- cholinergic agents sometimes treat depression
substance P receptor antagonist may work
also, vascular problems can cause dementia- often seen in stroke patients.
What are some antiseizure drugs that are used to treat depression?
carbamazepine and valproate. Maybe gabapentin.
What antidepressant can promote seizures?
buproprion (aka Wellbutrin)
What are two new underlined tricyclic antidepressants (which work as reuptake blockers)
amitriptyline and desipramine
What is the MOA of desipramine?
reuptake inhibitor with a special affinity for inihibiting NE reuptake.
What is an advantage of buproprion?
not as much weight gain as with some other antidepressants
MAO inhibitors: what type of interaction with MAO; what version of MAO is most effected?
irreversible MAO inhibition
Most anti-depressant effects mediated by inhibition of MAO-A
What are the pharmacokinetic properites of reuptake inhibitors (dosing times, absorption, side effects)
long half life permits once daily dosing
readily absorbed
slow GI motility and may induce constipation
be aware of exacerbation of glaucoma and tachycarrhythmias
