treatment of BPH include medical and surgical treatment.. here i discuss about pharmacotherapy of benign prostatic hyperpllasia

1. Pharmacotherapy of BPH
Dr. K. Preethi
Final yr PG
Dept of Pharmacology

2. Contents
• Introduction
• Medical treatment
• Surgical treatment

3. Introduction
• Benign Prostatic Hyperplasia
• Most common condition in elderly men
• >50% men demonstrate histopathologic BPH
by age 60 yrs
• 90% by age 80 yrs

4. Normal BPH
Hypertrophied
detrusor muscle
Obstructed urinary
flow
PROSTATE
BLADDER
URETHRA
Roehrborn CG, McConnell JD. In: Walsh PC et al, eds. Campbell’s Urology. 8th ed. Philadelphia, Pa: Saunders; 2002:1297-1336.

5. pathophysiology
• Hypertrophy of bladder neck, smooth muscle
of the prostate, prostatic capsule, proximal
urethra
• On contraction causes obstructive voiding
symptoms- dynamic component of BPH
• Increased prostatic mass mechanically blocks
the urethra – static component of BPH

6. Symptoms
Obstructive Symptoms
• Hesitancy
• Weak stream
• Straining to pass urine
• Prolonged micturition
• Feeling of incomplete
bladder emptying
• Urinary retention
Irritative Symptoms
• Urgency
• Frequency
• Nocturia
• Urge incontinence

7. Treatment
• Watchful waiting
• Pharmacological treatment
• Surgical treatment

8. Watchful waiting
• Regular follow ups
• In patients with mild symptoms
• Patients with moderate symptoms who are
not bothered by their symptoms

9. Medical management
• Non selective alpha 1 antagonists
a) short acting: Prazosin, Alfuzosin
b) long acting: Terazosin, Doxazosin
• Selective alpha 1 A antagonists
Tamsulosin, Silodosin
• 5- alpha reductase inhibitors
Finasteride, Dutasteride
• Miscellaneous
PDE 5 inhibitor – Tadalafil
GnRH agonists – Naferelin acetate, Leuprolide

10. Distribution of Alpha Receptors in the
Prostate and Bladder
Pelvic Floor
External Sphincter
Internal Sphincter
Trigone
Detrusor
Prostate Gland

11. Alpha 1 blockers
• Relaxation of both bladder neck and prostatic smooth
muscle, thus decreasing pressure in the bladder and
urethra improve the urinary flow
• Improve the obstructive symptoms than irritative
symptoms
• Drugs are- Prazosin
Terazosin
Doxazosin
Alfuzosin
Tamsulosin
Silodosin

12. PRAZOSIN
• α1 > α2
• Potent inhibitor of cyclic nucleotide
phosphodiesterases
• Well absorbed orally
• Bioavailability 50 – 70 %
• Tightly bound to plasma proteins
• Metabolized in liver
• Duration of action 7 to 10 hrs
• Initial dose 1mg at bed time
• Off label use in BPH, 1-5mg, twice daily

13. Terazosin
• Structural analog of prazosin
• More soluble in water than prazosin
• More effective than finasteride in treatment of
BPH
• Bioavailability is 90%, highly protein bound
• t1/2 is 12 hrs, duration of action more than 18 hrs,
once daily dosing
• Metabolized in by demethylation, dealkylation in
liver
• 40% excreted in urine

14. • Contraindicated in patients with known
sensitivity to quinazolines
• Side effects – first dose hypotension, dizziness,
fatigue
• Used with caution in patients taking diuretics,
other antihypertensive agents,
phosphodiesterase 5 inhibitors
• Dosage: initially 1 mg daily at bed time,
10 mg/day for maximal effect in BPH

15. Doxazosin
• Structural analog of prazosin
• Bioavailability 65%, highly protein bound
• t1/2 is 20 hrs, duration of action around 36hr
• Metabolized in by demethylation, dealkylation
in liver
• Most of the metabolites are excreted in feces
• Contraindicated in patients with known with
sensitivity to quinazolines

16. • Used with caution in patients taking diuretics,
other antihypertensive agents,
phosphodiesterase 5 inhibitors, in hepatic
dysfunction
• Side effects – first dose hypotension, dizziness,
fatigue, headache
• Dosage: intially 1 mg, maintainace dose is
1 – 8mgdaily
• Extended release formulations are also available

17. Alfuzosin
• Used extensively for treatment of BPH, not approved
for treatment of HTN
• Bioavailability 64%
• t1/2 is 3-5 hrs
• Substrate for CYP3A4
• Contraindicated in patients with moderate to severe
hepatic impairment, known hypersensitivity, in
patients taking other CYP3A4 inhibitors
• Avoided in patients with prolonged QT syndrome
• Dosage: 10 mg extended release tablet daily

