Pharmacology – Antidepressants

(Depression or OCD) is considered the most common mental illness.
Depression

Most antidepressants prevent neuronal reuptake of multiple neurotransmitters. SSRIs selectively inhibit reuptake of _______________ (serotonin or sodium).
serotonin

(Fluoxetine or Amitriptyline) is the prototype of serotonin reuptake inhibitors (SSRIs).
Fluoxetine

TCAs inhibit reuptake of ________________ (norepinephrine or monoamine oxidase).
norepinephrine

MAOIs prevent metabolism of neurotransmitters, _____________ (decreasing or increasing) the amount of neurotransmitters available to bind with receptors.
increasing

Antidepressant effects are believed to result from changes in the number and sensitivity of norepinephrine or serotonin __________________ (metabolites or receptors).
receptors

The patient taking an antidepressant should be instructed to expect that depressive symptoms will start to improve in:
A. 2-4 hours
B. 2-4 days
C. 2-4 weeks
D. 2-4 months
C. 2-4 weeks

MAO inhibitors should not be administered with SSRIs in order to avoid:
A. additive hypotensive effects
B. liver toxicity
C. sedation
D. serotonin syndrome
D. serotonin syndrome

Your client taking phenelzine (Nardil) should avoid eating:
A. eggs
B. aged cheeses
C. onions
D. strawberries
B. aged cheeses

When a patient has just started on antidepressant therapy, it is most important to monitor for:
A. social skills
B. suicidal thoughts
C. exercise routines
D. cigarette smoking
B. suicidal thoughts

You are taking care of a 70-year-old woman who is depressed and is on an SSRI. Which of the following will you monitor over the next 3 months?
A. blood glucose levels
B. smoking
C. visual disturbances
D. weight loss
D. weight loss

Fluoxetine (Prozac) should be taken in the morning to avoid which of the following side effects?
A. blurred vision
B. hypotension
C. insomnia
D. nausea
C. insomnia

Selective Serotonin Reuptake Inhibitors (SSRI)
escitalopram (Lexapro)
fluoxetine (Prozac, Prozac Weekly, Sarafem)
paroxetine (Paxil, Paxil CR)
sertraline (Zoloft)

Tricyclic Antidepressants (TCA)
amitriptyline (Elavil)
imipramine (Tofranil)

Monoamine Oxidase Inhibitors (MAOI or MAO inhibitors)
phenelzine (Nardil)
tranylcypromine (Parnate)

Others
bupropion (Wellbutrin, Zyban)
venlafaxine (Effexor)

Mood Stabilizer
lithium (Eskalith, Lithobid)

bipolar disorder
A mood disorder in which the person alternates between the hopelessness and lethargy of depression and the overexcited state of mania.

major depression
A severe form of depression that interferes with concentration, decision making, and sociability; A very serious mood disorder in which people lose interest in life and can no longer find enjoyment in anything

mania
A sympton of bi-polar disorders, it is characterized by an abnormally elevated mood, accompanied by a speeding up of thought processes and activities and an abnormally decreased need for sleep.

monoamine oxidase
A class of antidepressant drug that inhibits monoamine oxidase, which breaks down neurotransmitters, to increase levels of those neurotransmitters.

norepinephrine
Also known as noradrenaline, it is involved in controlling alertness and wakefulness and is implicated in mood disorders such as depression and mania. Adrenoceptor agonist prototype: acts at all alpha and at beta1 adrenoceptors; used as vasoconstrictor. Causes reflex bradycardia. Tox: ischemia, arrhythmias, HTN

serotonin
A neurotransmitter involved in sleep, wakefulness, appetite, aggression, impulsivity, sensory perception, temperature regulation, pain suppression, and mood. Lower levels = depression.

serotonin syndrome
-Rapid development of hyperthermia, hypertension, rigidity, autonomic instability, and mental status changes that can include coma and delirium; MAOI should not be administered with SSRI’s or potent TCA’s due to development of this condition, Fever > 102, change in mental status, agitation, confusion, restlessness, flushing, diaphoresis, myoclonus (muscle twitching or jerks), tremors

tyramine
Indirectly acting sympathomimetic prototype: releases or displaces norepinephrine from stores in nerve endings. Usually inactive by the oral route because of high first pass effect but will cause potentially lethal hypertensive responses in patients taking MAO inhibitors; Adrenergic, indirect agonist

