IC19 Erectile dysfunction Flashcards
definition
incidence
- Persistent (at least 6 months) inability to achieve/ maintain erection for sufficient duration & firmness to complete sexual intercourse
- Affects QOL
- Increased incidence with age (>40years)
How erection works
changes in BF
Smooth muscle relaxes → more space for blood to enter
Changes in blood flow:
* Corpora cavernosa fills up with blood ⇒ increases inflow
* Swelling → compression of venules against tunica albuginea ⇒ reduced outflow
flaccid vs erection (difference in BF)
Flaccid
Blood flow into penis = blood flow out of penis
Erection
Erection arterial flow into penis > venous outflow
How erection works
activation by PNS
ACh, Prostaglandins + overall effect
Ach
* increases creation of nitric oxide (NO)
* Increases activity of guanylate cyclase
* Increases cyclic guanosine monophosphate (cGMP)
Ach & prostaglandins E
* Increases adenylyl cyclase
* Increases cyclic adenosine monophosphate (cAMP)
Overall effect
Smooth muscle relaxation & vasodilation ⇒ increase blood inflow
Functional hormonal system
purpose of testosterone, testing & treatment
- Testosterone → encourage libido (sexual drive)
Low testosterone ≠ ED, may have normal sexual fx - No need to test for patients with no symptoms
- If have symptoms + low testosterone levels ⇒ can replace
physiology of detumescence
1. Deactivating PNS
* cGMP deactivated by phosphodiesterase type 5 [PDE5]
* Vasodilation stops & vasoconstriction occurs
* Prevents inflow of blood to penis
2. Activated SNS
* Induces smooth muscle contraction via α2 adrenergic receptors of arterioles
* Reduction in blood flow
3. Serotonin
Postulated inhibitory effects on sexual arousal
etiology of ED
- organic
- psychogenic
- mixed
- others
etiology: (1) organic
systems affected
Vascular: lack of BF entering penis due to narrowing of vessels
* Atherosclerosis, peripheral vascular disease (PVD), HTN, DM
Hormonal
* Hypogonadism → reduced testosterone
* Hyper-prolactinemia → suppression of testosterone production
Nervous: loss of sensation
etiology: (1) organic
medication induced + MOA
BP control
* Clonidine, Methyldopa, Beta Blockers (with the exception of Nebivolol), Thiazides Diuretics
* Decreases penile BF
Anticholinergics
* Tricyclic antidepressants, 1st generation AH, phenothiazines
* Decreases ACh activity
Dopamine antagonists
* Metoclopramide
* Dopamine can cause sexual arousal/ stimulation
Serotonin Selective Reuptake Inhibitors (SSRIs)
* Increases Serotonin in brain/ Decreased testosterone
5ARIs
* Finasteride, Dutasteride
* Decreases testosterone
CNS depressants
* Benzodiazepines, anticonvulsants
* Suppress perception of psychic stimulus (increased drowsiness)
etiology: (2) psychogenic
Due to thoughts/ feelings (psychological) rather than physical pathology
Malaise, loss of attraction, stress, performance anxiety, mental disorders, sedation
etiology: (4) others
Social habits: smoking, excessive alcohol intake, illicit drug use
Obesity
signs & symptoms of ED
- Loss of interest in sexual activities, performance anxiety
- Depression, anger, low self-esteem, embarrassment
- Disharmony in a relationship
evaluation of ED
Sexual health inventory for men (SHIM)
Signs & symptoms
Sexual health inventory for men (SHIM)
* Mild to no ED: 17 - 21 points
* Moderate to severe ED: <11 points
Workup to identify underlying causes of ED
* Medical hx/ medications → organic causes
* Social hx
* Surgical hx
* Lab results → blood glucose, lipid profile, testosterone (only if symptomatic)
evaluation for CVD
indication, reasoning, when to test, management of CVD
- Required for all patients with ED
- Possible early symptom of comorbid CVD
Sexual activity → SNS activation may increase BP & HR ⇒ increased risk of MI
When to test
* Low risk of CVD: ok
* unknown/ not low risk: exercise stress testing to evaluate exercise capacity
* unstable/ severe symptomatic CVD: defer until condition stabilise
Cardiac rehabilitation & regular exercise → good for reducing risk of CV complications with sexual activity
non-pharmacological management
Address modifiable RF
* Stop smoking, weight control, control glucose/ BP/ lipids, exercise, decrease alcohol intake
Psychotherapy
Devices: vacuum erection devices
Surgery: penile implant
pharmacological management
- PDE5 inhibitor
- testosterone replacement
- alprostadil
(1) PDE5i: MOA
