Erectile Dysfunction Flashcards by Jordan Cyr

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

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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

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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

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What are the risk factors for erectile dysfunction?

age
lifestyle (tobacco, obesity, sedentary)
medical conditions
medications

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What is the most common cause of erectile dysfunction?

vascular causes

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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

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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

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Which medical condition sees a higher prevalence of erectile dysfunction?

diabetes

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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

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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

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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

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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

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How might age be a cause of erectile dysfunction?

testosterone levels decline with age which can lead to decreased libido and secondary ED

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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)

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What are common psychogenic causes of erectile dysfunction?

stress, performance/anxiety
fear of STIs or pregnancy, relationship issues
depression, other mental disorders
others

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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

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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

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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

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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

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What are the goals of therapy for erectile dysfunction?

improve sexual satisfaction and intimacy
improve sexual quality of life
improve overall quality of life

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What are the non-pharmacologic treatment options for erectile dysfunction?

improve diet and exercise
smoking cessation
limit alcohol/recreational drug use
psychotherapy

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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

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What is 1st line for erectile dysfunction?

PDE5 inhibitors

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What are examples of PDE5 inhibitors?

sildenafil
vardenafil
tadalafil

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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