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53 Cards in this Set
- Front
- Back
Monoamine hypothesis of affective disorders
What is the final common pathways of all drugs that are effective in treating depression? |
elevation of NE in the synapse
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Monoamine hypothesis of affective disorders
Therapeutic activity of antidepressant drugs takes about 3 weeks to become apparent. Why is this? |
thought to be due to compensatory changes in the following receptors:
-presynaptic alpha2 -postsynaptic beta The antidepressant drugs cause down regulation - or desensitization - of the receptors. |
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Monoamine hypothesis of affective disorders
Etiology of depression may be related to what receptor ratio? |
may be related to elevated postsynaptic beta/alpha1 ratio
This elevated ratio declines after several weeks of anti-depressant therapy since many drugs desensitize post-synaptic beta receptors. |
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Monoamine hypothesis of affective disorders
Which group of adrenergic receptors is not desensitized by antidepressant drugs? |
postsynaptic alpha1 receptors are NOT desensitized
(postsynaptic beta & presynaptic alpha2, however, ARE desensitized) |
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Name the neurotransmitters that are degraded by MAO-A.
Name the neurotransmitter that is degraded by MAO-B. |
MAO-A degreades NE & 5-HT
MAO-B degrades DA |
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Describe differences between phenylzine and tranylcypromine.
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Phenylzine: irreversible inhibition of MAO-A and MAO-B
Tranylcypromine: prolonged, reversible inhibition of MAO-A |
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Besides the effects on alpha2 and beta receptors, MAOI's cause compensatory changes in this receptor.
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serotonergic receptors in the limbic system
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Name the 2 MAOI's discussed in class.
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1) phenylzine
2) tranylcypromine |
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The structure of tranylcypromine resembles that of this adrenergic agonist.
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The structure of tranylcypromine resemebles that of amphetamine.
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Which foods should a patient taking phenlyzine be advised NOT to eat?
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Patient taking a MAOI, such as phenylzine, should not eat foods high in tyramine, like beer & yellow cheese. This could lead to fatal HTN crisis.
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An MAOI and this pain reliever should not be administered together, as hyperpyrexia and convulsions may occur.
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Concurrent administration of a MAOI and MEPERIDINE may cause hyperpyrexia and. convulsions
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What toxic effect may result from the concomitant use of more than one antidepressant?
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Serotonin syndrome (muscle rigidity, hyperpyrexia, convulsions, coma, even death)
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Besides the toxic effects that can occur due to high levels of tyramine, administration of meperidine, & use of more than one antidepressant, what are the toxic effects of MAOIs?
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-postural hypotension (2ndary to peripheral alpha1 desensitization)
-insomnia, impotence, CNS stimulation (2ndary to excessive autonomic activity) -weight gain (uncertain mechanism) |
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Describe the specific toxic effects of each class of antidepressant in the case of an overdose (Learning Objective #3):
-MAOI -TCA -SSRI |
MAOI: CNS depression & cardiovascular collapse
TCA: cardiac conduction defects SSRI: it is difficult for a patient to OD on SSRIs - this is a reason why SSRIs are so often prescribed to treat depression |
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Name the 2 TCA's discussed in class.
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1) amitriptyline
2) imipramine |
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Just as the structure of tranylcypromine resembles amphetamine, which class of drugs does the structure of TCA resemble?
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Structure of TCA resembles phenothiazine antipsychotic drugs.
(However, TCA is not effective in treating psychosis). |
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TRUE OR FALSE
MAOI's and TCA produce CNS stimulation. |
FALSE
MAOI's produce CNS stimulation BUT... TCA's do NOT produce CNS stimulation. |
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TRUE OR FALSE
TCA's can cause sedation or fatigue. |
TRUE
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Describe the mechanism of action of TCA's
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TCA's increase synaptic concentrations of NE and/or 5-HT by inhibiting reuptake pumps
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Why don't TCA serum levels correlate with their therapeutic activity?
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-Pump inhibition occurs w/in hours of dose but therapeutic activity does not occur for several weeks because TCA's must induce changes in receptor sensitivity.
