Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PR3152 Finals > Men's Health (incl Pharmacology) > Flashcards

Men's Health (incl Pharmacology) Flashcards

1
Q

Describe the pathogenesis of BPH.

A

There are 2 components to BPH - the static component, where prostate tissue is enlarged due to hormonal action of DHT; dynamic component, where urethra outlet is narrowed due to agonism of a1 receptors and activation of smooth muscle tissue. These lead to urethral obstruction.

In the early phases, the bladder muscle is able to force urine through the narrowed urethra. Over time, this results in hypertrophy to overcome the obstruction. Once the detrusor muscle has achieved the highest rate of hypertrophy, it decompensates. The muscle becomes irritable and overly sensitive, contracting abnormally to small amounts of urine in bladder, resulting in various urinary symptoms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define Benign Prostatic Hyperplasia (BPH).

A

BPH is characterized by non-malignant growth of some components (e.g. transitional zone) of the prostate.

It is a progressive condition, with the presence of lower urinary tract symptoms (LUTS), and can negatively impact one’s quality of life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the signs and symptoms of BPH?

A

(Early phase) Obstructive/voiding symptoms
- Dribbling
- Sensation of incomplete emptying
- Hesitancy
- Weak stream
- Straining
- Intermittent flow

(Late phase/left untreated) Irritative/storage symptoms
- Urinary incontinence
- Dysuria
- Nocturia
- Frequency
- Urgency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

State various assessments of BPH.

A

1) Digital Rectal Exam (DRE): Normal prostate should be smooth; additional lumps might indicate BPH -> need for further evaluation

2) Ultrasonography

3) Maximum urinary flow rate

4) Prostate-specific antigen (PSA)
- Elevation may be a good indicator of BPH; positively correlated to prostate volume
- >1.5ng/mL indicate likely progression of BPH

5) Post-void residual (PVR)
- <100mL: normal
- >200mL: inadequate emptying

6) Medication history assessment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the classification of the different severities of BPH, according to the American Urology Association Scoring Index (AUA - SI).

A

Mild: 7 or less. Asymptomatic or mildly symptomatic.

Moderate: 8-19. Both obstructive and irritative symptoms definitely present.

Severe: 20 or more. Symptomatic + 1 or more complications of BPH.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the approach as to whether pharmacological treatment should be started in a patient diagnosed with BPH.

A

If patient
- Has mild BPH or
- Has moderate/severe BPH but unbothered by symptoms (does not affect QoL),
Do NOT start pharmacological treatment. Conduct watchful monitoring instead (more frequent monitoring of LUTS symptoms, labs etc).

Start clinical treatment if
- patient is bothered by symptoms, or
- if complications occur.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List the non-pharmacological strategies to manage BPH.

A
  • Limit caffeine and alcohol intake
  • Limit fluid intake at night
  • Advise patients to take their time to completely empty their bladders on each occasion
  • Consider removing medications that can exacerbate urinary symptoms, if there are no strong indications/has alternatives.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

State the MoA of a1 receptor antagonists.

A

Reversibly inhibit a1 adrenergic receptors on smooth muscles of prostate, prostatic urethra, bladder neck and peripheral vasculature (non-selective).

This leads to decrease in muscle tone, relaxation of smooth muscle, relieving bladder obstruction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the indications for a1 receptor antagonists?

A

General:
- For patients with moderate to severe symptomatic BPH, AND prostate size <40g

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Do a1RAs reduce prostate size and/or delay BPH progression and need for surgery?

A

No. It only provides symptomatic relief.

Signs and symptoms of BPH are likely to recur if medication is discontinued.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the onset of the vasodilatory effect of a1RAs.

A

Relatively fast (days to weeks)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Compare and contrast non-selective and uroselective a1RAs (including comparison for need to dose titrate)

A

Non-selective a1RAs antagonise both peripheral vascular and urinary a1 receptors.
- E.g. doxazosin, terazosin
- Need to titrate slowly to therapeutic dose, to minimise risks of hypotension and syncope

Uroselective a1RAs target urinary a1 receptors selectively hence lesser risks of hypotension.
- E.g. alfuzosin, tamsulosin, silodosin
- Dose titration not necessary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List the side effects of a1RAs.

