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124 Cards in this Set
- Front
- Back
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Clinicians diagnose depressive disorders according to the ____________________.
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Diagnostic and Statistical Manual of Mental Disorders
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What is the estimated prevalence of depression?
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16%
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What two trends are important regarding depression?
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1. Increased rates of depression.
2. Decreased age of onset. |
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In what gender is depression more common?
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Female
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What is the typical onset of depression agewise?
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25-30 yo
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What typically precipitates the initial episode of depression?
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Stressful life events.
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Depressive symptoms appearing later in life (Late-onset syndrome) typically occurs in what patients?
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Those with underlying neurological disorders.
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Describe the genetic component of depression.
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Depression and suicide tend to cluster in families.
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What is the likelyhood of a person developing depression if a 1st degree relative becomes ill?
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1.5-3x more likely to develop depression.
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What are the risk factors for reocurring depression?
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1. 1st degree relative with depression.
2. 1st episode before age 20 3. >2 prior episodes 4. H/O recurrence within 1 year after medication was discontinued |
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Describe the biogenic amine hypothesis for depression?
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Depletion of NE, 5-HT and DA in the synapses. Not specific.
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Expected 5-HT levels in a depressed individual
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Decreased
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Expected NE levels in a depressed individual
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Decreased
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Expected NE levels in a manic patient
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Increased
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Expected 5-HT levels in a manic patient
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Decreased
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Describe the dysregulation hypothesis of depression
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Rather than focus on the activities of neurotransmitter systems, this theory focuses on the failure of homeostatic regulation.
A decreased in the receptor sensitivity is implicated. THIS THEORY ADDRESSES WHY ANTI-DEPRESSANT EFFECTS ARE CHRONIC RATHER THAN ACUTE. |
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Describe the 5HT/NE hypothesis
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Basically it states that both the serotenergic and noradrenergic systems must be functional for an antidepressant effect to be exerted.
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Describe the biological markers that support a biological hypothesis
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1. Neuroendocrine - many patients have neuroendocrine abnormality (Cortisol/TSH)
2. Sleep - REM earlier and have decreased slow-wave sleep, disruption of slep and early morning awakening. |
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Describe the Neurokinin theory
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Suggests that Neurokinins have antidepressant properties, focus of research
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Describe the structural abnormalities associated with depression
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Decreased hippocampal volume after episode, deep white matter lesions
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Name Endocrine disorders associated with depression
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Hypothyroidism
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Describe deficiency states associated with depression
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Pernicious anemia, Wernicke's encephalopathy, severe anemia
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Describe infections associated with depression
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Influenza, TB, AIDs
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Describe metabolic disorders associated with depression.
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Hypokalemia
Hyponatremia |
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Describe cardiovascular events associated with depression
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1. Post MI
2. Post CVA 3. CHF |
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Describe neurologic disorders associated with depression.
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1.Alzheimers
2.Parkinsons 3.Post CVA 4.MS |
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Describe psychiatric disorders associated with depression.
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1.Anxiety disorders
2.Eating disorders 3.Schizophrenia 4.Substance dependence |
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Describe some medications associated with depression
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Alcohol Propranolol Diuretics Baclofen 5-FU Metoclopramide Ondansetron Reserpine Hydralazine OC's Brompheniramine INTERFERON-alpha Metronidazole Theophylline Methyldopa Clonidine Steroids Digoxin Isotretinoin NSAIDs
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SIGECAPS
Signs of Depression |
Sleep distrubance
Interest, loss of Guilt Energy, loss of Concentration (Poor) Appetite changes Psychomotor changes Suicidial Ideation |
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Suicide Risk factors (9)
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Elderly
H/O prior attempts Feelings of hopelessness Living alone Substance abuse Anniversary of a loss Unemployment Family history Lack of support system |
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Which gender attempts to commit suicide more often?
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Female
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Which gender SUCCEEDS in committing suicide more?
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Men
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Overall Tx Goals
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1. Reduce depressive symptoms
2. Return patient to an optimal level of functioning |
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Nonpharmacologic Tx
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1. Psychotherapy
2. Electric convulsive Tx 3. Light therapy |
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How long before antidepressant effects are typically seen?
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2-4 weeks after initial dose
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How long of a trial must be given to each agent?
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4 weeks
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Describe the improvement scheme for AD therapy(ie appetite, mood...)
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First sleep, appetite and energy levels improve BEFORE the mood... Risk factor for suicide
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What ADR's are associated with Dopamine reuptake inhibition?
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Psychotic features, activation.
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What ADR's are associated with serotonin reuptake inhibition?
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N/V/D, Anxiety, Sexual dysfunction, insomnia
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What ADR's are associated with Norepinephrine reuptake inhibition?