-Also, serum levels do not correlate with therapeutic activity due to high lipid solubility, extensive binding to serum proteins and many active metabolites. |
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Besides the effects related to drug interactions and overdose, describe the toxicity and side effects of TCA's.
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-arrythmia, tremor, insomnia (sympathomimetic)
-sedation with tolerance developing after 2 weeks (antihistaminic) -dry mouth, blurred vision, tachycardia, urinary retention (antimuscarinic) |
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TCA effects can be enhanced by use of these 2 drugs.
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1) antipsychotics
2) methylphenidate These drugs interfere w/ hepatic metabolism. |
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TCA effects can be reduced by use of this class of drug.
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Barbiturates increase hepatic metabolism of TCA's, thereby reducing TCA effects.
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If your patient is taking amitriptyline (a TCA) and she is experiencing pronounced sedative effects, you might ask her if she is also taking and/or using these 2 CNS depressants:
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1) alcohol
2) barbiturates These can produce additive sedative effects, as they are CNS depressants |
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TRUE OR FALSE
Second/Third generation antidepressants are better tolerated and much more effective compared to TCA's. |
FALSE
2nd/3rd generation antidepressants have fewer "promiscuous" receptor blockage activity and DO tend to be better tolerated than TCA's... HOWEVER, 2nd/3rd are NOT more effective compared to TCA's. |
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List the 7 2nd/3rd generation antidepressants discussed inclass.
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1) trazodone
2) nefazodone 3) venlafaxine 4) bupropion 5) amoxapine 6) maprotiline 7) mirtazipine |
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Describe the difference between 2nd/3rd generation antidepressants and TCAs.
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2nd/3rd generation antidepressants inhibit 5-HT reuptake to a greater extent than NE.
TCA's equally inhibit both NE and 5-HT reuptake pumps. |
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These 2 drugs inhibit 5-HT 2A receptors and inhibit 5-HT reuptake moreso than NE reuptake.
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trazodone & nefazodone
They are 2nd/3rd generation antidepressants. |
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Describe trazodone side effects & the receptors involved in these side effects .
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Trazodone can
1) induce prapism due to alpha1 blockage 2) induce drowsiness due to H1 receptor blockage |
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Venlafaxine
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-2nd/3rd generation antidepressant
-5-HT >>> NE pump inhibition -inhibit DA reuptake -effective in treating major depression & anxiety |
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Bupropion
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-2nd/3rd generation antidepressant
-weak inhibition of monoamine reuptake -significant side effect is dose-dependent increase in seizures -contraindicated in patients taking Zyban for smoking cessation -contraindicated in epileptic patients |
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Amoxapine
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-2nd/3rd generation
-antipsychotic metabolite -extrapyramidal side effects due to DA receptor antagonism |
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Maprotiline
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-2nd/3rd generation
-potent NE reuptake inhibitor -few sedative side effects |
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Mirtazipine
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-2nd/3rd generation
-blocks 5-HT and alpha2 receptors (UNIQUE!) -also blocks H1 receptor which can lead to sedation -likely to induce weight gain |
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For each patient below, name the 2nd/3rd generation antidepressant that you might NOT WANT to presribe
1) Patient who smokes 1 pack a day and is taking Zyban 2) Patient who is morbidly obese and is trying to lose weight 3) Patient with a history of seizures |
1) Patient taking Zyban // bupropion
2) Obese patient trying to lose weight // mirtazipine 3) Patient with history of seizures // bupropion |
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Which class of antidepressants is the most prescribed class for treatment of depression and anxiety disorders?
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SSRI's
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Describe the mechanism of SSRIs.
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They inhibit 5-HT reuptake
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What is the SSRI prototype drug?
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fluoxetine (Prozac)
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Describe the half-life of SSRIs.
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SSRIs have a long half life (>50h). In addition, each SSRI has active metabolites.
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While SSRIs are usually well tolerated, list some of their side effects.
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-nausea
-insomnia -anxiety -decreased libido -erectile dysfunction These are 2ndary to excessive 5-HT |
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Describe mechanism of lithium as a mood-stabilizing drug.
