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Treatment for Mr. McCracken

Jimmy McCracken, 62 yo Male

Chief Complaint

“I'm up four or five times a night feeling that I have to urinate, and then when I get to the bathroom all I do is dribble. I'm very lightheaded when I stand up, and sometimes I don't make it to the bathroom in time. I have a girlfriend now, but I am finding it difficult to be intimate with her. Also, going to the bathroom all night is really impacting my love life."

“I’m experiencing frequency to urinate throughout the night and its impacting my life.”

HPI

Jimmy McCracken is a 62-year-old man, with a long-standing history of UTIs. He has a history of urosepsis requiring hospitalization. He is being evaluated because of complaints of worsening urinary hesitancy, nocturia, and dribbling. He also has a new complaint of ED.

We are going to do a 3rd line treatment

  • Continue Glyburide/Metformin
  • Terazosin (increased to 20 mg)
  • Finasteride (5mg)
  • Vacuum assisted device if impotence continues on the 2 week f/u
  • Stop ibuprofen
  • (b/c + Guaiac test)
  • Add acetaminophen
  • (max 3g daily)
  • Stop saw palmetto
  • Add Pygeum africanum
  • Stop TCA
  • Stop Claritin

Physical Exam

ROS

GEN - White Obese male in NAD; well-kept appearance; A & O x 3

VS - BP 110/60, P 85, RR 18, T 37°C (98.6F); Wt 115.2 kg(253.9#), Ht 6'0″ BMI 34.4

SKIN - Vertical scars on neck and lower back from laminectomies

HEENT - PERRLA; EOMI; TMs WNL; nose and throat clear w/o exudate or lesions

NECK/LYMPH NODES - Supple w/o LAD or masses; thyroid in midline

Head: (+) HA

CV:(+)lightheadedness

Throat: (-)dysphagia

GI:(-)dyspepsia (-) abd pain, (-)hematemesis,

GU:(+)frequency,(+)nocturia,(+)incontinence→ BPH, (-)rectal bleeding,

Repro:(+)impotence, (+) 1 new partner,

LUNGS/THORAX - CTA, distant sounds

CV - RRR w/o murmurs

ABD - Soft, NTND w/o masses or scars; (+) BS

GENIT/RECT - Testes , penis circumcised w/o DC; guaiac (+) stool

MS/EXT - Neurovascular intact;

distal pulses 1–2+

NEURO - DTRs 2+; CNs II–XII

grossly intact

PMH

Family History

  • Father died of massive MI at age 78
  • Mother died of natural causes at age 91

Social History

  • HTN
  • Laminectomy- 10 years ago
  • BPH with urge incontinence
  • Chronic UTIs
  • Type 2 DM (well controlled with glyburide/metformin)
  • ED
  • Obesity
  • Hx headaches
  • Osteoarthritis
  • Allergies to medication?

High school graduate worked for 35 years in a grocery store; retired 7 years ago. Married once. Wife deceased 6 months ago (stroke); one daughter, two granddaughters. Lives alone but is socially active. Recently started dating a 59-year-old woman he met through his square-dancing group. Patient is emphatic about maximizing the use of natural products in his therapy, including continued use of saw palmetto. Used smokeless tobacco x 35 years; heavy ETOH in the past, occasional glass of wine now.

  • Monogamous?
  • Condom use?
  • Last STI screen?

Labs

GU Consult

Surgical Indications

Patient treated for UTI 2 weeks ago with Cipro 250 mg Q 12 h x 3 days.

Urine clear; negative for glucose.

Bladder examination with ultrasound revealed postvoid residual estimate of 200 mL.

Prostate approximately 35 g, benign.

AUA Symptom Score = 20.

Uroflowmetry (Qmax) = 8 mL/s.

