Erectile Dysfunction Flashcards
Erectile dysfunction is defined as…
Persistent/recurrent inability to achieve/maintain an erection of sufficient rigidity to perimit satisfactory sexual activity for at least 3 months
Sexual dysfunction is more encompassing but may include ED
Recall that an erection occurs via complex interaction between…
Vascular, hormonal, neurological, and psychological systems
The neurological pathway of erection physiology focuses on…
ACh increasing levels of cGMP, cAMP, and nitric oxide - resulting in smooth muscle relaxation that increases arterial blood flow.
ED may occur via any abnormality in…
Vascular, hormonal, neurologic, or psychogenic systems
Up to 25% of ED cases are ____
Medication-induced
Notably with temporal timing
Major risk factors for ED include…
Older age
Lifestyle factors (tobacco, obesity, sedentary)
Medical conditions
Medications
Vascular causes of ED are mostly centered around…
Disease states that compromise vascular flow to corpora cavernosum - most common cause of ED
Associated medical conditions that cause vascular ED include….
Diabetes
Atherosclerosis
HTN
Renal or liver disease
Cigarette smoking
Radiation
ED in healthy men with no other symptoms may be associated with…
Early (subclinical) signs of CAD
Both ED and CAD are linked - both consequences of endothelial dysfunction, leading to restrictions in blood flow
If a person presents with ED they should have these checked…
BP, BG, cholesterol
ED is more prevalent in those with diabetes, compared to those without. This is due to…
Vascular and neurogenic mechanisms
Risk of ED associated with diabetes is related to…
Duration and degree of glycemic control
ED often occurs ____ than in those without diabetes, and may be…
Earlier - may be the presenting symptom
Response to PDE5 inhibitors seems to be ____ in patients with diabetes, therefore…
Lower - higher doses are frequently needed
Regarding the neurological system of ED, sexual arousal causes nerve impulses to travel from the brain, via spinal cord to the genital region:
Conditions that impair nerve conduction to the brain include…
Spinal cord injury
Stroke
Pelvic trauma
Prostate surgery
Regarding the neurological system of ED, sexual arousal causes nerve impulses to travel from the brain, via spinal cord to the genital region:
Conditions that impair nerve conduction to penile vasculature include…
Parkinson’s
Alzheimer’s
MS
Epilepsy
Diabetic or alcoholic neuropathy
Regarding the hormonal aspect of ED, this is the main hormone involved…
Testosterone
Testosterone levels ____ with age, which could contribute to…
Decline = Decreased libido - secondary ED
Common causes of ED that may be psychogenic include…
Stress
Performance anxiety, fear, relationship issues
Depression, other mental disorders
To help with psychogenic-related ED, this could be tried…
Psychotherapy as monotherapy or as adjunct to pharmacologic treatment - typically see greater response compared to organic (vascular) disease
Diagnosis of ED usually involves the following…
Analysis of sexual, medical, social, and medication history - can use standardized questionnaires
Physical exam (pulses, hypogonadism)
Lab tests sometimes
Goals of therapy for ED treatment include…
Improving sexual satisfaction + intimacy
Improving sexual quality of life
Improve overall quality of life
Non-pharmacologic treatment for ED include…
Improve diet + exercise
Smoking cessation
Limit alcohol + recreational drug use
Psychotherapy
Efficacy of non-pharm treatment is…
A good recommendation to improve overall health - may be sufficient alone in some cases
May improve effectiveness of treatment
Usually recommended in adjunction to drug therapy
1st line therapy for ED is…
PDE5 inhibitors
PDE5 inhibitors include these 3 drugs…
Sildenafil
Vardenafil
Tadalafil
They have different PK profiles
Phosphodiesterases is an enzyme that inactivates ____, which function is to…
cGMP - helps with smooth muscle relaxation + inflow of blood into corpora
The phosphodiesterase that is most prominent in the corpora cavernosa is…
Type 5
MOA of PDE5 inhibitors is to…
Inhibit PDE5 enzyme that degrades cGMP in corpora cavernosa. Facilitates erection by prolonging action of cGMP, enhancing nitric oxide-induced smooth muscle relaxation and vasodilation
When using PDE5 inhibitors, ____ is still required to achieve erection.
Sexual stimulation
Efficacy of PDE5 inhibitors are…
Any differences between the 3 in the class? What improves it?
Similar between the 3 PDE5 inhibitors
Improved with education
Are dose related (80% at low dose, further 20% at high dose)
The 1st dose of a PDE5 inhibitor can be efficacious, but…
Will likely see improved success, with successive doses
A PDE5 inhibitor should be tried ____ times before judging success
6-8 times
Non-response is determined by a trial of ____ tries under ____ at max dose.
4-6 tries under optimal conditions at max dose
If a patient has non-response to a PDE5 inhibitor, does that mean they cannot use the other drugs in the class?
No - failure with one PDE5 inhibitor does not rule out a trial of another one.
Peak onset of PDE5 inhibitors are ____, therefore, patients should take them…
60 minutes (120 minutes for tadalafil) - take 30-60 minutes prior to intercourse
Duration of PDE5 inhibitors are…
Which one is unique?
About 4 hours, and can be up to 10-12 hours.
Tadalafil duration is up to 36 hours
Tadalafil = “weekend drug”
All PDE5 inhibitors are metabolized via…
CYP 3A4
Sildenafil + vardenafil = 2C9
Double check dosing in hepatic impairment
THe PDE5 inhibitors that need renal dose adjustments are…
Sildenafil + tadalafil
Most common AE’s with PDE5 inhibitors include…
Vasodilation - headache, flushing, dyspepsia
Dizziness, rash, rhinitis
Other possible AE’s asides from vasodilatory effects from PDE5 inhibitors include…
Back and muscle pain (tadalafil)
Hypotension (sildenafil + vardenafil > tadalafil)
Color visual changes, blurred vision, increased light sensitivity
These are contraindicated with PDE5 inhibitors, because…
Nitrates - vasodilator action of nitrates are amplified and may be fatal
How long should nitrates and PDE5 inhibitors be spaced out?
Sildenafil + vardenafil - 24 hours
Tadalafil - 48 hours
Other notable DI’s with PDE5 inhibitors include…
CYP3A4 inducers + inhibitors - may have to adjust dose
Non-selective alpha1 blockers - possibility of further hypotensive effects
Other antihypertensives are fine as long as BP is OK
Serious AE’s with PDE5 inhibitors include…
Priapism (long, painful erection lasting 4+ hours)
Chest pain
Sudden, unilateral hearing or vision loss
Possibility of QT prolongation with vardenafil
Sexual activity increases possibility of experiencing ____ - therefore, we should avoid use of PDE5 inhibitors in those at high risk of…
Ischemic events and MI - avoid in those with high risk of CV events (unstable angina, severe HF, recent stroke/MI, high risk arrythmia, uncontrolled HTN)
For those 65+ we should start PDE5 inhibitors at…
The lowest possible dosing first, for CV safety
Alprostadil is another medication for ED that works by…
Stimulating increased production of cAMP, causes smooth muscle relaxation of tissues in corpora to restrict venous outflow
Alprostadil is available as…
Intracavernosal injection
Intraurethral insert
Which alprostadil formulation showed better efficacy?
Intracavernosal
However note that onset (¬10 minutes) and duration (¬1 hour) is still similar between both
Notable AE’s with alprostadil include…
Pain (IC - penile fibrosis, IU - urethral pain, burning sensation in partner)
Vasodilatory effects similar to PDE5 - headache, hypotension, dizziness
Rare - priapism; but more common compared to PDE5
Papaverine is another ____ injection that works by…
Intracavernosal injection - inhibits cavernosal phosphodiesterase, inhibiting breakdown of cAMP causing smooth muscle relaxation
Papaverine is typically used in lower doses combined with other intracavernosal injections because of…
Dose-limiting AE’s
Priapism, corporal fibrosis, hypotension, hepatotoxicity
Phentolamine is another ____ injection that works by…
Intracavernosal injection - non-selective alpha blocker that increases cholinergic tone, improving cavernosal filling
Similar to papaverine, phentolamine is also used in combination with other intracavernosal injections to…
Minimize AE’s while maintaing efficacy
Vacuum erection devices work by…
Using a pump that is activated to produce vacuum pressure, drawing arteriolar blood into the corpora cavernosa
Non-invasive and good efficacy in stable mature relationships
With female sexual dysfunction, ____ are not effective. If vaginal symptoms are an issue, we could try…
PDE5 inhibitors - vaginal symptoms = topical estrogen to help enhance lubrication, decrease dyspareunia