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Depresses noradrenergic or serotonergic transmission by decreasing formation of postsynaptic 2nd messengers
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TRUE OR FALSE
Lithium is effective at preventing manic episodes but is not used in acute treatment of the manic phase of bipolar disorder. |
TRUE
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Lithium levels must be kept between 0.6-1.2 mEq/L. What happens if lithium reaches 1.5-3 mEq/L?
Above 3 mEq/L? |
> 1.5-3 mEq/L : ataxia, drowsiness, muscle rigidity
> 3 mEq/L : cardiac arrythmia, seizures, coma |
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Describe elimination of lithium.
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Lithium is eliminated almost entirely by the kidney. Renal excretion is related to sodium intake, so sodium loading causes an increased Li excretion, while sodium depletion causes Li retention.
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What are the mild, yet common, side effects of lithium that occur within the first week of administration?
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-GI irritation
-muscular weakness -tremors -edema Tolerance usually develops to these side effects. |
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Name the 2 idiosyncratic toxicities of lithium.
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1) nontoxic goiter and decreased T3 and T4 levels
2) renal toxicity resembling nephrogenic diabetes insipidus |
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Regarding drug interactions with lithium, name the 2 drugs discussed that can cause Li intoxication.
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1) Diuretics, especially thiazides: Na depletion leads to Li retention
2) NSAIDS: they increase Li reabsorption |
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List the 5 clinical uses of antidepressants as discussed in class.
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1) major depression
2) enuresis (TCA) 3) ADHD (atmoxetine) 4) anxiety (SSRIs -- which also treat phobias, OCD, PTSD) 5) ?? efficacy in the case of treating chronic pain, fibromyalgia, migraines |
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Learning Objective #1
List the primary targets of the following: 1) MAOIs 2) TCAs 3) 2nd/3rd generation 4) SSRIs |
Learning Objective #1
List the primary targets of the following: 1) MAOIs: inhibit MAO-A and/or MAO-B; induce compensatory changes in alpha2, beta and serotonergic receptors 2) TCAs: inhibit NE and/or 5-HT reuptake pumps; eventually induce receptor sensitivity changes 3) 2nd/3rd generation: inhibit 5-HT reuptake to a greater extent than NE 4) SSRIs: inhibit 5-HT reuptake pumps |
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Learning Objective #2
List common adverse effects of the following: 1) MAOIs 2) TCAs 3) 2nd/3rd generation 4) SSRIs |
List common adverse effects of the following:
1) MAOIs: postural hypotension, insomnia, CNS stimulation, weight gain 2) TCAs: arrythmia, tremor, insomnia, dry mouth, blurred vision, tachycardia, urinary retention, initial sedation followed by tolerance 3) 2nd/3rd generation: specific to particular drug but includes prapism, drowsiness, seizures, extrapyramidal side effects, weight gain 4) SSRIs: nausea, insomnia, anxiety, decreased libido |
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Learning Objective #2
Identify drug and dietary interactions for the following: 1) MAOIs 2) TCAs 3) 2nd/3rd generation 4) SSRIs |
Identify drug and dietary interactions for the following:
1) MAOIs: tyramine & hypertensive crisis; meperidine & hyperpyrexia + convulsions 2) TCAs: antipsychotics & methyphenidate cause enhanced TCA effects; barbiturates cause reduced TCA effects; EtOH & barbiturates cause sedative effects 3) 2nd/3rd generation: bupropion is contraindicated in patients taking Zyban for smoking cessation 4) SSRIs: nothing specific, but as always, serotonin syndrome may result with use of other antidepressants |
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Learning Objective #3
How do you treat TCA overdose? How do you treat serotonin syndrome? |
Treating TCA overdose: pacing required
Treating serotonin syndrome: intravenous fluids, oxygen therapy, cooling blankets, medications for high blood pressure, and a ventilator to support breathing |
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Learning Objective #4
What effects does lithium have on neurotransmitter action? |
Lithium depresses noradrenergic or serotonergic transmission by decreasing formation of postsynaptic 2nd messengers
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