Fluoxetine Sertraline Paroxetine Citalopram Escitalopram Fluvoxamine

SSRIs Mechanism Indications Side effects/toxicity

5-HT reuptake inhibitors Onset of action: 4-6 wks Indications Depression Anxiety disorders Bulimia Side effects Nausea/vomiting Sexual dysfunction Serotonin Syndrmoe

Venlafaxine Desvenlafaxine Duloxetine Milnacipran Sibutramine

SNRIs Mechanism Indications Side effects/toxicity

Inhibit serotonin & NE reuptake Indications Depression Anxiety disorders Pain from diabetic peripheral neuropathy Fibromyalgia Obesity Side effects Elevated BP Nausea

Fatigue Flashcards by Michelle Cancel

B.D. is a 50 YO male who has been feeling tired for the past 2-3 mo. The onset of tiredness is gradual. He can’t fall asleep at night b/c he is “thinking about stuff”. No matter how much he sleeps, he doesn’t feel energetic in the morning. He has stopped working out because of the lack of motivation and focal weakness & dyspnea. His mother committed suicide when he was 2 YO. Aside from obesity & trace ankle edema, he has a normal physical exam.

What are you thinking?

Depression

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What are some important questions you should be asking when a patient presents with fatigue?

What does low energy mean to patient?

Obtain a sleep history to determine if the patient is excessively sleepy during the day
Inquire about weakness/loss of physical strength
Explore of the patient has decreased exercise tolerance due to dyspnea on exertion
Ask about mood symptoms
Review medication list
Review chronic medical conditions in the PMH that can cause fatigue

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What is a typical physical exam of a patient with fatigue?

Pallor, tachypnea
BMI, neck circumference
Jaundice
Edema seen in CHF, CKD & liver disease
Pulmonary rales, displaced PMI, S3, JVD
Coarse hair, “hung up” reflexes, weight gain
Rash, synovitis of joints
Fever, lymphadenopathy, heart murmur

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What is the differential diagnosis of fatigue?

Psychiatric: depression/anxiety, substance abuse
Sleep disorder: OSA, insomnia
Endocrine: thyroid, DM, adrenal insufficiency
Medication: side effects
Heme/Onc: anemia, cancer
Infections: HIV, endocarditis, TB, Lyme
Chronic Systemic Diseases: heart, lung, kidney, liver, neuro, rheum

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What is the appropriate diagnostic studies for fatigue?

CBC
Sleep Study
BMP
LFTs
TSH & free T4
Cortisol
Echocardiogram
Age appropriate cancer screening
- Colonoscopy, mammogram
HgA1c
Pulmonary function tests
Rheumatoid factor, ANA, ESR, CRP
CXR
Cortisol
HIV
Urine Drug Screen

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What are the DSM-V criteria used to make the diagnosis of depression?

At least 5/9 symptoms, including depressed mood or anhedonia, lasting 2 weeks
SIG E CAPS
- Sleep disturbance
- Interest loss
- Guilt or worthlessness
- Energy loss or fatigue
- Concentration problems
- Appetite or weight change
- Psychomotor agitation or retardation
- Suicidal ideation

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What are some other diagnostic considerations with depressed patients?

Persistent depressive disorder (dysthmia)
- Chronic (2+ yrs) low grade (<5/9) depression
Seasonal affective disorder
- Reduced daylight in temperate regions
Substance induced depression
- Alcoholic
General medical condition
- Pancreatic cancer
Bipolar disorder
- Ask about past manic episodes
Normal grief/bereavement needs to be distinguished from depression

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A 31 YO presents c/o depression. Which of the following rules out the possibility of the patient having major depressive disorder?

She has recently gained weight
Her sleep pattern has changed so that she wakes up in the morning before her alarm rings
She reports being depressed since her miscarriage 2 yrs ago
She was hospitalized for mania 10 yrs ago
She reports feeling like a worthless person

She was hospitalized for mania 10 yrs ago

If a patient only has 1 manic episode, no matter how many major depressive episodes, she is bipolar

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What is the definition of a manic episode?

What are the common symptoms?

What is hypomania?

Distinct period of elevated, expansive or irritable mood & abnormally increased energy or activity lasting 1 wk
Symptoms
- Distractibility
- Irresponsible/hedonistic
- Grandiose
- Racing thoughts
- Psychomotor agitation
- Decreased neep for sleep
- Pressured speech
Hypomanic lasts 4 days, not impaired in functioning or psychotic, not hospitalized

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Upon completing the USMLE Step I a rising M3 runs out of the testing center shouting “I’m the smartest man in the world”. His roommate reports that for 2 wks he has stopped sleeping, been quite irritable & talks incessantly. He is brought in for evaluation after attempting to use his student loan money to buy a lamborghini. Which of the following is the most likely diagnosis?