Depression
– Etiology unknown; 2 major theories
– Deficiency of norepinephrine and/or serotonin & change in receptors (monoamine neurotransmitter dysfunction)
– Excessive secretion of hypothalamic corticotropin-releasing factor (CRF) & change in cortisol receptors (neuroendocrine theory)
– Other factors: genetic, environmental

Antidepressants
– 3 main groups used to treat major depressive disorders
– Selective serotonin reuptake inhibitors (SSRI)
– Tricyclic antidepressants (TCA)
– Monoamine oxidase inhibitors (MAOI)
– A 4th group is now available, Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
– See chart p. 178-179 – dosage and indications for use in adults and children

All Antidepressants
– Increase availability of serotonin and/or norepinephrine at synapses in brain, producing changes in # and sensitivity of receptors
– Effective in relieving depression
– Differ in adverse effects
– Administered orally
– Undergo first pass metabolism in liver, excreted by kidneys
– Therapeutic effects seen after administration for 2-4 weeks
– Interact with each other

SSRIs
Examples: fluoxetine (Prozac), sertraline (Zoloft)

– Drugs of first choice for treatment of depression
– Better tolerated than TCAs; usually taken once daily PO
– Mech of Action
– Block reuptake of serotonin into pre-synaptic nerve endings,
increasing serotonin level at synapse
– Adverse effects:
– Nausea, vomiting, weight loss, sexual dysfunction (decreased
libido, difficulty achieving orgasm), nervousness, insomnia
– Serotonin syndrome – often from drug interaction
– Increased risk of GI bleeding – avoid using with NSAID,
aspirin, warfarin
– Contraindications:
– Hypersensitivity to drug, use of MAOI within last 14 days

TCAs
Examples: amitriptyline (Elavil), imipramine (Tofranil)

– 2nd line drugs for treatment of depression
– Poor choice for suicidal patient – OD lethal
– Mech of Action:
– Block reuptake of norepinephrine & serotonin at nerve endings
– Adverse Effects:
– Sedation, orthostatic hypotension, anticholinergic effects, weight gain, impotence, cardiac conduction disturbances
– Other indications for use:
– Short-term treatment of enuresis in children > 6 years
– Anxiety disorders
– Neuropathic pain
– Contraindications:
– Hypersensitivity to drug; within 14 days of MAOI; pregnancy; seizures; severe renal, hepatic, or heart disease; glaucoma; acute schizophrenia

MAO inhibitors
Examples: phenylzine (Parnate), tranylcypromine (Nardil)
– 3rd line drugs for treatment of depression
– For patient not responsive to other antidepressants
– Many food and drug interactions
– Mech of Action:
– Inhibit production of monoamine oxidase (MAO), an enzyme that breaks down serotonin and norepinephrine
– Adverse Effects:
– Anxiety, agitation, orthostatic hypotension, anticholinergic effects, weight gain
– Avoid tyramine rich foods: aged cheese, bananas, figs, chianti, (risk of severe hypertension); OTC adrenergic cold medications; CNS stimulants; SSRIs; TCAs; meperidine; buspirone (BuSpar)

Bupropion – Do not confuse with buspirone!
(Wellbutrin, Wellbutrin SR, Zyban)
– Miscellaneous antidepressant
– Also marketed as Zyban (sustained-release form) – for smoking cessation
– Mech of Action:
– Inhibits reuptake of dopamine, NE, serotonin at nerve endings in CNS
– Adverse Effects:
– Seizures (in clients with seizure disorders), dry mouth, headache, N/V, anxiety, insomnia, constipation
– Less CV effects, no sexual side effects
– Contraindications:
– Hypersensitivity to drug; seizure disorder; anorexia nervosa; bulimia; concurrent use with MAOI

Mood-Stabilizing Agent
lithium carbonate (Eskalith, Lithobid)
– Indic for use:
– Bipolar disorder, to treat & prevent manic phase
– Mech of Action:
– Unknown; increased activity of GABA, stabilizes nerve sensitivity by altering Na ion transport in nerve cells
– Excreted unmetabolized by kidneys
– Reabsorbed by kidney in exchange for Na
– Low Na levels, increased lithium reabsorption and risk of toxicity
– Narrow therapeutic range
– 0.5 – 1.2 mEq/L *** NORMAL RANGE
– Dose based on serum lithium levels
– Monitored 2 – 3 times/week initially; maintenance q 3 months
– Draw levels 12 hours after last dose
– Lower doses needed for: older adults, those on diuretics, low salt diet, or with renal impairment
– Adverse Effects:
– Metallic taste, hand tremors, nausea, polyuria, muscle weakness, edema, weight gain, reversible leukocytosis (elevated WBC count)
– Elevated drug levels – vomiting, diarrhea, ataxia, dizziness, muscle twitching
– Toxicity (drug levels > 2.5 mEq/L)
– Nystagmus, tremors, confusion, oliguria, hallucinations, convulsions, coma, death
– Safe use guidelines: see p. 183