A
  • General: muscle weakness, fatigue, back pain
  • Intra-operative floppy iris syndrome (IFIS)
  • headache, dizziness, first-dose syncope, orthostatic hypotension (non-selective > selective; consider administering at bedtime to decrease these SE.)
  • delayed/retrograde ejaculation (uroselective > non-selective; < sexual dysfn than 5ARIs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is tamsulosin metabolised?

A

In the liver, by CYP3A4 and CYP2D6 enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the dose of tamsulosin? (FYI)

A

0.4mg orally once daily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is tamsulosin eliminated?

A

Urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

State the MoA of 5-alpha reductase inhibitors (5ARIs).

A

Inhibit Type II 5-alpha reductase in prostate tissues. Decreases the conversion of testosterone to DHT, reducing prostate size.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

State the compelling indications for use of 5ARIs. (4)

A
  • Patients with moderate to severe LUTS with large prostate (>40g)
  • Patients who want to avoid surgery
  • Patients who are intolerant to side effects of a1RAs
  • PSA >1.5ng/mL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Do 5ARIs slow progression of BPH and delay need for surgery?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the onset of effect of 5ARIs.

A

Slow onset of action (may take up to 6-12 mths to decrease prostate size)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

List the side effects of 5ARIs. (5 total)

A
  • Ejaculatory disorders (reduced semen, delayed ejaculation)
  • Decreased libido
  • ED
  • Gynecomastia, breast tenderness
  • Hypotension (less compared to a1RAs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

State the indications for use of PDE-5Is in BPH.

A
  • Add-on therapy, especially for patients with BPH + ED
  • Increasing evidence of monotherapy for BPH, but still controversial
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

State the general indications for use of combination therapies in BPH.

A

Patients with moderate to severe symptoms (AUA - SI score of 8 and above) and prostate size >25g

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which PDE-5I is FDA-approved for use in BPH?

A

Tadalafil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Do PDE-5Is have an effect on prostate size?

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

List the specific indications and considerations (pros and cons) for each combination therapy for BPH.

A

1) a1RA + 5ARI
- Reserved for symptomatic pts with enlarged prostate
- Dilatory effect (fast onset) + dec in prostate size (slow onset)
- Disadvantage: Worsen or new onset ED

2) 5ARI + PDE-5I
- Mitigate sexual adverse effects that may arise from concomitant ED/5ARI
- Do not initiate PDE-5I if pt has unstable angina (due to nitrate use)

3) a1RA + PDE-5I
- Dual vasodilator therapy
- Rarely used due to possible severe life-threatening hypotension
- Keep doses of both drugs as low as possible
- Optimise a1RA dose first before adding PDE-5I
- Does not have an effect on prostate size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

State the indications for use of anti-muscarinics in BPH.

A

Add-on for patients with irritative voiding symptoms, which mimic overactive bladder.

PVR must be <250mL (if not too much urine will be retained in bladder upon initiation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

State the dose of Finnasteride. (FYI)

A

5mg orally once daily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How is Finasteride metabolised?

A

CYP3A4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How is Finasteride eliminated?

A

50% excreted unchanged in faeces

Metabolites also found in urine and faeces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Define erectile dysfunction (ED).

A

Persistent (6 months or more) inability to achieve or maintain an erection of sufficient duration and firmness to complete satisfactory intercourse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is the normal range of testosterone levels?

A

300-1000ng/dL (10-40nmol/L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Are testosterone levels a good gauge of whether a patient has ED?

A

No. Testosterone levels should be assessed in perspective of reported patient symptoms. Low testosterone does not necessarily equate to ED.

34
Q

Describe the physiology of an erection

A

Parasympathetic system is activated upon sexual arousal. Acetylcholines (ACh) are released
- Inc NO -> Inc guanylate cyclase activity -> Inc cGMP
- Inc ACh and Prostgladin E -> Inc adenylyl cyclase -> Inc cAMP

Leads to smooth muscle relaxation and vasodilation (via a2 adrenergic receptors).

