Erectile Dysfunction Flashcards
What is erectile dysfunction?
the persistent/recurrent inability to achieve or maintain an erection of sufficient rigidity to permit satisfactory sexual activity for at least 3 months
How does an erection occur?
complex interaction between the vascular, hormonal, neurological, and psychological systems
-when stimulated, ACh produces an erection through multiple pathways which ultimately increases the levels of cGMP, cAMP, and nitric oxide
-this results in smooth muscle relaxation which increases arterial blood flow, allowing the corpora to fill with blood
How does erectile dysfunction occur?
any abnormality in the vascular, hormonal, neurologic, or psychogenic system
- ~80% of ED cases related to organic disease (vascular, hormonal, or neurologic causes)
- < 10% of ED cases are due to psychogenic factors
-up to 25% of ED cases are medication-induced
What are the risk factors for erectile dysfunction?
age
lifestyle (tobacco, obesity, sedentary)
medical conditions
medications
What is the most common cause of erectile dysfunction?
vascular causes
What are vascular causes of erectile dysfunction?
disease states that compromise vascular flow to the corpora cavernosum
-diabetes
-atherosclerosis
-hypertension
-renal disease
-liver disease
-excessive cigarette smoking
-radiation
How is ED a predictor of CAD?
ED and CAD are linked as they are both consequences of endothelial dysfunction, leading to restrictions in blood flow
-ED in healthy men may be associated with early signs of CAD
-if persons present with ED, they should have BP, BG, and cholesterol checked
Which medical condition sees a higher prevalence of erectile dysfunction?
diabetes
Why do diabetics have a higher prevalence of erectile dysfunction?
due to vascular and neurogenic mechanisms
-risk related to duration and glycemic control
-occurs at an earlier age than in those without diabetes and may be a presenting symptom
How does response rate of PDE5 inhibitors differ in diabetics?
response seems to be lower than in those w/o diabetes
-higher doses are frequently needed
How can neurologic diseases cause erectile dysfunction?
sexual arousal causes nerve impulses to travel from the brain via the spinal cord to the genital region
What are some neurologic conditions that might cause erectile dysfunction?
conditions that impair nerve conduction to brain:
-spinal cord injury
-stroke
-pelvic trauma, prostate surgery
conditions that impair nerve conduction to penile vasculature:
-Parkinsons, Alzheimers, MS, epilepsy
-diabetic neuropathy, alcoholic neuropathy
How might age be a cause of erectile dysfunction?
testosterone levels decline with age which can lead to decreased libido and secondary ED
Differentiate primary and secondary hypogonadism.
primary hypogonadism:
-can occur with normal aging process or surgical removal of testes
secondary hypogonadism:
-can result from hypothalamic or pituitary disorders
-hypo/hyperthyroidism
-may result from hyperprolactinemia (rarely)
What are common psychogenic causes of erectile dysfunction?
stress, performance/anxiety
fear of STIs or pregnancy, relationship issues
depression, other mental disorders
others
What is the treatment for psychogenic causes of erectile dysfunction?
psychotherapy as monotherapy or as an adjunct to pharmacologic treatment
typically see a greater response than with organic disease
What are some drug-induced causes of erectile dysfunction?
recreational drugs; opioids, alcohol, cigarettes, anabolics
psychotropics (SSRI, OLZ, RIS, TCA, MAOIs); lithium; diazepam
CV: thiazides, BBs, CCBs, digoxin, acetazolamide, spironolactone, clonidine, methyldopa, gemfibrozil
5-alpha reductase inhibitors
antiandrogens (leuprolide, ketoconazole, spironolactone)
dopamine antagonists (metoclopramide, phenothiazines)
anticonvulsants: CBZ, phenytoin, phenobarbital
What are the various mechanisms for drug-induced erectile dysfunction?
anticholinergic activity
increased prolactin levels which inhibits T production
suppress T (diminished libido)
suppress psychogenic stimuli
reduce blood flow to penis
What are the components in the diagnosis of erectile dysfunction?
sexual history
medical and surgical history
social history
medication history
physical exam
lab tests - sometimes
What are the goals of therapy for erectile dysfunction?
improve sexual satisfaction and intimacy
improve sexual quality of life
improve overall quality of life
What are the non-pharmacologic treatment options for erectile dysfunction?
improve diet and exercise
smoking cessation
limit alcohol/recreational drug use
psychotherapy
What is the evidence for non-pharmacologic therapy in erectile dysfunction?
good recommendations to improve overall health
may be sufficient in some cases
may help improve effectiveness of treatment
What is 1st line for erectile dysfunction?
