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122 Cards in this Set
- Front
- Back
what are the common initial complaints of depression?
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fatigue
headache insomnia GI disturbances anorexia weight loss chronic pain loss of interest inactivity loss of sexual desire general feeling of despondency |
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what are the three simple classifications of depression?
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reactive/secondary depression
major depressive bipolar affective |
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what are the diagnostic features of reactive depression?
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aka secondary depression
commonly presents as depression, anxiety, bodily complaints, tension, guilt caused by loss (adverse life events, physical illness) common association with drugs and other psychiatric disorders may respond spontaneously |
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what type of depression accounts for more than 60% of all depressions?
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reactive/secondary depression
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what are the diagnostic features of major depressive disorders?
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a precipitating life event is not adequate to explain the degree of depression
unresponsive to changes in life may occur at any age biologically determined commonly presents as abnormal sleep rhythms, decreased motor activity, decreased libido, decreased appetite |
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what treatments are usually effective in major depressive disorders?
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antidepressants
electroconvulsive therapy |
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what are the diagnostic features of bipolar affective disorder?
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characterized by cyclic episodes of mania and depression
may be misdiagnosed as major depressive if hypomanic episodes are missed lithium carbonate stabilizes mood antipsychotics to treat mania antidepressants to treat depression |
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why is it difficult to establish the efficacy of antidepressant drugs?
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1) factors inherent in the disease state
- no physiologic msmt of improvement - high rate of spontaneous remission - high placebo response 2) need for further studies relating [drug] to efficacy 3) lack of adequate model |
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why is there a high "noise-to-signal" ratio in experiments dealing with antidepressants?
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high rate of spontaneous remission
high placebo response |
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what is the current animal model for antidepressant drug trials?
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put a rat in a tub of water, it gets stiff
if the rat takes longer to get stiff after administration of the antidepressant, then the drug is "good" |
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what are the therapies for depression?
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1) psychotherapy
2) tricyclic antidepressants (TCAD) 3) "second gen" antidepressants 4) MAO inhibitors (old) 5) electroconvulsive therapy (ECT) |
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what is the best treatment for depression?
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electroconvulsive therapy
the "gold standard" for treatment of depression |
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what are the drawbacks to ECT as a treatment for depression?
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it is expensive and not likely to be a permanent solution
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how is ECT done?
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pt is given a neuromuscular blocker which paralyzes them
the pt is then given an anesthetic and a seizure is electrically induced seizure lasts > 30 sec |
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what type of drug is amitriptyline?
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tertiary amine tricyclic antidepressants
NE, 5-HT reuptake inhibitor antidepressant |
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what are the side effects of amitriptyline?
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strong sedation
strong anti-muscarinic effects strong hypotensive effects strong cardiac effects |
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what is amitriptyline used to treat?
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depression
treatment for chronic pain of a neural origin (diabetic neuropathy) |
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what is required for an antidepressant drug to be good for treating neurologic pain?
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blockade of reuptake of norepinephrine AND serotonin
**must be both** |
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what type of drug is nortriptyline?
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secondary amine tricyclic antidepressant
selective norepinephrine-reuptake inhibitor antidepressant |
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what drug is a metabolite of amitriptyline?
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nortriptyline
when a methyl group is removed from the nitrogen in amitriptyline (occurs in the liver), nortriptyline is produced |
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what does nortriptyline block the uptake of?
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norepinephrine
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what are the side effects of nortriptyline?
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some sedation
some antimuscarinic effects some hypotensive effects some cardiac effects decreased intensity compared to amitriptyline |
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what type of drug is fluoxetine?
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selective serotonin-reuptake inhibitor
antidepressant |
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what is the advantage of selective serotonin-reuptake inhibitors, compared to tricyclic antidepressants?
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fewer side effects
virtually no sedation, anti-muscarinic effects, hypotensive effects, or cardiac effects |
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what type of drug is citalopram?
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selective serotonin-reuptake inhibitor
antidepressant |
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what type of drug is paroxetine?
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selective serotonin-reuptake inhibitors
antidepressant |
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what type of drug is sertraline?
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selective serotonin-reuptake inhibitors
antidepressant |
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uptake of what is blocked by fluoxetine?
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serotonin
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uptake of what is blocked by citalopram?
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serotonin
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uptake of what is blocked by paroxetine?
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serotonin
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what type of drug is duloxetine?
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serotonin/norepinephrine-reuptake inhibitor
antidepressant |
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what type of drug is venlafaxine?
