NURS 660 Exam 2 Study Guide 2023

NURS 660 Exam 2 Study Guide 2023. Know the major side effects, adverse reactions, drug interactions, applicable lab tests to order when the medication is prescribed and during treatment, the neurotransmitters they work on, pregnancy risk, and mechanism of action of the following medications. Also Stahls indicates the neurotransmitters the drug targets at the beginning of each drug. Include this by the name.  AmitriptylineMajor side effects: CONTRAINDICATED in cardiovascular disorders, anticholinergic effects may be pronounced; moderate to marked sedation can occur, Suicide risk especially within first 4 weeks of therapy Adverse Reactions: dry mouth, constipation, urinary hesitancy or retention, blurred vision, sedation, orthostatic hypotension, weight gain, nausea and vomiting, gynecomastia, and changes in libido Drug Interactions: (TONS) most significant drug interactions are those that increase the plasma level of the TCA and thereby increase the risk of cardiotoxicity, such as can occur with the concurrent use of SRIs, cannabis, and sympathomimetics. Hyperpyrexia can occur with MAOIs and TCAs Applicable Lab Tests: ECG should be done with QT correction and repeated after 3 weeks. Plasma levels can be assessed to assure delivery of an adequate dosage and to support patient adherence Neurotransmitters: serotonin and norepinephrine -more potently blocks reuptake of serotonin. It also has high affinity for histamine H1 and muscarinic M1 receptors Pregnancy Risk: “C” Risk cannot be ruled out Mechanism of Action: blocks reuptake of both serotonin and norepinephrine at presynaptic neuron, but more potently blocks reuptake of serotonin. It also has a high affinity for histamine H1 and muscarinic M1 receptors; compared with other cyclic antidepressants, amitriptyline is highly sedating, associated with weight gain, and anticholinergic side effects  Bupropion Common uses:  FDA Approval: Major Depressive D/O, Seasonal Affective D/O, Nicotine Addiction  Off Label: Bipolar Depression, ADHD, Sexual dysfunction MOA:  Blocks norepinepherine reuptake pump, thus increasing norepinepherine neurotransmission  Dopamine is inactivated by norepinepherine reuptake in the frontal cortex (where there are limited dopamine transmitters). Because of this, bupropion can increase dopamine in the frontal cortex. Additionally, the dopamine reuptake pump is blocked which increases dopaminergic neurotransmission.  Inhibits CYP450 2D6 Neurotransmitters:  Norepinepherine and dopamine Side Effects:  Dry mouth, constipation, nausea, weight loss, anorexia, myalgia, insomnia, dizziness, HA, abd pain, tinnitus, agitation, sweating, rash, hypertension  LIFE THREATENING SE: rare seizures, hypomania, induction of mania, activation of SI Drug interactions:  Tramadol-increases the r/o seizures  Can increase levels of TCAs  Use with caution with MAOIs  Increases r/o HTN if combined with nicotine replacement therapy  r/t 2D6 inhibition- can theoretically interfere with analgesic action of codeine, increase levels of beta blockers, and increase levels of atomoxetine, could increase thioridazine concentrations to deadly levels Labs/tests:  BP at baseline and periodically throughout treatment Pregnancy risk:  Not generally recommended for use during pregnancy, especially the first trimester.  Risk vs benefit is the determining factor in using bupropion during pregnancy.  Epidemiological studies don’t show increased r/o congenital malformations overall or of cardiovascular malformations.  Carbamazepine Common uses:  FDA Approval: Partial seizures with complex symptomatology, generalized tonic clonic seizures, mixed seizure patterns, pain associated with true trigeminal neuralgia, acute mania/mixed mania  Off Label: glossopharyngeal neuralgia, bipolar depression, bipolar maintenance, psychosis, schizophrenia MOA:  Use dependent blocker of voltage sensitive sodium channels.  