Download NURS 660 Exam 2 Questions and Answers: Sertraline, Duloxetine, and Paroxetine and more Exams Nursing in PDF only on Docsity!
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Sertraline Major Adverse Reactions - ANS ✓-Rare seizures
- Rare induction of mania
- Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24) Sertraline lab tests - ANS ✓none for healthy individuals Sertraline Major drug interactions - ANS ✓-Tramadol increases the risk of seizures in patients taking an antidepressant
- Can increase TCA levels; use with caution with TCAs or when switching from a TCA to sertraline
- Can cause a fatal "serotonin syndrome" when combined with MAOIs, so do not use with MAOIs or for at least 14 days after MAOIs are stopped,Do not start an MAOI for at least 5 half-lives (5 to 7 days for most drugs) after discontinuing sertraline
- May displace highly protein bound drugs (e.g., warfarin)
- Can rarely cause weakness, hyperreflexia, and incoordination when combined with sumatriptan or possibly with other triptans, requiring careful monitoring of patient
- Possible increased risk of bleeding, especially when combined with anticoagulants (e.g., warfarin, NSAIDs)
- NSAIDs may impair effectiveness of SSRIs
- Via CYP450 2D6 inhibition, sertraline could theoretically interfere with the analgesic actions of codeine, and increase the plasma levels of some beta blockers and of atomoxetine
- Via CYP450 2D6 inhibition sertraline could theoretically increase concentrations of thioridazine and cause dangerous cardiac arrhythmias
- Via CYP450 3A4 inhibition, sertraline may increase the levels of alprazolam, buspirone, and triazolam
- Via CYP450 3A4 inhibition, sertraline could theoretically increase concentrations of certain cholesterol lowering HMG CoA reductase inhibitors, especially simvastatin, atorvastatin, and lovastatin, but not pravastatin or fluvastatin, which would increase the risk of rhabdomyolysis; thus, coadministration of sertraline with certain ----HMG CoA reductase inhibitors should proceed with caution
- Via CYP450 3A4 inhibition, sertraline could theoretically increase the concentrations of pimozide, and cause QTc prolongation and dangerous cardiac arrhythmias
- Via CYP450 3A4 inhibition, sertraline could theoretically increase the concen Sertraline neurotransmitters and moa - ANS ✓-Boosts neurotransmitter serotonin
- Blocks serotonin reuptake pump (serotonin transporter)
- Desensitizes serotonin receptors, especially serotonin 1A receptors
- Presumably increases serotonergic neurotransmission
- Sertraline also has some ability to block dopamine reuptake pump (dopamine transporter), which could increase dopamine neurotransmission and contribute to its therapeutic actions Sertraline pregnancy risks - ANS ✓Not generally recommended for use during pregnancy, especially during first trimester Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn
•Rare activation of mania, depression, or suicidal ideation •Rare worsening of coexisting seizure disorders Duloxetine Major Drug Interactions - ANS ✓CYP2D6 inhibitors (duloxetine, paroxetine, fluoxetine, bupropion) cimetidine, and valproic acid can increase drug concentration •Concomitant use of potent CYP1A2 inhibitors (fluvoxamine, cimetidine, quinolone antimicrobials [eg, ciprofloxacin, enoxacin]) should be avoided •Serotonin release by platelets is important for maintaining hemostasis. Combined use of SSRIs or SNRIs (such as duloxetine) and NSAIDs, and/or drugs that affect anticoagulation has been associated with an increased risk of bleeding •CYP2D6 and 1A2 enzyme inducers, such as rifamycin, nicotine, phenobarbital, can lower levels •May cause serotonin syndrome when used within 14 days of MAO inhibitors •May increase risk of cardiotoxicity and arrhythmia when used with tricyclic antidepressants vccccccccccccc Duloxetine lab tests - ANS ✓check blood pressure at baseline and when increasing dose *Not recommended for patients with severe renal function impairment (creatinine clearance less than 30mL/min) or end-stage renal disease *Not recommended for patients with hepatic function impairment Duloxetine neurotransmitters and moa - ANS ✓-Blocks serotonin and noradrenergic reuptake pumps, increasing their levels within hours, but antidepressant effects take weeks. ------Effect is more likely related to adaptive changes in serotonin and norepinephrine receptors systems •Weakly blocks dopamine reuptake pump (dopamine transporter) Duloxetine pregnancy risk - ANS ✓-Category C. =Generally not recommended for the treatment of headache or neuropathic pain during pregnancy. Neonates exposed to duloxetine or other SNRIs or SSRIs late in the third trimester have developed complications necessitating extended hospitalizations, respiratory