The corpora cavernosa fills up with blood. Swelling causes compression of venules against tunica albuginea, which decrease the outflow of blood.

Parasympathetic system is subsequently deactivated by PDE-5, which deactivates cGMP

35
Q

What are the different types of ED and their respective causes?

A

Organic ED
1) Vascular: atherosclerosis, PVD, HTN, DM

2) Hormonal: hypogonadism, hyperprolactinemia

3) Nervous:
* Central: Spinal cord trauma or disorders, Stroke, CNS Tumors
* Peripheral: Diabetes, Neuropathy, Urethral surgery

4) Medication-induced (antihypertensives, anticholinergics, SSRIs, 5ARIs, anticonvulsants)

Psychogenic ED
- Thoughts/feelings
- Malaise, loss of attraction, stress, performance anxiety, mental disorders, sedation

Others
- Social habits e.g. smoking, excessive alcohol intake, illicit drug use
- Obesity

36
Q

Describe the clinical presentation of ED.

A
  • Loss of interest in sexual activities
  • Depression, low self-esteem
  • Performance anxiety, embarrassment
  • Anger
37
Q

Describe the classification of severity of ED using the Sexual Health Inventory for Men (SHIM).

A

Mild/no ED: 17-21 pts
Moderate to severe ED: <11 pts

38
Q

List the pertinent patient information involved in evaluation of ED. (7 total)

A
  • Medication history/ Current medications
  • Social history
  • Surgical history (esp genitourinary area)
  • Lab results (testosterone, blood glucose, lipid profile)
  • CVD risk evaluation (stress testing in those with unknown/moderate-to-high risk)
  • Sexual Health Inventory for Men score
  • Signs and symptoms
39
Q

List the non-pharmacological strategies in managing ED.

A

Address modifiable risk factors
- Smoking cessation
- Weight control
- Limit alcohol intake
- Exercise
- Control glucose, BP, lipid levels

Psychotherapy (stress assessment; therapy)

Devices (e.g. vacuum erection devices);

Surgery (e.g penile implants)

40
Q

State the general starting dose for Sildenafil. (FYI)

A

4mg OD

41
Q

How is Sildenafil metabolised?

A

CYP3A4 (major), CYP2C9 (minor)

42
Q

How is Sildenafil eliminated?

A

Metabolites largely excreted in faeces

43
Q

Describe the place in therapy of PDE-5Is in ED.

A
  • First-line agents for ED
44
Q

List the side effects of PDE-5Is. (~6)

A

1) Ocular disturbances (mostly sildenafil and vardenafil due to PDE-6 affinity)
- NAION
- Light sensitivity
- Reversible issues with blue-green discrimination

2) Muscle pain (esp w tadalafil w PDE-11 affinity)

3) QTc prolongation (mostly w vardenafil)

4) Vasodilatory effects (Headache, dizziness, hypotension, rhinitis, flushing, muscle and back pain)

5) Sudden hearing loss (rare; may co-present with tinnitus and dizziness)

6) Prolonged erections; priapisms (seek ED treatment if lasts for 3h or more)

45
Q

Compare and contrast the different types of PDE-5Is for ED, in terms of onset of action, duration of action and administration requirements.

A

Administration before intercourse
- Sildenafil and Vardenafil: 1h before
- Avanafil: 30min before
- Tadalafil: up to 36h before

Onset of action
- Sildenafil and Vardenafil: 15min to 1h
- Avanafil: 15-30min
- Tadalafil: 15min to 2h

Duration of action
- Sildenafil and Vardenafil: 4h
- Avanafil: 6h
- Tadalafil: 36h

Administration requirements
- Sildenafil and Vardenafil: Take on empty stomach
- Tadalafil and Avanafil: take regardless of food

TLDR:
- Tadalafil longest duration of action (36 hours), the rest (4-6 hours)
- Other than Tadalafil, the rest have to take 30-60 mins before sex
- T and A can take regardless of food, V and S take before food on empty stomach.

