NURSING 101 Pharmacology Depression STUDY GUIDE.

Pharmacology Depression Depression Mood Disorder: Depression Areas of the Brain Affected by Depression and the symptoms that they mediate include the following: • Hippocampus: memory impai rments, feelings of worthlessness, hopelessness, and guilt • Amygdala: anhedonia, anxiety, reduced motivation • Hypothalmus: increased or decreased sleep and appetite; decreased energy and libido • Other limbic structures: emotional alterations • Frontal Cortex: depressed mood; problems concentrating • Cerebellum: psychomotor retardation/agitation Antidepressant Medications: • Elevate the mood • Alleviate other symptoms associated with moderate to severe depression • Selected agents are used to treat anxiety d/o, bulimia nervosa, & premenstural dysphoric d/o • May take 2-4 weeks for patient to see symptom relief Neurotransmitters • Antidepressants work to increase the concentration of serotonin, norepinephrine, and /or dopamine in the body. • Although other neurotransmitters have been implicated in the pathophysiology of depression, disturbances in serotonin and norepinephrine have been the most extensively studied. Action of Antidepressant Medications • Psychopharmacology – Action • TCAs, heterocyclics, SSRIs, SNRIs – Block reuptake of norepinephrine, serotonin, and/or dopamine by blocking the presynaptic reuptake of the neurotransmitters or block receptors at nerve endings • MAOIs – inhibit the enzyme monamine oxidase (MAOI’s), monamine oxidase is an enzyme that is known to inactivate the monamines: serotonin, norepinephrine, and dopamine Side Effects are R/T their specific neurotransmitter receptor-blocking action • Blockade of norepinephrine reuptake results in side effects of tremors, cardiac arrhythmias, sexual dysfunction, and hypertension • Blockade of serotonin reuptake results in side effects of GI disturbances, increased agitation, and sexual dysfunction • Blockade of dopamine reuptake results in side effects of psychomotor activation • Blockade of acetylcholine results in dry mouth, blurred vision, constipation, and urinary retention. • Blockade of histamine reuptake results in sedation, weight gain, and hypotension Classification of Antidepressants • Tricyclic and tetracyclic (TCA) • Atypical Antidepressants (Heterocyclics) – Serotonin Norepinephrine Reuptake Inhibitors (SNRI) – Norepinephrine & Dopamine Reuptake Inhibitors (NDRI’s) • Selective Serotonin Reuptake Inhibitors (SSRI) • Monamine Oxidase Inhibitors (MAOIs) Tricyclic Antidepressants Marketed in the 1950’s Tricyclic antidepressants: block the reuptake serotonin and norepinephrine from going back into the nerve cell thus increasing availibility of these neurotransmitters in the brain. TCA’s also block the action of acetylcholine (causing anticholineric effects) and histamine (causing sedation) Tricyclic Antidepressants (TCA’s) • Amitriptyline (Elavil) • Amoxapine (Ascendin) • Clomipramine (Anafranil) • Desipramine (Norpramin) • Doxepin (Sinequan) • Imipramine (Tofranil) • Nortriptyline (Aventyl; Pamelor) • Protriptyline (Vivactil) • Trimipramine (Surmontil) Tricyclic Antidepressants – Side effects • Anticholinergic effects; dry mouth, blurred vision, urinary retention, constipation • Sedation • Orthostatic hypotension • Cardiac problems: arrhythmias, tachycardia, changes in AV conduction • GI distress: nausea, vomiting • Weight gain • Lowers seizure threshold • Photosensitivity • Blood dyscrasias • Exacerbation of Mania TCA’s are contraindicated in the acute recovery phase following MI , in individuals with angle-closure glaucoma and with concomitant use of MAOIs. TCAs • Tricyclic antidepressants (TCAs) should not be prescribed for patients at risk for suicide because lethal doses are only three to five times the therapeutic dose, and more than 1 g of a TCA is often toxic and may be fatal. • Death may result from cardiac arrhythmia, hypotension, or uncontrollable seizures. TCA’s Off Label Uses (non-FDA approved) • Panic disorder • Bulimia • Chronic pain (migraine, tension h/a, diabetic neuropathy, post herpetic neuralgia) • Phantom limb pain • Chronic itching • Premenstrual symptoms Interactions (with tricyclics) • Psychopharmacology – Interactions (tricyclics) • Increased effects of tricyclics with bupropion, cimetidine, haloperidol, SSRIs, and valproic acid • Decreased effects of tricyclics with rifamycin, carbamazepine, and barbiturates • Hyperpyretic crisis, convulsions, and death can occur with MAO inhibitors • Hypertensive crisis can occur with clonidine • Decreased effects of levodopa and guanethidine • Potentiation of pressor response with direct-acting sympathomimetics Atypical (Heterocyclic) Antidepressants