Interacts at a specific site of the alpha pore-forming subunit of voltage sensitive sodium channels  Inhibits the release of glutamate Neurotransmitters:  Glutamate Side Effects:  Sedation, dizziness, confusion, unsteadiness, HA, N/V/D, blurred vision, benign leukopenia, rash  LIFE THREATENING SE: rare aplastic anemia, agranulocytosis, severe dermatologic reactions (SJS, pupura), rare cardiac complications, rare induction of psychosis or mania, SIADH, incraesed frequency of generalized convulsions, activation of SI Drug interactions:  Enzyme inducing antiepileptics (phenobarbital, phenytoin, primidone) may increase the clearance of carbamazepine and lower the plasma levels  3A4 inducers can lower the plasma concentrations  3A4 inhibitors (nefazodone, fluvoxamine, fluoxetine) can increase plasma levels  Can increase levels of clomipramine, phenytoin, and primidone  Can decrease levels of : tylenol, clozapine, benzos, dicumarol, doxycycline, theophylline, warfarin, haldol… as well as of other anticonvulsants.  Can decrease the level and effectiveness of hormonal contraceptives  Combined use with other anticonvulsants may lead to altered thyroid function  Combines use with Li may increase risk of neurotoxic effects  Depressive effects are increased by other CNS depressants Labs/tests:  Before starting treatment: Blood count, liver, kidney, and thyroid function  During treatment: Blood count q 2-4 wks for 2 mo, then q 3-6 mo throughout treatment, liver and kidney functions q 6-12 mo  COnsider monitoring sodium levels because of the possibility of hyponatremia  *those with Asian ancestry should consider testing for the presence of HLA-B*1502 allele- if present, they shouldn’t be treated with carbamazepine Pregnancy risk:  Use during the first trimester may increase risk of neural defects  For bipolar treatment carbamazepine should generally be discontinued before anticipated pregnancies  Citalopram (Celexa) Side effects Sexual dysfx (dose dependent), decreased appetite, nausea, diarrhea, constipation, dry mouth, insomnia, sedation, agitation, tremors, sweating, bruising, bleeding, hyponatremia (rare, mostly in elderly), SIADH Adverse effects RARE seizures, mania induction, activation of suicidal ideation Drug interactions Tramadol (seizures), Increase TCA, Serotonin syndrome when added with MAOIs (Don’t start MAOIs until 5-7 days after discontinuing drug), Increased risk of bleeding with NSAIDS warfarin, Increased risk of QT syndrome with taking CYP 450 2C19 i.e. cimetidine, Can increase levels of some beta blockers Relevant labs None Neurotransmitters serotonin and histamine Pregnancy risk Not recommended especially during 1st trimester; can lead to cardiac issues in fetus, Not been proven to be harmful to fetus, More bleeding at delivery and irritability/sedation of newborn, Taken during late pregnancy is associated with gestational HTN and preeclampsia; neonate can develop complications requiring hospitalization i.e. respiratory support, tube feeding, cyanosis, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hyponatremia, hyperreflexia, tremors, jitteriness, irritability and constant crying. Trace amounts found in breast milk MOA Boosts serotonin, Blocks serotonin reuptake, desensitizes serotonin receptors esp. serotonin 1A, and increases serotonergic neurotransmission autoreceptors Clomipramine Anafranil (Clomipramine) SRI, TCA, treats OCD Side effects Blurred vision, constipation, urinary retention, increased appetite, dry mouth, nausea, diarrhea, heartburn, unusual taste in mouth, wt gain, fatigue, weakness, dizziness, sedation, headache, anxiety, nervousness, restlessness, sexual dysfx, sweating Adverse effects paralytic ileus, hyperthermia, lowered sz threshold, orthostatic hypoTN, sudden death, arrhythmias, tachycardia, long QT, hepatic failure, EPS, increased ICP, rare induction of mania, rare activation of suicidal ideation and behavior suicidality drug interactions Tramadol- increased risk for SZ, MAOIs- serotonin syndrome, Do not start an MAOI for at least 5 half-lives (5 to 7 days for most drugs) after discontinuing clomipramine, Anticholinergic drugsparalytic ileus/hyperthermia, Fluoxetine, paroxetine, bupropion, duloxetine, and other CYP450 2D6 inhibitors-increase TCA concentrations, Fluvoxamine-decrease the conversion of clomipramine to desmethyl-clomipramine, and increase clomipramine plasma concentrations, Cimetidine-TCAs and cause anticholinergic symptoms, Phenothiazines or haloperidol- increase TCA, Clomiparmine- alter effects of antihypertensive drugs, TCAs with sympathomimetic agents may increase sympathetic activity, TCAs may inhibit hypotensive effects of clonidine, Methylphenidate-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 clomipramin Labs to order before prescribing Baseline ECG is recommended for patients over age 50/family Hx or cardiac history, BMI, glucose, lipid panel, Patients at risk for electrolyte disturbances (e.g., patients on diuretic therapy) should have baseline and periodic serum potassium and magnesium measurements Labs to order during treatment Weight and BMI during treatment; if they have gained >55 of initial weight consider switching to another antidepressant, Patients at risk for electrolyte disturbances (e.g., patients on diuretic therapy) should have baseline and periodic serum potassium and magnesium measurements Neurotransmitters NE, Serotonin Pregnancy risk Clomipramine crosses the placenta, Adverse effects have been reported in infants whose mothers took a TCA (lethargy, withdrawal symptoms, fetal malformations) Some drug is found in mother’s breast milk; Recommended either to discontinue drug or bottle feed Divalproex Major side effects: life threatening pancreatitis (black box warning), hepatotoxicity, SIADH, pancytopenia, thrombocytopenia, Steven-Johnson syndrome, psychosis, suicidality, hallucinations, encephalopathy, coma Adverse Reactions/a, n/v, asthenia, somnolence, thrombocytopenia, dyspepsia, dizziness, diarrhea, abd pain, tremor, alopecia, weight & appetite changes, constipation, nervousness, emotional liability, insomnia, peripheral edema, petechiae, tinnitus, abnormal gait, vision change, myalgia Drug Interactions:UGT1a4 substrate, UGT2B7 inhibitor, CYP1A2 inducer, antiepileptic agent. Interaction characteristics: antiplatelet effects, CNS depression, hyperammonoemia, hyponatremia Pregnancy Risk: Avoid in pregnancy if possible. Risk vs. benefits, Recommend folic acid supplementation in 1st trimester. Mechanism of Action: It may work by interfering with the voltage -sensitive sodium channels (vssc’s) by enhancing the inhibitory actions of y-aminobutyric acid (GABA), & regulating downstream signal transduction cascades, although it is not clear which action regulates mood. It may also interact with VSSC ion channels and indirectly block glutamate actions (Stahl, p 374) Labs: Valproic acid levels: in mania 50-125mcg/ml ; TOXIC level is over 175 mcg/ml. Draw lab just before morning dose. Steady state: 2-4 days. Also: LFTs at baseline, then frequently during 1st 6 months, cbc w diff coag studies at baseline, then periodically also before planned surgery. During pregnancy, serum drug levels; ammonia levels  Duloxetine  Common uses:  FDA Approval: Major depressive d/o, diabetic peripheral neuropathic pain, fibromyalgia, generalized anxiety d/o, chronic musculoskeletal pain  Off Label: stress urinary incontinence, neuropathic pain/ chronic pain MOA:  Boosts serotonin, norepinepherine, and dopamine  Blocks serotonin reuptake pump- which increases serotonin neurotransmission  Blocks norepinepherine reuptake pump- increasing norepinephrine neurotransmission  Desensitizes serotonin 1A receptors and beta adrenergic receptors  Because dopamine in inactivated by norepinephrine reuptake in the frontal cortex (which lacks a lot of dopamine transporters), duloxetine can increase dopamine  Weakly blocks dopamine reuptake pump and may increase dopamine neurotransmission Neurotransmitters:  Serotonin, norepinephrine, and dopamine Side Effects:  N.D, decreased appetite, dry mouth, constipation (dose dependent), insomnia, sedation, dizziness, sexual dysfunction, sweating, increase in BP, urinary retention  LIFE THREATENING SE: rare seizures, induction of