Term
| monoamine theory of depression |
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Definition
-deficiency of aminergic transmission in the CNS might be causative of depression (not 100% proven)
-an excess of aminergic transmission could result in mania
NE, ser, dop |
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Term
| amine hypothesis of major depression |
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Definition
-serotonin and NE are stored in vesicles then released, taken up by transporters
-CREB = cyclic AMP response element binding protein --> affects transcription and plays a role in the blockage of transporters |
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Term
| neurotrophic hypothesis of major depression |
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Definition
-depresse persons hav fewer dendrites and those dendrites have fewer innervated dendritic sprouts, or spines on them
-leads to a lack of communication
-BDNF: brain derived neurotrophic factor is decreased in depression
-BDNF is transcribed by CREB |
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Term
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Definition
Tyrosine-->DOPA-->Dopamine(DA)
- DA synthesized in pre-synaptic terminal
-stored in vesicles: DA-->NE
-NE released via vesicles
-NE degraded by monoamine oxidase (MAO) |
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Term
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Definition
-NE released from vesicle on presynaptic membrane
-reabsorbed pre-synaptically by **NE TRANSPORTER**
**NE transporter also has a site of action for amphetamine |
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Term
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Definition
Tryp-->5-HTP-->5-HT(serotonin)
-same vesicular storage and release as NE
-ser degraded by MAO: main mechanism of metabolism |
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Term
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Definition
**SEROTONIN TRANSPORTER takes up 5-HT from extracellular synapse to be repacked into vesicle
**serotonin transporter also has sites of action for Fluoxetine (prozac) and Fenfluramine (Fen-Phen, acts like an amphetamine)
-post-synaptically: Na ion channel receptor and Gprotein coupled receptor |
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Term
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Definition
| **located in the LOCUS COERULEUS in the pons** |
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Term
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Definition
| **located in the RAPHE NUCLEI in the pons** |
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Term
| NE and serotonin pathways |
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Definition
-both have cell bodies originating in the pons
-both pathways go through parallel tracks and innervate the same places
(NE - locus coeruleus
ser - raphe nuclei) |
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Term
| reciprocal innervation of NE and 5-HT neurons |
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Definition
-NE and 5HT neurons regulate each other's activities
-both cell bodies are in the pons
-direct connection between NE-->5HT
-can affect each other's firing and post-synaptic activity
*affecting one system really affects BOTH systems |
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Term
| drugs used in the treatment of depression |
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Definition
-SSRIs: citralopram
-atypical antidperessants: bupropion, mirazepine
-SNRIs: venlafaxine
-TCAs
-MAOIs
-ECT |
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Term
| site of action of antidepressants |
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Definition
-primary action is to BLOCK REUPTAKE
(atypicals are NOT reuptake inhibitors) |
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Term
SSRIs
selective serotonin reuptake inhibitors |
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Definition
*CITALOPRAM*
-easy to use
-safety in overdose
-relative tolerability
-cheap
-broad spectrum of uses |
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Term
SNRIa
selective serotonin and norepinephrine uptake inhibitors |
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Definition
*VENLAFAXINE*
-best tolerated in extended release form
-has a short half life |
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Term
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Definition
*MIRTAZAPINE*
-potent H1 histamine receptor blocker-->sedating effect
-blocks 5HT-2 and alpha-2-adrenergic receptors too
*BUPROPION*
-weakly blocks dopamine transporter and nicotinic acetylcholine receptors
-NOT sedating
-also used for smoking cessation |
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Term
TCAs
tricyclic antidepressants |
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Definition
-among the earliest drugs used but not as much currently
-SE profile that makes them untolerable to some patients
-possible to take a lethal OD
-block reuptake of both NE and serotonin |
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Term
MAOIs
monoamine oxidase inhibitors |
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Definition
-increase concentration of DA, NE, ser in synapse
-act by covalently modifying MAO
-very efficacious in depression
-need to does 2-3 times/day
-must have tyramine free diet
-SE profile makes then intolerable to some patients
-lethal overdose is possible |
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Term
| absorption and distribution of antidepressants |
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Definition
-most are well absorbed
-most are widely distributed |