Amphetamine intoxication
Bipolar disorder
Hyperthyroidism
Schizophrenia

Bipolar disorder

Meets criteria for manic episode

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What are the characteristics of normal grief/bereavement?

Minor weight loss
Minor sleep disturbance
Mild guilty feelings
Illusions, thinking saw loved on in a crowd of people
Attempts to return to work & social activities
Crying/expressing sadness
Symptoms improved in a couple months, resolved at one year
Anti-depressants not indicated
Shock & denial if unexpected

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What are the characteristics of complicated grief/depression?

Significant weight loss
Significant sleep disturbance
Intense feelings of guilt/worthlessness
Hallucinations or delusions of having contact w/ deceased person
Resumes few if any work or social activities
Contemplates or attempts suicide
Disabling symptoms for months, symptoms persisting after 1 year
Anti-depressants should be used
Failure to adjust to loss w/ changes in personality

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Your 75 YO male patient just lost his wife of 52 yrs to cancer. If he experiences normal bereavement/uncomplicated grief which of the following responses would be normal?

Initial loss of appetite w/ mild weight loss
Feelings of worthlessness
Threatening suicide
Intense disabling grief for the next 2 yrs
Feelings of hopelessness

Initial loss of appetite w/ mild weight loss

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Before you plan to administer pharmacotherapy to a diagnosed depressive patient, what else do you need to discuss & document in your note?

Documentation of Suicide Risk Assessment

Worst clinical outcome: suicide
Difficult to predict
Asking about suicidal ideation will not increase a patient’s risk or “give them the idea”
Failure to assess & document suicide risk assessment represents a significant malpractice risk

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What are the risk factors for completed suicide?

*women try more, men succeed more*

SAD PERSONS

Sex male (Caucasian at higher risk)
Age teenagers or elderly
Depression
Previous suicide attempts in patient or FaHx
Ethanol or other drug use/addiction or impulsivity
Rational thinking absent, command hallucinations
Sickness, chronic medical condition or pain, 3+ meds
Organized plan w/ means (ex: has a gun)
No spouse (divorced, widowed)
Social supporting lacking, no children, church or job

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Which statement encapsulates the highest risk factor for suicide completion?

His wife just left him on account of his drinking
He is an atheist w/ a gun
He is a 60 YO male police officer
He is feeling hopeless about his prostate cancer
He still walks w/ a limp after jumping off a bridge last year & you can see noose marks on his neck from his attempted hanging last week

Previous attempts is the biggest risk factor for suicide completion

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What are some important factors to consider when selecting anti-depressants?

Cost/insurance formulary
Ease of administration/dosing frequency
Side effect profile
Potential drug interactions
Co-morbid medical conditions
Other approved drug indications that may apply to your patient
Toxicity in overdose in suicidal patients
Drugs used by family members

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What are the SSRIs?

Fluoxetine
Sertraline
Paroxetine
Citalopram
Escitalopram
Fluvoxamine

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SSRIs

Mechanism
Indications
Side effects/toxicity

5-HT reuptake inhibitors
Onset of action: 4-6 wks
Indications
- Depression
- Anxiety disorders
- Bulimia
Side effects
- Nausea/vomiting
- Sexual dysfunction
- Serotonin Syndrmoe

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What is Serotonin Syndrome?

How is it treated?

What are the symptoms?

Symptoms
- High fever
- Autonomic instability
- Seizures
- Confusion
- Myoclonus
- Flushing
Treated with cyproheptadine
May result from combining SSRI with:
- MAOI, TCA, SNRI, meperidine, tramadol, St. John’s Wort

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What should you consider when you have a fatigue patient w/o improvement?

Reconsider your differential diagnosis
Use an objective measure to evaluate for improvement
- PHQ-9 Patient health questionnaire
- Hamilton Rating Scale for Depression
Search the medical literature for a randomized trial to guide your treatment

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What are the SNRIs?

Venlafaxine
Desvenlafaxine
Duloxetine
Milnacipran
Sibutramine

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SNRIs

Mechanism
Indications
Side effects/toxicity

Study These Flashcards

Inhibit serotonin & NE reuptake
Indications
- Depression
- Anxiety disorders
- Pain from diabetic peripheral neuropathy
- Fibromyalgia
- Obesity
Side effects
- Elevated BP
- Nausea

What are the TCAs?