hypomania, activation of SI Drug interactions:  Can increase TCA levels  Can cause fatal serotonin syndrome when combined with MAOIs  Possible increased r/o bleeding, especially when combined with anticoagulants  1A2 inhibitors (fluvoxamine) increase plasma levels of duloxetine  Smoking may reduce plasma levels of duloxetine (induces 1A2)  2D6 inhibitors (paroxetine, fluoxetine, quinidine) may increase plasma levels  Because of 1A2 inhibition could theoretically increase clearance of theophylline and clozapine  Because of 2D6 inhibition could interfere with analgesic actions of codeine and increase the levels of some beta blockers and atomoxetine  Because of 2D6 inhibition, could increase concentrations of thioridazine and cause dangerous arrhythmias Labs/tests:  BP before and during treatment Pregnancy risk:  Not generally recommended for use in pregnancy, especially in the first trimester  Continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus  Neonates exposed to SSRIs and SNRIs late in the third trimester have developed complications  Escitalopram Side effects:  Sexual Dysfunction  GI upset (decreased appetite, nausea, diarrhea/constipation)  CNS (insomnia but also sedation, agitation, Headache)  Autonomic (sweating)  Bruising and rare bleeding  Hyponatremia (mostly in elderly)  SIADH (syndrome of inappropriate antidiuretic hormone secretion) Adverse reactions: Rare: seizures, mania induction, activation of suicidal ideation and behavior. Drug Interactions:  Tramadol (seizures);  Serotonin syndrome when combined with MAOI (do not start MAOI until 5-7 days after d/c of escitalopram or at least 14 days after MAOI stopped)  increased risk of bleeding with anticoagulants (e.g., warfarin, NSAIDs);  NSAIDs may decrease effectiveness of SSRI. Do not take with Pimozide. No labs necessary. Mechanism of Action: Serotonin. Blocks serotonin reuptake pump (serotonin transporter); desensitizes Serotonin 1A autoreceptor, presumably increases serotonergic neurotransmission. Pregnancy risk: Not recommended during 1st trimester.  Fluoxetine Side effects:  Sexual Dysfunction  GI upset (decreased appetite, nausea, diarrhea/constipation)  CNS (insomnia but also sedation, agitation, Headache)  Autonomic (sweating)  Bruising and rare bleeding  Hyponatremia (mostly in elderly)  SIADH (syndrome of inappropriate antidiuretic hormone secretion) Adverse reactions:  Rare: seizures, mania induction, activation of suicidal ideation and behavior. Drug Interactions:  Tramadol (seizures); Serotonin syndrome when combined with MAOI (do not start MAOI until 5 weeks after d/c of fluoxetine or at least 14 days after MAOI stopped)  Increased risk of bleeding with anticoagulants (e.g., warfarin, NSAIDs); NSAIDs may decrease effectiveness of SSRI. Do not take with Pimozide (may cause QTc prolongation and dangerous cardiac arrhythmias)  Can increase TCA levels when switching to or from TCA; can increase levels of some beta blockers, codeine and atomoxetine via CYP2D6 inhibition, also increase thioridazine levels leading to dangerous cardiac arrhythmias;  May reduce the clearance of diazepam or trazodone; increase levels of alprazolam, buspirone, triazolam via CYP 3A4 inhibition; may increase levels of atorvastatin, simvastatin, lovastatin causing rhabdomyolysis via CYP 3A4. Labs: No labs necessary. Pregnancy risk: Not recommended during 1st trimester. Mechanism of Action: Works on Serotonin. Blocks serotonin reuptake pump (serotonin transporter); desensitizes Serotonin 1A autoreceptor, presumably increases serotonergic neurotransmission. Also has antagonistic property at 5HT2C receptors, which increase Norepinephrine and Dopamine neurotransmission.  Fluvoxamine (Luvox) o SSRI used for OCD, social anxiety, panic disorder, GAD, PTSD. Used for depression but not FDA approved  Dosage: o 100mg to 300mg OCD, 100mg to 200mg depression o Start at 50mg go up every 4-7 days, For CR start at 100mg go up 100 weekly o Discontinue taper to avoid withdrawal  Side effects o Insomnia and diarrhea, nausea, sexual dysfunction, constipation