PDE5 inhibitors
What are examples of PDE5 inhibitors?
sildenafil
vardenafil
tadalafil
What is the role of PDE5?
inactivates cGMP (which helps with smooth muscle relaxation and inflow into corpora)
-PDE5 is prominent in the corpora cavernosa
What is the MOA of PDE5 inhibitors?
inhibit the PDE5 enzyme that degrades cGMP in the corpora cavernosa
this facilitates an erection by prolonging the action of cGMP which enhances nitric oxide-induced smooth muscle relaxation and vasodilation
What improves the efficacy of PDE5 inhibitors?
efficacy is improved with education
-1st dose can be efficacious, but can see improved success with successive doses
How many times should a PDE5 inhibitor be tried to judge success?
try 6-8 times before judging their success
non-response in 4-6 tries under optimal conditions at max dose
What is the efficacy of PDE5 inhibitors?
similar for all 3: success rates from 60-70%
What does the effect of PDE5 inhibitors depend on?
effect is dose related
-80% of effect at low dose
-further 20% at high dose
What should be done with failure of one PDE5 inhibitor?
failure with one PDE5 inhibitor does not rule out a trial of another
How do the PDE5 inhibitors compare in terms of peak onset?
sildenafil: 60 min
tadalafil: 120 min
vardenafil: 60 min
How do the PDE5 inhibitors compare in terms of duration of action?
sildenafil: ~ 4 hours (up to 12 hours)
tadalafil: up to 36 hours
vardenafil: ~ 4 hours (up to 10 hours)
What is the impact of food on PDE5 inhibitors?
sildenafil: high-fat meal delays onset
tadalafil: food has no impact
vardenafil: high-fat meal decreases absorption
How should PDE5 inhibitors be taken?
30-60 min prior to intercourse
-120 min for tadalafil
arousal is still needed
When do PDE5 inhibitors require dosing adjustments?
hepatic disease
renal disease (except vardenafil)
How are PDE5 inhibitors metabolized?
all metabolized via CYP 3A4 (major pathway)
sildenafil & vardenafil: CYP 2C9 (minor pathway)
What are the drug interactions of PDE5 inhibitors?
nitrates –> severe hypotension (CI)
CYP 3A4 inducers and inhibitors (caution)
-ketoconazole, protease inhibitors, erythromycin, GJ
non-selective a1-blockers –> hypotension
-terasozin and doxasozin
How long should nitrates be avoided after using a PDE5 inhibitor?
48 hrs if tadalafil
24 hrs if sildenafil or vardenafil
How is the PDE5 inhibitor and a1-blocker drug interaction managed?
space dosing by 4-6 hrs if used together
Can antihypertensives be used with PDE5 inhibitors?
okay as long as BP is fine
What does sexual activity increase the risk of in those with serious CVD?
sexual activity increases the chances of experiencing ischemic events and MI
Which PDE5 inhibitor has the option for daily dosing?
tadalafil
What are the common adverse effects of PDE5 inhibitors?
most common:
-headache
-flushing
-dyspepsia
-dizziness
-rash
-nasal congestion/rhinitis
overall well-tolerated
What are some less common side effects of PDE5 inhibitors?
back and muscle pain - tadalafil
-inhibition of PDE11 in skeletal muscle
hypotension - sildenafil and vardenafil > tadalafil
-inhibition of PDE1
-8-10 mmHg SBP and 5-8 mmHg DBP within an hour
-lasts a few hours
color visual changes
-inhibition of PDE6 in the retina
-blurred vision, light sensitivity
-loss of blue-green differentiation; dose-related
Which PDE5 inhibitor have the greatest risk of loss of blue-green differentiation?
sildenafil > vardenafil > tadalafil
What are the rare but serious adverse effects of PDE5 inhibitors?
sudden unilateral hearing loss
NAION - sudden, unilateral, vision loss
QT prolongation (vardenafil)
priapism
chest pain
What is priapism?
long, painful erection > 4 hrs
it is a medical emergency
What is the MOA of alprostadil?
stimulates increased production of cAMP and cause smooth muscle relaxation of tissues in the corpora & restricts venous outflow
What are the routes of administration for alprostadil?
intracavernosal injection
intraurerthral insert
How should alprostadil be used?
inject 10-30 min pre-sex
When should the alprostadil dose be reduced?
if erection lasts > 1 hr
What can be said about the onset and duration of alprostadil?
quick on, quick off
-onset: 10 min
-duration: 1hr or less
What are the adverse effects of alprostadil?
IC: penile fibrosis; rotate site, massage site upon injection
IU: urethral pain; may cause burning sensation in partner
others: dizziness, decrease HR, headache, hypotension
Which agent is priapism more common with?
injectable alprostadil
What is the MOA of papaverine?
inhibits cavernosal PDE (non-selective), thereby decreasing catabolism of cAMP and causing smooth muscle relaxation
What is the onset and duration of papaverine?
rapid onset (10 min) with a DoA < 1hr
What is the use of papaverine?
used in lower doses combined with other ICI therapies b/c of dose-limiting AEs
What is the MOA of phentolamine?
non-selective alpha-blocker; it increases cholinergic tone leading to improved cavernosal filling
What is the use of phentolamine?
used in combination only
-monotherapy requires high doses which cause hypotension and dose limiting AEs
Can testosterone be used for erectile dysfunction?
should not prescribe if ED is the only issue but can still help with the symptoms
What is a vacuum erection device?
plastic cylinder is placed over the penis, the pump is activated to produce vacuum pressure and arteriolar blood is drawn into the corpora cavernosa
What are the pros and cons of vacuum erection devices?
pros:
-non-invasive
-good efficacy in stable, mature relationships
-can be used alone or in combination with ICIs
cons:
-tightness
-non-discreet
-bleed risk if on blood thinners
What are the treatment options for female sexual dysfunction?
treatment options are limited
-PDE5i: not effective, could maybe decrease SSRI AEs
-topical estrogen: may enhance lubrication, decrease dyspareunia
-testosterone: controversial
What is flibanserin?
to treat generalized hypoactive sexual desire disorder
risk of severe hypotension and fainting
only modest improvement with some contraindications
