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64 Cards in this Set
- Front
- Back
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what does Ach control? DA? NE? 5HT? glutamate? GABA? |
Ach- memory, motor control |
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where does NE arise from and where does it project to |
arises from locus cereulus (dorsal bundle)--> *projections involved in learning, memory, anxiety, & psychosis (lesions--> depression)
also arises from lateral tegmental area (median forebrain bundle)--> projects to diencephalon & spinal cord |
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where do serotonergic (5-HT) neurons arise from |
raphe nucleus--> projects to cortex, cerebellum & spinal cord (lesions--> depression, anxiety, compulsion, psychosis) |
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what is the monoamine hypothesis |
drugs that decrease NE / 5HT will cause depression * & vise versa |
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what beneficial effect does 5ht have specifically with neurons |
5ht promotes neurogenesis through BDNF
*thus anti-depressants promote neurogenesis by inc serotonin (prevent neurodegeneration) |
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what is the common effect of an antidepressant |
since there is a lot of NT in the cleft, over time, it'll cause downregulation of a1 and b1 adrenergic receptors and 5ht2 receptors
-Inc 5-HT & NE receptors (sensitivity) -Inc receptor-G protein signaling -Induce neurotrophic factors promoting neurogenesis |
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how does stress have an effect on the body/neurons
(glutamate hypothesis) |
stress --> increase glutamate --> direct effect on neuron --> atrophy of dendrites --> decrease volume in hippocampus, amygdala, & prefrontal cortex---> depression |
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what is ketamines effect |
ketamine is an NMDA-R antagonist.
*theoretically blocks glutamate from causing depression |
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what are the ways that NTs do reuptake and degradation |
specific transporter (NE/NET, 5-HT/SERT) uptakes NT & repackages it into secretory granules (reuptake 1*) |
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list the TCAs in descending order of SE |
amitriptyline > imipramine >
nortriptyline > desipramine
(ami & imi are tertiary amines, nor & des secondary, less SEs & drug interactions) |
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what is the MOA for TCA |
compete with NE & 5-HT at the transporters NET & SERT --> prevent reuptake 1--> acute inc in NE & 5-HT & chronic down-regulation of presynaptic alpha2 (NE) & 5-HT1A, 1D, 2, 7 & post-synaptic 5-HT2a autoreceptors--> Inc NE & 5-HT in synaptic cleft |
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what are the main SE of TCAs |
-anticholinergic: blurred vision, sweating, dry mouth, urinary retention, constipation -prolonged QT interval (don't combine w others who do this) (SSRIs & SNRIs do not have anti-muscarinic, anti-histaminic, & anti-adrenergic effects--> less neg SEs) |
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what are the 2 big complications to watch out for when giving TCA
Can OD--> death w/ TCAs? |
resp depression---> coma---> death &
YES, need to assess suicide risk before giving bcs can be used for this |
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what drugs should NOT be given with TCA |
Alcohol--> CNS depression Anticholinergic agents Insulin, oral hypoglycemic agents--> hypoglycemia MAOI--> toxicity and SSRi (can cause serotonin syndrome) |
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what are the pharmacokinetics of TCA |
rapidly absorbed, strongly bound to albumin |
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who do you have to be careful in giving TCA to |
BPH pts--> worsens urinary retention cardiac arrhythmia pts--> exacerbates this elderly--> even longer half-life, toxicity more likely |
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what are some other uses for TCA |
anxiety disorders, enuresis (imipramine), OCD, neuropathic pain (amytriptyline) |
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_________, like amitripyline can be used to treat neuropathic pain
MOA? |
SNRIs: Venlafaxine Desvenlafaxine Duloxetine
MOA: block NE & 5-HT reuptake w/o affecting cholinergic, adrenergic, or histamine receptors* = less SEs |
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what are the SE of SNRIs (venlafaxine, desvenlafaxine, Duloxetine) |
(more activity at SERT than NET) Dizziness dry mouth anorexia SOMNOLENCE increased sweating NAUSEA (mc) sexual dysfxn *possible serotonin syndrome (Duolextine) |
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what is an additional SE that we must watch out for w/ venlafaxine (specifically at high doses)? |
HTN |
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who should NOT be taking duloxetine (SNRIs)? |
hepatic insufficiency pts on MOAis, dopamine antagonists, or certain antipsychotics--> serotonin syndrome |
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what are the MAOIs?
