Genitourinary

Question 1

α-blockers : Examples

Answer 1

• Doxazosin
• Tamsulosin
• Alfuzosin

Question 2

α-blockers : Indications

Answer 2

1) 1st line in BPH

2) Add-on treatment in resistant hypertension

Question 3

α-blockers : MOA

Answer 3

• α1-adrenoceptors are found mainly in smooth muscle, including in blood vessels and the urinary tract (the bladder neck and prostate in particular).
• Stimulation induces contraction; blockade induces relaxation.
• α1-blockers therefore cause vasodilatation and a fall in blood pressure (BP), and reduced resistance to bladder outflow.

Question 4

α-blockers : Adverse Effects

Answer 4

• Postural hypotension
• Dizziness
• Syncope
  (most prominent after 1st dose)

Question 5

α-blockers: Contraindications

Answer 5

• Existing postural hypotension

Question 6

α-blockers: Interactions

Answer 6

• Other anti-hypertensive (may be intentionally used for therapeutic aim)
• -> omit 1 dose of other anti-hypertensives when starting this medication

Question 7

α-blockers : Prescribing

Answer 7

• Oral

- Best to take at night time

Question 8

α-blockers: Monitoring

Answer 8

• Efficacy dependent on urinary symptoms

Question 9

α-blockers: Patient Education

Answer 9

• Explain about side effect after 1st dose

Question 10

Antimuscarinics - Examples

Answer 10

• Oxybutynin
• Tolterodine
• Solifenacin

Question 11

Antimuscarinics - Indications

Answer 11

• Reduce urinary frequency, urgency and urge incontinence in overactive bladder

Question 12

Antimuscarinics - MOA

Answer 12

• Antimuscarinic drugs bind to muscarinic receptors, where they act as a competitive inhibitor of acetylcholine.
• Contraction of the smooth muscle of the bladder is under parasympathetic control.
• Blocking muscarinic receptors therefore promotes bladder relaxation, increasing bladder capacity.
• In patients with overactive bladder, this may reduce urinary frequency, urgency and urge incontinence.
• Antimuscarinics help in overactive bladder through antagonism of the M3 receptor, which is the main muscarinic receptor subtype in the bladder.
• Solifenacin is more selective for the M3 receptor, which may reduce side effects.

Question 13

Antimuscarinics - Adverse Effects

Answer 13

• Dry mouth
• Tachycardia, constipation + blurred vision
• Urinary retnetion

Question 14

Antimuscarinics - Contraindications

Answer 14

• UTI

Question 15

Antimuscarinics - Caution

Answer 15

• Elderly especially with dementia
• Angle-closure glaucoma : dangerous rise in intraocular pressure
• Arrhythmias
• Urinary retention

Question 16

Antimuscarinics - Interactions

Answer 16

• Tricyclic antidepressants (causes more adverse effects)

Question 17

Antimuscarinics - Prescribing

Answer 17

• only prescribe for urge incontinence after an adequate trial of bladder retraning

Question 18

Antimuscarinics - Monitoring

Answer 18

• Review within a month of starting therapy to check response and SE

Question 19

Antimuscarinics - Patient education

Answer 19

• Medication relaxes bladder
• reduces how often they need to pass water
• Explain SE - dry mouth
• Safety net- in elderly, stop if there is drowsiness and confusion

Question 20

Phosphodiesterase (type 5) inhibitors : Examples

Answer 20

Sildenafil

Question 21

Phosphodiesterase (type 5) inhibitors: Indications

Answer 21

1) Erectile dysfunction

2) Primary pulmonary hypertension

Question 22

Phosphodiesterase (type 5) inhibitors : MOA

Answer 22

• PDE type 5 (PDE-5) is found predominantly in the smooth muscle of the corpus cavernosum of the penis and arteries of the lung.
• For an erection to occur, sexual stimulation is required.
• This releases nitric oxide (NO), which stimulates cyclic guanosine monophosphate (cGMP) production, causing arterial smooth muscle relaxation, vasodilatation and penile engorgement.
• As PDE-5 is responsible for the breakdown of cGMP, inhibition of this enzyme by sildenafil increases cGMP concentrations, improving penile blood flow and erection quality.
• Sildenafil does not cause an erection without sexual stimulation.
• In the pulmonary vasculature, sildenafil causes arterial vasodilatation by similar mechanisms and so is used to treat primary pulmonary hypertension.

Question 23

Phosphodiesterase (type 5) inhibitors : Adverse Effects

Answer 23

SE due to vasodilator:

• Flushing
• Headache
• Dizziness
• Nasal congestion

More serious:

• Hypotension
• Tachycardia
• Palpitation
• Visual disorders (colour distortion)

Question 24

Phosphodiesterase (type 5) inhibitors : Contraindication

Answer 24

• Stroke
• ACS
• Cardiovascular disease

Question 25

Phosphodiesterase (type 5) inhibitors : Caution

Answer 25

- Hepatic or renal impairment

Question 26

Phosphodiesterase (type 5) inhibitors : Interactions

Answer 26

Should not be prescribe with: - nitrated or nicorandil (increases nitric oxide conc, increased vasodilation) Caution with other vasodilators: - α-blockers - CCB Cytochrome P450 inhibitors: - e.g. amiodarone, diltiazem + fluconazole - SE increased

Question 27

Phosphodiesterase (type 5) inhibitors : Prescribing

Answer 27

- Take 1 hour before sex (max 1 dose a day) | - if taken with food, onset of effect is delayed

Question 28

Phosphodiesterase (type 5) inhibitors : Monitoring

Answer 28

- Review for therapeutic efficacy and SE | - Pulmonary hypertension - review regularly with a specialist

Question 29

Phosphodiesterase (type 5) inhibitors : Patient Education

Answer 29

- Explain: drug will not produce an erection without sexual stimulation but only helps them have and maintain it.

Question 30

5α-reductase inhibitors: Examples

Answer 30

Finasteride

Question 31

5α-reductase inhibitors: Indications

Answer 31

BPH - 2nd line after α-blockers - improve LUTs (urinary retention, poor floor)

Question 32

5α-reductase inhibitors: MOA

Answer 32

- 5α-reductase inhibitors reduce the size of the prostate gland. - They do this by inhibiting the intracellular enzyme 5α-reductase, which converts testosterone to its more active metabolite dihydrotestosterone. - As dihydrotestosterone stimulates prostatic growth, inhibition of its production by 5α-reductase inhibitors reduces prostatic enlargement and improves urinary flow. - However, it can take several months for this effect to become evident clinically. - For this reason, an α-blocker is usually preferred for initial therapy, with a 5α-reductase inhibitor added if the response is poor or if the prostate is particularly bulky.

Question 33

5α-reductase inhibitors: Adverse Effects

Answer 33

- Impotence + reduced libido - Gynaecomastia - Hair growth - Breast cancer

Question 34

5α-reductase inhibitors: Contraindications

Answer 34

- Pregnant women

Question 35

5α-reductase inhibitors: Interactions

Answer 35

None

Question 36

5α-reductase inhibitors: Prescribing

Answer 36

- Oral

Question 37

5α-reductase inhibitors: Monitoring

Answer 37

- Follow-up 3-6 months to review LUTs and SE | - Continue check-ups every 6-12 months while on treatment

Question 38

5α-reductase inhibitors: Patient Education

Answer 38

- Main of treatment is to reduce the bulk of the prostate gland - -> relive compression on the tube and easier to pass urine - May take upto 6 months for symptoms to improve - SE: less keen to have sex, inability to get or keep an erection