Erectile Dysfunction Flashcards
Define erectile dysfunction.
Persistent (at least 6 months) inability to achieve / maintain an erection of sufficient duration and firmness to complete satisfactory intercourse
Describe the physiology behind an erection
HINT: Blood flow, smooth muscle, parasympathetic system and functional hormonal system
Arterial blood flow into penis increases while venous blood flow out of penis decrease
Upon erection, smooth muscle relax to allow the corpora cavernosa to fill up with blood. Swelling occurs and thus, the compression of venules against the tunica albuginea
Parasympathetic system is activated due to ACh. Increase nitric oxide lead to increase in activity of GMP and hence cGMP. Furthermore, ACH and prostaglandin E also increasea adenyl cyclase and cAMP. Therefore, smooth muscle vasodilation occurs, increasing blood flow
The production of testosterone also encourages libido
Describe what happens after an erection when the penis is flaccid.
Deactivation of parasympathetic system occurs when cGMP is deactivated by PDE5
Activation of sympathetic system occurs when alpha 2 adrenergic receptors are induced causing smooth muscle contraction and reducing blood flow
What are the subgroups of organic etiology behind ED? In each subgroup, name an example.
Vascular: Arteriosclerosis, peripheral vascular disease, hypertension, diabetes
Hormonal: Hypogonadism, hyper-prolactinemia (suppress testosterone production)
Nervous system:
- Central: stroke, CNS trauma, spinal cord injuries
- Peripheral: Diabetes, Neuropathy and urethral surgery
Medication induced: too many
Name the medications associated with ED and their mode of action.
NOTE: To refer to notes for alternatives to consider
Clonidine, methyldopa, beta blockers (except nebivolol), thiazide diuretics
- Decrease penile blood flow
Anticholinergics: decrease ACh activity
Dopamine antagonist (e.g. metaclopramide): decreases dopamine
Selective serotonin reuptake inhibitors : decrease serotonin and testosterone
5ARI: Finasteride, Dutasteride : decrease testosterone
CNS depressants (e.g. benzodiazepam, anticonvulsants): suppress psychic stimulus
What are some psychogenic etiology of ED
Malaise
Loss of attraction
Stress
Performance anxiety
Mental disorders
Sedation
What are other etiology of ED?
Smoking
Obesity
Alcohol
Illicit drug use
What are the signs and symptoms of ED besides the inability to achieve an erection?
Loss of interest in sexual activity
Depression
Performance anxiety
Embarrassment
Anger
Low self esteem
Disharmony in a relationship
How is an erectile dysfunction diagnosed?
Assess patient sign and symptoms
Use sexual health inventory for men scoring system
Identify underlying cause of erectile dysfunction by checking medical. social and surgical history
Conduct any labs if needed (blood; lipid; testosterone)
What does the score in SHIM mean?
Mild / no ED: 17-21
Moderate to severe: < 11
Why is a CV evaluation needed for all patients with erectile dysfunction?
Sexual activity causes sympathetic activation. Increase BP and HR. Increasing the risk of myocardial infarction
What should I do for patients who come back with high risk of CVD from their CV evaluation?
Cardiac rehabilitation
Regular exercise
What are some nonpharmacological advice to give patients with ED?
Address the modifiable risk factors such as smoking cessation, weight control, control glucose, BP and lipids; exercise and decrease alcohol intake
Psychotherapy
VED
Surgery
What are some pharmacological agents to consider giving patients?
PDE5 inhibitors
Testosterone replacement
Alprostadil
What is the mechanism of action of PDE5 inhibitors?
- Inhibit PDE5 enzyme
- Induce catabolism of cGMP
- Enhance cGMP activity
- Induce smooth muscle relaxation
- Erection
What are the 4 agents of PDE5 inhibitors used in ED?
Sildenafil
Vardenafil
Tadalafil
Avanafil
Can PDE5 inhibitors work immeadiately?
No. Requires sexual stimulation to enhance erection and hence adviced to take it before sex
Which PDE5 inhibitors require hepatic dose adjustment?
Sildenafil, Vardenafil and Tadalafil
Which PDE5 inhibitors require renal dose adjustment?
Sildenafil and Tadalafil
Which PDE5 inhibitors must be taken on an empty stomach?
Sildenafil
Vardenafil
What group of patients should a lower initial dose be considered?
Patients > 65y
Those on alpha blockers
Those with renal failure
Those taking CYP3A4 inhibitors
What are the general adverse effects of PDE5 inhibitors?
Headache
Rhinitis
Backache
Flushing
Muscle and back pain
Dizziness
Hypotension
What are some major adverse events to look out for those on PDE5i?
Prolonged erection: to seek ED if > 4h
Sudden hearing loss
QTc prolongation : Vardenafil
Muscle pain due to tadalafil high PDE 2 affinity
What is a red flag seen in sildenafil and vardenafil and why does this occur?
Ocular problems such as color discrimination, sensitive to light, norarteritic anterior ischemic optic neuropathy (NAION)
Both agents have increased affinity to PDE6 in the retina
What are some risk factors of NAION? Why does it occur?
Risk factors: DM, smoking, HTN, CVD, Dyslipidemia, more than 50 years
Happens when blood flow to optic nerve is blocked
What are potential drug drug interactions to consider for those on PDE5 inhibitors?
Nitrates
Antihypertensives
Alcohol
CYP3A4 inhibitors: Increase PDE5 inhibitor concentration
How should safety be monitored for those on PDE5 inhibitors?
Check for BP, side effects, DDI and cardiac health status
What should you check for in the event of a failure upon initiation of PDE5 inhibitors? If not, what should be done?
Check if the PDE5i was
- Administered with food
- timing and frequency of dosing
- Lack of adequate sexual stimuli
- Titrated to max dose
Change to a different class or consider invasive therapy
What is the purpose of testosterone?
Restore serum testosterone to normal range
What are the indications of using testosterone for ED?
Symptomatic hypogonadism which is confirmed by low libido and serum testosterone concentration
What are the adverse drug reactions of testosterone therapy for ED?
Irritability
Aggressive behavior
Undesirable hair growth
High BP
Hepatotoxicity
Dyslipidemia
Polycythemia
Prostatic hyperplasia
Who is contraindicated for use of testosterone?
Those with prostate cancer
What are the monitoring parameters for testosterone in ED? How often should they be monitored?
Serum testosterone within 1-3 months and 6-12 months
Discontinue if no improvement after 3 months
Describe the mechanism of action for alprostadil.
Stimulates adenyl cyclase and increase cAMP
Induce smooth muscle relaxation causing an erection
What is DDI to avoid with use of alprostadil?
PDE5 inhibitors
What are the routes of administration for alprostadil?
Intraurethral and intracavernosal (preferred)
What is the ADR associated with intraurethral alprostadil?
Pain
Warmth / burning sensation
Voiding difficulties
Bleeding / spotting priapism
Partners may experience vaginal burn / itch
What are the advantages and disadvantages of using alprostadil intracavernosal?
Advantage: High efficacy
Disadvantages
- Invasive
- May lack spontaneity as need to be done before sex
- Great risk of ADR such as priapism, bleeding, hematoma and fibrosis
- Fear of needles
- Complicated administration
