1.

ALPHA ADRENERGIC BLOCKERS

Phenoxybenzamine is a nonselective alpha-adrenergic receptor blocker that antagonizes both
alpha-1 and alpha-2 receptors. This nonselectivity leads to a higher incidence of adverse effects,
which has led to decreased use of this agent in clinical settings. Phenoxybenzamine induces
subjective improvement in urinary flow rates when compared with placebo. It may improve
daytime and nighttime urinary frequency. Symptoms improve in 75% of patients.
MECHANISM OF ACTION: Alpha blocker, noncompetitive alpha-adrenergic blockade of post
ganglionic synapses in smooth muscle, exocrine glands
PHARMACOKINETICS
Half-Life: 24 hr
Onset: Several hours
Duration: 3 days
Bioavailability: 20-30%
Metabolism: Extensively metabolized in liver
Metabolite: N-phenoxyisopropyl-benzylamine
Excretion: Urine & feces

ADVERSE EFFECTS
Orthostatic Fatigue Vomiting
hypotension Malaise Inhibition of
Tachycardia Sedation ejaculation
Dizziness Dry mouth Miosis
Drowsiness Nausea Nasal congestion

Prazosin is currently approved for the treatment of hypertension. Prazosin improves urine flow
rates by relaxing smooth muscle. Relaxation is produced by blocking alpha-1 adrenoreceptors in
the bladder neck and prostate. The advantage of prazosin over nonselective alpha-adrenergic
blockers includes a lower incidence of adverse effects. Because of availability of longer-acting,
once-daily selective agents, however, the clinical utility of prazosin for BPH has been reduced.
Prazosin improves urinary flow rate and frequency of micturition. Subjective improvement is
observed in 82% of patients treated. When increasing dosages, administer the first dose of each
increment at bedtime to reduce syncopal episodes. Although doses above 20 mg/d do not
usually increase efficacy, some patients may benefit from up to 40 mg/d.

MECHANISM OF ACTION: Alpha-1 blocker inhibits postsynaptic alpha-adrenergic receptors,

causing arterial and venous dilation and a subsequent decrease in blood pressure
ABSORPTION
Bioavailability: 43-82%
Onset: ~2 hr
Duration: 10-24 hr
Peak effect: 2-4 hr
Peak plasma time: 2-3 hr
DISTRIBUTION
Protein bound: 97%
METABOLISM
Hepatic metabolization (extensive)
ELIMINATION
Half-life elimination: 2-3 hr
Excretion: Urine (6-10%); rest in feces (via bile)
ADVERSE EFFECTS:
1-10% Drowsiness (8%) Weakness (7%)
Dizziness (10%) Headache (8%) Asthenia (6.5%)
 Nausea (5%) Syncope Abnormal liver function tests
Palpitation (5%) Fever Impotence
FREQUENCY NOT DEFINED Rash Pancreatitis
(SELECTED) Abdominal discomfort/pain Urinary incontinence
Edema Diarrhea
Orthostatic hypotension Vomiting