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serotonin/norepinephrine-reuptake inhibitor
antidepressant |
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uptake of what is blocked by duloxetine?
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serotonin
norepinephrine |
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what conditions is duloxetine used to treat?
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depression
neurologic pain |
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uptake of what is blocked by venlafaxine?
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serotonin
norepinephrine |
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what is the advantage of serotonin/norepinephrine-reuptake inhibitors, compared to tricyclic antidepressants?
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fewer side effects
virtually no sedation, anti-muscarinic effects, hypotensive effects, or cardiac effects |
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what type of drug is bupropion?
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atypical antidepressant
unknown mechanism of action |
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what is bupropion used to treat?
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smoking cessation (3-month treatment period)
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what are the side effects of bupropion?
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seizures at doses greater than 450mg
**doses must be limited** |
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what is the generic name for prozac?
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fluoxetine
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what is the generic name for paxil?
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paroxetine
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what is the generic name for zoloft?
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sertraline
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what is the generic name for effexor?
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venlafaxine
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what is the generic name for wellbutrin?
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bupropion
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what type of drug is mirtazapine?
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atypical antidepressant
blocks postsynaptic 5-HT2 receptors blocks norepinephrine reuptake |
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what is blocked by mirtazapine?
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postsynaptic 5-HT2 receptors
norepinephrine receptors |
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what is mirtazapine used to treat?
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depressed patients with insomnia
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what are the side effects of mirtazapine?
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strong sedation
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what type of drug is trazodone?
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atypical antidepressant
serotonin-reuptake inhibitor |
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what are the side effects of trazodone?
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strong sedation
no anti-muscarinic effects few hypotensive effects few cardiac effects |
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what conditions is trazodone used to treat?
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insomnia
**strong sedation and no anti-muscarinic effects** |
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what are the side effects of trazodone?
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strong sedation
no anti-muscarinic effects weak hypotensive effects no cardiac effects |
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how long does it take for any antidepressant to take effect?
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4-6 weeks
**side effects occur immediately** |
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why are patients usually discouraged by antidepressant medications?
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time to onset of antidepressant effects is 4-6 weeks, however negative side effects begin immediately
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how does efficacy compare between antidepressants?
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approximately the same
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how should an antidepressant drug be chosen for a patient?
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efficacy is approximately the same between differing antidepressants
choice is usually made based on which has the side effects the patient best tolerates |
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what is the cause of drug interactions with tricyclic antidepressants?
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since TCAD's block the amine reuptake pump, any drugs that use the reuptake pump (e.g. guanethidine) will not be able to enter neurons
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what are the effects of TCAD overdose?
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causes arrhythmias
- ventricular tachycardia (>120 bpm) - bundle branch block - cardiac arrest grand mal seizures |
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what are the side effects of selective serotonin-reuptake inhibitors?
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usually limited to nausea and vomiting
headache sexual dysfunction |
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what are the side effects of fluoxetine?
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AGITATION
RESTLESSNESS nausea/vomiting headache sexual dysfunction |
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why must fluoxetine always be taken in the morning?
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fluoxetine (in particular among the SSRIs) is associated with agitation and restlessness
if it were taken at night, the patient wouldn't be able to sleep |
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what are the two drugs that are approved by the FDA to treat obsessive compulsive disorder?
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fluoxetine
clomipramine |
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what is the monamine theory of depression?
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predicts that the disruption of NE, 5-HT, and DA neurotransmision plays a key role in the development of depression
1) TCADs block reuptake of NE/5-HT 2) ECT causes seizures 3) MAOIs decrease degradation of NE/5-HT 4) SSRIs block reuptake of NE/5-HT **1-4 all lead to an increase in amine in the synapse |
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why does it take 4-6 weeks for the onset of antidepressant effects?
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Before Tx: NTs are released at pathologically low levels and exert steady-state levels of autoinhibitory feedback
Acute Tx: increased release/duration of NTs in synaptic cleft, which causes stimulation of inhibitory autoreceptors, w/ inc. NT synthesis and inhibition of exocytosis chronic Tx: constant stimulation of inhibitory autoreceptors causes their down-regulation and overall desensitization of the inhibitory effect |
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what is the drug of choice for manic-depressive syndrome?