Study These Flashcards

Amitriptyline
Nortriptyline
Imipramine
Desipramine
Clomipramine
Doxepin
Amoxapine

**TCAs** * Mechanism * Indications * Side effects/toxicity

* Block the reuptake of NE & SE * Indications * Depression * OCD * Nocturnal enuresis * Side effects * Sedation * Orthostasis * Tachycardia * Urinary retention * Dry mouth * Risk of seizures * Coma * Cardiac arrhythmia * Death (overdose)

\_\_\_\_\_\_\_\_\_\_ is a tricyclic antidepressant that inhibits the reuptake of NE more strongly than 5-HT.

**Nortriptyline**

What are the MAOIs?

* Tranlcypromine * Phenelzine * Isocarboxazid * Selegiline

**MAOIs** * Mechanism * Indications * Side effects/toxicity

* Increases the levels of amine NTs (NE, 5-HT, DA) by impairing degradation * Indications * Atypical depression * Anxiety * Side effects * Hypertensive crisis w/ tyramine ingestion & serotonin syndrome * Orthostasis * Weight gain

A 40 YO male c/o persistent depression w/ weight gain & hypersomnia. You prescribe tranylcypromine. A few days later he is in the ER with fever, tachycardia, myoclonus & confusion. BP 130/60. Which of the following does NOT explain his presentation? * He had recently been taking fluoxetine * He received meperidine during a colonoscopy * He was drinking merlot & eating parmesan * He took tramadol & cyclobenzaprine after throwing out his back moving a sofa * He uses amitriptyline for diabetic neuropathy

**He was drinking merlot & eating parmesan** Eating tyramine rich foods would lead to hypertensive crisis, not serotonin syndrome

**Buproprion** * Use * Mechanism * Side effects

* Approved for depression & smoking cessation * Increases NE & DA by inhibiting reuptake * Side effects * Insomnia * Headache * Seizures * No sexual side effects, unlike the serotonergic agents

A 13 YO female is brought into the ER with a seizure. On exam her BMI is 15, she has lanugo & is bradycardic. She states she has been taking a friend's anti-depressant for 1 wk to treat her low mood. Which drug has the girl most likely been taking? * Buproprion * Amitriptyline * Mirtazapine * Selegiline * Fluoxetine

**Buproprion** carries the risk of seizures, especially in patients w/ eating disorders

**Mirtazapine** * Mechanism * Side effects

* α2-antagonist that increases release of NE & serotonin, 5-HT₂ & 5-NT₃ receptor antagonist * Side effects * Sedation * Increased appetite * Weight gain * Dry mouth

**Lithium** * Use * Side effects

* Approved for bipolar mania * Side effects * Tremor * Hypothyroidism * Nephrogenic diabetes insipidus * Teratogenic (Ebstein's anomaly) * Acne * Leukocytosis * Narrow therapeutic window

**Buspirone** * Mechanism * Use * Side effects

* Serotonin receptor agonist * RDA approved for generalized anxiety disorder * Side effects * Dizziness * Drowsiness * Headache * Nausea

A 48 YO woman comes to your office complaining of fatigue & tiredness. No obvious abnormalities on physical exam. BP normal, BMI not increased, menopause at 45, normal fasting blood glucose. ## Footnote **What are the top 3 endocrine diagnoses?** **How would you test for them?**

* **Adrenal Insufficiency** * ACTH stimulation test * **Hypothyroidism** * TSH * **Hypercalcemia** * Comprehensive metabolic panel

Your patient has hypercalcemia, hypophosphatemia, hypercalciuria & elevated PTH. **What is the diagnosis?** **What are the treatments?**

**Primary Hyperparathyroidism** * Do nothing * Remove parathyroid tumor (surgery) * Cinacalcet (Sensipar)

What are the actions of PTH in the body? \*First Aid\*

* _Increases_ bone resorption of Ca²⁺ & PO₄^3- * _Increases_ kidney resorption of Ca²⁺ in distal convoluted tubule * _Decreases_ reabsorption of PO₄^3- in proximal convoluted tubule * _Increases_ 1,25-(OH)₂D₃ (calcitriol) production by stimulating kidney 1α-hydroxylase

# Fill in the blanks: GI Ca²⁺ absorption = \_\_\_\_\_% \_\_\_\_% in duodenum & jejunum Energy-dependent, cell-mediated process regulated by \_\_\_\_\_\_\_\_\_\_\_. Passive diffusional _________ pathway.

GI Ca²⁺ absorption = **20-70%** **90%** in duodenum & jejunum Energy-dependent, cell-mediated process regulated by **1,25(OH)₂D**. Passive diffusional **paracellular** pathway.