Alfuzosin is indicated for the treatment of the signs and symptoms of BPH. Alfuzosin is an alpha-1
blocker of adrenoreceptors in the prostate. Blockade of adrenoreceptors may cause smooth
muscles in the bladder neck and prostate to relax, resulting in improvement in urine flow rate
and reduction in symptoms of BPH.
MECHANISM OF ACTION: Selective antagonist of postsynaptic alpha-1-adrenoceptors; blockade
of adrenoreceptors in the prostate, prostatic capsule, bladder neck and prostatic urethra
ABSORPTION
Bioavailability: 49%
Peak Plasma Time: 8 hr
Peak Plasma Concentration: 13.6 ng/mL
AUC: 194 ng.hr/mL
DISTRIBUTION
Protein Bound: 82-90%
Vd: 3.2 L/kg
METABOLISM
Hepatic P450 enzyme CYP3A4
ELIMINATION
Half-life: 5-10 hr
Excretion: Feces (69%); urine (24%)
ADVERSE EFFETCS:
1-10% Dizziness (5.7%) Pharyngitis (1-2%)
Abdominal pain (1- Dyspepsia (1-2%) URT infection (3%)
2%) Fatigue (2.7%) Sinusitis (1-2%)
Back pain (1-2%) Headache (3%) Upper respiratory
Brochitis (1-2%) Impotence (1-2%) infection (3%)
Constipation (1-2%) Nausea (1-2%)
POSTMARKETING REPORTS
General disorders: Edema
Cardiac disorders: Tachycardia, chest pain, angina pectoris in patients with pre-existing
coronary artery disease, atrial fibrillation
Gastrointestinal disorders: Diarrhea
Hepatobiliary disorders: Hepatocellular and cholestatic liver injury (including cases with
jaundice leading to drug discontinuation)
Upper respiratory system: Rhinitis
Reproductive system: Priapism
Dermatology: Rash, pruritus, urticaria, angioedema, toxic epidermal necrolysis
Vascular disorders: Flushing
Blood and lymphatic system disorders: Thrombocytopenia
Terazosin is a quinazoline compound that counteracts alpha1-induced adrenergic contractions of
bladder neck, facilitating urinary flow in the presence of BPH. It is indicated for the treatment of
symptomatic BPH and hypertension. Its effect on voiding symptoms and flow rates is dose-
dependent. It improves irritative and obstructive voiding symptoms. Improvement in flow rate is
objective. A Hytrin starter pack is available for easy dosing progression to 5 mg.
MECHANISM OF ACTION: Blocks postsynaptic alpha-1 receptor; alpha blockade causes arterial
and venous dilation. Selective agents cause less tachycardia than do nonselective agents
 ABSORPTION
Bioavailability: 90%
Onset (hypertension): 3 hr
Onset (benign prostate hyperplasia): 2 weeks
Duration: 24 hr
Peak response (benign prostate hyperplasia): 4-6 weeks
Peak plasma time: 1 hr
DISTRIBUTION
Protein bound: 90-94%
Vd: 25-30 L
METABOLISM
Metabolized extensively via hydrolysis, O-demethylation, and N-dealkylation in liver
Metabolites: 6- and 7-O-demethyl terazosin, piperazine derivative, diamine metabolite
ELIMINATION
Half-life: 9-12 hr
Renal clearance: 9-12.5 mL/min
Excretion: Feces (55-60%); urine (40%)
ADVERSE EFFECTS:
>10% Somnolence (3-5%) Flulike syndrome
Dizziness (10-20%) Palpitation (4%) (2.4%)
Asthenia (2-13%) Nausea (2-4%) Tachycardia (2%)
1-10% Edema (3%) Amblyopia (1-2%)
Hypotension (3-7%) Sinusitis (3%) Blurred vision (1-
Rhinitis/nasal Dyspnea (2-3%) 2%)
congestion (2-6%) Fatigue (2.5%) Impotence (1-2%)
Lightheadedness (3- Headache (2.5%) Syncope (1%)
5%) Back pain (2.4%)