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Sexual dysfunction, insomnia, tachycardia, tremor
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Describe Seratonin syndrome: What causes it and what are it's symptoms?
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Associated with concurrent use of medications inhibiting the reuptake of serotonin.
Sx: Confusion, Seizures, Tachycardia, Agitation, Hyperthermia, Tremor, Coma, HTN and Ataxia |
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TCA's are typically classified as (sedating/activating) antidepressants?
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Sedating
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Amitriptyline - CLASS
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TCA Tertiary Amine
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Clomipramine - CLASS
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TCA Tertiary Amine
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Doxepin - CLASS
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TCA Tertiary Amine
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Impiramine - CLASS
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TCA Tertiary Amine
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Trimipramine - CLASS
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TCA Tertiary Amine
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Desipramine - CLASS
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TCA - Secondary Amine
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Nortriptyline - CLASS
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TCA - Secondary Amine
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Protriptyline - CLASS
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TCA - Secondary Amine
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Which TCA's are more efficacious per studies?
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None, none are superior to others
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What NT's do TCA's block the reuptake of?
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5-HT, DA and NE
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Besides the typicaly NT reuptake inhibition, what receptors are also blocked by TCA's?
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Cholinergic, Histaminergic and Alpha-1
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Are TCA's considered 1st line?
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No
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Off label uses of TCA's
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Trigeminal and post-herpetic neuralgias, diabetic neuropathy, enuresis and migraine prophylaxis.
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Which class of TCA's are preferred and why?
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Secondary amines, they have LESS anticholinergic
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Which class of antidepressants in particular is fatal in overdose?
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TCA's
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ADR's associated with TCA's
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1.Anticholinergic
2.Antihistaminergic 3.Alpha-1 adrenergic blockade 4.Cardica conduction delays (heart block with those with preexisting conduction abnormalities.) 5.Drowsiness, weakness, lethargy, fatigue 6.Excessive perspiration 7.Sexual dysfunction 8.Seizures 9.Weight Gain |
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Advantages of TCA's
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1.Well established efficacy
2.Generics available 3.Once daily dosing 4.Sedation 5.Effective for non-mood disorders |
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Disadvantages of TCA's
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1.High rates of discontinuation
2.Dose titration normally required 3.Wide differences in metabolism among individuals 4.Overdose may be fatal 5.Weight gain 6.Sexual dysfunction |
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Relevant PK considerations as far as TCA's
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1. Rapid absorption
2. First past metabolism 3. Food DOES NOT AFFECT ABSORPTION 4. Large Vd 5. Highly protein bound 6. Heavy hepatic metabolism 7. T1/2 is 24 hours, so qd |
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Which CYP isoenzymes metabolize TCA's
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CYP1A2
CYP2D6 (Different in people) CYP3A4 |
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Two major drug interactions with TCA's
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1.Alcohol - Increase risk of seizures
2.Buproprion - Increase risk of seizures |
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Venlafaxine - CLASS
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SNRI
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SNRI
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Serotonin Noradrenergic Reuptake Inhibitors
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Duloxetine - CLASS
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SNRI
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Which TCA is indicated for OCD?
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Clomipramine
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Which TCA is indicated for depression or anxiety associated with Alcoholism?
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Doxepin
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Which TCA is indicated for children experiencing enuresis?
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Imipramine
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Venlafaxine MOA
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Inhibits reuptake of: 5-HT and NE and WEAKLY DA
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Is venlafaxine a possible 1st line?
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Yes
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Venlafaxine is generally regarded as a (Activating/Sedating) antidepressant
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Activating
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ADR's associated with Venlafaxine
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Nausea
Constipation Dry mouth Dizziness Sweating Sexual dysfunction Agitation HA Insomnia |
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What DOSE related side effect may be observed with higher doses of Venlafaxine?
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Increases in blood pressure
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Is weight gain typically associated with Venlafaxine?
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It is rare
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PK considerations for Venlafaxine
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1.Food has no effect on absorption
2.Not highly protein bound 3.Metabolized by 2D6 4.BID dosing normally used due to active metabolite (O-desmethylvenlafaxine) |
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Which Class/Drug is associated with the worst sexual dysfunction by far?
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Venlafaxine
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Significant drug interactions for Venlafaxine
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MAO-Inhibitors, TCA's and other serotonergic meds
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Describe dosing method for Venlafaxine
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Must be titrated
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FDA indications for Duloxetine
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Depression, diabetic neuropathic pain
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MOA of Duloxetine
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5-HT, NE reuptake inhibition. Weak inhibitor of DA
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ADR associated with Duloxetine
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Insomnia, nausea, fatigue, diarrhea, dry mouth, dizziness, constipation, sexual dysfunction, MAY INCREASE LFTs
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Which AD's can raise LFTs?