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Term
| metabolism and elimination of antidepressants |
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Definition
-most metabolized by P450 then glucuronidation
-many have active metabolites
-most take several days to be eliminated
venlafaxine (SNRI) and bupropion (atyp) have short half-lives |
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Term
| common adverse effects of antidepressants |
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Definition
-sedation
-hypotension
-antimuscarinic
-GI
-weight gain
-sexual effects |
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Term
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Definition
**nausea and GI symptoms
**sexual effects, decreased libido, sexual dysfunction
-mild restlessness, headaches, insomnia
from activation of serotonin receptors |
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Term
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Definition
serotonin AE:
**GI effects
**sexual side effects
noradrenergic AE:
-agitation
-increase blood pressure |
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Term
| adverse effects of atypical antidepressants |
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Definition
Mirtazapine:
**sedation
-increased appetite, weight gain
-GI effects
Bupropion:
-dizziness
-agitation
-tremor
-anexoria
-potential for seizures at high doses |
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Term
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Definition
tertiary:
**antimuscarinic: dry mouth, dizziness, mental clouding, constipation, blurred vision
**sedation (from histamine block)
**hypotension
-weight gain
-sexual
-extreme CNS depression-->suicide |
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Term
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Definition
-orthostatic hypotension
-weight gain
-sexual effects |
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Term
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Definition
**DO NOT give with TCAs or SSRIs, may cause serotonin syndrome
-potentiate effect of other CNS depressants
-prolongs cardiovascular effects of indirectly-acting sympathomimetic amines |
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Term
| suicide risk and overdose danger |
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Definition
-increased risk of suicidal ideation in patients <25y.o.
TCAs: lethal arrhythmias, BP changes, altered mental status
MAOIs: autonomic instability, psychotic symptoms, confusions, seizures
-other antidepressants are safer by comparison |
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Term
| tolerance and physical dependence |
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Definition
-some tolerance to sedative and automonic TCA effects
-some tolerance to initial nausea of SSRIs
-physical dependence following abrupt withdrawal |
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Term
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Definition
-occurs with abrupt discontinuation after taking med for at least 6 weeks
-antidepressant discontinuation symptoms: flu-like, malaise, insomnia, nausea, imbalance, sensory disturbances, hyperarousal
-more likely to occur with a longer duration of treatment and shorter half life of drug
-may get recurrence of morbidity (get depressed again)
TAPER OFF! |
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Term
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Definition
-most metabolism is through CYP450's
-SSRIs esp. compete with metab of other drugs
-TCAs and MAOIs potentiate alcohol and other CNS depressants
-MAOIs should never be combined with SSRIs or SNRIs |
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Term
| safety of antidepressants at different ages |
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Definition
-safer in pregnancy than untreated depression
-risk:benefit ratio in children uncertain
-risks in geriatric patients higher due to decreased metabolic clearance |
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Term
| drugs to treat bipolar disorder |
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Definition
mood stabilizers:
-lithium
-anticonvulsive drugs: valproic acid, carbazepine, lamotrigine, ripiprazole |
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Term
| pharmacologic properties of lithium |
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Definition
-therapeutic doses have NO psychotropic effects in normal individuals
-not a sedative, euphoriant or depressant
-does not negatively effect ionic balance
**alters release and second messenger actions of biologic amines** |
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Term
| therapeutic index of lithium |
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Definition
**LOW, VERY NARROW**
1: therapeutic effect
2: mild toxicity
3: acute intoxication
4: coma
5: death
1-->5 can happen in a week
need a compliant patient |
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Term
adverse effects of lithium
(with long-term use) |
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Definition
Renal
-nephrogenic diabetes insipidus: lose ability to concentrate urine, excessive free water clearance (reversible)
Thyroid
-decreases thyroid function (reversible) |
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Term
| therapeutic uses of lithium |
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Definition
-bipolar disorder to treat acute mania, often in combo with anticonvulsants/psychotics
-adjunct to antidepressants in severe, recurrent depression or supplement in major depression |
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