what is their MOA? |
Phenelzine Tranylcypromine Seleginline (transdermal delivery)
MOA: irreversibly inactivate MAO--> block MAO degradation of NE, 5-HT & other endogenous amines |
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There are 2 types of MAO, MAO-A & MAO-b.
which MAO is more related to depression? |
MAOa = depression (most MAOIs target MAOa preferentially*)
(MAOb= parkinsons) |
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which MAOI is a MAOb inhibitor specifically |
selegiline (transdermal patch)
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what are the SE of MAOi |
sexual dysfxn weight gain *OD---> CNS stimulation--> seizures (opposite TCAs, which cause CNS depression) |
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phenelzyine has what associated SE (MAOI) |
hepatotoxicity (rare) |
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what foods should you NOT eat while on MAOis? Why? |
aged cheese, pods of fava beans, yeast extract, herring (smoked fish)
= tyramine induced hypertensive crisis--> active tyramine causes incr NT leakage--> MAO-a that normally inactivates these NTs is inactivated--> NTs increase BP |
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what are the drug interactions with MAOis
*DO NOT GIVE WITH THESE DRUGS* |
CNS stimulants (appetite suppressants, decongestants, ephedrine, levodopa)--> HTN crisis |
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what is the first line antidepressant drug
why? |
SSRIs: Citalopram Fluoxetine Paroxetine Sertraline Escitalopram
*fewer SEs & less dangerous OD than others*
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what is the MOA for SSRIs (citalopram, fluoxetine, paroxetine, sertraline, escitalopram) |
selectively block SERT (5-HT transporter)---> Inc level of 5-HT in the synaptic cleft
*via eventual down-regulation of 5-HT autoreceptors (autoreceptors are self-inhibitory) |
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what are the SEs of SSRIs?
what SE has been a/w fluoxetine specifically? |
Sexual dysfunction headache *possible inc suicide risk in children/ adolescents (monitor in first few wks) *Serotonin Syndrome *Withdrawal *may induce switch to mania in bipolar pts
Fluocetine--> akathesia |
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if you withdraw ssri what sx can appear?
How can you avoid this? |
myoclonus, malaise, chill, muscle aches, sleep disturbances, GI sx
*switch to a long acting SSRI (fluoxetine) & discontinue slowly |
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what are the drug interactions with ssri
*DO NOT give these drugs w/ SSRIs** |
should NOT be used with; TCAs or MAOIs--> Serotonin syndrome lithium--> seizures |
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Serotonin Syndrome results from high levels of circulating 5-HT (caused by any drugs/combos that cause this)
Describe what occurs? |
akathisia-like restlessness, muscle twitches & myoclonus, hyperreflexia, sweating, shivering & tremor---> seizures, coma
*self-limiting (resolves if you remove offending agent- Selegiline, St. John's wort) |
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which ssri is the most sedating, which is the most stimulating? |
sedating = paroxetine
(sertraline is most moderate, neither sedating or stimulatory) |
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What else are SSRIs used to tx?