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Duloxetine and Trazodone
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Describe relevant PK information for Duloxetine
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1.Well absorbed
2.Food WILL delay extent and rate of absorption 3.Heavy hepatic metabolism |
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Significant Duloxetine ADR's
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Nausea
LFTs Sexual Dysfunction |
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Describe dosing method for Duloxetine
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Must titrate
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Advantages of Venlafaxine
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ER formulation available
Relatively safe in overdose Minimal Drug interactions |
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Disadvantages of Venlafaxine
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1.High rates of Sexual dysfunction
2.Cost 3.Potential for increased blood pressure 4.Dose titration required |
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SSRI's are typically considered which line of therapy?
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1st
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ADR's common to all SSRI's
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Nausea, HA, sleep disturbances, anxiety, sexual dysfunction, tremor
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Fluoxetine has been associated with the most __________________.
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Agitation (Activating)
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Paroxetine has been associated with the most ____________________.
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Sedation, weight gain
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Sertaline has been associated with the most ______________.
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Diarrhea
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CYP450 considerations as far as SSRI's
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Fluoxetine and Paroxetine are potent 2D6 inhibitors
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Describe the PK of Fluoxetine
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2-3 day half life of active and 7-9 days of active metabolite, so qd or qW weekly dosing used. CAN SELF TAPER
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Drug interactions are most likely with which SSRI's
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Fluoxetine, paroxetine
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Drug interactions are least likely with which SSRI's?
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Citalopram, escitalopram
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Major interaction associated with SSRI's
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Warfarin! May increase INR
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Effect of 5-HT2 antagonism?
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Reduced Anxiety, Insomnia, Sexual dysfunction
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Trazodone - MOA
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5-HT2 antagonist, 5-HT reuptake inhibitor
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Nefazodone - MOA
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5-HT2 antagonist and 5-HT reuptake inhibitor
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Main use of Trazodone in the market?
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Sedative-hypnotic
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ADR's associated with Trazodone/Nefadazone
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SEDATION, ORTHOSTATIC HYPOTENSION, somnolence, dry mouth, nausea, ha, constipation
PRIAPISM BLACK BOX ON NEFADAZONE: HEPATOTOXICITY! |
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PK considerations for Nefazodone
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Food decreses extent of absorption and bioavailability of nefazodone
Half life - 2-4 hours, therefore BID dosing |
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Drug interactions for Nefazodone
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CYP3A4 POTENT INHIBITOR
Alprazolam, Carbamazepine, Digoxin, Statins (Rhabdo), MAOIs, PI's, Buspirone |
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Drug interactions for Trazodone
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Antipsychotics, Alcohol, MAOI, Digoxin, phenytoin, Warfarin, Carbamazepine
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How would you dose Trazodone?
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QHS! Major sedation
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Buproprion- CLASS
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Mixed DA/NE Reuptake inhibitor
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Buproprion Indications
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Depression, Seasonal affective disorder and SMOKING CESSATION
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ADR for Buproprion
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Dry mouth, insomnia, HA, N/V, agitation, anxiety, dizziness, tremor, constipation.
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Buproprion is contraindicated in which group?
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Those having seizures
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MAJOR Drug interactions for buproprion
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Antipsychotics, AD's (Esp TCAs) and Alcohol DUE TO SEIZURE THRESHOLD LOWERING!
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Maximum daily dose of Buproprion
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450mg/day
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Mirtazapine MOA
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Enhances central NE and 5-HT activity through antagonism of central presynaptic alpha 2 adrenergic autoreceptors and heteroreceptors.
Also blocks 5-HT types 2 and 3, cholinergic and histamine receptors |
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Mirtazapine blocks 5-HT2 receptors which reduces _____________.
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Anxiety, insomnia and sexual dysfunction
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Mirtazapine blocks 5-HT3 receptors which reduces _________________.
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Nausea
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Common ADR associated with Mirtazapine
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Sedation, increased appetite, weight gain, constipation, dry mouth
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Does food affec the rate or extent of absorption of Mirtazpine?
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Nope
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Normal dosing frequency for Mirtazapine
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QD
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What do you do if Mirtazapine dosing results in activaiton rather than sedation?
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Adjust administration time
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Phenelzine - Class
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Non-selective MAOI
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Tranylcypromine- Class
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Non-selective MAOI
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MOA of non-selective MAOI's
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Increases concentrations of NE, 5-HT and DA within the neuronal synapse due to inhibition of MAO enzyme
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Selegiline - CLASS
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MAO-I type B selective
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