How does the calcium receptor on PTH-secreting cells operate?

* Increased serum Ca²⁺ normally decreases PTH * Elevated PTH in this patient means there is something wrong with the gland itself

PTH controls Ca²⁺ balance directly & indirectly through \_\_\_\_\_\_\_.

**1,25(OH)₂D**

What are the signs & symptoms of hypercalcemia?

* None * General * Fatigue & weakness * GI * Constipation * Nausea & vomiting * Abdominal pain (ulcers) * Bone * Osteoporosis * Renal * Polyuria & polydipsia * Renal stones * Neuro/cognitive * Impaired memory, confusion, depression * Drowsiness * Coma

What is the diagnostic evaluation of hypercalcemia?

* Patient history & review of old labs * Serum calcium * Albumin * Phosphorus * PTH * If low --\> PTHrP * 24 hr urine calcium & creatinine * Abdominal X-ray * Bone mineral density study

What are the differential diagnoses for Hypercalcemia?

* **PTH dependent** (high or inappropriately not suppressed) * Primary hyperparathyroidism * Familial hypocalciuric hypercalcemia * Parathyroid carcinoma (very rare) * **PTH independent** (low) * _Malignancy_ * Granulomatous disease * Vitamin D toxicity

What is the epidemiology of primary hyperparathyroidism?

* Common * 1/1,000 post-menopausal women * **F:M = 2:1** * 80-85% adenomas * 5-12% 2 or more adenomas * 8-15% hyperplasia * \<1% carcinomas

What are the Primary Hyperparathyroidism Familial Syndromes?

* MEN1 * MEN2 * Familial Hyperparathyroidism * Familial Hyperparathyroidism & jaw tumors

What is the pneumonic for primary hyperparathyroidism? \*First Aid\*

**"stones, bones, groans & psychiatric overtones"** * Hypercalcemia * Hypercalciuria (renal stones) * Weakness & constipation (groans) * Osteitis fibrosa cystica (bones) * Depression (overtones)

What are the indications for surgery in Primary Hyperparathyroidism?

* Symptomatic hypercalcemia * Calcium 1 mg/dl above upper limit of nl * Nephrolithiasis * Osteoporosis/Fragility fractures * Renal insufficiency * Age \<50 yrs * Patient preference

Why can patients w/ primary hyperparathyroidism have hypercalciuria if PTH increases calcium reabsorption? Why can they have hypophosphatemia?

Transport max for Ca²⁺ is saturated PTH inhibits phosphate absorption in the proximal tubule

What are the possible ways to do parathyroidectomy?

* Conventional neck exploration * Minimally invasive parathyroidectomy

Describe a minimally invasive parathyroidectomy

* Small incision * Local anesthesia * Must have preoperative localization * Ultrasound * 99m-technetium sestamibi * CT scan * Intraoperative parathyroid hormone monitoring * Need to see 50% decrease in PTH after removal of suspected adenoma

What is the medical management for hyperparathyroidism?

* Optimize hydration * Avoid calcium sparing diuretics * Normal calcium intake * Optimize vitamin D status * Potential use of a calcimimetic * Calcium sensing receptor agonist * **Cinacalcet** (Sensipar)

What are the mechanisms of hypercalcemia of malignancy?

* PTH related protein (PTHrP) * Osteolytic bone metastases * Unregulated 1,25-dihydroxy-vitamin D production * Osteoclast activating factors * Ectopic PTH (rare)

What is PTH related protein? Where is it found? Why is it important?

* N-terminal homology w/ PTH * Not measured by PTH assays * Found in normal tissues * May be important in fetal development * Chr 12 (PTH on 11)

What are the characteristics of **MEN 1**? (Wermer syndrome) \*First Aid\*

* **3 P's** * **P**arathyroid tumors * **P**ituitary tumors (prolactin or GH) * **P**ancreatic endocrine tumors (Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas) * Presentation: kidney stones & stomach ulcers

What are the characteristics of **MEN 2A**? (Sipple Syndrome) \*First Aid\*

* **2 P's** * **P**heochromocytoma * **P**arathyroid hyperplasia * Medullary thyroid carcinoma (secretes calcitonin) * *ret* gene mutation

What are the characteristics of **MEN 2B**? \*First Aid\*

* **1 P** = **P**heochromocytoma * Medullary thyroid carcinoma (secretes calcitonin) * Oral/intestinal ganglioneuromatosis (mucosal neuromas) * Associated w/ _marfanoid habitus_ * *ret* gene mutation

Fatigue Flashcards

(56 cards)