Doxazosin is indicated for the treatment of urinary outflow obstruction and irritative symptoms
associated with BPH and hypertension. It inhibits postsynaptic alpha-adrenergic receptors,
resulting in vasodilation of veins and arterioles and a decrease in total peripheral resistance and
blood pressure. It is a long-acting alpha1-blocking agent with a profile similar to that of terazosin.
Doxazosin improves irritative and obstructive voiding symptoms.
MECHANISM OF ACTION
Hypertension: Blocks postsynaptic alpha1 receptors; alpha blockade causes arterial,
arteriolar, and venous dilation; decreases total peripheral resistance and blood pressure
Benign prostatic hyperplasia (BPH): Blocks alpha1 receptors in prostatic stromal and bladder
tissues; reduces sympathetic tone-induced urethral stricture responsible for BPH symptoms
ABSORPTION
Bioavailability: Immediate release, 65%; extended release, 54-59%
Onset (antihypertensive response): Peak, 4-8 hr
Onset (BPH response): Initial, 2 wk; peak, 4-6 weeks
Duration: 24 hr
Peak plasma time: 2-3 hr
DISTRIBUTION
Protein bound: 99%
Vd: 1-3.4 L/kg
METABOLISM
Metabolized extensively in liver
Metabolites: 6- and 7-O-demethyl metabolites, 6'- and 7'-hydroxy metabolites, other minor
metabolites (activity unknown)
ELIMINATION
 Half-life: Immediate release, 22 hr; extended release, 15-19 hr
Dialyzable: HD, no
Total body clearance: 83-140 mL/min
Excretion: Feces (65%), urine (0.6-9%)
ADVERSE EFFECTS
>10% Upper respiratory tract Hypotension (1-2%)
Dizziness (5-19%) infection (URTI) (5%) Nausea (1-2%)
Fatigue (8-12%) Edema (3-4%) Orthostatic hypotension
Headache (6-10%) Rhinitis (3%) (dose related) (0.3-2%)
1-10% Dyspnea (1-3%) Anxiety (1%)
Vertigo (7%) Abdominal pain (2%) Palpitations (1%)
POSTMARKETING EXPERIENCE
Autonomic Nervous System: Priapism
Cardiovascular System: Cerebrovascular accidents, dizziness postural, myocardial infarction
Central and Peripheral Nervous System: Hypoesthesia, paresthesia
Endocrine System: Gynecomastia
Gastrointestinal System: Gastrointestinal obstruction, vomiting
General Body System: Fatigue, hot flushes, malaise
Heart Rate/Rhythm: Bradycardia, cardiac arrhythmias
Hematopoietic: Leukopenia, purpura, thrombocytopenia
Liver/Biliary System: Abnormal liver function tests, hepatitis, hepatitis cholestatic, jaundice
Musculoskeletal System: Muscle cramps, muscle weakness
Psychiatric: Agitation, anorexia, nervousness
Respiratory System: Bronchospasm aggravated
Skin Disorders: Alopecia, urticaria, skin rash, pruritus
Special Senses: Blurred vision, intraoperative Floppy Iris Syndrome
Urinary System: Hematuria, micturition disorder, micturition frequency, nocturia and
polyuria
Tamsulosin is indicated for the treatment of the signs and symptoms of BPH. It is an alpha-
adrenergic blocker specifically targeted to alpha-1 receptors. Tamsulosin has the advantage of
producing relatively less orthostatic hypotension; it requires no gradual up-titration from the
initial dosage. It inhibits postsynaptic alpha-adrenergic receptors, resulting in vasodilation of
veins and arterioles and a decrease in total peripheral resistance and blood pressure. It improves
irritative and obstructive voiding symptoms.
MECHANISM OF ACTION: Blocks alpha1a adrenergic receptor in smooth muscle of prostate,
decreasing bladder neck and urethral resistance
ABSORPTION
Bioavailability: Fasting, 30%
Onset: 4-8 hr
Peak plasma time: With food, 6-7 hr; fasting, 4-5 hr
DISTRIBUTION
Protein bound: 90%
Vd: 0.2 L/kg or 16 L
METABOLISM
Metabolized in liver
Metabolites: Glucuronide and sulfate conjugates (inactive)
ELIMINATION
Half-life: 14-15 hr
Excretion: Urine (76%), feces (21%)
ADVERSE EFFECTS:
>10% Orthostatic hypotension (6- Rhinitis (13-18%)
Headache (19-21%) 19%)
Abnormal ejaculation (8- Skin rash (7%) Sinusitis (2-4%)
18%) Pharyngitis (5-6%) Abdominal discomfort (2-
Dizziness (15-17%) Diarrhea (4-6%) 3%)
Arthralgia (11%) Myalgia (5%) Bitter taste (2-3%)
Infection (9-11%) Chest pain (4%) Decreased libido (1-2%)
1-10% Cough (3-4%) Insomnia (1-2%)
Asthenia (8%) Somnolence (3-4%)
Back pain (7-8%) Nausea (2-4%)
POSTMARKETING REPORTS
Priapism (rare)
Signs and symptoms of orthostasis, including syncope
Infrequent reports of dyspnea, palpitations, hypotension, atrial fibrillation, arrhythmia, and
tachycardia
Visual impairment
During cataract and glaucoma surgery, a variant of small pupil syndrome known as
Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha1
blocker therapy
Skin desquamation including reports of Stevens-Johnson syndrome, erythema multiforme,
and dermatitis exfoliative
Constipation, vomiting, and epistaxis
Allergic-type reactions (eg, skin rash, urticaria, pruritus, angioedema, respiratory symptoms)
have been reported with positive rechallenge
Dry mouth
2. 5-ALPHA REDUCTASE INHIBITORS
Finasteride is indicated for the treatment of symptomatic BPH in men with an enlarged prostate.
When combined with doxazosin, it can also reduce the risk of symptomatic progression of BPH.
Finasteride inhibits conversion of testosterone to DHT, causing serum DHT levels to decrease. It
is beneficial in men with prostates larger than 40 g and can improve symptoms and reduce
prostatic size by 20-30%. Reduction in prostate size is sustained for 5 years following treatment.
Finasteride improves urinary flow rate by 2 mL/s.
MECHANISM OF ACTION: Selective inhibitor of type 1 & type 2 isoforms of 5-alpha-reductase;
suppresses serum dihydrotestosterone levels by inhibiting the conversion of testosterone to
dihydrotestosterone
ABSORPTION
Bioavailability: 65%
Onset: 6 months (BPH); >3 months (hair loss)
Peak plasma time: 2-6 hours
DISTRIBUTION
Protein bound: 90%
Vd: 76 L
METABOLISM
Hepatic CYP3A4
Metabolites: t-butyl side chain monohydroxylate, monocarboxylic acid metabolite (active)
ELIMINATION
Half-life: 6 hours
Excretion: Feces (57%); urine (39%)
ADVERSE EFFECTS
1-10% Breast enlargement (0.5- <1%
Erectile dysfunction (1.3- 1.8%) Breast tenderness (0.4-
8.1%) Ejaculation disorder (0.8- 0.7%)
Decrease libido (1.8-6.4%) 1.2%) Rash (0.5%)
 POSTMARKETING REPORTS:
Neoplasms: Male breast cancer
Breast disorders: Breast tenderness and enlargement
Nervous system/psychiatric: Depression
Hypersensitivity reactions: Rash, pruritus, urticaria, and angioedema (including swelling of
the lips, tongue, throat, and face)
Reproductive system: Sexual dysfunction that continued after discontinuation of treatment,
including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders;
male infertility and/or poor seminal quality (normalization or improvement of seminal quality
has been reported after discontinuation of finasteride); testicular pain

