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3152 - nat > ic16, ic19 BPH, ED > Flashcards

ic16, ic19 BPH, ED Flashcards

1
Q

What is the prostate composed of?

A

Epithelial (glandular) tissue
Stimulated by DHT

Smooth muscle tissue
Contains a-1 adrenergic receptors

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2
Q

How does BPH occur?

A

1) Static component (involving epithelial tissue)
Testosterone → DHT by 5a reductase
Prostate tissue enlarges

2) Dynamic component (involving smooth muscle)
A1 receptors activated
Smooth muscle constrict, causes narrowing of urethra

1 + 2 = Urethral obstruction, Symptoms

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3
Q

How does bladder become over-sensitive long term?

A

Initially, bladder can force urine through narrowed urethra
Over time, bladder hypertrophy and decompensates
Bladder becomes overly sensitive, contract abnormally to small amounts of urine

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4
Q

What are some Obstructive symptoms? (6 points)

When does this occur?

A

Hesitancy
Weak stream
Sensation of incomplete emptying
Dribbling
Straining
Intermittent flow

Early in disease

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5
Q

What are some Irritative symptoms? (5 points)

When does this occur?

A

Dysuria (burning sensation)
Frequency
Nocturia
Urgency
Urinary Incontinence

Occurs after years of untreated BPH

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6
Q

What is a normal Postvoid Residual?

What is the cut-off for Anti-muscarinic use?

A

< 100ml

Must be < 250ml

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7
Q

What does Prostate Specific Antigen (PSA) help to predict?

A

Predict progression of BPH

but not specific, could be high due to cancer

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8
Q

Medications and how they contribute to BPH symptoms (5 points)

A

Anticholinergics (eg. antihistamines)
→ Decrease bladder contractility

Opioid analgesics
→ Increase urinary retention

Diuretics
→ Increase urinary frequency

Testosterone (DHT)

A1 adrenergic agonist
→ Contract SM

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9
Q

Non-pharm methods for BPH (4 points)

A

Limit fluid intake at night

Minimise caffeine and alcohol intake

Schedule voiding, empty completely and often

Avoid medications that can exacerbate symptoms eg. diuretics

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10
Q

When to treat BPH? (3 points)

A

When patient is bothered (QOL > 3)
→ Pharmacotherapy

When Uroflow < 10ml/s + PVR > 100ml
→Do surgery

When:
Urinary retention
Haematuria
Recurrent UTI
Bladder stones (calculi)
→Do TURP (surgery)

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11
Q

When do we do watchful waiting?

A

When patient has mild symptoms OR patient is not bothered by symptoms despite having moderate or severe symptoms

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12
Q

Examples of Alpha 1 Antagonists?

Where do they act on?

A

TeD ATaS

Non Selective (Peripheral vessels + Urinary a1 adrenergic receptors)
Terazosin
Doxazosin

Selective a1 antagonist
Alfuzosin
Tamsulosin
Silodosin

Act on the smooth muscle, cause SM relaxation and vasodilation

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13
Q

Difference between Non-selective A1 antagonists VS Selective

A

Non selective:
block peripheral vascular and urinary a1 adrenergic receptors → Cause hypotension

Selective:
Only blocks urinary receptors

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14
Q

Effect of Alpha 1 Antagonists

A

Effective in reducing obstructive symptoms with small prostate (< 40g)
Fast onset

Does not reduce prostate size or PSA
BPH can still progress and Surgery is still needed

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15
Q

Most common side effects for Non-selective and Selective A1 antagonists

A

Non-selective:
Dizziness (take medication at bedtime)

Selective:
Ejaculatory disturbances (Silodosin highest, Alfuzosin lowest)

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16
Q

What must we always check before dispensing A1 antagonists?

A

If patient is going to do cataract surgery

Tamsulosin may cause Intraoperative Floppy Iris Syndrome (IFIS)

If yes, either hold 14 days before surgery or initiate after surgery completed

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17
Q

Absolute contraindication with Non-selective A1 Antaognist

A

History of syncope

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18
Q

What is the MOA of 5a reductase inhibitor?

2 examples of 5ARI

Where does 5ARI act on?

A

Inhibit 5a reductase inhibitor (Type 2), which inhibits Testosterone → DHT

Finasteride, Dutasteride

Acts on glandular tissue, to reduce size of prostate

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19
Q

Who are 5ARI indicated for?

A

Patients with moderate or severe LUTS + Large prostate (> 40g)

if PSA > 1.5ng/mL

20
Q

Effect of 5ARI (2 points)

A

Reduces size of prostate

Decreases PSA levels

21
Q

Counselling points of 5ARI (2 points)

A

1) Slow onset, takes 6-12 months to decrease prostate size

2) Teratogenic
Pregnant or Females of child bearing age should NOT handle these agents

22
Q

Side effects of 5ARI (3 points)

A

Ejaculatory disorders
Decreased libido
Erectile dysfunction

23
Q

What should we do before initiating 5ARI?

A

Obtain baseline PSA

24
Q

What does PDE5i stand for?