Nursing Implications
Assess:
– signs & symptoms of depression (agitation, feelings of worthlessness, decreased pleasure)
– risk for suicide
– support system
– coping mechanisms
– TCA – obtain baseline and follow-up EKG’s, monitor drug levels
– Lithium – obtain baseline renal, cardiac, and thyroid function studies; electrolyte levels. Monitor serum Na levels during treatment
– Obtain baseline vital signs, weight
– Check for drug interactions – many!
– Observe for worsening depression, or suicidal ideation or tendencies
– Provide for safety, check for orthostatic hypotension
– Generally, give TCAs at bedtime, SSRIs in AM; give lithium with meals
– Signs of lithium toxicity – withhold dose and contact physician
– Teach patient – do not stop abruptly, (esp. drugs with short half-life) to avoid withdrawal symptoms
– Do not take St. John’s Wort – interacts with antidepressants – may result in severe hypertension
– See p. 172 Patient Teaching; & p. 188 – 191

escitalopram (Lexapro)
SSRI, Antidepressant, This drug may be used for GAD (generalized anxiety d/o) as well as depression., MOA: Increases availability of serotonin at postsynaptic receptor sites in CNS, Minimal interaction, sedation and weight gain. Possible initial anxiety, least side effects, well tolerated, Its SSRI for Depression, and Generalized anxiety, or social anxiety, causes 3 S’s and this one specifically can cause ejaculatory disorders, nausea, sweating, fatigue, and Somnolence, Serotonin syndrome, Suicide risk, Sexual dysfunction, Headache, dizziness, Sleep disruption

fluoxetine (Prozac, Prozac Weekly, Sarafem)
SSRI, Antidepressant, Less ANS adverse effects and cardiotoxic potential than tricyclics. Tox: CNS stimulation, sexual dysfunction, seizures in overdose, serotonin syndrome.

paroxetine (Paxil, Paxil CR)
Antidepressant, Which SSRI has the most anticholinergic side effects & is most commonly associated with sexual side effects?, GAD, OCD, PTSD, Panic disorders, social anxiety disorder (SAD), ejaculatory disorders, nausea, sweating, fatigue, and Somnolence, Serotonin syndrome, Suicide risk, Sexual dysfunction, Headache, dizziness, Sleep disruption

sertraline (Zoloft)
Antidepressant – SSRI, MOA: block reuptake of serotonin in pre-synaptic space, Obsessive-compulsive disorder (OCD), I:depression, enuresis, PTSD, anxiety, OCD, Drug used for the treatment of depression, anxiety, and PTSD, 1. Few drug interactions, well-tolerated

amitriptyline (Elavil)
Antidepressant, TCA which can cause cardiac arrhythmias, Tricyclic Antidepressant, TCA widely used in the treatment of chronic pain and migraine prophylaxis?, A first line drug for Peripheral Neuropathy, Depression. In young adults and kids suicidal ideation may be worse. Gradually decrease dosage. s/s: n/v/constipation, difficulty urinating, pain in hands and feet, sweating, appetite and weight changes.

imipramine (Tofranil)
Tricyclic Antidepressant, Oldest TCA. Effective in childhood enuresis. Caution with children, CV effects. More effective than newer antidepressants., S:Imipramine (Tofranil), Anticholinergic, Sedation, Weight gain, MOA: block reuptake of NE and 5HT (serotonin), First choice for major depression

phenelzine (Nardil)
MAOI antidepressant, MAOI; last choice for Tx depression; SE = HTN crisis (w/ tyramine), serotonin syndrome, Irreversible Monoamine Oxidase Inhibitor = antidepressan, MAOI ANTIDEPRESSANT. Used to manage symptoms not responsive to other antidepressant meds. Drug effects may persist 2-3 weeks after discontinued. Abrupt withdrawal = rebound hypertension. Side effects are constipation, nausea, other GI symptoms, suicidal ideation may increase, interacts with TYRAMINE-containing foods. Tyramine elevates BP and can cause hypertensive crisis. Start with lowest dose possible. Should not be taken with other sympathomimetic drugs, can lead to hypertensive crisis. Chocolate and caffeine can cause hypertension.

tranylcypromine (Parnate)
MAOI antidepressant, Depression. Blocks the action of the enzyme that breaks down the bodys moodelevating chemical, Inhibits the enzyme monoamine oxidase which breaks down the MAO neurotransmitter including serotonin and NE. Efficacy is similar to other antidepressants but dietary restrictions and potential drug interactions make this drug less desirable. Insomnia, nausea, agitation, and confusion can all result. Potential for hypertensive crisis or serotonin syndrome with concurrent use of other antidepressants, contraindicated with people taking other antidepressants, tyramine rich foods could bring hypertensive crisis, many drug interactions.Lag period 2-4 weeks, monitor BP, LFT’s, suicide precautions, teach interaction

bupropion (Wellbutrin, Zyban)
Atypical Antidepressant, Inh Dopamine reuptake; tx: depression, ADHD, smoking cessation; less sexual dysfunction; CI: pts w/ seizures or head trauma, Atypical antidepressant; acts as a stimulate and suppresses appetite; antidepressant effects begin in 1 to 3 weeks; does not affect serotonergic, cholinergic, or histaminergic transmission; does not cause weight gain; similar structure to amphetamines; increases sexual desire and pleasure; many uses, Energizing, few sexual side effects, less weight gain. Can cause seizures at high doses. Possible increase in anxiety and insomnia

venlafaxine (Effexor)
SNRI(Serotonin-Norepinephrine Reuptake Inhibitors), Antidepressant, Action: SNRIs->prevent reuptake of 5-HT and NE. Inhibits 5-HT more than NE, A cross between TCA’s and SSRI’s. Has been shown to have high efficacy in treatment of GAD (General Anxiety Disorder) and depression. Side effects are similar to SSRI’s (it can also increase BP)., Name the prototype drug-of-choice to treat generalized anxiety disorder (or depression, panic disorder/PTSD or social phobia), Caution in pts with cardiovascular disease, ECG monitored recommended

lithium (Eskalith, Lithobid)
Antimanic, Drug Treatment for Bipolar Disorders, Mood Stabilizers, prevent or control mania, NT stabilization, inhibits excitatory NT (NE, DA), Enhances 5HT to help with depression, used for acute maina, bipolar depression. Narrow toxic range, renal elimination, 1-3 weeks to see effect, intentional tremor, weight gain, polyuria, polydipsia, interacts with OTC and caffeine, take 2 to 3 times a day, salt intake should remain constant during treatment, treating bipolar (manic-depressive) disorder, acute mania and prophylaxis of unipolar and bipolar disorder. Only mood stabilizer that has consistently shown to decrease the risk of suicide for bipolar patients, Antimanic, mood stabilizing agent. Side Effects: Drowsiness, dizziness, headache, dry mouth, thirst, GI upset, Nausea/Vomiting, fine hand tremors, hypotension, arrhythmias, pulse irregularities, polyuria, dehydration, weight gain, Alters sodium transport in nerve and muscle cells by inhibiting the phosphoinositol cascade. Its antimanic effects may be the result of increased reuptake of norepinephrine. Some say it “effects shift toward intraneuronal metabolism of catecholamines.” What to know is that it affects neuronal signaling cascades, likely involving cAMP (RS), Excreted unmetabolized by kidneys, Reabsorbed by kidney in exchange for Na, Low Na levels, increased lithium reabsorption and risk of toxicity, Narrow therapeutic range = 0.5 – 1.2 mEq/L, Dose based on serum lithium levels, Monitored 2 – 3 times/week initially; maintenance q 3 months, Draw levels 12 hours after last dose, Lower doses needed for: older adults, those on diuretics, low salt diet, or with renal impairment, Adverse Effects:, Metallic taste, hand tremors, nausea, polyuria, muscle weakness, edema, weight gain, reversible leukocytosis (elevated WBC count), Elevated drug levels – vomiting, diarrhea, ataxia, dizziness, muscle twitching, Toxicity (drug levels > 2.5 mEq/L), Nystagmus, tremors, confusion, oliguria, hallucinations, convulsions

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