(DOC for depression) |
bulimia OCD Anxiety disorders |
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name the atypical antidepressants |
bupropion |
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what is the MOA of bupropion (Wellbutrin) |
inhibits reuptake of NE & DA (dopamine) |
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the effects of the inc DA levels caused by Buproprion are used for what other treatment? |
cessation of smoking |
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what are the SE of bupropion
What drug should NOT be used w/ buproprion? Why? |
dry mouth Insomnia
*DO NOT use w/ MAOIs--> hypertensive crisis |
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what is the MAO for nefazadone |
5ht2 antagonist
--> increases 5HT levels |
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what are the SE of nefazadone |
dry mouth |
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what are the drug interactions with nefazadone |
strong interactions w/ triazolam (facilitates sleep), alprazolam (benzodiazepine tx for acute anxiety) |
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what is the MOA of mirtazapine |
acts as an antagonist at presynaptic alpha2AR autoreceptor & heteroreceptors--> Increase levels of NE & 5HT |
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what are the SE of mirtazapine |
weight gain
*agranulocytosis (rare)--> elevated liver fxn tests |
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Mirtazapine should NOT be used w/ ___________ |
MAOIs |
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generally, it is thought to best continue antidepressant tx for how long after a relapse |
continue at least 6 months following relapse
*always reduce gradually *monitor during 1st 6 months of discontinuation--> increased risk of relapse during this time |
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If a patient w/ depression is complaining about the sedative effects of their medication, you may consider switching them to what drug? |
Buproprion
or 2nd choice MAOI
*only ones that don't have sedation as SE, may actually cause insomnia* |
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if a patient needs an antidepressant but is wary about gaining weight, which drug should you prescribe her? |
SSRI
or alternative--> busipirone |
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What is the best drug to tx a patient w/ depression & SEVERE insomnia? |
TCA (amitriptyline)
*TCAs, cause the most anti-histamine sedation, amitriptyline has the most severe sedatory effects |
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If a patient w/ depression is going to quit treatment d/t sexual dysfunction, what medication should you switch to? |
Bupropion
*only one that doesn't cause sexual dysfunction* |
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what is the path behind bipolar disorder |
deficiency of catecholamines & 5-HT --> depression & excess of catecholamines (NE & Dopamine) --> mania
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Lithium is the DOC for bipolar disorder maintenance
what is the MOA for lithium
(lithium carbonate & lithium citrate |
inhibits inositol monophosphatase--> prevents the hydrolysis of inositol phosphate to inositol prevents phosphorylation of proteins involved in apoptosis & amyloid formation *regulation of G proteins & mimics effects of Na+ |
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why do you have to be careful with giving lithium if your patient is on a low Na+ diet or thiazides (decr Na+)
what will occur if a pt on Lithium also takes osmotic diuretics? |
low Na+ diet or thiazides-->
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what are some mild SE of lithium |
-polyuria or polydipsia--> nephrogenic diabetes insipidus -hypothyroidism -sedation -fine tremor -worsening acne *discontinuing lithium---> significant risk of bipolar relapse |
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what are some adverse effects of Lithium use in pregnancy |
ebsteins malformation (CV defect) "floppy baby" syndrome (d/t hypotonia) neonatal goiter CNS depression
*secreted in milk |
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Lithium has a low therapeutic index & serum concentration should be monitored.
what are the severe SE of lithium that may occur w/ toxicity? |
mental confusion |
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what are the drug interactions with lithium
*DO NOT USE these drugs together! |
thiazide diuretics- depletion of na+ causes retention of lithium & toxicity |
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what are the other uses of lithium |
acute mania (but valproic acid or cabamazepine is better) |
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What are the DOCs for treating acute mania in bipolar disorder? |
Valproic acid & Carbamazepine (anticonvulsants)
(not great for long-term maintenance) |
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what is valproic acids SE |
Transient GI sx- nv, anorexia
SEs are mild |
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can you substitute valproic acid for lithium? |
no, in the beginning it is equally effective, but after a few weeks, it is not as efficacious for maintenance |
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carbamazepine's side effects are what |
acute intoxication: coma, hyperirritability, convulsions, respiratory depression (tx like a TCA OD) long term: drowsiness, vertigo ataxia, blurred vision, n/v (avoided w/ short use) blood dyscrasia (unlikely to occur) |
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What is the role of antipsychotics in the tx of bipolar disorder? |
adjunct therapy w/ lithium |
