Sheehy GU lecture

Question 1

LO#1 List male lower urinary tract symptoms (LUDS)

Answer 1

interrupted stream, fullness, frequency, hesitation, weak stream, dribbling, urgency stream

Question 2

LO#1 explain how α1 adrenergic receptor antagonists relive LUDS

Answer 2

α1A receptors + NE

• Muscle contraction
• Bladder outlet obstruction

α1D receptors + NE

• Detrusor instability

α1 antagonists compete with NE

• Reduce spasm
• Promote muscle relaxation
• Improve urine flow

Question 3

α1 adrenergic receptor antagonists: Clinical summary

Answer 3

Best monotherapy for prompt relief of symptoms (days)

Question 4

terazosin and doxazosin

Answer 4

alpha-1 AR >>>>> alpha 2 AR

Not uroselective

AE: postural hypotension, dizziness, fatigue

drug interactions: PDE-5 inhibitors (sildenafil and vardenfil)

Question 5

Tamsulosin

Answer 5

alpha 1A = alpha 1D > alpha 1B specificity

uroselectivity for ARs 1a, 1d, 1b

Drug interactions: PDE-5

CYP34

AE: reduced ejaculation, IFIS (intraoperative flippy iris syndrome)

Question 6

Silodosin

Answer 6

alpha 1A = alpha 1D > alpha 1B

uroselective for AR 1a, 1,d, 1b

AE: reduced ejaculation, IFIS

Drug interactions: PDE-5

Question 7

Alfuzosin

Answer 7

non-specific alpha 1 anatognists

urothelial selective: yes for alpha 1

AE: QT prolongation

Drug interactions: PDE-5

CYP3A4 inhibitor

Question 9

alpha 1 AR anatagonists

Answer 9

Terazosin, Doxazosin, Silodosin, tamsulsosin,

Question 10

5alpha- inhibitors

Answer 10

Finasteride, dutasteride

Prevents enlargement and shrinks prostate

Delayed action

Shrinkage and symptom relief takes 3-6 months

alpha 1’s work in an hour or so

Question 11

finasteride

Answer 11

SpeciFIc inhibitor SAR-2

Question 12

dunasteride

Answer 12

DUal inhibitor SAR-1 & 2

Question 13

Finasteride and dunasteride

Answer 13

reduce prostate DHT by 90%

reduce serum T 15-20%

F reduces serum DHT (70%); D reduces serum DHT (90%)

PSA reduced (50%)

fin > SAR 2; dun SAR 1 + SAR 2 selectivities

1-2%: gynecomastira; 2-4% ejaculation disturbances; 4-6% depressed libido; 7-8% erectile dysfunction (growing tits, cant cum, dont care, cant get hard)

Question 14

finasteride and dunasteride AEs and the reason it’s ok for certain patients with common issues

Answer 14

1-2%: gynecomastira; 2-4% ejaculation disturbances; 4-6% depressed libido; 7-8% erectile dysfunction (growing tits, cant cum, dont care, cant get hard)

no need to adjust this drug to factor in age or renal dysfunction, no known drug interactions, metabolized by CYP3A so be careful when giving to a CYP3A4 inhibitor

Question 15

combination therapy

Answer 15

combination therapy:
α1 adrenergic antagonist + 5α reductase inhibitor

• When to use:
• Severe symptoms of BPH
• Known to have large prostate
• No response from monotherapy

• Long term combination therapy significantly improves patient symptoms (66%) versus either drug alone

Question 16

PDE-5 inhibitors

Answer 16

erectile dysfunction

Consistent or recurrent inability to acquire or sustain an erection of sufficient rigidity and duration for sexual intercourse

• Risk factors
• Obesity
• Smoking
• Stress
• Cardiovascular disease
• Adverse drug effect
• Diuretics, antidepressants(SSRIs)

Question 17

Physiology of penile erection

Answer 17

Physiology of penile erection

• Blood flows into corpora cavernosa and corpus spongiosum (glans penis)
• Nitric oxide facilitates smooth muscle relaxation
• Maximize blood flow
• Penile engorgement
• Relaxed smooth muscle leads to blood in sinusoids and a rigid organ