Urine Analysis

  • Color = straw
  • Appearance = clear
  • SG = 1.010
  • pH 6.5
  • glucose (–)
  • bilirubin (–)
  • ketones (–)
  • blood (–)
  • urobilinogen 0.2 mg/dL
  • nitrite (–)
  • leukocyte esterases (–);

  • Epithelial cells= occasional per hpf
  • WBC = occasional per hpf
  • RBC = none seen
  • Bacterial = trace
  • Amorphous = none seen
  • Crystals = 1+ calcium oxalate
  • Mucus = none seen
  • Culture not indicated

Assessment

  • BPH with urge incontinence
  • DM
  • ED
  • Symptomatic hypotension secondary to medication
  • Normocytic anemia possibly secondary to UGI bleed
  • Headaches
  • Osteoarthritis
  • HTN- well controlled
  • Obesity

Patients who:

  • did not improve after medical therapy
  • do not want medical therapy but request active treatment
  • present with a strong indication for therapy (refractory urinary retention, renal insufficiency due to BPH, bladder stones, recurrent urinary tract infection, recurrent haematuria refractory to 5α-reductase-inhibitors).

Surgical Procedures

Prostates < 30ml and without a middle lobe

  • Transurethral Incision of the Prostate (TUIP)

Prostates 30-80ml

  • Transurethral Resection of the Prostate (TURP)
  • Alternatives for high risk patients
  • Transurethral electrovaporization (TUVP)
  • Laser Treatments

Prostates > 80ml

  • Open Prostatectomy

Treatment Evaluation

Other Recommended Tests

Treatment Evaluation

Maximal Urinary Flow rate

  • <15 ml/sec indicates obstruction

Post void residual urine

  • > 200ml indicates BPH
  • Catheter or Bladderscan

Transurethral Resection of the Prostate (TURP)

Labs

  • PSA
  • Urinalysis
  • blood, protein, leukocytes, bacteria, glucose
  • CMP
  • Electrolytes
  • BUN & Creatinine
  • Blood Glucose, HgA1C

AUA Symptom Index → Improvement of score

  • frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency

Physical Exam:

  • Vitals → BP decreased
  • DRE (Digital Rectal exam)
  • Basic Neuro Exam

Uroflowmeter

European Association of Urology

Indications

  • high-risk patients presenting with recurrent urinary retention as an alternative to catheterization
  • patients not fit for surgery

Complications

  • encrustation, UTI, chronic pain

Prostatic Stents

Transurethral microwave therapy (TUMT)

  • patients who
  • prefer to avoid surgery
  • no longer respond to medication
  • do not want long term medication
  • high risk patients w/ recurrent urinary retention

Emerging therapies

Non-surgical procedures

  • Intraprostatic Botox Injections
  • Intraprostatic Alcohol Injections
  • High-intensity focused ultrasound (HIFU)
  • Chemoablation of the prostate
  • Water induced thermotherapy (WIT)
  • Plasma energy in a saline environment (PlasmaKinetic)

+ Guaiac

  • Repeat CBC and guaiac test. If positive, refer for endoscopy.

Diabetes

  • Diet & Activity
  • Continue maintenance with Glyburide/Metformin
  • Need more history of diabetes to determine future plan of action.

Patient Education

Main Medication Side Effects of Treatment

  • Terazosin (increased to 20 mg)
  • dizziness, hypotension
  • alcohol may increase side effects
  • Finasteride (5mg)
  • decreased sex drive
  • inability to maintain erection

Follow Up in 2 weeks to assess medication response & impotence.

Improve BPH symptoms by:

  • Reducing the amount of fluid you drink, especially just before bed
  • Limiting the amount of alcohol and caffeine you drink. These drinks can make you urinate more often.
  • Avoiding cold and allergy medicines that contain antihistamines or decongestants. These medicines can make the symptoms of BPH worse.
  • “Double Voiding”
  • empty your bladder, wait a moment, relax, and try to urinate again.

Headaches

  • Avoid triggers
  • Need more history of headaches to determine plan.

Allergies

  • Get rid of cat or shave cat.
  • Consider allergist consult

for possible allergy

immunotherapy injections

Patient Education

Transurethral Needle Ablation of the Prostate (TUNA)

  • indicated in high-risk patients unfit for surgery

Vaporization

Lasers!!!

Enucleation

(Glucovance) Glyburide/metformin 5/500 mg po BID

Clinical Course

Mr McCracken's blood pressure increased to 130/90, and the BPH and ED symptoms improved remarkably after your recommendations were implemented. Over the ensuing weeks, he continued to experience occasional urgency and hesitancy, so 6 months later he opted for laser prostatectomy. This procedure was successful in alleviating his symptoms.

QUESTIONS?

References

Kälble, T., Lucan, M., Nicita, G., Sells, R., Revilla, F. B., & Wiesel, M. (2005). EAU guidelines on renal transplantation. European urology, 47(2), 156-166.

Lee M (2014). Chapter 67. Benign Prostatic Hyperplasia. In DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L (Eds), Pharmacotherapy: A Pathophysiologic

Approach, 9e. Retrieved January 26, 2015 from http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310521.

McNicholas T, Kirby R. (2011). Benign prostatic hyperplasia and male lower urinary tract symptoms (LUTS). Clin Evid (Online);pii:1801

McVary, K. T. (2003). Clinical Evaluation of Benign Prostatic Hyperplasia.Reviews in Urology, 5(Suppl 4), S3–S11.

Meng M.V., Walsh T.J., Chi T.D. (2014). Urologic Disorders. In Papadakis M.A., McPhee S.J., Rabow M.W. (Eds), Current Medical Diagnosis & Treatment 2015. Retrieved

January 23, 2015 from http://accessmedicine.mhmedical.com/content.aspx?bookid=1019&Sectionid=57668615.

Murdock N, Solbing R (2009). Chapter 31. Benign Prostatic Hyperplasia. In Linn W.D., Wofford M.R., O'Keefe M, Posey L (Eds), Pharmacotherapy in Primary Care. Retrieved

January 26, 2015 from http://accesspharmacy.mhmedical.com/content.aspx?bookid=439&Sectionid=39968677.

Santos Dias, J. (2012). Benign prostatic hyperplasia: Clinical manifestations and evaluation. Techniques in Vascular and Interventional Radiology, 15(4), 265-269.

Wilt, T., Ishani, A., MacDonald, R., Rutks, I., & Stark, G. (1998). Pygeum africanum for benign prostatic hyperplasia. CochraneDatabase of Systematic Reviews, 1.

Poole, V., & Peterson, A. M. (2005). Pharmacotherapeutics for Advanced Practice: A Practical Approach.

http://emedicine.medscape.com/article/437359-overview#a0104

http://0-www.uptodate.com.library.touro.edu/contents/measurement-of-prostate-specific-antigen?source=machineLearning&search=BPH&selectedTitle=8~150&sectionRank=2&anchor=H3#H3

http://0-www.uptodate.com.library.touro.edu/contents/epidemiology-and-pathogenesis-of-benign-prostatic-hyperplasia?source=related_link

http://0-www.uptodate.com.library.touro.edu/contents/medical-treatment-of-benign-prostatic-hyperplasia?source=machineLearning&search=BPH+alpha+blocker&selectedTitle=1~150&sectionRank=1&anchor=H619703198#H619703198

http://patients.uroweb.org/bpe/surgical-treatment/

MOA

Drugs Therapy Problem List

Excretion

  • Glyburide/metformin 5/500 mg po BID
  • Amitriptyline 50 mg po at bedtime (HA prophylaxis)
  • Terazosin 10 mg po QD
  • Saw palmetto 200 mg po BID
  • Ibuprofen 800 mg po BID
  • Claritin-D 24-hour one tablet po daily (allergy to cats)

Epidemiology

  • Affects ~1/3 of men > 50 years old
  • Evident in up to 90% of men by age 85 years.
  • As many as 14 million men in the US and 30 million worldwide have symptoms of BPH.
  • The prevalence in African American men and white men is similar. BPH tends to be more severe and progressive in African American men, which is possibly due to higher testosterone levels, 5-alpha-reductase activity, androgen receptor expression and growth factor activity.

Precautions

Both act as antihyperglycemic agents, reduce blood glucose and improve glycemic control.

Glyburide stimulates functioning pancreatic beta cells to produce insulin, reducing blood glucose. Extrahepatic effects may be involved but mechanism is still unknown. Metformin improves glucose tolerance by lowering basal and postprandial plasma glucose levels. It has 3 specific actions that are to decrease hepatic glucose production, decrease intestinal glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Glyburide is 50% biliary and 50% renal. Metformin is Renal

alcohol intake, excessive due to increase risk of lactic acidosis and or hypoglycemia, elderly there is an increased risk of lactic acidosis, renal dysfunction there is an increased drug exposure and risk of lactic acidosis, calcium deficiency, increased risk for development of subnormal vit B12 levels, stress, potential loss for glycemic control, surgical procedures requiring food or fluid restriction can interrupt therapy

Cobalamin deficiency, hypoglycemia, abdominal pain, diarrhea, nausea, vomiting, dizziness, headache, URI

*Serious, but rare adverse effects: Lactic acidosis, hemolytic anemia, cholestatic jaundice syndrome

HbA1c twice yearly in patients who are meeting their goals and every 3 months if medication is being changed. Blood Glucose self-monitoring. Renal function annually, and more frequent if renal impairment. Vitamin B12 levels every 2-3 years

Reference: Micromedex

Terazosin 10 mg po QD

Saw palmetto 200 mg po BID

*MOA: is an alpha-1-selective adrenoceptor in the neck of the urinary bladder and prostate gland, thereby producing relaxation of smooth muscles in these sites. Causes vasodilation resulting in orthostatic hypotension by inhibiting alpha-1-adrenoceptors

*Absorption:Peak time is 1 hour

*Distribution:Protein binding

*Metabolism:Hepatic

*Excretion:Fecal and renal

Saw Palmetto

*Adverse effects: Back pain, stomach pain, change in sex drive, constipation, cramping, diarrhea, difficulty urinating, headache, impotence, nausea, dizziness

Plant, the ripe fruit is used. Known for its use in decreasing symptoms of an enlarged prostate. It shrinks the inner lining that puts pressure on the tubes that carry urine, it does not reduce the enlargement and should therefore only be used in mild to moderate BPH. Used to increase urine flow to promote relaxation (as a sedative) and to enhance sexual drive

*Caution: liver damage, pancreas damage

Unknown if safe for periods longer than 30 days

May slow clotting, stop use 2 weeks before surgery

Ibuprofen 800 mg po BID

Terazosin 10 mg po QD

Amitriptyline 50 mg po at bedtime

*Precautions: Syncope, sudden LOC, orthostatic hypotension, priapism

*Patient Education: avoid activities requiring mental alertness or coordination, may cause dizziness, slowly rise from sitting or lying position, drug may cause nasal congestion and asthenia, take drug at night time to minimize side effects, no alcohol while taking this medication

Ibuprofen

*MOA: nonsteroidal anti-inflammatory that exhibits analgesic and antipyretic activities by inhibiting prostaglandin synthesis

*BB warning: Increase the risk of CVA and stroke, Can cause serious GI effects including bleeding

*Contraindication: Asthma, urticaria, allergic reaction

Adverse Effects

*Precautions:Known cardiac disease, Known GI problems, Can increase fluid retention, May slow clotting, Hypotension, Caution in liver dysfunction

*Drug interaction: moderate with glyburide (increases the effects of ibuprofen -unknown mechanism)

*Adverse Effects: dizziness, headache, hypotension, fluid retention, dizziness

*Metabolism liver

*Excretion is renal

Don’t drink or smoke while taking

*MOA: TCA that exhibits sedative properties, it promotes neuronal activity by blocking the membrane pump mechanism which is responsible for the absorption of serotonin and norepi in serotonergic and adrenergic

neurons

*Metabolism is hepatic

P450 CYP2D6, excreted renal

Claritin-D 24-hour (Loratadine/Pseudoephedrine sulfate) one tablet po daily (allergy to cats)

Claritin D

*MOA: second generation H1 histamine antagonist. Structure closely resembles TCAs.

Contraindication is urinary retention, severe CAD

*Precautions: DM, elderly greater than 60 years old, hepatic insufficiency, hypertension, hyperthyroidism, ischemic heart disease, prostatic hypertrophy, renal impairment

*Adverse Effects: xerostomia, insomnia, pharyngitis

Monitor CNS stimulation or depression

*Drug can cause: decreased mental alertness or coordination, dizziness, somnolence, anticholinergic effects, headache, insomnia, nervousness, fatigue

Patient should not drink alcohol

BPH

Amitriptyline 50 mg po at bedtime

*Precautions: Use caution in patients with impaired liver function, Use caution in patients with history of urinary retention due to the anticholinergic effects. Use caution in patients undergoing and elective surgery

*Adverse effects: Weight gain, constipation, xerostomia, dizziness, headache, somnolence, blurred vision, cardiac dysrhythmia, agranulocytosis, hepatotoxicity, jaundice, depression, suicidal thoughts

Patient should not drink alcohol while taking this drug

Monitoring

Other medical conditions to rule out

Prostatic enlargement is dependent on androgen dihydrotestosterone (DHT). In the prostate gland type II 5-alpha-reductase metabolizes circulating testosterone into DHT, which acts locally. There are a large number of alpha-1-adrenergic receptors in the smooth muscle of the stroma, the capsule of the prostate and the bladder neck. When these receptors get stimulated via the DHT, it causes an increase in smooth muscle tone, which can worsen the symptoms associated with BPH.

Presentation

  • Urethral Stricture
  • Bladder Neck Contracture
  • Prostate Cancer
  • Bladder Cancer
  • Bladder Calculi
  • Urinary Tract Infection, Prostatitis
  • Neurogenic Bladder
  • DM- Pt has Type 2 DM controlled
  • PUD

Natural History

Irritative:

  • Urgency
  • Frequency
  • Nocturia
  • Double voiding

Obstructive:

  • Straining to urinate
  • Hesitancy
  • Decreased flow rate
  • Postvoid dribbling
  • Sensation of incomplete bladder emptying

AUA (American Urological Association) Symptom Index Scale

DHT binds to androgen receptors in the cell nuclei and can cause hyperplasia, which potentially results in BPH. The hyperplasia may restrict the flow of urine from the bladder. As the prostate enlarges, the surrounding capsule prevents it from radially expanding and that causes urethral compression. In addition, the irritation from urethral compression causes the bladder to thicken and hypertrophy and itself to be more irritable. Therefore, the bladder now has increased sensitivity to small volumes of urine and causes increased urinary frequency. Eventually the bladder may gradual weaken and lose the ability to empty completely, which leads to the increased residual urine volume and urinary retention.

Total score: 0-7 mild symptoms; 8-19 moderate symptoms; 20-35 severe symptoms

Symptom

Index

Scale

AUA= 20 Severe

Medication

Natural History

Goals of Pharmacotherapy

  • Glyburide/metformin 5/500 mg po BID
  • Amitriptyline 50 mg po at bedtime (HA prophylaxis)
  • Terazosin 10 mg po QD
  • Saw palmetto 200 mg po BID
  • Ibuprofen 800 mg po BID
  • Claritin-D 24-hour one tablet po daily (allergy to cats)

  • An enlarged prostate does not constitute medical tx in all cases.

Alpha Blocker goal (Terazosin, doxazosin, tamsulosin, alfuzosin, silodosin):

  • Relax the smooth muscle of the bladder neck, prostate capsule and prostatic urethra
  • Acts against bladder outlet obstruction

Goals of Pharmacotherapy

5-Alpha-Reductase Inhibitor goal (Finasteride and dutasteride):

  • Block the conversion of testosterone to DHT (dihydrotestosterone is a necessary androgen for prostate development)
  • Decreases PSA
  • Decrease the prostate volume (size)
  • contributing to lower PSA levels
  • Reduce serum PSA level by 50% in first 3-6 months
  • 60 to 69 years-old normal range— 0 to 4.5 ng/mL (blacks); 0 to 3.5 (whites)
  • Improve maximum flow rate and prostate volume

Treatment

Pygeum africanum

“As the physician assistant in the team, you perform a literature search on the use of saw palmetto for BPH. You discover that there are reports of the dietary supplement both improving and worsening symptoms of ED. Because the patient's ED symptoms began while he was taking saw palmetto, you decide that it is plausible that saw palmetto could be contributing to ED symptoms. In addition, your readings indicate that saw palmetto should really only be used by patients with mild to moderate BPH.

Alternative Treatment

Based on this information, your recommendation is to stop the saw palmetto. However, because the patient is emphatic about wanting to continue a natural product, you search for alternative dietary supplements that may provide some benefit for this patient's BPH without contributing to ED. Would Pygeum africanum be a reasonable option to consider?”

Pygeum africanum

Terazosin (Hytrin) (Currently taking 10 mg)

  • 1-20 mg capsules (1mg, 2mg, 5mg, 10mg) Titrate to 10 mg
  • Sig: 1 cap PO daily
  • Qty: 100
  • Refills: 1

Adverse effects: Syncope (Esp. 1st dose), dizziness, somnolence, asthenia, nausea, nasal congestion, palpitations,impotence, orthostatic hypotension, blurred vision, peripheral edema, priapism (rare)

Avoid: Verapamil, other antihypertensives

  • Extract of bark from an African plum tree.
  • In a meta-analysis of 18 randomized controlled trials, active treatment improved symptoms 2x more than placebo and peak urinary flow rates by 23% (UpToDate, 2002)

  • Therefore, Pygeum africanum

would be a reasonable option

to consider replacing Saw

Palmetto in regards to positive

evidence provided from the

18 RCTs.

5α - reductase inhibitors

6 month treatment then assess

Adverse effects: Decrease libido, impotence, ejaculatory failure, gynecomastia. Finasteride can falsify the PSA level by 50% after 6 months of treatment. Use with caution in hepatic insufficiency. Swallow don’t chew.

α adrenergic antagonist or α blockers

Finasteride (Proscar)

  • 5 mg tabs (alone or in combination with doxazosin)
  • Sig: 1 tab PO daily
  • Qty: 100
  • Refills:1

Dutasteride (Avodart)

  • 0.5 mg capsules (with/without tamsulosin 0.4 mg PO daily)
  • Sig: 1 cap PO daily
  • Qty: 90
  • Refills: 1

5α - reductase inhibitors

Doxazosin (Cardura)

  • 4-8 mg scored tablets (1mg, 2mg, 4mg, 8mg) (increase every 1-2 weeks)
  • Sig: 1 tab PO daily
  • Qty: 100
  • Refills: 1

Adverse effects: Syncope (Esp. 1st dose), dizziness, HA, drowsiness, weakness, palpitation, GI upset, edema, orthostatic hypotension, dyspnea, vertigo, depression, nervousness, rash, urinary frequency, blurred vision, reddened sclera, epistaxis, dry mouth, nasal congestion, priapism (rare)

Avoid: impaired liver function, monitor BP

Tamsulosin HCl (Flomax)

  • 0.4 mg capsules (May increase to 0.8 mg if response is inadequate in 2-4 weeks)
  • Sig: 1 cap PO daily 30 min after meal
  • Qty: 100
  • Refills: 1

Adverse effects: Dizziness, HA,

abnormal ejaculation,

caution with sulfa allergy

Avoid: Cimetidine, warfarin

α adrenergic antagonist or α blockers (Cont.)

α adrenergic antagonist or α blockers

Prazosin (Minipress)

  • 1-5 mg capsules (1mg, 2mg, 5mg)
  • Sig: 1 cap PO daily
  • Qty: 250
  • Refills: 0

Adverse effects: Dizziness, fatigue, hypotension, edema, dyspnea, priapism (rare)

Avoid: ETOH, propranolol, diuretics

α adrenergic antagonist or α blockers (Cont.)

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