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lithium ("mood-stabilizing" drug)
- combined with antipsychotics when mania breaks through - combined with antidepressants when depression breaks through |
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therapeutic window for lithium
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VERY narrow (1.0-2.0 mEq/L)
**give multiple daily doses of extended release form to avoid a peak in drug concentration** |
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how is lithium reabsorbed in the kidney?
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only in the proximal tubule by the same mechanism governing sodium reabsorption in the proximal tubule
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what is the effect of diuretics on patients taking lithium?
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increased proximal reabsorption of sodium causes enhanced reabsorption of lithium cuasing toxic levels of lithium to build up
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what is the effect of a low-sodium diet on patients taking lithium?
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low sodium diet causes extreme reabsorption of sodium from the proximal tubule which causes enhanced reabsorption of lithium which can lead to toxic levels of lithium to build up
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what are the uses for lithium?
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bipolar disorder
- add antidepressants to tx breakthrough depression - add antipsychotics to tx breakthrough mania depression |
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what is the mechanism of action for lithium?
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the mechanism is unknown
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what are the side effects of lithium?
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SEs at therapeutic doses: nausea, diarrhea, drowsiness, polyuria, polydipsia, weight gain
SEs at high doses: mental confusion, hyperreflexia, gross tremor, seizures leading to death |
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what is the effect of diuretics on patients taking lithium?
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increased proximal reabsorption of sodium causes enhanced reabsorption of lithium cuasing toxic levels of lithium to build up
|
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what is the effect of a low-sodium diet on patients taking lithium?
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low sodium diet causes extreme reabsorption of sodium from the proximal tubule which causes enhanced reabsorption of lithium which can lead to toxic levels of lithium to build up
|
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what are the uses for lithium?
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bipolar disorder
- add antidepressants to tx breakthrough depression - add antipsychotics to tx breakthrough mania depression |
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what is the mechanism of action for lithium?
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the mechanism is unknown
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what are the side effects of lithium?
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SEs at therapeutic doses: nausea, diarrhea, drowsiness, polyuria, polydipsia, weight gain
SEs at high doses: mental confusion, hyperreflexia, gross tremor, seizures leading to death |
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why does lithium cause polyuria and polydipsia?
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lithium inhibits the action of ADH, so the patient loses excessive water (polyuria) and a subsequent increase in thirst (polydipsia)
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opiate vs. opioid
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opiate: compound derived from the opium poppy
opiod: synthetic/natural compound with opiate properties, but not derived from the opium poppy |
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what kind of drug should come to mind when you see a phenanthrene ring?
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opiate
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what are the strong phenanthrene opioid agonists?
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morphine
hydromorphone oxymorphone oxycodone |
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what are the mild/moderate phenanthrene opioid agonists?
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codeine
hydrocodone |
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what are the mixed agonist-antagonist phenanthrene opioids?
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nalbuphine
buprenorphine **stimulate some, but not all receptors** |
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what are the antagonist phenanthrene opioids?
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naloxone
naltrexone |
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what are the strong phenylheptylamine opioid agonists?
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methadone
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what are the phenylpiperidines?
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opioids
strong agonists: meperidine, fentanyl mild/moderate agonist: diphenoxylate |
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what are the morphinens?
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opioids
strong agonist: levorphanol mixed agonist-antagonist: butorphanol |
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what are benzomorphanes?
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opioids
mixed agonist-antagonist: pentazocine |
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how are opiates metabolized?
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mostly converted to polar metabolites by glucuronide conjugation, and then undergo renal excretion
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define endorphins
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endogenous peptides with opiate-like properties
"endogenous morphine" |
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what is the precursor protein for beta-endorphins?
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pro-opiomelanocortin (POM)
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what endorphins are derived from pro-opiomelanocortin (POM)?
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beta-endorphins
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what is the precursor protein for the enkephalins?
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proenkephalin
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what endorphins are derived from the precursor protein, proenkephalin?
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the enkephalins (met- and leu-enkephalins)
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what is the precursor protein for the dynorphins?
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prodynorphin
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what endorphins are derived from the precursor protein prodynorphin?
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the dynorphins (dynorphin A and dynorphin B)
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mu receptor
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opioid receptor for beta-endorphins from the POM protein
stimulation causes supraspinal and spinal analgesia, euphoria, respiratory depression, and constipation |
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kappa receptor
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opioid receptor for dynorphins (endorphins derived from prodynorphin)
stimulation causes supraspinal and spinal analgesia, dysphoria, and psychotomimetic effects |
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delta receptor
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opioid receptor for enkephalins (endorphins derived from proenkephalin)
stimulation causes supraspinal and spinal analgesia |
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what is supraspinal analgesia?