18. Tamsulosin
• Benzene sulfonamide
• More effective in treatment of BPH, little effect on BP
• Well absorbed
• t1/2 is 5 – 10 hrs
• Extensively metabolized by CYPs
• Contraindicated in patients with sulfa allergy, in
patients taking CYP inhibitors
• Side effect is retrograde ejaculation, intra operative
floppy syndrome
• Dosage: 0.4mg starting dose, maintain with 0.4-0.8mg

19. Silodosin
• Selective for α1A receptors
• t1/2 is 13-14 hrs
• Metabolized by glucuronidation
• Dosage: 8 mg daily
• Side effects: retrograde ejaculation
• Contraindicated in patients with renal
impairment, severe hepatic impairment

20. 5 alpha reductase inhibitors
• In prostate, testosterone converted to
dihydroxy testosterone ( DHT ) by 5 alpha
reductase enzyme.
• DHT increases the growth in prostate
• Drugs: Finasteride
Dutasteride

21. Two 5-Reductase (5AR) Isoenzymes
Convert Testosterone to DHT
Testosterone
Type II 5AR
Type I 5AR Prostate
enlargement
DHT

22. Near Complete DHT Suppression Requires Inhibiting
Both 5AR Isoenzymes
Dutasteride
Dutasteride
Finasteride
Prostate
volume
reduced
Bartsch G et al. Eur Urol. 2000;37:367380.
DHTTestosterone
Type II 5AR
Type I 5AR

23. Finasteride
• Inhibits type 2 isoform of 5 alpha reductase
• Bioavailability 63%
• t1/2 is 6-8 hrs
• Dosage 5 mg daily
• Excreted in urine, semen
• Effective only in patients with palpably enlarged
prostate
• Contraindicated in patients with obstructive
uropathy or prostate cancer

24. Dutasteride
• Inhibits both isoforms of 5 alpha reductase
• Bioavailability 60%
• Half life is 5 wks
• Metabolized by cytochrome p 450
• Dosage: 0.5mg daily
• Side effects: decreased libido, ejaculatory
dysfunction, impotence, gynaecomastia

25. 5 alpha reductase inhibitors and alpha
blocker combination
• 0.5mg Dutasteride & 0.4 mg Tamsulosin
combination
• Used in treatment of symptomatic BPH in men
with enlarged prostate

26. PDE 5 INHIBITORS
• MAO: Selective inhibitor of cGMP specific
PDE5
• Decreases cGMP conc. in corpus cavernosa &
pulmonary arteries, in smooth muscles of
prostrate, bladder & blood vessels.
TADALAFIL
• Half life – 17 hrs. Metabolized by CYP 450
• Dosage: 5 mg daily
• C/ I: patients using nitrates. Not combined
with alpha blockers due to risk of bp lowering

27. • Also used in pulmonary hypertension, erectile
dysfunction
• If erection lasting for more than 4 hrs-
requires emergency treatment.
• Stop- if sudden loss of vision in one or both
eyes, if sudden decrease or loss of hearing
• Drug Interactions: CYP inhibitors increase
Tadalafil exposure, and CYP inducers decrease
exposure

28. Phytochemical Agents
• Plant derived non nutritive compounds.
• Active ingredients & dosage of active
medication not known
• Mechanism of action is not clear
• Pumpkin
- Flavonoids
- Hypoxia rooperi
- Saw palmetto- berry extracts
-African plum

29. Novel approaches
• Gene therapy
• COX-2/ LOX-5 inhibitors
• Vit D3 analogue
• Antibody dendrimer conjugates
• Oxytocin antagonists
• Radio nucleotide therapy
• NX-1207

30. SURGICAL TREATMENT
INVASIVE MINIMALLY INVASIVE
- Open prostatectomy
-Transurethral resection of
prostate( TURP)
-Transurethral incision of prostate
(TUIP)
- Transurethral electro
vaporizations (TUEV)
- Transurethral microwave
thermotherapy (TUMT)
- Transurethral needle ablation
- Laser ablation
- High intensity focused
ultrasound
- Transurethral ethanol
ablation
- Water induced
thermotherapy

31. REFERENCES
• GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS
OF THERAPEUTICS - 12th Ed.
• Pharmacology and Pharmacotherapeutics SATOSKAR ,
23rd edition -
• KATZUNG BASIC AND CLINICAL PHARMACOLOGY 12th
edition
• Essentials of medical pharmacology KD TRIPATI ,7th
edition
• Principles of Pharmacology HL SHARMA , KK SHARMA,
2nd edition
• RANG AND DALE PHARMACOLOGY – 7th edition

32. • Clinical pharmacology Bennett and Brown,11th
edition
• www. ijp online.com, benign prostatic
hyperplasia: An overview of existing treatment
• Benign Prostatic Hyperplasia Treatments,
Therapeutic class review, jan 23, 2015,
Medicaid administration

33. thank you