support, and tube feeding. Respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying consistent with a toxic effect of the drug or drug discontinuation syndrome have been reported Paroxetine (Paxil) Major Side effects SSRI Commonly Prescribed for Major depressive disorder (paroxetine and paroxetine CR) Obsessive-compulsive disorder (OCD) Panic disorder (paroxetine and paroxetine CR) Social anxiety disorder (social phobia) (paroxetine and paroxetine CR) Posttraumatic stress disorder (PTSD) Generalized anxiety disorder (GAD) Premenstrual dysphoric disorder (PMDD) (paroxetine CR) Vasomotor symptoms (Brisdelle) Some patients may experience relief of insomnia or anxiety early after initiation of treatment - ANS ✓Withdrawal effects can be more common or more severe with paroxetine than with some other SSRIs
- Sexual dysfunction (dose-dependent; men: delayed ejaculation, erectile dysfunction; men and women: decreased sexual desire, anorgasmia)
- Gastrointestinal (decreased appetite, nausea, diarrhea, constipation, dry mouth)
- Mostly CNS (insomnia but also sedation, agitation, dose-dependent tremors, headache, dizziness)
- Weight gain
- Activation (short-term; patients with diagnosed or undiagnosed bipolar or psychotic disorders may be more vulnerable to CNS-activating actions of SSRIs
- Autonomic (dose-dependent sweating)
- Bruising and rare bleeding
- SIADH (syndrome of inappropriate antidiuretic hormone secretion)
Hepatic Impairment: Lower dose [initial 10 mg/day (12.5 mg CR), maximum 40 mg/day (50 mg/day CR)] Cardiac Impairment Preliminary research suggests that paroxetine is safe in cardiovascular patients Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood Paroxetine pregnancy risks - ANS ✓Not generally recommended for use during pregnancy, especially during first trimester Epidemiological data have shown an increased risk of cardiovascular malformations (primarily ventricular and atrial septal defects) in infants born to women who took paroxetine during the first trimester (absolute risk is small) Unless the benefits of paroxetine to the mother justify continuing treatment, consider discontinuing paroxetine or switching to another antidepressant Paroxetine use late in pregnancy may be associated with higher risk of neonatal complications, including respiratory distress At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child For many patients this may mean continuing treatment during pregnancy SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include
respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying Paroxetine neurotransmitters and moa - ANS ✓-Boosts neurotransmitter serotonin
- Blocks serotonin reuptake pump (serotonin transporter)
- Desensitizes serotonin receptors, especially serotonin 1A autoreceptors
- Presumably increases serotonergic neurotransmission
- Paroxetine also has mild anticholinergic actions
- Paroxetine may have mild norepinephrine reuptake blocking actions Fluvoxamine (Luvox) SSRI Major Side Effects Commonly Prescribed for Obsessive-compulsive disorder (OCD) (fluvoxamine and fluvoxamine CR) Social anxiety disorder (fluvoxamine CR) - ANS ✓*Fluvoxamine's sigma 1 agonist properties may contribute to sedation and fatigue in some patients Notable Side Effects Sexual dysfunction (men: delayed ejaculation, erectile dysfunction; men and women: decreased sexual desire, anorgasmia) Gastrointestinal (decreased appetite, nausea, diarrhea, constipation, dry mouth) Mostly CNS (insomnia but also sedation, agitation, tremors, headache, dizziness) Note: patients with diagnosed or undiagnosed bipolar or psychotic disorders may be more vulnerable to CNS-activating actions of SSRIs Autonomic (sweating) Bruising and rare bleeding Rare hyponatremia Fluvoxamine Major Adverse Reactions - ANS ✓Rare seizures Rare induction of mania
Via CYP450 3A4 inhibition, fluvoxamine could theoretically in Fluvoxamine lab tests - ANS ✓None for healthy individuals Renal Impairment Consider lower initial dose Hepatic Impairment Lower dose or give less frequently, perhaps by half; use slower titration Cardiac Impairment Preliminary research suggests that fluvoxamine is safe in these patients Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood Fluvoxamine neurotransmitters and moa - ANS ✓Boosts neurotransmitter serotonin Blocks serotonin reuptake pump (serotonin transporter) Desensitizes serotonin receptors, especially serotonin 1A receptors Presumably increases serotonergic neurotransmission Fluvoxamine also binds at sigma 1 receptors Fluvoxamine pregnancy risks - ANS ✓Controlled studies have not been conducted in pregnant women Not generally recommended for use during pregnancy, especially during first trimester Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment
(recurrence of depression, maternal health, infant bonding) to the mother and child For many patients this may mean continuing treatment during pregnancy Exposure to SSRIs early in pregnancy may be associated with increased risk of septal heart defects (absolute risk is small) SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying Venlafaxine (Effexor) Major Side Effects SNRI Commonly Prescribed for (FDA approved in bold) •Depression •Generalized anxiety disorder •Panic disorder •Social phobia - ANS ✓Constipation, dry mouth, sweating, blurry vision, loss of appetite, nausea, weight loss or gain, hypertension, headache, asthenia, dizziness, tremor, dream disorder, insomnia, somnolence, abnormal ejaculation, impotence, orgasm disorder, sweating, itching, sedation, nervousness, restlessness Venlaxafine Major Adverse Reactions - ANS ✓•Serotonin syndrome •Rare hepatitis •Rare activation of mania or suicidal ideation •Rare worsening of coexisting seizure disorders
hyperreflexia, tremor, jitteriness, irritability, and constant crying consistent with a toxic effect of the drug or drug discontinuation syndrome have been reported Venlafaxine neurotransmitters and moa - ANS ✓-Blocks serotonin and norepinephrine reuptake pumps, increasing their levels within hours, but antidepressant effects take weeks. Effect is more likely related to adaptive changes in serotonin and norepinephrine receptor systems over time •Weakly blocks dopamine reuptake pump (dopamine transporter) Agomelatine (Valdoxan) NRI Major Side Effects - ANS ✓-Nausea and dizziness are most common
- Other adverse reactions are somnolence, fatigue, insomnia, headache, anxiety, diarrhea, constipation, upper abdominal pain, vomiting, hyperhidrosis
- Increase of transaminase levels *Stop if transaminase levels reach 3 times the upper limit of normal Agomelatine Major Adverse Reactions - ANS ✓-Rare hepatitis, hepatic failure
- Theoretically rare induction of mania (class warning)
- Rare activa-tion of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24) (class warning) Agomelatine drug interactions - ANS ✓Use of agomelatine with potent CYP 1A2 inhibitors (e.g., fluvoxamine) is contraindicated Tramadol increases the risk of seizures in patients taking an antidepressant (class warning) Agomelatine dosing range - ANS ✓Usual Dosage Range 25 - 50 mg/day at bedtime
Agomelatine lab tests - ANS ✓Liver function tests before initiation of treatment and then at 3 weeks, 6 weeks, 12 weeks, 24 weeks, and thereafter when clinically indicated When increasing the dose, liver function tests should be performed at the same frequency as when initiating treatment Liver function tests should be repeated within 48 hours in any patient who develops raised transaminases Renal Impairment Drug should be used with caution Hepatic Impairment Contraindicated Cardiac Impairment Dose adjustment not necessary Agomelatine pregnancy risk - ANS ✓Not generally recommended for use during pregnancy, especially during first trimester Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child For many patients this may mean continuing treatment during pregnancy Agomelatine neurotransmitters and moa - ANS ✓Actions at both melatonergic and 5HT2C receptors may be synergistic and increase norepinephrine and dopamine neurotransmission in the prefrontal cortex; may resynchronize circadian rhythms that are disturbed in depression No influence on extracellular levels of serotonin
- Can be added to SSRIs to reverse SSRI-induced sexual dysfunction, SSRI-induced apathy (use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation)
- Can be added to SSRIs to treat partial responders - Often used as an augmenting agent to mood stabilizers and/or atypical antipsychotics in bipolar depression - ANS ✓-Tramadol increases the risk of seizures in patients taking an antidepressant
- Can increase TCA levels; use with caution with TCAs or when switching from a TCA to bupropion
- Use with caution with MAOIs, including 14 days after MAOIs are stopped (for the expert)
- There is increased risk of hypertensive reaction if bupropion is used in conjunction with MAOIs or other drugs that increase norepinephrine
- There may be an increased risk of hypertension if bupropion is combined with nicotine replacement therapy
- Via CYP450 2D6 inhibition, bupropion could theoretically interfere with the analgesic actions of codeine, and increase the plasma levels of some beta blockers and of atomoxetine
- Via CYP450 2D6 inhibition, bupropion could theoretically increase concentrations of thioridazine and cause dangerous cardiac arrhythmias Bupropion lab tests *Don't have to taper when d/c! - ANS ✓Recommended to assess blood pressure at baseline and periodically during treatment Renal Impairment Lower initial dose, perhaps give less frequently Drug concentration may be increased Patient should be monitored closely