Dutasteride is indicated for the treatment of BPH as monotherapy or in combination with

tamsulosin. Dutasteride improves symptoms, reduces urinary retention, and may decrease the
need for BPH-related surgery. It inhibits 5alpha-reductase isoenzymes types I and II. This agent
suppresses conversion of testosterone to DHT by more than 95%, causing serum DHT levels to
decrease.
MECHANISM OF ACTION: Selective inhibitor of type 1 and type 2 isoforms of 5-alpha-reductase;
suppresses serum dihydrotestosterone levels by inhibiting the conversion of testosterone to
dihydrotestosterone
ABSORPTION
Bioavailability: 60%
Onset: 1-2 weeks
Peak plasma time: 2-3 hours
DISTRIBUTION
Protein bound: 99%
Vd: 300-500 L
METABOLISM
Hepatic P450 enzyme CYP3A4 & CYP3A5
Metabolites, major: 4'-hydroxydutasteride, 6-hydroxydutasteride (as active as parent), 1,2'-
dihydrodutasteride
ELIMINATION
Half-life: 5 weeks (at steady state)
Excretion: Feces (40%), urine (<1%)
ADVERSE EFFECTS:
Adverse reactions decrease with duration of treatment, except for gynecomastia
1-10% <1% Prostate cancer (high
Impotence Dizziness grade)
Decreased libido FREQUENCY NOT
Ejaculation disorder DEFINED
Breast disorders Cardiac failure

POSTMARKETING REPORTS
Immune system disorders: Hypersensitivity reactions, including rash, pruritus, urticaria,
localized edema, serious skin reactions, and angioedema
Neoplasms: Male breast cancer
Psychiatric disorders: Depressed mood
Reproductive system and breast disorders: Testicular pain and testicular swelling
3. PHOSPHODIESTERASE 5 ENZYME INHIBITORS
 Tadalafil is a PDE5 selective inhibitor. Inhibition of PDE5 increases cGMP activity, which increases
vasodilatory effects of nitric oxide. Sexual stimulation is necessary to activate response. Tadalafil
has been approved by the FDA for the treatment of BPH signs and symptoms.
PDE5 inhibition has been shown to induce smooth muscle relaxation in the lower urinary tract. It
has also been approved for the treatment of simultaneous BPH and ED.
Increased sensitivity for erections may last 36 h with intermittent dosing. Low-dose daily dosing
may be recommended for more frequent sexual activity (ie, twice weekly); men can attempt
sexual activity at anytime between daily doses.
MECHANISM OF ACTION
Erectile dysfunction: Inhibits PDE-5, increasing cyclic guanosine monophosphate (cGMP) to
allow smooth-muscle relaxation and inflow of blood into corpus cavernosum
Pulmonary arterial hypertension (PAH): Inhibits PDE-5, increasing cGMP to allow relaxation
of pulmonary vascular smooth-muscle cells and vasodilation of pulmonary vasculature
ABSORPTION
Duration: 36 hr
Peak plasma time: Erectile dysfunction, 0.5-6 hr; PAH, 2-8 hr
DISTRIBUTION
Protein bound: 94%
Vd: Erectile dysfunction, 63 L; PAH, 77 L
METABOLISM
Metabolized in liver by CYP3A4
ELIMINATION
Half-life: Erectile dysfunction, 15-17.5 hr; PAH (not on bosentan), 35 hr
Total body clearance: Erectile dysfunction, 2.5 L/hr; PAH (not on bosentan), 1.6 L/hr
Excretion: Feces (61%), urine (36%)
ADVERSE EFFECTS:
>10% Nasal congestion Arthralgia
Headache (11-42%) (9%) Change in color
Myalgia (1-14%) Gastroesophageal vision
Respiratory tract reflux disease (1- Conjunctival
infection (3-13%) 3%) hyperemia
Nasopharyngitis (2- Hypertension (1- Dyspnea
13%) 3%) Epistaxis
Dyspepsia (1-13%) Bronchitis (2%) POSTMARKETING
Flushing (1-13%) Genitourinary tract REPORTS
Back pain (2-12%) infection (2%) Hypotension
Nausea (10-11%) <1% Visual Loss
1-10% Amnesia Hearing loss
Angina pectoris Priapism