- inhibit PDE5 enzyme which induces catabolism of cGMP
- enhance cGMP activity → induce smooth muscle relaxation ⇒ erection
(1) PDE5i: indication & requirements
First line agents → that is if no symptomatic hypogonadism (lack of testosterone)
REQUIRES sexual stimulation → then can cause & enhance erection
Failure rates ~30-40%
(1) PDE5i: drugs available
- sildenafil
- tadalafil
- vardenafil
- avanafil
(1) PDE5i: sildenafil
starting dose, dose range, onset & duration of action, dose adj, food
- 50 mg PO 1 hour before intercourse
- 25-100 mg
- 15-60 mins
- 4h
- Empty stomach
- May require hepatic & renal dose adjustments
(1) PDE5i: tadalafil
starting dose, dose range, onset & duration of action, dose adj, food
- 5 mg PO up to 36 hours before intercourse
- 5-20 mg
- 2.5-5 mg PO daily (Daily dose)
- 15 mins - 2 hours
- 36h
- Regardless of food
- May require hepatic & renal dose adjustments
(1) PDE5i: vardenafil
starting dose, dose range, onset & duration of action, dose adj, food
- 10 mg PO 1 hour before intercourse
- 5-20 mg
- 25-60 mins
- 4h
- Empty stomach
- May require hepatic dose adjustments
(1) PDE5i: avanafil
starting dose, dose range, onset & duration of action, dose adj, food
- 100 mg PO 30 mins before intercourse
- 50-200 mg
- 15-30 mins
- 6h
- Regardless of food
(1) PDE5i: indications for lower dose
- Patients ≥ 65y/o
- those taking alpha blockers
- Patients with renal failure
- Taking CYP3A4 Inhibitors: may increase the serum concentrations of PDE5 Inhibitors
(1) PDE5i: SE
general + specific for each drug
- Headache, rhinitis, flushing, muscle & back pain, dizziness, hypotension
- Prolonged erections & priapism
Must seek ED treatment if >4 hours - Sudden hearing loss (very rare)
May be present with tinnitus & dizziness - QTc prolongation (Vardenafil)
- Muscle pain (esp Tadalafil with PDE11 affinity)
- Ocular problems (sildenafil & vardenafil with affinity to PDE6 in retina)
Reversible problems with colour discriminating (blue from green)
Sensitivity to light
ischemia of optic nerve due to hypoperfusion caused by PDE5i
Risk factors: DM, smoking, HTN, CVD, dyslipidemia, and age >50 y/o
Patients with sudden decreased vision or vision loss to stop use and look for immediate medical attention
(1) PDE5i: DDI
- nitrates + PDE5I ⇒ potentially fatal hypotension
Should avoid nitrates 12 hours after avanafil, 24 hours after sildenafil/ vardenafil & 48 hours after tadalafil - Increased risk of hypotension: Using multiple antihypertensives & Alcohol intake
- CYP3A4 inhibitors ⇒ increases concentration of PDE5I
(2) testosterone replacement: purpose
Restore serum testosterone levels to normal range (300–1100 ng/dL; 10.4– 38.2 nmol/L)
(2) testosterone replacement: indication
hypogonadism with symptoms ⇒ first line
(1) decreased libido
(2) low serum testosterone concentrations
(2) testosterone replacement: SE
c/i
irritability, aggressive behaviour, undesirable hair growth, BP, hepatotoxicity, dyslipidemia, polycythemia, prostatic hyperplasia (C/I for prostate Cancer)
(2) testosterone replacement: dosage form
IM injection, buccal, patches, topical gel, body spray, nasal spray & PO
(2) testosterone replacement: monitoring
serum testosterone within 1–3 months and at 6- to 12- month intervals
* discontinue if no improvement after 3 months
(3) alprostadil: MOA
- prostaglandin E1 analog stimulates adenyl cyclase → increased cAMP
- Induce smooth muscle relaxation ⇒ erection
(3) alprostadil: background
sexual stimulation, onset, DDI
- NOT REQUIRE sexual stimulation
- Fast onset: 5-10 mins
- DDI: cannot use with PDE5I
(3) alprostadil: dosage forms
- intraurethral pellet
- intracavernosal
(3) alprostadil: intraurethral pellet
duration of action
30-60 mins
(3) alprostadil: intraurethral pellet
SE
- pain, warmth or burning sensation in the urethra
- Voiding difficulties, bleeding or spotting
- Priapism
- partners may experience vaginal burning or itching
(3) alprostadil: intracavernosal
benefits
Better efficacy; preferred route
(3) alprostadil: intracavernosal
risks & disadvantages
- higher risks of priapism, bleeding, hematoma, fibrosis
Disadvantages:
* Fear of needles, invasiveness
* lack of spontaneity
* Complicated administration technique
(3) alprostadil: intracavernosal
titration
Titration in healthcare setting to duration of ≤1 hr, then self-administered no more than 3x per week