Hepatic Impairment Lower initial dose, perhaps give less frequently Patient should be monitored closely In severe hepatic cirrhosis, bupropion XL should be administered at no more than 150 mg every other day Cardiac Impairment Limited available data Evidence of rise in supine blood pressure Use with caution Bupropion neurotransmitters and moa - ANS ✓-Boosts neurotransmitters norepinephrine/noradrenaline and dopamine
- Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing norepinephrine neurotransmission
- Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, bupropion can increase dopamine neurotransmission in this part of the brain
- Blocks dopamine reuptake pump (dopamine transporter), presumably increasing dopaminergic neurotransmission Bupropion pregnancy risk - ANS ✓Controlled studies have not been conducted in pregnant women Epidemiological studies do not indicate increased risk of congenital malformations overall or of cardiovascular malformations In animal studies, no clear evidence of teratogenicity has been observed; however, slightly increased incidences of fetal malformations and skeletal variations were observed in rabbit studies at doses approximately equal to and greater than the maximum recommended human doses, and greater and decreased fetal weights were observed in rat studies at doses greater than the maximum recommended human doses Pregnant women wishing to stop smoking may consider behavioral therapy before pharmacotherapy
- Rare induction of mania
- Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24) Clomipramine major drug interactions - ANS ✓-Tramadol increases the risk of seizures in patients taking TCAs
- Can cause a fatal "serotonin syndrome" when combined with MAOIs, so do not use with MAOIs or at least for 14 days after MAOIs are stopped
- Do not start an MAOI for at least 5 half-lives (5 to 7 days for most drugs) after discontinuing clomipramine
- Use of TCAs with anticholinergic drugs may result in paralytic ileus or hyperthermia
- Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors may increase TCA concentrations
- Fluvoxamine, a CYP450 1A2 inhibitor, can decrease the conversion of clomipramine to desmethyl-clomipramine, and increase clomipramine plasma concentrations
- Cimetidine may increase plasma concentrations of TCAs and cause anticholinergic symptoms
- Phenothiazines or haloperidol may raise TCA blood concentrations
- May alter effects of antihypertensive drugs
- Use of TCAs with sympathomimetic agents may increase sympathetic activity
- TCAs may inhibit hypotensive effects of clonidine
- Methylphenidate may inhibit metabolism of TCAs
- Activation and agitation, especially following switching or adding antidepressants, may represent the induction of a bipolar state, especially a mixed dysphoric bipolar II condition sometimes associated with suicidal ideation, and require the addition of lithium, a mood stabilizer or an atypical antipsychotic, and/or discontinuation of clomipramine Clomipramine lab tests - ANS ✓-Baseline ECG is recommended for patients over age 50
- Monitoring of plasma drug levels is potentially available at specialty laboratories for the expert
- Since tricyclic and tetracyclic antidepressants are frequently associated with weight gain, before starting treatment, weigh all patients and determine if the patient is already overweight (BMI 25.0-29.9) or obese (BMI ≥30)
- Before giving a drug that can cause weight gain to an overweight or obese patient, consider determining whether the patient already has pre-diabetes (fasting plasma glucose 100-125 mg/dL), diabetes (fasting plasma glucose > 126 mg/dL), or dyslipidemia (increased total cholesterol, LDL cholesterol and triglycerides; decreased HDL cholesterol), and treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management
- Weight and BMI during treatment While giving a drug to a patient who has gained >5% of initial weight, consider evaluating for the presence of pre-diabetes, diabetes, or dyslipidemia, or consider switching to a different antidepressant
- EKGs may be useful for selected patients (e.g., those with personal or family history of QTc prolongation; cardiac arrhythmia; recent myocardial infarction; uncompensated heart failure; or taking agents that prolong QTc interval such as pimozide, thioridazine, selected antiarrhythmics, moxifloxacin, sparfloxacin, etc.)
- Patients at risk for electrolyte disturbances (e.g., patients on diuretic therapy) should have baseline and periodic serum potassium and magnesium measurements Clomipramine neurotransmitters and moa - ANS ✓-Boosts neurotransmitters serotonin and norepinephrine/noradrenaline
- Blocks serotonin reuptake pump (serotonin transporter), presumably increasing serotonergic neurotransmission
- Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission
- Presumably desensitizes both serotonin 1A receptors and beta adrenergic receptors
- Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, clomipramine can increase dopamine neurotransmission in this part of the brain