Became available 1980’s Can affect one or two of the 3 neurotranmitters: serotonin, norepinephrine, dopamine Blocks serotonin and norepinephrine reuptake, and also are weak inhibitor of dopamine Meds: • Bupropion (Zyban, Wellbutrin) • Maprotiline (Ludiomil) • Mirtazapine (Remeron) • Trazadone (Desyrel) • Nefazodone (Serzone) Atypical (Heterocyclic) Antidepressants Side Effects • anticholinergic effect • Hypotention • Cardiotoxicity • insomnia/agitation • GI distress • dry mouth • Sedation • Dizziness • Tachycardia • headache • N/V, constipation • priapism (trazadone), • Seizures (Wellbutrin) • hepatic failure (warning with nefazodone/Serzone) • NMS and tardive dyskinesia (with amoxapine/Ascendin) Atypical Antidepressants Heterocyclics Serotonin & Norepinephrine Reuptake Inhibitors (SNRI’s): block the reuptake of serotonin and norepinephrine in the brain Side effects: Nausea, dry mouth, constipation, difficulty urinating, tremors, dizziness, somnolence, insomnia, headache, sexual dysfunction, palpitations, agitation/anxiety, Meds: • Venlafaxine (Effexor, Effexor XR), • Duloxetine (Cymbalta) • Desvenlafaxine (Pristiq) Norepinephrine & Dopamine Reuptake Inhibitors (NDRI’s): Norepinephrine & Dopamine Reuptake Inhibitors (NDRI’s): blocks the reuptake of norepinephrine and dopamine. Side Effects: anticholenergic effect, seizures, insomnia/agitation Meds: • Buproprion (Wellbutrin, Wellbutrin SR and XL) • Zyban Monoamine Oxidase Inhibitors • The enzyme monoamine oxidase (MAO) inactivates norepinephrine, dopamine, epinephrine, and serotonin. By inhibiting monoamine oxidase, the levels of these neurotransmitters rise. Monoamine Oxidase Inhibitors Danger of inhibiting monoamine oxidase – Hypertensive Crisis • Tyramine • Foods and medications to be avoided(Townsend pg 411) • Marked HTN with severe headache, stiff neck, photophobia, palpitations Side effects: dizziness, headache, orthostatic hypotention, constipation, N/V, dry mouth, tachycardia, palpitations, hypomania Meds: ▪ Isocarboxazid (Marplan) ▪ Phenelzine (Nardil) ▪ Tranylcypromine (Parnate) ▪ Selegiline Transdermal system (Emsam) Tyramine Containing Foods • Psychopharmacology – Avoid foods and medications high in tyramine when taking MAOIs. These include Aged cheese Caviar Wine; beer Raisins Chocolate; colas Pickled herring Coffee; tea Yeast products Sour cream; yogurt Broad beans Smoked and processed meats Soy sauce Beef or chicken liver Cold remedies Canned figs Diet pills Alert: MAOI’s • Ginseng, ephedra, ma-huang, and St. John’s wort may lead to palpitations, heart attack, and hypertensive crisis when taken with antidepressant MAOIs • Ginseng may lead to manic episodes when given in combination with MAOIs such as tranylcypromine sulfate. • An excessive dose of anise may interfere with MAOIs. • An increase use of brewer’s yeast with MAOIs can increase blood pressure. Interactions (MAOIs) • Psychopharmacology – Interactions (MAOIs) • Hypertensive crisis with amphetamines, methyldopa, levodopa, dopamine, epinephrine, norepinephrine, reserpine, vasoconstrictors, or foods with tyramine • Hypertension, hypotension, coma, convulsions, and death with narcotic analgesics • Additive hypotension with antihypertensives • Additive hypoglycemia with antihyperglycemic agents • Potentially fatal reactions with all other antidepressants, carbamazepine, buspirone, sympathomimetics, tryptophan, dextromethorphan, CNS depressants, and amphetamines (avoid use within 2 weeks of each other) Selective Serotonin Reuptake Inhibitors • SSRI’s (selective serotonin reuptake inhibitors) block the reuptake of serotonin into the nerve terminal of the CNS, so there is more serotonin at the serotonergic synapse • Citalopram (Celexa) SSRI’s • Escitalopram (Lexapro) • Fluoxetine (Prozac, Sarafem) • Fluxoxamine (Luvox) • Paroxetine (Paxil, Paxil CR) • Sertraline (Zoloft) • Vilazodone (Viibryd) also acts as a partial serotonergic agonist • Vortioxetine (Brintellix) Psychotherapeutic Combinations • Symbyax= fluoxetine (Prozac) combined with olanzapine (Zyprexa) • Limbitrol= Chlordiazepoxide (Librium) and fluoxetine (Prozac) • Etrafon= Perphenazine (Trilafon) and amitriptyline (Elavil ) SSRI Side Effects • Nausea • Dry mouth • Headache • Diarrhea • Nervousness, agitation or restlessness • Sexual dysfunction • rash • Increased sweating • Weight gain • Drowsiness • Insomnia Interactions (SSRIs) • Toxic, sometimes fatal, reactions have occurred with concomitant use of MAOIs • Increased effects of SSRIs with cimetidine, L-tryptophan, and lithium • Concomitant use of SSRIs may increase effects of hydantoin, tricyclic antidepressants, benzodiazepine, beta-blockers, carbamazepine, clozapine, haloperidol, phenothiazine, St. John’s