46
Q

In which groups of patients should a lower initial dose of PDE-5Is be started?

A
  • Age 65 and above
  • Taking alpha blockers
  • Renal failure
  • Taking CYP3A4 inhibitors (e.g. itraconazole, erythromycin, cimetidine, ketoconazole, clarithromycin, grapefruit or grapefruit juice, ritonavir, saquinavir)

Basically CYP3A4is are: Macrolide, Azoles, Grapefruit, PK inhibitor

47
Q

What are some follow-up actions to be taken if PDE-5I therapy fails for a patient?

A
  • Enquire if patient is administering PDE-5I correctly (administration with food?, timing and freq of dosing, got sexual stimulation?)
  • Encourage pt to try at least 5-6 times
  • Titrate dose if needed
  • If all modifiable factors have been addressed and Pt alr at maximum dose, switch to another PDE-5I or proceed with other more invasive therapy
48
Q

What are the indications for use of testosterone replacement in ED?

A
  • Symptomatic hypogonadism (decreased libido AND decreased serum testosterone levels)
49
Q

Describe the monitoring of ED in patients undergoing testosterone replacement.

A
  • Monitor in 1-3 months upon initiation/ after titration of therapy; once serum levels stable, every 6-12 months
  • Discontinue if no improvement in ED after 3 months
50
Q

List the side effects of testosterone replacement

A
  • Aggressive behavior
  • hair growth
  • Irritability
  • hepatotoxicity
  • Increased BP
  • Polycythemia (inc RBC count -> blood become thicker and incr risk of clogs)
  • dyslipidemia
  • prostatic hyperplasia
51
Q

State the various classes of medications that may worsen ED

A

1) Anticholinergics (Tricyclic antidepressants, Antihistamines, Phenothiazines)

2) Dopamine antagonists (e.g Metoclopramide)

3) SSRI

4) 5-ARIs (Finasteride, Dutasteride)

5) CNS Depressants (benzodiazepines, anti-convulsants)

6) Clonidine, Methyldopa, BBs (except Nevibolol), Thiazide diuretics

52
Q

State when Anti-muscarinic may be indicated in BPH and when it should NOT be started.

A

Add on for patients with irritative/storage symptoms ONLY if PVR < 250mL.

53
Q

State the considerations when selecting pharmacological treatment for BPH (5 total)

A
  • LUTS Severity (AUA-SI score),
  • Prostate size,
  • Concurrent comorbidities,
  • PSA value,
  • Presence of irritative/storage symptoms.
54
Q

What can be done for a patient with AUA-SI score 17 but does not feel bothered by his symptoms?

A
  • Reassessment of symptoms using the AUA-SI, annually or more frequent
  • Lifestyle changes/non-pharmacological measures in the meantime
55
Q

Name examples of non-selective alpha adrenergic inhibitors

A
  • Doxazosin
  • Terazosin
  • Prazosin (not recommended for BPH)
56
Q

Name examples of selective alpha adrenergic inhibitors

A

Alfuzosin, Sidolosin, Tamsulosin

57
Q

What are the contraindication(s) of alpha adrenergic antagonists?

A

Concurrent use with another a1RA (e.g. prazosin, epinephrine)

58
Q

What should be done to reduce risk of IFIS if patient has BPH and is doctor wants to start on alpha adrenergic antagonist?

A
  • Hold off initiating a1RAs until cataract surgery is complete OR
  • Stop 2-3 weeks before surgery
59
Q

Patient with BPH going for corneal surgery in 3 weeks time. Patient’s current medication list: Tamsulosin, Finasteride.

What should you tell the patient?

A

Nothing. IFIS only a risk if patient going for cataract surgery.

60
Q

State when non-selective a1RAs may be preferred over selective a1RAs and when it is not (1 point each)

A

Non-selective a1RAs
1) may be beneficial in patients with concurrent HTN that need additional BP-lowering effect (but should NOT be monotherapy).
2) Avoid in patients with history of syncope (fainting)

Selective a1RAs are used in patients who don’t need added BP-lowering effect.