Which PDE5i is approved for BPH?
Dose?

Side effect of PDE5i

A

Phosphodiesterase 5 Inhibitor

Tadalafil 5mg OD

Significant hypotension

25
Q

MOA of PDE5i in BPH

A

Affects smooth muscle

Does not affect prostate size

26
Q

What are the 2 combination of drugs for BPH?

A

Alpha 1 Antagonists + 5ARI

FD DTa
Specifically:
Finasteride + Doxazosin
Dutasteride + Tamsulosin

27
Q

Benefits of A1 Antagonist + 5ARI

A

Alpha blockers → fast onset
5ARI → slow onset

For symptomatic patients with enlarged prostate

28
Q

Benefits of 5ARI + PDE5i

A

PDE5i helps to mitigate sexual adverse effects from 5ARI

29
Q

Risk of Alpha 1 Antagonist + PDE5i

A

Both drugs may cause hypotension, use selective alpha blocker instead

Will not decrease prostate size

Optimise Alpha 1 Antagonist dose first before adding PDE5i

30
Q

What drug should be used for irritative bladder symptoms? Example?

What is the MOA?

A

Anti-muscarinics
eg. Oxybutynin
Trospium
“-terodine”
“-fenacin”

MOA:
Decrease involuntary contraction of bladder

31
Q

When can Anti-muscarinics be used

A

PVR < 250ml

32
Q

Physiology of Erection

A

(On the tissue level)
1) Smooth muscle relaxes
→ Corpora Cavernosa fills up with blood
→ Swelling causes a compression of venules

(On the molecular level)
2) Activation of Parasympathetic system
Acetylcholine (Ach) increases Nitric Oxide
→ Increase cGMP
Prostaglandin E increases cAMP
Result: High cGMP, cAMP
→ SM relaxation and Vasodilation → Increase blood inflow

33
Q

Physiology of Detumescence

A

Deactivate Parasympathetic system
cGMP is deactivated by PDE-5 → Cause vasoconstriction / Stop vasodilation

Activate Sympathetic system
Smooth muscle contraction via a2 adrenergic receptors → Reduction of blood flow

34
Q

4 causes of ED

A

Organic:
Vascular
Hormonal
Nervous
Medication induced

Psychogenic:
Feelings

Mixed:
Organic + Psychogenic

Others:
Social habits eg. smoking, alcohol, drug use

35
Q

What is the role of Testosterone?

Normal range of Testosterone

A

To encourage libido

300-1000ng/dl

36
Q

When is Testosterone replacement indicated?

After giving, how to monitor Testosterone?

A

For patients with ED and symptomatic hypogonadism eg. decreased libido

Monitor Testosterone once at first 3 months, and every 6-12 months intervals

Stop if no improvement after 3 months!

37
Q

What is PDE5i

Examples of PDE5i (4 points)
and starting doses

A

Phosphodiesterase 5 inhibitor

SVTA
Sildenafil 50mg
Vardenafil 10mg
Tadalafil 5mg
Avanafil 100mg

38
Q

MOA of PDE5i

A

Inhibit PDE5 enzyme (that breaks down cGMP) → cGMP increases → arterial SM relaxation → Increased arterial flow → Erection

Still require sexual stimulation!

39
Q

Which PDE5i needs to be taken daily?
Why?

A

Tadalafil

Duration of action is 36hrs, so does not need to be taken just before intercourse

40
Q

Which PDE5i needs to be taken before food?

A

Sildenafil
Vardenafil

41
Q

When should a lower dose of PDE5i be used? (4 points)

A

1) Patients > 65 yo

2) Taking alpha blockers

3) Renal failure

4) Taking CYP3A4 inhibitors → Increase serum conc of PDE5i

42
Q

Side effects of PDE5i (7 points)

A

Headache

Hypotension

Priapism
Erection last more than 4hrs, Need to go ED

Hearing loss

QTC prolongation (Vardenafil)

Muscle pain (Tadalafil)

Ocular problems
In Sildenafil and Vardenafil
- Green blue colour discrimination
- Ischemia of optic nerve

43
Q

DDI with PDE5i (4 points)

A

Nitrates
Can cause fatal hypotension
Space 24hrs after sildenafil or vardenafil, 48hrs after tadalafil

Alcohol

Anti-hypertensives

CYP3A4 Inhibitors
Increase conc of PDE5 inhibitors

44
Q

What is Alprostadil?

MOA?

A

Prostaglandin E1 analogue

Increases cAMP → SM relaxation

Does not require sexual stimulation to work!

45
Q

Onset of action of Alprostadil

Dosage forms of Alprostadil

A

5 - 10 mins

1) Intraurethral pellet

2) Intracavernosal injection
Better efficacy
Has highest risk of priapism

46
Q

Who is most likely to benefit from combination therapy of Alpha 1 Antagonist + 5ARI? (3 points)

A

1) Moderate symptoms
IPSS >8
QOL 5-6

2) Prostate size > 25g

3152 - nat (16 decks)

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