wort, sumatriptan, sympathomimetics, tacrine, theophylline, and warfarin • Concomitant use of SSRIs may decrease effects of buspirone and digoxin • Many SSRIs have an interaction with grapefruit juice that can lead to possible toxicity • Serotonin syndrome can occur with concurrent use of other drugs that increase serotonin Serotonin Syndrome (SS) • SSRI’s and SNRI’s increase the availability of 5- HT (serotonin) which relieves depression but can also cause the hyper-sertonergic state known as Serotonin Syndrome. Serotonin Syndrome (SS) cont… SS develops very quickly and is characterized by: • Mental changes i.e. agitation, confusion, or hypomania • Altered muscle tone i.e. hyperreflexia, rigidity, twitching, or tremor • Autonomic changes i.e. hyper or hypotension, tachycardia, or diaphoresis • CNS changes i.e. incoordination, coma, or seizures • Hyperthermia with temperatures as high as 101 F to 107 F (30 C to 41.6 C) Mnemonic Serotonin Syndrome: HARMED • Hyperthermia • Autonomic instability • Rigidity • Myoclonus • Encephalopathy • Diaphoresis Serotonin Syndrome (SS) Treatment cont… Treatment is supportive: • Controlling hyperthermia with antipyretics and cooling devices • Treating muscle rigidity and twitching with clonazepam (Klonopin), benztropine (Cogentin), and lorazepam (Ativan) • Anticonvulsants for seizures secondary to serotonin syndrome Proposed Criteria:SSRI Discontinuation Syndrome:d/c or reduction in dose of SSRI after a period of use of at least 1 mo. Two or more of the following symptoms develop within 1-7days of d/c or reduction: • Dizziness, lightheadedness, vertigo, or feeling faint • Nausea and/or emesis • Headache • Tremor • Fatigue • anxiety • Shock like sensations (paresthesias) • Insomnia • Irritability • Diarrhea • Gait instability • Visual disturbances Symptoms cause significant distress or impairment in social, occupational functioning Symptoms not due to medial condition Mnemonic Antidepressant Discontinuation Syndrome: FINISH • Flu-like symptoms • Insomnia • Nausea • Imbalance • Sensory Disturbances • Hyperarousal (anxiety/agitation) • ALL ANTIDEPRESSANT MEDICATIONS SHOULD BE TAPERED GRADUALLY TO PREVENT WITHDRAWAL SYMTPOMS Contraindications/precautions for Antidepressants – Contraindicated in known hypersensitivity (SSRIs, MAOIs, tricyclics); acute phase of recovery from myocardial infarction; angle-closure glaucoma (tricyclics); and concomitant with MAOIs (TCAs, heterocyclics, SSRIs, SNRIs) – Caution with elderly or debilitated patients; patients with hepatic, cardiac, or renal insufficiency; psychotic patients; patients with benign prostatic hypertrophy; and those with history of seizures (tricyclics, MAOIs) Monitor patient for the following side effects • Psychopharmacology – Side effects • May occur with all chemical classes – Dry mouth, sedation, nausea – Discontinuation syndrome with abrupt withdrawal • Most commonly occur with tricyclics and heterocyclics – Blurred vision, constipation, urinary retention, orthostatic hypotension, reduction of seizure threshold, tachycardia, arrhythmias, photosensitivity, weight gain Monitor patient for the following side effects • Psychopharmacology – Side effects • Most commonly occur with SSRIs and SNRIs – Insomnia, agitation, headache, weight loss, sexual dysfunction, serotonin syndrome • Most commonly occur with MAOIs – Hypertensive crisis – Application site reactions (transdermal system) • Miscellaneous side effects – Priapism (with trazadone) – Hepatic failure (with nafazodone-rare but FDA D/C in USA and Canada) Patient/Family Education • Continue medication even though symptoms have not subsided, can take up to 4 weeks for therapeutic effect • Use caution when driving or operating machinery • Do not discontinue abruptly :SSRI withdrawal (N, vertigo, insomnia, h/a, malaise, nightmares, return of prescribed symptoms) • Rise slowly: orthostatic hypotension ; report to MD all side effects, notify MD priapism/go to ED • Monitor diet if prescribed MAOI: hypertensive crisis • Avoid alcohol can potential effects of meds • Do no double up if missed dose: serotonin syndrome (changes in mental status, restlessness, myoclonus, hyper-reflexia, tachycardia, labile BP, diaphoresis, shivering, tremors • Be aware of risks if pregnant • Wear sunblock/sunglasses photosensitivity Caution All antidepressants carry an FDA black box warning for increased risk of suicidality in children and adolescents. As these drugs take effect, and mood begins to lift, the individual may have increased energy with which to implement a suicide plan. The nurse should be particularly alert to sudden lifts in mood. The End!! Show Less