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analgesia caused by stimulation of receptors in the cortex and limbic area
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what causes opioids to have high abuse potential?
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stimulation of the mu opioid receptor
(stimulation of kappa receptors causes dysphoria, so it decreases abuse potential) |
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what opioid receptor is stimulated by morphine?
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mu receptor
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what opioid receptor is stimulated by methadone?
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mu receptor
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what opioid receptor is stimulated by fentanyl?
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mu receptor
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what opioid receptor is stimulated by sufentanil?
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mu receptor
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what opioid receptor is stimulated by buprenorphine?
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partial agonist of mu receptors
antagonist of kappa receptors |
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what opioid receptors are antagonized by naloxone?
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mu, delta, and kappa receptors
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what opioid receptors are antagonized by naltrexone?
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mu, delta, and kappa receptors
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what is the advantage of buprenorphine?
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it is a partial agonist with very high affinity for the mu receptor (causes excellent analgesia with low addiction/abuse potential)
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if endorphins stimulate multiple opioid receptors, why are they so specific for one receptor type?
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they are only released at a certain type of opioid receptor
1) enkephalins stimulate mu and delta receptors, but are only released at delta receptors 2) endorphins stimulate mu and delta receptors, but are only released at mu receptors 3) dynorphins stimulate mu, delta, and kappa receptors, but are only released at kappa receptors |
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where is the density of opioid receptors highest?
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dorsal horn of the spinal cord
nucleus raphe magnus locus ceruleus hypothalamic nuclei thalamic nuclei |
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what is the effect of opioids binding to receptors?
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bind to neurons transmitting pain impulses and alter the progression of the impulse
bind sites in the limbic system, which changes the emotional response to pain (does NOT cause analgesia) |
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what is the effect of mu-opioid receptor stimulation on presynaptic primary sensory neuron central terminals?
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the presynaptic opioid receptor is a G-protein coupled receptor inhibits voltage gated calcium channels in the synaptic nerve terminal, which blocks exocytosis of pain sensory neurotransmitters (CGRP, substance P, glutamate)
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what is the effect of mu-opioid receptor stimulation on postsynaptic secondary sensory relay neurons?
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the postsynaptic opioid receptor is a G-protein coupled receptor stimulates voltage gated potassium channels in the cell membrane of a post-synaptic axon terminal
stimulates efflux of potassium (increases potassium conductance out of the cell), which causes hyperpolarization of the post-synaptic neuron and blocks action potential transmission |
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what is the mechanism of developing tolerance and dependence to opiates?
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mu opioid receptors inhibit adenylate cyclase and stimulate a potassium channel
with acute administration of opiates, conversion of ATP to cAMP is inhibited thereby inhibiting PKA, and then blocking activation of CREB (a transcription factor responsible for transcription of adenylate cyclase) and activation of a sodium channel with chronic administration of opiates, CREB and subsequently adenylate cyclase transcription is up-regulated, so the same dose of morphine cannot inhibit all of the adenylate cyclase molecules; cAMP levels return to nearly normal, activating PKA and subsequently the sodium channels allowing for easier depolarization |
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what is the theory behind patient-controlled analgesia (PCA) pumps?
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gives patients control over when they receive more pain medication, so they have less fear about the pain returning; this decreases the total amount of pain-killers the patient needs and increases the efficacy because the drug is given before the pain returns
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what are the CNS effects of opiates?
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analgesia
euphoria sedation respiratory depression cough suppression miosis |
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what are the peripheral effects of opiates?
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1) increases tone of GI tract, but decreases peristalsis (causes constipation)
2) increases tone of bronchial tube smooth muscle (induces asthma attack in an asthmatic) 3) increases smooth muscle of ureters, bile duct, etc (causes more pain if pt has gall/kidney stones) |
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why do opiates causes paradoxical increase in pain in patients with kidney/gall stones?
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cause contraction of smooth muscle in the ureters and/or bile duct, which causes squeezing of the stone and more pain
Solutions: increase the narcotic dose or use ketorolac (an NSAID; doesn't inc. smooth muscle tone) |
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what is the major drawback of opiates?
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respiratory depression
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what receptors mediate the cough suppression caused by opiates?
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opiate and non-opiate receptors
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what is indicated by a patient in a coma with miosis (pupillary constriction)?
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opiate overdose
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