61
Q

What are the contraindications of 5ARIs?

A

pregnant/females of child-bearing age (teratogenic)

62
Q

What is an important thing to do before initiating 5ARI?

A

Obtain PSA level -> not easily interpretable after initiation

63
Q

Who would benefit most from Tadalafil monotherapy for BPH?

A

Patient who are: younger, low BMI and higher baseline symptoms

64
Q

What are examples of antimuscarinic agents?

A

Oxybutynin, Tolterodine, Solifenacin

65
Q

Which PDE5is need to be taken before food (empty stomach)?

A

Verdanafil and Sildenafil

66
Q

Which PDE5is can be taken before without regards to food?

A

Tadalafil and Avanafil

67
Q

What are the DDIs for PDE5i? (3 total)

A
  • Multiple antihypertensives (incr risk of hypotension)
  • Alcohol (hypotension)
  • CYP3A4 inhibitors (e.g. itraconazole, erythromycin, cimetidine, ketoconazole, clarithromycin, grapefruit or grapefruit juice, ritonavir, saquinavir)

Basically CYP3A4is are: Macrolide, Azoles, Grapefruit, PK inhibitor

68
Q

Contraindications of PDE5i use

A

Concurrent use of Nitrates.

  • Nitrates should be avoided for 12 hrs after avanafil, 24 hrs after sildenafil or vardenafil, and 48hrs after tadalafil
69
Q

What is/are the contraindication for testosterone replacement?

A

Prostate cancer

70
Q

What is the MOA of Alprostadil (Prostaglandin E1 analogue)

A

Stimulate adenyl cyclase and ↑ cAMP -> inducing smooth muscle relaxation -> erection

71
Q

What are the DDIs of Alprostadil

A

concurrent use with PDE5i

72
Q

What is the benefit of Alprostadil over PDE5i?

A

Does not require stimulation to work

73
Q

Compare and contrast Intraurethral and Intracavernosal Alprostadil

A

1) Intracavernosal Alprostadil preferred over intraurethral route due to better efficacy

2) Intracavernosal Alprostadil has higher risk of priapism, bleeding, hematoma (bruising), fibrosis

3) Disadvantage of Intracavernosal also include: fear of needles, invasiveness, lack of spontaneity, complicated administration technique

4) Intraurethral Alprostadil has unique side effects of warmth or burning sensation in urethra, vaginal burning and itching due to route of administration

74
Q

Which PDE5i most associated with muscle pain?

A

Tadalafil

75
Q

Which PDE5i most associated with QT prolongation?

A

Vardenafil

76
Q

Which PDE5i most associated with ocular side effects

A

Sildenafil and Vardenafil

77
Q

List the complications of BPH (total 5).

A

Complications of BPH include: hematuria, acute urinary retention, urinary incontinence, recurrent UTI, bladder stones.

78
Q

What is the PSA level at which BPH likely to progress?

A

> 1.5ng/mL

79
Q

What is the MOA of PDE5i?

A

Specifically inhibits PDE5 enzyme in penis -> ↑ cGMP levels in response to NO-released by sexual stimulation, which results in smooth muscle relaxation and ↑blood flow to the corpora cavernosa, producing an erection

80
Q

Which a1 antagonist most associated with IFIS?

A

Tamsulosin

81
Q

Describe the physiology of Detumescence

A

1) Deactivation of Parasympathetic System
* cGMP is deactivated by an enzyme called phosphodiestarase type 5 (PDE-5) -> stops the vasodilation (prevents the ↑ inflow of blood into penis)
* PDE-5 is the predominant enzyme found in penis

2) Activated Sympathetic System
* Induces smooth muscle contraction via α2 adrenergic receptors of arterioles resulting in a reduction of blood flow

3) Serotonin has been postulated to have inhibitory effects on sexual arousal

82
Q

When should PDE5i be stopped due to ADR?

A

Stop use and seek medical attention if ocular problems, hearing problems or priapism occurs (all are rare but serious)

PR3152 Finals (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions