Brainscape's Knowledge GenomeTM

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


See full index

imed3004 COPY > Drug treatment of Prostate Diseases and Erectile Dysfunction > Flashcards

Drug treatment of Prostate Diseases and Erectile Dysfunction Flashcards

1
Q

What kind of organ is the prostate?

A

Fibromuscular and glandular

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

What are the zones of the prostate?

A

Central zone

Transitional zone (20% cancers)

Peripheral zone (70% cancers)

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

Where in the prostate are androgen receptors located?

A

In both stomal and epithelial cells

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

What does DHT do? How is it produced?

A

Acts on androgen R 10x more strongly than testosterone

It is produced by 5-alpha reductase (type 2 isoenzyme in the prostate)

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

What kind of receptor is the androgen receptor?

A

It is a cytosolic receptor which goes to the nucleus and acts as a transcription factor

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

What part of the prostate undergoes overgrowth?

A

Nodular overgrowth occurs in the transitonal zone

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

What causes overgrowth?

A

Androgens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Does BPH cause cancer to develop?

A

No it does not predispose to cancer.

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

What are the symptoms of BPH?

A

Obstructive symptoms

Irritative symptoms: dysuria, frequency, urgency, nocturia

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

Why are alpha1 antagonists used?

A

Alpha1 receptors trigger contraction of smooth muscles in the prostate.

Thus using them relieves irritation and increases blood flow to the prostate

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

What are the side effects of alpha 1 antagonists?

A

Fall in BP

Postural hypotension

Tiredness

Headache

Ejaculatory dysfunction (tamsulosin)

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

What DDIs do alpha1 antagonists have?

A

They interact with phosphodiesterase-5 inhibitors (sildenafil or verdenafil) to potentiate hypotension.

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

What are the alpha1 inhibitors in use today?

A

Prazosin

Terazosin

Tamulosin (some selectivity for the bladder)

Alfuzosin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which alpha1 inhibitor is most commonly associated with ejaculatory dysfunction?

A

Tamulosin

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

What are 5-alpha reductase drugs used for?

A

Indicated for moderate to severe BPH, reduces prostate volume, improves symptoms and flow, reduces disease progression, decreases requirement for surgery.

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

How are alpha1 inhibitors and 5-alpha reductase inhibitors different?

A

5-alpha reductase inhibitors actively stop progression of the disease and cause regression in size of the prostate. Alpha1 inhibitors only affect muscles.

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

What are the side effects of 5 alpha reductase inhibitors?

A

Sexual function reduced

Ejaculatory problems

Gynocomastia

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

How do androgens affect the prostate?

A

They increase its size (prostate growth is androgen dependent)

Prostate cancer development is also dependent on androgens

Anti-androgen therapy kills cancer cells and reduces proliferation however, eventually prostate becomes castrate resistant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the androgen receptor antagonists used for advanced prostate cancer?

A

Flutamide

Bicalutamide

Nitrutamide

Enzalutamide

Cyproterone acetate

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

What are the inhibitors of androgen production subclasses?

A

GnRH analogues: Leuprotide, goserelin

Inhibitors of CYP17A1: Abiraterone acetate

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

How is maximal blockade of androgen receptors achieved?

A

Combination of GnRH agonist with androgen receptor antagonist

The effect of these is better than either one alone.

22
Q

What is flutamide? How is it typically used?

A

A non-steroidal synthetic androgen receptor antagonist (competitive inhibitor)

Used with GnRH agonist to prevent flare of disease from GnRH therapy.

23
Q

What are the side effects of flutamide, enzalutamide, and cyproterone acetate?

A

Anti-androgen effects:

Gynaecomastia

Hot flashes

Reduced libido

Reduced muscle mass, increased visceral fat

Insulin resistance, hyperglycaemia, metabolic syndrome

Osteoporosis and increased risk of low trauma fracture

Diarrhoea

Abnormal liver function tests

Side effects shared by all these drugs.

24
Q

What is enzalutamide?

A

Newer androgen receptor inhibitors.

Higher affinity than bicalutamide

Reduced efficacy of AR nuclear translocation impairing both DNA binding and coactivator recruitment

25
Q

What is cyproterone acetate?

A

A progesterone derived hormone. Binds multiple androgen receptors.

26
Q

Which of the drugs has been shown to work even in castrate resistant prostate cancer?

A

Enzalutamide

27
Q

What is the function of cyproterone acetate?

A

It Does 2 things:

Competes with DHT for androgen receptor (partial agonist)

Suppresses hypothalamic GnRH secretion

28
Q

Why do GnRH agonists work to block testosterone production?

A

GnRH secretion normally occurs in a pulsatile manner

When given constantly it blocks gonadotrophic secretion.

Beware: It creates an initial flare in testosterone when used.

29
Q

What are the side effects of GnRH agonists?

A

Same as flutamide, enzalutamide, and cyproterone acetate:

Bloackage of androgen receptors has anti-androgenic effects.

30
Q

How are GnRH agonists administered?

A

Subcutaneous or IM injection

Also used for other conditions were suppression of gonadotrophins is indicated (Endometriosis, precocious puberty, IVF)

31
Q

What does abiraterone acetate do?

A

Specifically inhibits cytochrome P450 (cyp)17A1 which is an essential enzyme in the biosynthesis of testosterone.

Inhibits androgen production in testis and adrenal.

Combined with prednisolone for treatment in metastatic castration-resistant prostate cancer

32
Q

What are the side effects of abiratone acetate?

A

Hypertension and hypokalaemia due to ACTH driven elevated mineralocorticoid levels - prevent with concurrent prednisolone administration. This is due to production of aldosterone increasing.

Abnormal liver function tests - monitor LFTs monthly

33
Q

What drugs are used in patients with skeletal metastases from prostate cancer?

A

Zolendronic acid (bisphosphonates)

Denosumab (RANKL inhibiting antibodies)

Both are osteoporosis therapies

34
Q

What are side effects of using osteoporosis drugs in skeletal metastases?

A

Can cause hypocalcaemia or osteonecrosis of the jaw.

35
Q

What is erectile dysfunction?

A

Inability to get or maintain an erection for sexual intercourse

36
Q

How is erection controlled?

A

Higher cortical centers in the brain control sexual attraction

Pre-optic and paraventricular centers

Spinal cord parasympathetic pathways (S2 to S4)

Neurovascular events result in the release of the neurotransmitter nitric oxide from both nerves and endothelial cells

37
Q

What is erectile dysfunction an indicator of?

A

Future cardiovascular events in both diabetic and non-diabetic men

38
Q

What does NO do to endothelial smooth muscle cells?

A

NO activates a receptor on the endothelial cell which activates adenylyl cyclase which converts GTP to cGMP which stimulates a cascade of events which open blood vessels to the corpus cavernosum.

39
Q

What are the drugs used in people with erectile dysfunction?

A

Phosphodiesterase inhibitors - 5. (sildenafil)

They block the degradation of cGMP by PDE5s

40
Q

What could potentially cause erectile dysfunction?

A

Depression

Anxiety

Androgen deficiency

Arterial disease

Drugs (Antihypertensives and SSRIs)

Diabetes mellitus

41
Q

What are the phosphodiesterase inhibitors in use?

A

Sildenafil (Viagra)

Vardenafil (Levitra)

Tadalafil (Cialis)

42
Q

What do PDE-5 inhibitors do?

A

Increase cGMP in response to nitric oxide release resulting in increased smooth muscle relaxation and vascular engorgement

Only acts in presence of sexual stimulation

No effect on libido or in men with normal erectile function

43
Q

What are the side effects of PDE-5 inhibitors?

A

Headache

Facial flushing

Nasal congestion

Dyspepsia

Side effects are usually mild and transient

Rarely could increase nonarteritic anterior ischaemic optic neuropathy

44
Q

What are the PDE subtype selectivity and specific side effects?

A

Sildenafil binds to PDE-6. Subtype 6 is expressed in retina which means there can be blue discolouration seen which only lasts 2 - 3 hours.

Tadalafil binds to PDE-11 PDE-11 is found in skeletal muscle which means tadalafil can cause back and muscle pain.

45
Q

How long are sildenafil and tadalafil effective for?

A

Sildenafil: 30 - 120 minutes action (half life of 4 hours)

Tadalafil has a duration of action of 36 hours

46
Q

When are PDE-5 inhibitors contraindicated?

A

Men who are also taking nitrates for heart disease to avoid hypertension

Caution in men with severe CVD

Severe postural hypotension

Severe aortic stenosis

Retinitis pigmentosa

Introduce with caution in men using alpha blockers

47
Q

Who benefits most from PDE-5 inhibitors?

A

ED from most causes (organic or psychogenic) have been shown to benefit.

Efficacy of 60 - 80% but reduced efficacy in more severe ED

48
Q

Who has lower responsiveness to PDE-5 inhibitors?

A

Post radical prostatectomy

Diabetics

49
Q

Why is intracavernosal alprostadil (synthetic form of ProstaGlandin E1) not used as often as the other medication?

A

Despite 70 - 80% efficacy it is limited by its adverse effects:

Penile pain (10 - 20%)

Penile fibrotic changes (5 - 10%)

Priapism (1%) - if this occurs it can be countered by pseudoephedrine

50
Q

What alternative intracavernosal drug combinations are used?

A

Papaverine (non-specific PDE inhibitor)

Phentolamine (non-selective alpha adrenergic antagonist)

Alprostadil

51
Q

What can be administered to patients with erectile dysfunction due to low androgen levels?

A

Androgen replacement therapies. No role in management in anyone else.

52
Q

When is transurethral alprostadil used? What are the effects?

A

Used as an intraurethral suppository with the aid of an applicator

Less effective than intracavernosal injections

Systemic absorption can result in hypotension

imed3004 COPY (50 decks)

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