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10/3/2008 1 M ’H th Mens Heath: Update on Preventative Medicine and Medication Management Daniel Lewis PharmD BCPS Daniel Lewis, PharmD, BCPS Pharmacy Specialist, Internal Medicine October 17, 2008 Objectives Discuss the role of preventative medicine in the aging male aging male Assess the role of chemoprevention to reduce the risk of prostate cancer Evaluate new studies and impact on the treatment of benign prostatic hyperplasia A l h i f d ffi i Analyze approaches to improve saf ety and efficacy in the use of PDE5 inhibitors for the treatment of erectile dysfunction

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Page 1: M’Men’s HthH eathukyce.cecentral.com/assets/961/Friday_10-20 AM_Lewis.pdf · M’Men’s HthHeath: ... • AlAnalyze approaches to improve safety and efficacy in the use of PDE‐5

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1

M ’ H thMen’s Heath: Update on Preventative Medicine and 

Medication Management

Daniel Lewis PharmD BCPSDaniel Lewis, PharmD, BCPSPharmacy Specialist, Internal MedicineOctober 17, 2008

Objectives

• Discuss the role of preventative medicine in the aging maleaging male

• Assess the role of chemoprevention to reduce the risk of prostate cancer

• Evaluate new studies and impact on the treatment of benign prostatic hyperplasia

A l h i f d ffi i• Analyze approaches to improve safety and efficacy in the use of PDE‐5 inhibitors for the treatment of erectile dysfunction 

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Know the Facts

• One in five American men have heart disease

• One in three American adults have hypertension

• Three in four American men are overweight

• Nine in ten lung cancer deaths are caused by cigarrette smokingcigarrette smoking

Mortality Associated with Men

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Heart Disease in Kentucky• CVD in Kentucky

– Prevalence is 8.9%• Top 5 in the US

– Ranged from 3.5 % in the US Virgin Islands to 10.4 % in West Virginia

• Kentucky’s other honors– Smoking Rate

• Rated first in 2005

– Diabetes Rate• Rated 8th in 2005

– Obesity• Over 2/3 of adults are overweight in KY

• 1 of 4 is morbidly obese

JAMA. 2006;295:549 –555.

Man’s Limitations

• Smoke and drink more 

– Generally lead less healthy lifestyles 

• Put off routine checkups 

– Ignore symptoms ofg y pa health problem 

• Join in risky and dangerous behaviors 

Menshealthnetwork.org

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Live Sensibly….

“among a thousand l l dipeople, only one dies 

a natural death, the rest succumb to irrational modes of living”

Maimonides, A.D. 1135‐1204

Preventative CareAging Male

• Immunization

– Influenza and pneumococcal

• Screening

– Identification of asymptomatic disease or risk

• Lifestyle Changes

B h i l l– Behavioral counsel

• Chemoprevention

– Use of drugs to prevent disease

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Health Screening GuidelinesMen’s Health

• Blood Pressure

• Cholesterol

• Colon Cancer 

– Colonoscopy

• Diabetes

• Prostate Cancer

– Digital Rectal Exam 

• Weight

Prostate Health

• 30 million men suffer from prostate conditions

– 50% of men in their 60s and 90% in their 70s have BPH symptoms

• 230,000 men diagnosed with prostate cancer annually

– 30,000 deaths,

• Prostatitis affects 35% of men aged 50 and older

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Prostate Cancer

• Incidence increasing 2% each year

– Likely due to increased awareness & screening programs

• 218,890 patients diagnosed in 2007

– 2,880 in Kentucky

• 27 050 deaths in 200727,050 deaths in 2007

– 310 in Kentucky

Pop Quiz!!

• A healthy diet is one of the most important d t i t f i kdeterminants of cancer risk.

True

FalseFalse

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Diet and Cancer Connection

• For non‐smokers, diet and physical activity are the most important modifiable determinants of cancer risk 

• Nutritional factors account for one‐third of d h

American Cancer Society www.cancer.org February 2007

cancer deaths

Potential Diet‐Related Cancers

• Colorectal

B t

• Prostate

Kid• Breast

• Mouth/Esophagus

• Laryngeal

• Stomach

• Lung

• Kidney

• Endometrial

• Cervical

• Pancreatic

g

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Diet & Prostate Cancer

• Lycopene

– MOA:  works as an antioxidant to protect DNA from oxidative stress

– Source – tomatoes 

– Tomato sauce intake associated with a 35% reduction in risk of prostate cancer

• Independent of fruit & vegetable intakeIndependent of fruit & vegetable intake

• Meta‐analysis

– Compared high vs. low intake of tomatoes

– 10‐20% reduction in prostate cancer riskGiovannucci et al J Natl Cancer Inst 94: 2002                                               Etminan et al Cancer Epidemiol Biomarkers Prev 13: 2004

Diet & Prostate Cancer

• Vitamin E• Vitamin E 

– MOA: works as an antioxidant to protect DNA from oxidative stress

– Alpha‐Tocopherol Beta‐Carotene (ATBC)

• Men randomized to 50 IU of alpha‐tocopherol daily vs. l b

Heinonen et al.  J Natl Cancer Inst 90: 1998

placebo

• 40% decreased risk of prostate cancer

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Diet & Prostate Cancer

• Selenium

– Nutrition Prevention of Cancer Trial

• Randomized men to receive selenium vs. placebo

• 50% reduction in risk of prostate cancer

– Supported by other prospective studies

– Selenium & Vitamin E Cancer Prevention Trial (SELECT) 

• Prospective trial looking at combined and single agents for the prevention of prostate cancer

• Results expected in 2013

Diet & Prostate Cancer

• Milk and calcium• Milk and calcium

– Increased intake of calcium has been associated with an increased risk for prostate cancer

– Health Professionals Follow Up Study (HPFS)

• > 2,000 mg of calcium daily had a 5x increased risk for t t d t < 500 d il

Giovannucci et al.  Cancer Res 58: 2004

prostate cancer compared to < 500 mg daily

• Recommended daily allowance – 1000‐1500 mg may still be beneficial for prevention of colon cancer and osteoporosis

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Diet & Prostate Cancer

• Dietary Fat– Saturated fat and red meat consumption associated with an increased risk for cancer

• Dietary Fiber– Limited evidence suggests high fiber consumption may decrease risk of cancer

• Recommendations:– Limit intake of animal fat & red meat sources, eat fruits and vegetables, watch calcium intake, consider vitamin E  & selenium supplementation

Benign Prostatic Hyperplasia (BPH)

• Stromal and epithelial cell hyperplasia in the prostate

P l f di i t d ith• Prevalence of disease associated with age

– 25% by 50 yrs of age

– 50% by age 60 yrs

– 90% by age 85 yrs

• Presents with uninary tract symptoms (LUTS)

b d– Obstructive and irritative symptoms

– Weak stream, hesitancy, increased frequency, urgency, nocturia

– Prevalence of symptoms also increase with age

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Benign Prostatic Hyperplasia (BPH)

• BPH may or may not cause symptoms

• Degree of prostate enlargement

– Not associated with symptoms

– Not correlated to presence of prostate cancer

Diagnosis of BPHAUA guidelines

Rev Urol. 2006; 8(Suppl 4): S10–S17

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Treatment of BPHSymptom control

• Mild to moderateHow often have you had the sensation of not emptying your bladderMild to moderate 

– Limited symptoms

– Watchful waiting

• Moderate to severe 

– Bothersome symptoms

not emptying your bladder

How often have you had to urinate again within two hours

Have you found that you have stopped and started again while urinating

Have you had a weak stream

Have you had to strain to begin urination

– Medical therapy

– Surgical options

y g

Have you found it difficult to postpone urination

How many times/night have you had to get up to urinate

Pharmacologic management of BPHα – blockers

• Decrease prostatic smooth muscle tone

– Provides symptom relief

• Agents equally effective

– Reduction of LUTS

• Differ in selectivity and adverse effects

5 Alpha reductase inhibitors

L i t t ti dih d t t t• Lowers serum intraprostatic dihydrotestosterone

– Reduces the size of the prostate

– Provides symptom relief

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Management of BPHDoxazosin

• Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)Prevent Heart Attack Trial (ALLHAT)

– Doxazosin arm stopped early

• 25% higher risk of CVD events

• 80% increased risk of HF at one year

• Not recommended for monotherapy of HTN in patients with cardiac riskwith cardiac risk

– Recommend concomitant use of diuretic

• Patients with both HTN and BPH

JAMA. 2000;283(15):1967-75

Available agents for treatmentBPH

Drugs Daily Dose Titration Onset (peak relief)

α – blockers

Terazosin 1‐10 mg Start 1 mg and double q2wks 

1‐2 wks (4wks)

Doxazosin 1‐8 mg Start 1 mg and double q2wks*

1‐2 wks (4wks)

Alfuzosin 10 mg None 1‐7 days (2wks)

Tamsulosin◊ 0.4‐0.8 mg Start 0.4 mg and ↑ 1‐7 days (2wks)

5 Alpha reductase inhibitors

Finasteride 5 mg None  3‐6 months (12 mo)

Dutasteride 0.5 mg None  3‐6 months (12 mo)

*Available in ER formulation, ◊ Uroselective = least effect on BP

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Combination Therapyα – blocker and 5 Alpha reductase inhibitor

• Medical Therapy of Prostatic Symptoms (MTOPS) t i l(MTOPS) trial

– Doxazosin, finasteride, combination, or placebo

– Endpoints for combination:

• Reduced risk of clinical progression by 66%

• Symptom scores improved in all therapy groups

• Adverse effects similar between monotherapy and combination

• Not beneficial for patients with PSA < 1.5 ng/ml

N Engl J Med 2003; 349:2387

Combination therapyMedical Therapy of Prostatic Symptoms (MTOPS) trial

N Engl J Med 2003; 349:2387

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Other Management OptionsSaw Palmetto

• Popular herbal remedy 

C fli ti lt di• Conflicting results regarding efficacy

– Modest to no clinical benefit

• Saw Palmetto for BPH trial

– No difference in symptom scoresscores

– No change in urinary flow rates

N Engl J Med 2006; 354:557-66

Erectile dysfunctionObjectives

• Define erectile dysfunction (ED)

• Discuss the most common causes and preventative strategies for ED

• Review pharmacologic treatment options and adverse effects

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Erectile DysfunctionDefinition

Persistent inability to achieve and maintain an erection that is sufficient for intercourseerection that is sufficient for intercourse

Incidence

• 20‐30 million American men suffer from ED

– Age dependent

– Behavioral riskehavioral risk

– Associated comorbidity

Feldman, HA.  J Urol 1994; 151:54.

Risk factors for ED

• Chronic Disease– Diabetes mellitus

• Medication use– 25% of cases are due toDiabetes mellitus

– Hypertension

– Obesity

– Dyslipidemia

– Cardiovascular disease

– Smoking

di i

25% of cases are due to medications

– Include commonly used medications

• Antidepressants

• Spirololactone

• Thiazide diuretics

– Medication use

– Depression

• Alcohol

• B‐blockers

JAMA 2002; 288:351‐57.

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Erectile Physiology

• Requires vascular, neurologic, hormonal and psychological systems– Vascular

• Adequate arterial inflow and sufficient generation of nitric oxide– Low nitric oxide synthase concentrations found in smokers, diabetics and 

testosterone deficiency.– Role for PDE‐5 inhibitors and testosterone

– Hormonal• Testosterone 

– Enhances libidoEnhances libido– Maintains adequate nitric oxide synthase

– Psychogenic• Depression

– Loss of interest, lack of libido – Performance anxiety

Drugs associated with EDDrug Class Proposed mechanism Notes

Anticholinergics•Antihistamines•Antidepressants 

Anticholinergic activity Non‐sedating antihistamines not associated with ED

p

Dopamine agonists•metoclopramide

Increase prolactin levels Decrease testosterone production

Estrogens/antiandrogens•Spironolactone•Ketoconazole

Suppress testosterone mediated stimulation of libido

CNS depressants•Narcotics

Suppress perception of stimuliNarcotics

•Benzodiazepines•ETOH

stimuli

Agents that decrease flow•Diuretics•B‐blockers•Central sympatholytics

Reduced arterial flow to corpora

Safer antihypertensivesinclude:•Calcium channel blockers•ACE/ARB

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Treatment of ED

• Identification of underlying cause– Treatment of co‐morbiditiesTreatment of co morbidities– Eliminate modifiable risk

• Available therapies– Oral PDE‐5 inhibitors– Intra‐urethral alprostadil– Intracavernous vasoactive drug injectionV i i d i– Vacuum constriction devices

– Penile prosthesis implant

• Balance invasiveness, risk and effectiveness options preferred

Cardiac Risk Stratification

Low Risk – Initiate treatment for ED / Resume sexual activityModerate Risk – Further evaluation needed High Risk – Stabilize cardiac condition prior to initiation of treatment

Am J Cardiol 2000;86:62F-68F

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Treatment of EDPhosphodiesterase type‐5 (PDE‐5) inhibitors

• MOA: Inhibition of PDE5 enzyme results in increased arterial blood flow smooth muscle relaxationarterial blood flow, smooth muscle relaxation, vasodilation and erection

• Agents similar in respect to efficacy

• Differ in dosage, duration and PK

– Tadalafil may be administered 36 hrs prior to intercourse

l d ff f l• Similar adverse effect profile

– Headache, flushing

– Contraindicated in patients taking nitrates

– Safe with other anti‐HTN meds 

Phosphodiesterase Type‐5 (PDE‐5) Inhibitors

Drug Dose Onset Duration Instruction

Sildenafil 25‐100 mg 30‐60 minutes 12 hrs ↓ Efficacy ifSildenafil 25‐100 mg 30‐60 minutes 12 hrs ↓ Efficacy if taken with fatty meal

Tadalafil 10‐20 mg

2.5‐5 mg daily

30‐120 min 36 hrs No effect with meal

Vardenafil 5‐20 mg  30 min ↓ Efficacy if taken with fatty ymeal

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PDE‐5 inhibitorsVisual Effects

• Disturbances in color perception

– Inhibition of PDE‐6 

– Sildenafil and vardenafil

• Nonarteritic anterior ischemic optic neuropathy (NAION)

– Potential permanent vision lossPotential permanent vision loss

– Often underlying cardiac risk factors

• Age > 50, HTN, dyslipidemia, DM

– DC drug if visual disturbances present

Nonresponsive to TherapyErectile dysfunction

• Assess adequate use of therapy

I l i f lif l h– Inclusive of lifestyle changes

• Counsel on medication usage

– Proper administration

– Concurrent CYP‐3A4 inducers (rifampin)

• Consider re‐trial

– Ensure 7‐8 doses

– Consider titration of dosage

• Potential for alternative therapy

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Pharmacist’s Role

• Counseling on the role of annual exams

• Drug selection counseling and monitoring• Drug selection, counseling and monitoring

– Avoidance of ADR

– Non‐pharmacologic measures for success

• Lifestyle adjustments

• Review medication profile

R l f l i h i• Role of alternative therapies

– Discuss the roles of chemoprevention in cancer prevention